CN111808057B - 利用α-O-烯基砜作为亲电试剂的铃木反应及其应用 - Google Patents
利用α-O-烯基砜作为亲电试剂的铃木反应及其应用 Download PDFInfo
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- CN111808057B CN111808057B CN201910285915.4A CN201910285915A CN111808057B CN 111808057 B CN111808057 B CN 111808057B CN 201910285915 A CN201910285915 A CN 201910285915A CN 111808057 B CN111808057 B CN 111808057B
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- FJZNNKJZHQFMCK-LRDDRELGSA-N 1-[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]-3-phenylurea Chemical compound C1(=CC(=CC(=C1[C@H]1[C@@H](C(=O)NC1)NC(=O)NC1=CC=CC=C1)F)OC)F FJZNNKJZHQFMCK-LRDDRELGSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- MXPCZHSTOIKVST-UHFFFAOYSA-N 1-[3-amino-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(2-hydroxyethoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=CC(N)=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OCCO)=C1 MXPCZHSTOIKVST-UHFFFAOYSA-N 0.000 description 1
- OXTVBHDILDPYAS-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OCCCO)=C1 OXTVBHDILDPYAS-UHFFFAOYSA-N 0.000 description 1
- DFUGYZQSDFQVPU-UHFFFAOYSA-N 1-benzofuran-3-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=COC2=C1 DFUGYZQSDFQVPU-UHFFFAOYSA-N 0.000 description 1
- WYXQQAYIAJRORT-UHFFFAOYSA-N 1-benzofuran-5-ylboronic acid Chemical compound OB(O)C1=CC=C2OC=CC2=C1 WYXQQAYIAJRORT-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- QOGNDJLSYMJGPP-UHFFFAOYSA-N 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound C1=NC(OC)=CC=C1B1OC(C)(C)C(C)(C)O1 QOGNDJLSYMJGPP-UHFFFAOYSA-N 0.000 description 1
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
- HNFMVVHMKGFCMB-UHFFFAOYSA-N 3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Chemical compound NC1=NC=CC=C1C1=NC2=CC=C(C=3C=CC=CC=3)N=C2N1C1=CC=C(C2(N)CCC2)C=C1 HNFMVVHMKGFCMB-UHFFFAOYSA-N 0.000 description 1
- UXNWIRHZMHGOCE-UHFFFAOYSA-N 3-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]benzoic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C1=CC=CC(C(O)=O)=C1 UXNWIRHZMHGOCE-UHFFFAOYSA-N 0.000 description 1
- NVVPMZUGELHVMH-UHFFFAOYSA-N 3-ethyl-4-[4-[4-(1-methylpyrazol-4-yl)imidazol-1-yl]-3-propan-2-ylpyrazolo[3,4-b]pyridin-1-yl]benzamide Chemical compound CCC1=CC(C(N)=O)=CC=C1N1C2=NC=CC(N3C=C(N=C3)C3=CN(C)N=C3)=C2C(C(C)C)=N1 NVVPMZUGELHVMH-UHFFFAOYSA-N 0.000 description 1
- HENXUFOAGXNWKH-UHFFFAOYSA-N 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=CN=CC(B2OC(C)(C)C(C)(C)O2)=C1 HENXUFOAGXNWKH-UHFFFAOYSA-N 0.000 description 1
- WCMLRSZJUIKVCW-UHFFFAOYSA-N 4-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=C(S)C=C1 WCMLRSZJUIKVCW-UHFFFAOYSA-N 0.000 description 1
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 1
- XBGWAKUQSRNWMA-UHFFFAOYSA-N 4-[6-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline Chemical compound C1CN(C)CCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C=2C3=CC=CC=C3N=CC=2)C=C1 XBGWAKUQSRNWMA-UHFFFAOYSA-N 0.000 description 1
- GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 1
- VWVKUNOPTJGDOB-BDHVOXNPSA-N Anhydrous tofogliflozin Chemical compound C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 VWVKUNOPTJGDOB-BDHVOXNPSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- ZNSPHKJFQDEABI-NZQKXSOJSA-N Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 Chemical compound Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 ZNSPHKJFQDEABI-NZQKXSOJSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- NPUXORBZRBIOMQ-RUZDIDTESA-N [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]-2-pyrrolidinyl]methanol Chemical compound C=1C(OCC=2C=CC(CN3[C@H](CCC3)CO)=CC=2)=CC(C)=CC=1CS(=O)(=O)C1=CC=CC=C1 NPUXORBZRBIOMQ-RUZDIDTESA-N 0.000 description 1
- ONSQLDCEJIIUJS-XVFCMESISA-N [(2r,3s,4r,5r)-5-(2-amino-4-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate Chemical compound NC1=NC(=O)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 ONSQLDCEJIIUJS-XVFCMESISA-N 0.000 description 1
- IYUGETBULGXAGK-NTCAYCPXSA-N [(E)-2-(benzenesulfonyl)-2-methoxyethenyl]benzene Chemical compound CO/C(=C\C1=CC=CC=C1)/S(=O)(=O)C2=CC=CC=C2 IYUGETBULGXAGK-NTCAYCPXSA-N 0.000 description 1
- IYUGETBULGXAGK-QINSGFPZSA-N [(Z)-2-(benzenesulfonyl)-2-methoxyethenyl]benzene Chemical compound CO/C(=C/C1=CC=CC=C1)/S(=O)(=O)C1=CC=CC=C1 IYUGETBULGXAGK-QINSGFPZSA-N 0.000 description 1
- DPIDNFWCDMXMDY-UHFFFAOYSA-N [4-(2-hydroxypropan-2-yl)phenyl]boronic acid Chemical compound CC(C)(O)C1=CC=C(B(O)O)C=C1 DPIDNFWCDMXMDY-UHFFFAOYSA-N 0.000 description 1
- QJYYVSIRDJVQJW-UHFFFAOYSA-N [4-(dimethylcarbamoyl)phenyl]boronic acid Chemical compound CN(C)C(=O)C1=CC=C(B(O)O)C=C1 QJYYVSIRDJVQJW-UHFFFAOYSA-N 0.000 description 1
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 1
- DTXBFSJBRGLOHO-UHFFFAOYSA-N [phosphono-[[4-(4-propan-2-yloxyphenyl)pyridin-2-yl]amino]methyl]phosphonic acid Chemical compound C1=CC(OC(C)C)=CC=C1C1=CC=NC(NC(P(O)(O)=O)P(O)(O)=O)=C1 DTXBFSJBRGLOHO-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005362 aryl sulfone group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125876 compound 15a Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229950000991 ipragliflozin Drugs 0.000 description 1
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- DGMLJJIUOFKPKB-UHFFFAOYSA-N n,n-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound C1=CC(N(C)C)=CC=C1B1OC(C)(C)C(C)(C)O1 DGMLJJIUOFKPKB-UHFFFAOYSA-N 0.000 description 1
- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- QGLVEAGMVUQOJP-UHFFFAOYSA-N prop-2-enylboronic acid Chemical compound OB(O)CC=C QGLVEAGMVUQOJP-UHFFFAOYSA-N 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- YGDICLRMNDWZAK-UHFFFAOYSA-N quinolin-3-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CN=C21 YGDICLRMNDWZAK-UHFFFAOYSA-N 0.000 description 1
- JLOLSBLXNMVKGY-UHFFFAOYSA-N quinolin-6-ylboronic acid Chemical compound N1=CC=CC2=CC(B(O)O)=CC=C21 JLOLSBLXNMVKGY-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- JWUBVPJWWYYRLJ-UHFFFAOYSA-N tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=N1 JWUBVPJWWYYRLJ-UHFFFAOYSA-N 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 description 1
- 229940030010 trimethoxybenzene Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- BFDBKMOZYNOTPK-UHFFFAOYSA-N vonoprazan Chemical compound C=1C=CN=CC=1S(=O)(=O)N1C=C(CNC)C=C1C1=CC=CC=C1F BFDBKMOZYNOTPK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/164—Unsaturated ethers containing six-membered aromatic rings
- C07C43/166—Unsaturated ethers containing six-membered aromatic rings having unsaturation outside the aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
本发明提供了一种利用α‑O‑烯基砜作为亲电试剂的Suzuki‑Miyaura偶联反应，它包括如下步骤：取α‑O‑烯基砜、有机硼试剂、配体、碱、催化剂于溶剂反应，即可。本发明还提供了该偶联反应的用途。本发明利用α‑O‑烯基砜作为亲电试剂进行Suzuki‑Miyaura偶联反应时，反应原料α‑O‑烯基砜制备简单、结构稳定，能够克服利用有机卤化物和磺酸作为Suzuki‑Miyaura偶联反应的亲电试剂时存在的不稳定、制备困难等缺点。同时，该反应的反应条件温和，能够兼容范围很广的杂环和各类官能团，同时产率高，能够实现大规模工艺生产。同时，本发明利用α‑O‑烯基砜作为亲电试剂进行Suzuki‑Miyaura偶联反应可以以高产率生成芳基糖苷和开链烯基醚，还可以制备二型糖尿病药物依格列净和2‑去氧依格列净，应用广泛。
Description
技术领域
本发明属于化学领域，具体涉及一种利用α-O-烯基砜作为亲电试剂的铃木反应及其应用。
背景技术
铃木反应，亦称Suzuki-Miyaura偶联反应，在有机合成和药物化学中具有不可替代的位置，能实现碳-碳键的构建，合成大量分子骨架。易得和稳定的有机硼试剂作为亲和试剂，在该类反应中发挥巨大作用。在Suzuki-Miyaura偶联反应最常用的亲电试剂是有机卤化物和磺酸，而该类化合物常存在反应活性低、不稳定、制备困难等缺点，发展可替代的亲电试剂显得非常重要。
砜代表化学中的一个基本官能团。砜的多功能性和一般稳定性使其成为许多复杂产品合成方案中的重要中间体。然而，与有机卤化物或磺酸酯相比，在交叉偶联反应中使用砜作为亲电试剂相对较少，主要原因如下：一是较少极化的C-SO2R键的氧化插入被认为更加困难；二是砜包含两个C-SO2键，在氧化插入步骤中存在选择性问题；三是在氧化插入时，生成的亚磺酸酯(RSO2-)易于进行脱去二氧化硫，得到R负离子，进一步以亲核试剂而不是亲电试剂重新进入催化循环，难以达到目的。例如，Yorimitsu小组报道了二芳基砜的分子内脱硫偶联，得到二芳基。
尽管存在上述挑战，在交叉偶联中利用砜作为亲电试剂已经取得了巨大进展。有趣的是，尽管乙烯基或芳基砜用作C(sp2)亲电试剂的历史更长，但自从Wenker和Julia课题组的开创性研究以来，这方面的研究一直处于休眠状态。大多数报道的方法使用格氏试剂作为亲核试剂，这极大地限制了它们的合成用途。
发明内容
本发明的目的是提供一种利用α-O-烯基砜作为亲电试剂的铃木反应及其应用。
本发明提供了一种利用α-O-烯基砜作为亲电试剂的Suzuki-Miyaura偶联反应，它包括如下步骤：取α-O-烯基砜、有机硼试剂、配体、碱、催化剂于溶剂反应，即可。
进一步地，所述偶联反应中α-O-烯基砜、有机硼试剂、配体、碱、催化剂的摩尔比为1:1～5:0.1～0.5:1～5:0.05～0.25；所述α-O-烯基砜与溶剂的摩尔体积比为0.1～10:1(mol/L)；
优选地，所述偶联反应中α-O-烯基砜、有机硼试剂、配体、碱、催化剂的摩尔比为1:1.5～2:0.1～0.2:2:0.1；所述α-O-烯基砜与溶剂的摩尔体积比为0.1～0.2:1(mol/L)；
更优选地，所述偶联反应中α-O-烯基砜、有机硼试剂、配体、碱、催化剂的摩尔比为1:2:0.2:2:0.1；所述α-O-烯基砜与溶剂的摩尔体积比为0.2:1(mol/L)。
进一步地，所述α-O-烯基砜的结构式如式Ⅰ所示：
其中，
当虚线为键时，式Ⅰ所述结构式如式ⅠA所示：
在式ⅠA中，
n为0～4的整数；
R1独立的选自取代或未取代的C1～C6烷基、-OR3，或任意两个R1连接成取代或未取代的3～6元杂环基；所述烷基的取代基为卤素、硝基、氨基、羟基、氰基、-OR3；所述杂环基的取代基为C1～C6烷基；
R2选自取代或未取代的芳基、取代或未取代的3～8元杂环基；所述芳基或杂环基的取代基为C1～C6烷基、卤素、C1～C6烷氧基、氰基、硝基、氨基、羟基；
R3选自苄基、TBS基团、TIPS基团、取代或未取代的3～6元杂环基；所述杂环基的取代基为取代或未取代的C1～C6烷基、-OR4；所述烷基的取代基为卤素、羟基、-OR4；
R4选自苄基、TBS基团、TIPS基团；
当虚线为无时，式Ⅰ所述结构式如式ⅠB或式ⅠC所示：
在式ⅠB或式ⅠC中，
R1独立的选自C1～C6烷基、芳基、-(CH)mOR5、C2～C9烯基；
R2选自取代或未取代的芳基、取代或未取代的3～8元杂环基；所述芳基或杂环基的取代基为C1～C6烷基、卤素、C1～C6烷氧基、氰基、硝基、氨基、羟基；
m为0～6的整数；
R5选自苄基、TBS基团、TIPS基团；
优选地，
在式ⅠA中，
n为2～3的整数；
R1独立的选自取代或未取代的甲基、-OR3，或任意两个R1连接成取代的6元杂环基；所述甲基的取代基为-OR3；所述杂环基的取代基为C4烷基；
R2选自取代或未取代的芳基、取代或未取代的6元杂环基；所述芳基或杂环基的取代基为C1～C3烷基、卤素；
R3选自苄基、TBS基团、TIPS基团、取代的6元杂环基；所述杂环基的取代基为取代的甲烷基、-OR4；所述烷基的取代基为-OR4；
R4选自苄基；
在式ⅠB或式ⅠC中，
R1独立的选自C1～C4烷基、芳基、-(CH)mOR5、C9烯基；
R2选自取代或未取代的芳基、取代或未取代的6元杂环基；所述芳基或杂环基的取代基为C1～C3烷基、卤素；
m为3；
R5选自TIPS基团。
进一步地，所述α-O-烯基砜为如下结构式之一：
进一步地，所述有机硼试剂选自芳基硼酸或硼酸酯；所述配体选自Ph3P或Cy3P·HBF4；所述碱选自KOH或NaOH；所述催化剂为含Ni的催化剂；所述溶剂为四氢呋喃或叔丁醇；
优选地，所述配体为Cy3P·HBF4；所述碱为KOH；所述催化剂为Ni(COD)2；所述溶剂为四氢呋喃。
进一步地，所述反应温度为60～80℃；所述反应时间为8-16h；优选地，反应时间为12-16h。
本发明还提供了一种用于前述的Suzuki-Miyaura偶联反应的亲电试剂，所述亲电试剂为如下结构式之一：
本发明还提供了一种芳基糖苷，所述芳基糖苷为利用前述的Suzuki-Miyaura偶联反应制备得到的芳基糖苷，其中，所述芳基糖苷如式Ⅱ所示：
其中，
n为0～4的整数；
R1独立的选自取代或未取代的C1～C6烷基、-OR3；所述烷基的取代基为卤素、硝基、氨基、羟基、氰基、-OR3；
R3选自苄基、取代或未取代的3～6元杂环基；所述杂环基的取代基为取代或未取代的C1～C6烷基、-OR4；所述烷基的取代基为卤素、羟基、-OR4；
R4选自苄基；
A环选自取代或未取代的芳基、取代或未取代的3～8元杂环基、取代或未取代苯并3～8元杂环基、二苯并噻吩基、二苯并呋喃基、取代的苯并环庚吡啶基；
所述芳基的取代基为取代或未取代的C1～C6烷基、卤素、C1～C6烷氧基、氰基、酯基、-NR6R7、-C(O)R8；
所述杂环基的取代基为C1～C6烷氧基、取代或未取代的C1～C6烷基、取代或未取代的3～8元杂环基、叔丁氧羰基、苄基、酯基；所述烷基的取代基为卤素、羟基；
所述苯并环庚吡啶基的取代基为＝R9；
R6、R7分别独立的选自C1～C6烷基；
R8选自C1～C6烷基、-NR5R6；
R9选自取代的3～8元杂环基；
优选地，
n为2～3的整数；
R1独立的选自取代或未取代的甲基、-OR3；所述甲基的取代基为-OR3；
R3选自苄基、取代的6元杂环基；所述杂环基的取代基为取代的甲基、-OR4；所述甲基的取代基为-OR4；
R4选自苄基；
A环选自取代或未取代的芳基、取代或未取代5～6元杂环基、取代或未取代苯并5～6元杂环基、二苯并噻吩基、二苯并呋喃基、取代的苯并环庚吡啶基；
所述芳基的取代基为-NR6R7、卤素、取代或未取代的甲基、甲氧基、羟基、酯基、-C(O)R8；
所述杂环基的取代基为甲氧基、取代的甲基、取代或未取代的6元杂环基、叔丁氧羰基、酯基、苄基；
所述苯并环庚吡啶基的取代基为＝R9；
R6、R7分别独立的选自甲基；
所述甲基的取代基为卤素、羟基；
R8选自甲基、-NR5R6；
R9选自取代的6元杂环基；
更优选地，所述芳基糖苷为如下结构式之一：
本发明还提供了一种开链烯基醚，所述开链烯基醚为利用前述的Suzuki-Miyaura偶联反应制备得到的开链烯基醚，其中，所述开链烯基醚如式Ⅲ所示：
在式Ⅲ中，
R10选自C1～C6烷基、-(CH)xOR11、C2～C9烯基；
x为0～6的整数；
R11选自苄基、TBS基团、TIPS基团；
优选地，
R10选自C4烷基、-(CH)xOR11、C9烯基；
m为3；
R11选自TIPS基团；
更优选地，所述开链烯基醚为如下结构式之一：
本发明还提供了前述的Suzuki-Miyaura偶联反应在制备二型糖尿病药物依格列净和/或2-去氧依格列净的应用。
本发明中提供的化合物和衍生物可以根据IUPAC(国际纯粹与应用化学联合会)或CAS(化学文摘服务社，Columbus，OH)命名系统命名。
关于本发明的使用术语的定义：除非另有说明，本文中基团或者术语提供的初始定义适用于整篇说明书的该基团或者术语；对于本文没有具体定义的术语，应该根据公开内容和上下文，给出本领域技术人员能够给予它们的含义。
“取代”是指分子中的氢原子被其它不同的原子或分子所替换。
本发明中所述化合物的结构均是指能够稳定存在的结构。
本发明取代基“-C(O)R7”的结构式为
本发明取代基“-OR2”的结构式为
本发明取代基“-NR5R6”的结构式为
本发明中碳氢基团中碳原子含量的最小值和最大值通过前缀表示，例如，前缀(Ca～Cb)烷基表明任何含“a”至“b”个碳原子的烷基。因此，例如，C1～C8烷基是指包含1～8个碳原子的直链或支链烷基；C1～C8烷氧基是指包含1～8个碳原子的烷氧基。
本发明中，3～6元杂环基是饱和或不饱和的单环杂环基，该单环杂环基有3～6个原子构成，该杂环中携带至少一个选自O、S或取代的氮原子、硅原子。
本发明中，卤素为氟、氯、溴或碘。
本发明中，苯并3～6元杂环基是指一个苯环并上一个3～6元杂环基。
本发明中，缩写为化学领域中常用缩写，如：TBS基团为叔丁基二甲基；TIPS基团为三异丙基硅基；Bn为苄基；tBu为丁基；Ph为芳基；Me为甲基；Et为乙基；Boc为叔丁氧羰基；Tol为甲苯基。
本发明中α-O烯基砜是指在烯基砜的α位连接一个氧，结构通式为
中，R1为环上的取代基，n为取代基的个数，R2为砜基上的取代基；
中，R1和R2均为相应基团上的取代基。
本发明中铃木反应就是Suzuki-Miyaura偶联反应。
本发明以α-O-烯基砜作为亲电试剂，可以有效进行Suzuki-Miyaura偶联反应，不会出现前述砜参与Suzuki-Miyaura偶联反应存在的诸多问题，反应原料α-O-烯基砜制备简单、结构稳定，能够克服利用有机卤化物和磺酸作为Suzuki-Miyaura偶联反应的亲电试剂时存在的不稳定、制备困难等缺点。同时，该反应的反应条件温和，能够兼容范围很广的杂环和各类官能团，同时产率高，能够实现大规模工艺生产。同时，本发明利用α-O-烯基砜作为亲电试剂进行Suzuki-Miyaura偶联反应可以以高产率生成芳基糖苷和开链烯基醚，还可以制备二型糖尿病药物依格列净和2-去氧依格列净，应用广泛。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品，通过购买市售产品获得。
缩写词
THF：四氢呋喃；LiHMDS：双三甲基硅基胺基锂；LDA：二异丙基氨基锂。
实施例1、本发明亲电试剂α-O-烯基砜的制备
1、1-苯砜基-3,4,6-三苄氧基-D-葡萄糖烯的合成(8a)
将间氯过氧苯甲酸(mCPBA，2.5g,11.26mmol,2.2equiv)在0℃的条件下分批次加入到溶有SI-1(3.24g,5.12mmol,1.0equiv)的二氯甲烷(DCM)的溶液中，在室温条件下搅拌2小时后，利用硅藻土过滤。滤液中加入饱和NaHCO3和Na2S2O3溶液搅拌10min，用二氯甲烷萃取，减压蒸馏。随后通过色谱柱进行纯化(石油醚/乙酸乙酯＝4:1)，得到SI-2(2.65g,3.99mmol)，收率为78％。
将SI-2(2.65g,3.99mmol,1.0equiv)在N2保护条件下溶于四氢呋喃(THF,25mL)中，0℃搅拌，随后将双三甲基硅基胺基锂(3.0mL,溶于正己烷溶液,浓度为2.0M,1.5equiv)逐滴加入其中。点板监测，反应完后使用饱和NH4Cl溶液淬灭反应，乙酸乙酯萃取后，减压蒸馏。硅胶柱进行纯化(石油醚/乙酸乙酯＝8:1)，得到白色固体8a(2.1g,3.79mmol)，收率为95％。1H NMR(CDCl3,400MHz)δ:7.95(d,J＝7.7Hz,2H),7.57(t,J＝7.5Hz,1H),7.46(t,J＝7.7Hz,2H),7.36–7.24(m,11H),7.23–7.14(m,4H),6.22(d,J＝3.0Hz,1H),4.73(d,J＝11.3Hz,1H),4.68(d,J＝11.6Hz,1H),4.60(d,J＝11.3Hz,1H),4.56(d,J＝11.6Hz,1H),4.35(d,J＝12.0Hz,1H),4.31(d,J＝12.0Hz,1H),4.26(dd,J＝6.1,3.0Hz,1H),4.19(ddd,J＝8.1,4.6,3.1Hz,1H),3.85(dd,J＝8.1,6.0Hz,1H),3.71(dd,J＝11.5,4.6Hz,1H),and3.66(dd,J＝11.5,3.1Hz,1H).13C NMR(CDCl3,101MHz)δ:152.61,138.07,138.04,137.81,137.49,133.96,129.11,128.73,128.65,128.51,128.39,128.12,127.97,127.94,127.68,127.53,105.80,79.89,74.87,73.86,73.41,71.45,and 67.61.IR(thin film,cm-1):3030,2866,1647,1448,1324,1160,1069,1026,734,725,696,685,and 613cm-1.HRMS(DART-TOF)calculated for C33H32NaO6S+[M+Na]+m/z 579.1812,found 579.1821.熔点:75.5–79.6℃.
2、1-(4-三氟甲基苯砜基)-3,4,6-三苄氧基-D-葡萄糖烯的合成(8b)
将SI-3(2.34g,6.0mmol,1.0equiv)和4-(三氟甲基)苯硫酚(1.07g,6.0mmol,1.0equiv)溶于15ml二氯甲烷中，氮气保护和0℃条件下缓慢加入BF3·Et2O(2.34g,6.0mmol,1.0equiv)。随后在室温条件下搅拌8h，用饱和NH4Cl溶液进行淬灭，用0.3N的NaOH溶液洗涤，无水Na2SO4干燥，减压蒸馏，硅胶色谱柱纯化(石油醚/乙酸乙酯＝4:1)，得到产物(1.37g,2.7mmol)，收率为45％。
在N2保护条件下，将上一步得到的产物(1.37g,2.7mmol,1.0equiv)溶于甲醇中，加入NaOMe(58mg,1.08mmol,0.4equiv)并在室温下搅拌2h，减压蒸馏。将旋干的混合体系溶解于N,N-二甲基甲酰胺(DMF,18mL)中，N2保护条件下，0℃，分批次加入NaH(864mg,21.6mmol,8.0equiv,分散在矿物油中,浓度为60％)，搅拌15min后，在10min内逐滴加入BnBr(3.69g,21.6mmol,8.0equiv)，移至室温搅拌15h，将反应液倾入冰水中淬灭，并用乙酸乙酯萃取(20mL x 3)，无水Na2SO4干燥，减压蒸馏，硅胶柱纯化(石油醚/乙酸乙酯＝10:1)，得到SI-4(1.61g,2.3mmol)，收率为85％。
将SI-4(1.61g,2.3mmol,1equiv)溶于15ml DCM中，0℃，分批加入间氯过氧苯甲酸(1.1g,5.06mmol,2.2equiv)，室温条件下搅拌2h，过滤，用饱和NaHCO3溶液淬灭反应，并加入Na2S2O3溶液搅拌10min。随后用DCM萃取，将有机层减压蒸馏，用硅胶色谱柱纯化粗产物(石油醚/乙酸乙酯＝5:1)，得到产物(1.43g,1.9mmol)，收率为85％。
将上一步得到的产物溶于20ml THF，在-78℃和N2保护条件下逐滴加入二异丙基氨基锂(LDA,1.8mL,溶解在正己烷中，浓度为2M,1.5equiv)，TLC板监测，-78℃条件下，饱和NH4Cl淬灭反应。将反应移至室温，用乙酸乙酯萃取，将有机层减压蒸馏，硅胶色谱柱纯化(石油醚/乙酸乙酯＝7:1)得到浅黄色泡沫状固体8b(1.16g,1.9mmol)，收率为82％。1H NMR(CDCl3,400MHz)δ:8.06(d,J＝8.2Hz,2H),7.69(d,J＝8.2Hz,2H),7.35–7.27(m,11H),7.22–7.16(m,4H),6.23(d,J＝3.1Hz,1H),4.73(d,J＝11.3Hz,1H),4.68(d,J＝11.6Hz,1H),4.60(d,J＝11.6Hz,1H),4.57(d,J＝11.6Hz,1H),4.39(d,J＝11.9Hz,1H),4.35(d,J＝11.9Hz,1H),4.26(dd,J＝5.9,3.1Hz,1H),4.22(ddd,J＝7.9,4.7,3.1Hz,1H),3.85(dd,J＝8.0,5.9Hz,1H),3.72(dd,J＝11.4,4.8Hz,1H),and 3.67(dd,J＝11.4,3.2Hz,1H).13C NMR(CDCl3,101MHz)δ:151.91,141.79,137.84,137.69,137.38,135.54(q,J＝33.1Hz),129.27,128.70,128.56,128.49,128.21,128.07,127.99,127.98,127.87,127.56,126.24(q,J＝3.7Hz),123.24(q,J＝273.7Hz),106.93,79.93,74.63,73.88,73.46,73.29,71.60,and 67.56.19F NMR(CDCl3,376MHz)δ:–63.18.IR(thin film,cm-1):3029,3006,2989,2866,1320,1275,1261,1166,1131,1105,1060,1015,764,749,713,696,and 605cm-1.HRMS(DART-TOF)calculated for C34H31F3NaO6S+[M+Na]+m/z 647.1686,found 647.1695.
3、1-苯砜基-3,4,6-三-叔丁基二甲基硅氧基-D-葡萄糖烯的合成(15a)
将SI-3(2.34g,6.0mmol,1.0equiv)和苯硫酚(792mg,7.2mmol,1.2equiv)溶于15ml二氯甲烷中，N2和0℃条件下，缓慢加入BF3·Et2O(1.28g,9.0mmol,1.5equiv)，室温条件下搅拌8h，饱和NH4Cl溶液淬灭，0.3N NaOH水溶液洗涤。将有机层用无水Na2SO4干燥，减压蒸馏，硅胶柱纯化(石油醚/乙酸乙酯＝4:1)，得到产物(2.73g,5.4mmol,收率为90％)。
在N2保护条件下，将上一步得到的产物(2.73g,5.4mmol,1.0equiv)溶于甲醇中，加入NaOMe(116mg,2.16mmol,0.4equiv)并在室温下搅拌2h，减压蒸馏。随后，将所得物质溶解于二氯甲烷(30mL)，N2和0℃条件下，加入2,6-二甲基吡啶(5.78g,54mmol,10.0equiv)和叔丁基二甲硅基三氟甲磺酸酯(TBSOTf，1.16g,43mmol,8.0equiv)，室温下搅拌8h，二氯甲烷稀释，饱和食盐水和二氯甲烷萃取(20mL x 3)，无水Na2SO4干燥后减压蒸馏，硅胶色谱柱纯化(石油醚/乙酸乙酯＝15:1)后得到TBS保护的产物SI-5(3.74g,5.1mmol,收率为95％)。
将SI-5(3.74g,5.1mmol,1equiv)溶于30ml二氯甲烷中，0℃条件下，分批加入间氯过氧苯甲酸(mCPBA，2.42g,11.2mmol,2.2equiv)，室温搅拌2h，硅藻土过滤，滤液加入饱和NaHCO3和Na2S2O3溶液搅拌10分钟，有机层减压蒸馏。旋干后，将所得混合物溶于20ml四氢呋喃中，N2和-78℃条件下，逐滴加入二异丙基氨基锂(LDA，3.8mL,溶于正己烷溶液中,浓度为2.0M,1.5equiv)，TLC监测，-78℃条件下使用饱和NH4Cl溶液淬灭，将反应液移至室温，乙酸乙酯萃取，无水Na2SO4干燥，将有机层减压蒸馏，硅胶柱纯化后得到白色固体15a(2.37g,3.8mmol)，收率为74％。1H NMR(CDCl3,400MHz)δ:7.95–7.90(m,2H),7.62–7.57(m,1H),7.52–7.46(m,2H),6.06(dd,J＝4.9,1.2Hz,1H),4.11(dddd,J＝6.9,5.2,3.2,1.6Hz,1H),4.03(ddd,J＝4.8,3.1,1.6Hz,1H),3.87(ddd,J＝4.4,3.2,1.2Hz,1H),3.74(dd,J＝11.2,5.6Hz,1H),3.69(dd,J＝11.2,6.6Hz,1H),0.88(d,J＝0.9Hz,9H),0.84(d,J＝0.9Hz,9H),0.73(d,J＝0.9Hz,9H),0.12(s,3H),0.10(s,3H),0.02(s,3H),0.00(s,3H),-0.01(s,3H),and-0.03(s,3H).13C NMR(CDCl3,101MHz)δ:151.50,138.64,133.68,129.06,128.58,106.59,83.15,68.78,66.86,60.54,25.99,25.91,25.70,18.37,18.13,17.89,-4.21,-4.43,-4.46,-4.83,-5.25,and-5.38.IR(thin film,cm-1):3005,2954,2929,2888,2857,1275,1259,1076,833,764,and 750cm-1.HRMS(DART-TOF)calculated for C30H56NaO6SSi3 +[M+Na]+m/z 651.2998,found 651.3001.熔点:103.4–105.6℃.
4、1-苯砜基-3-三异丙基硅氧基-4,6-O-二叔丁基硅基-D-葡萄糖烯的合成(15b)
将化合物15a(240mg,0.84mmol,1.0equiv)溶解于20mlTHF中，随后加入四丁基氟化铵(TBAF,溶解在THF中,浓度为1.0M,3.3mL,3.3equiv)，将反应液室温条件下搅拌2h，减压蒸馏，硅胶柱纯化(二氯甲烷/甲醇＝20:1)得到白色固体(260mg,0.91mmol,收率91％)。
将上一步所得的产物(240mg,0.84mmol,1.0equiv)溶解于5ml干燥DCM中，加入吡啶(0.2ml,2.52mmol,3equiv)，反应体系冷却到-35℃，在N2保护条件下逐滴加入(tBu)2Si(OTf)2(0.3ml,0.9mmol,1.08equiv)，在-35℃继续搅拌6h，使用饱和NH4Cl溶液淬灭反应。将反应液移至室温，用乙酸乙酯萃取，有机层用无水Na2SO4干燥，减压蒸馏，硅胶柱纯化(石油醚/乙酸乙酯＝3:1)得到无色油液产物(354mg,0.83mmol,收率99％)。
将上一步所得的产物(354mg,0.83mmol,1.0equiv)溶解于干燥DMF(5ml)，-35℃和N2保护条件下，逐滴加入咪唑(141mg,2.10mmol,2.5equiv)和三异丙基氯硅烷(TIPSCl，0.32ml,1.49mmol,1.8equiv)，-35℃条件下搅拌6h，饱和NH4Cl淬灭反应，将反应液移至室温，乙酸乙酯萃取，有机层无水Na2SO4干燥，硅胶柱纯化(石油醚/乙酸乙酯＝3:1)得到白色固体15b(435mg,0.75mmol,收率90％)。1H NMR(CDCl3,400MHz)δ:7.95–7.89(m,2H),7.70–7.63(m,1H),7.60–7.52(m,2H),5.97(d,J＝2.3Hz,1H),4.51(dd,J＝7.0,2.4Hz,1H),4.15(dd,J＝10.0,4.4Hz,1H),3.98(dd,J＝16.0,10.8Hz,1H),3.96(dd,J＝16.4,10.0Hz,1H),3.87(ddd,J＝14.8,10.0,3.6Hz,1H),1.16–1.08(m,21H),1.03(s,9H),0.95and(s,9H).13CNMR(CDCl3,101MHz)δ:151.40,138.04,134..14,129.28,,128.83,111.27,76.40,75.45,70.95,65.41,27.51,26.97,22.82,19.96,18.23,18.21,and 12.54.IR(thin film,cm-1):2941,2863,1649,1471,1331,1275,1260,1160,1130,1111,1065,1006,1076,826,765,and750cm-1.HRMS(DART-TOF)calculated for C29H50NaO6SSi2 +[M+Na]+m/z 605.2759,found605.2765.熔点:146.7.0–148.8℃.
5、本发明α-O-烯基砜(化合物15c-15h)的合成
本发明α-O-烯基砜(15c-15h)的合成路线如下：
其中，相应的糖底物SI-7～SI-12的结构式分别为：
将相应的糖底物(1当量)置于圆底烧瓶中，加入干燥的吡啶(糖底物浓度为0.3M)，随后加入乙酸酐(10当量)。室温搅拌15小时至反应完毕。加入水淬灭，乙酸乙酯萃取，用1N的盐酸洗3次，饱和碳酸氢钠洗，无水硫酸钠干燥，过滤，减压蒸馏。利用柱层析分离得到产物。
将上部反应得到的产物(1当量)溶解于二氯甲烷(产物浓度为0.3M)，氮气保护，冷却到0℃，依次加入苯硫酚(1.2当量)和BF3·Et2O(1.5当量)。室温下反应8小时，饱和氯化铵淬灭，二氯甲烷萃取，依次用0.3N氢氧化钠和饱和食盐水洗。无水硫酸钠干燥，过滤，减压蒸馏。柱层析分离产物。
将上一步所得的产物(1当量)溶于DCM中(产物浓度为0.3M)，冷却至0℃，分批加入间氯过氧苯甲酸(2.2当量)，室温条件下搅拌2小时，过滤，用饱和NaHCO3溶液淬灭反应，并加入Na2S2O3溶液搅拌10分钟。随后用DCM萃取，将有机层减压蒸馏，用硅胶色谱柱纯化粗产物(石油醚/乙酸乙酯＝5:1)。
将上一步得到的产物(1当量)溶于干燥THF(产物浓度为0.1M)，在-78℃和N2保护条件下逐滴加入LDA(浓度为2.0M,溶解在正己烷中,1.5当量)，TLC板监测，-78℃条件下，饱和NH4Cl淬灭反应。将反应移至室温，用乙酸乙酯萃取，将有机层减压蒸馏，硅胶色谱柱纯化(石油醚/乙酸乙酯＝7:1)得到α-O-烯基砜产物15c-15h。
(1)1-苯基砜-3,4,6-三苄氧基-D-半乳糖烯(15c)
1H NMR(CDCl3,400MHz)δ:7.89(br d,J＝8Hz,2H),7.53(br t,J＝8Hz,1H),7.39–7.25(m,13H),7.22–7.17(m,2H),7.17–7.12(m,2H),6.20(dd,J＝2.8,1.2Hz,1H),4.84(d,J＝11.6Hz,1H),4.69(d,J＝12.0Hz,1H),4.63(d,J＝12.0Hz,1H),4.52(d,J＝11.6Hz,1H),4.33–4.27(m,3H),4.25(d,J＝12.0Hz,1H),3.97(dt,J＝3.7,1.6Hz,1H),3.63(dd,J＝10.2,6.4Hz,1H),and3.54(dd,J＝10.2,6.4Hz,1H).13C NMR(CDCl3,101MHz)δ:151.44,138.25,138.18,137.82,137.68,133.68,128.99,128.62,128.46,128.33,128.32,128.01,127.84,127.74,127.67,127.65,127.58,107.14,78.69,73.59,73.43,71.58,71.52,70.46,and67.18.IR(thin film,cm-1):3028,3006,2989,2920,2865,1448,1324,1275,1260,1156,1100,1069,764,750,and 697cm-1.HRMS(DART-TOF)calculated forC32H32NaO6S+[M+Na]+m/z 579.1812,found 579.1820.熔点:73.0–74.3℃.
(2)1-苯砜基-3,4-二苄氧基-D-岩藻糖烯(15d)
1H NMR(CDCl3,400MHz)δ:7.93–7.87(m,2H),7.57(t,J＝7.5Hz,1H),7.42(t,J＝7.7Hz,2H),7.37–7.25(m,8H),7.20–7.16(m,2H),6.19–6.16(m,1H),4.89(d,J＝12.0Hz,1H),4.74(d,J＝12.0Hz,1H),4.64(d,J＝12.0Hz,1H),4.57(d,J＝11.6Hz,1H),4.33(t,J＝3.2Hz,1H),4.26–4.19(m,1H),3.70–3.67(m,1H),and1.21(d,J＝6.8Hz,3H).13C NMR(CDCl3,101MHz)δ:151.74,138.39,138.32,137.77,133.62,128.96,128.63,128.30,128.26,128.01,127.69,127.60,106.42,76.38,73.72,72.90,72.40,71.48,and15.72.IR(thin film,cm-1):3028,3005,2989,1320,1275,1260,1151,1108,1059,764,750,718,697,686,and 618cm-1.HRMS(DART-TOF)calculated for C26H26NaO5S+[M+Na]+m/z 473.1393,found 473.1401.
(3)1-苯砜基-3,4-二苄氧基-L-鼠李糖烯(15e)
1H NMR(CDCl3,400MHz)δ:7.96–7.91(m,2H),7.66–7.61(m,1H),7.56–7.50(m,2H),7.37–7.23(m,10H),6.24–6.20(m,1H),4.78(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.62(d,J＝11.6Hz,1H),4.58(d,J＝11.6Hz,1H),4.26(dd,J＝6.0,2.8Hz,1H),4.12–4.04(m,1H),3.49–3.43(m,1H),and1.29(d,J＝6.4Hz,3H).13C NMR(CDCl3,101MHz)δ:152.80,138.09,137.79,137.56,133.99,129.15,128.74,128.68,128.55,128.14,128.03,128.01,106.07,78.23,77.24,75.46,74.04,71.36,and16.89.IR(thin film,cm-1):3028,3005,2988,1446,1323,1275,1261,1159,1123,1060,764,750,724,697and 686cm-1.HRMS(DART-TOF)calculatedfor C26H26NaO5S+[M+Na]+m/z 473.1393,found 473.1401.熔点:62.8–64.4℃
(4)1-苯砜基-3,4-二苄氧基-D-阿拉伯糖烯(15f)
1H NMR(CDCl3,400MHz)δ:7.93–7.88(m,2H),7.65–7.59(m,1H),7.53–7.48(m,2H),7.35–7.23(m,10H),6.18(d,J＝4.8Hz,1H),4.70(s,2H),4.61(d,J＝12.0Hz,1H),4.54(d,J＝12.0Hz,1H),4.18(td,J＝4.2,3.6,1.0Hz,1H),4.11–4.05(m,2H),and3.72(ddd,J＝8.3,4.2,4.2Hz,1H).13C NMR(CDCl3,101MHz)δ:153.88,137.95,137.90,137.61,134.02,129.20,128.65,128.62,128.58,128.06,127.99,127.74,105.49,71.77,71.66,71.57,67.43,and66.10.IR(thin film,cm-1):3028,3005,2989,2870,1324,1275,1260,1163,1124,1074,764,750,and698cm-1.HRMS(DART-TOF)calculated for C25H24NaO5S+[M+Na]+m/z459.1237,found459.1238.熔点:105.8–107.3℃
(5)1-苯砜基-3,4-二苄氧基-D-木糖烯(15g)
1H NMR(CDCl3,400MHz)δ:7.93(d,J＝7.8Hz,2H),7.62(t,J＝7.5Hz,1H),7.50(t,J＝7.7Hz,2H),7.38–7.25(m,8H),7.13(m,2H),6.24(d,J＝4.6Hz,1H),4.65(d,J＝12.0Hz,1H),4.56(d,J＝12.0Hz,1H),4.51(d,J＝12.0Hz,1H),4.48(d,J＝12.0Hz,1H),4.24(dd,J＝11.6,4.0Hz,1H),4.05–3.95(m,2H),and3.67(m,1H).13C NMR(CDCl3,101MHz)δ:154.14,138.29,137.62,137.57,133.93,129.19,128.70,128.60,128.57,128.18,128.01,127.95,127.63,104.98,72.05,71.27,70.98,69.44,and66.52.IR(thin film,cm-1):3034,3006,2989,2870,1324,1275,1261,1161,1115,1076,764,749,and 698cm-1..HRMS(DART-TOF)calculated for C25H24NaO5S+[M+Na]+m/z 459.1237,found 459.1239.
(6)1-苯砜基-六苄氧基-D-麦芽糖烯(15h)
1H NMR(CDCl3,400MHz)δ:7.94–7.87(m,2H),7.43–7.35(m,3H),7.33–7.22(m,26H),7.17–7.09(m,4H),6.28–6.23(m,1H),5.22–5.16(m,1H),4.86(dd,J＝11.0,1.8Hz,1H),4.79–4.72(m,2H),4.67–4.59(m,2H),4.53(d,J＝4.5Hz,1H),4.50(d,J＝4.7Hz,1H),4.48–4.43(m,2H),4.41(d,J＝11.0Hz,1H),4.36–4.29(m,2H),4.29–4.24(m,1H),4.22–4.18(m,1H),4.12–4.08(m,1H),3.73(ddd,J＝9.2,5.1,2.0Hz,1H),3.67(ddd,J＝11.3,5.4,1.7Hz,1H),3.62(ddd,J＝11.3,5.4,1.7Hz,1H),3.60–3.57(m,2H),3.49–3.52(m,1H),3.49–3.46(m,1H),and3.37–3.32(m,1H).13C NMR(CDCl3,101MHz)δ:152.68,138.84,138.44,138.19,138.03,137.96,137.93,137.36,133.95,129.14,128.65,128.59,128.55,128.46,128.42,128.38,128.34,128.06,128.00,127.95,127.91,127.87,127.76,127.75,127.65,127.57,104.83,97.02,81.80,79.82,79.54,77.45,75.67,75.08,73.50,73.38,73.22,72.84,71.00,70.66,70.51,68.13,and 67.07.IR(thin film,cm-1):3028,3006,2920,1453,1275,1260,1070,764,749,and697cm-1.HRMS(DART-TOF)calculated forC60H60NaO11S+[M+Na]+m/z 1011.3749,found1011.3751.1H NMR(400MHz,Chloroform-d)δ3.73(ddd,J＝9.2,5.1,2.0Hz,1H),3.67(ddd,J＝11.3,5.4,1.7Hz,1H).
6、开链α-O-烯基砜的合成(化合物19)
将甲氧基甲基苯基砜(18,1.5equiv)溶于THF(15mL)，氮气保护，冷却到-78℃，LDA(9.0mmol,3.0equiv,溶于正己烷中,浓度为1.5M)缓慢滴加。搅拌15分钟后，氯磷酸二乙酯(4.5mmol,1.5equiv)缓慢加入。反应搅拌1小时，将相应醛(3.0mmol,1.0equiv)的THF溶液(5mL)缓慢滴加。恢复到室温，搅拌过夜。使用饱和NH4Cl溶液低温下猝灭，乙酸乙酯萃取，无水硫酸钠干燥，过滤，减压蒸馏，柱层析分离得到化合物19，包含Z/E两种构型产物，可以柱层析分离。
(1)化合物19a的制备
参照标准操作步骤，利用苯甲醛(3.0mmol,318mg)和甲氧基甲基苯基砜(3.3mmol)作为原料。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝4:1，得到化合物19a，E/Z＝5:1，黄色油状771mg，产率94％。
(E)-(2-甲氧基-2-苯砜基乙烯基)-苯(E-19a)
1HNMR(CDCl3,400MHz)(E-isomer)δ:8.01–7.95(m,2H),7.67–7.60(m,3H),7.58–7.52(m,2H),7.42–7.33(m,3H),7.23(s,1H),and3.87(s,3H).13C NMR(CDCl3,101MHz)δ:153.33,139.11,133.73,131.55,130.00,129.96,129.26,129.00,128.50,122.68,and61.98.IR(thin film,cm-1):3005,2989,2942,2844,1446,1346,1304,1276,1260,1148,1094,1056,956,764,751,717,686,655,and 616cm-1.HRMS(DART-TOF)calculated forC15H14NaO3S+[M+Na]+m/z 297.0556,found 297.0561.
(Z)-(2-甲氧基-2-苯砜基乙烯基)-苯(Z-19a)
1H NMR(CDCl3,400MHz)(Z-isomer)δ:7.83–7.77(m,2H),7.61–7.56(m,1H),7.49–7.44(m,2H),7.35–7.29(m,5H),6.32(s,1H),and3.74(s,3H).13C NMR(CDCl3,101MHz)δ:154.48,139.43,133.62,132.03,129.79,128.83,128.61,127.85,127.82,111.60,and58.37.IR(thin film,cm-1):3059,3023,2935,1626,1446,1322,1307,1233,1138,1081,974,916,751,729,687,and 627cm-1.HRMS(DART-TOF)calculated for C15H14NaO3S+[M+Na]+m/z 297.0556,found 297.0556.
(2)化合物19b的制备
参照标准操作步骤，利用3-甲基丁醛(3.0mmol,258mg)和甲氧基甲基苯基砜(3.3mmol)作为原料。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝4:1，得到化合物19b，E/Z＝1.8:1，无色油状602mg，产率79％。
(E)-(1-甲氧基-4-甲基-1-戊烯基)-砜基苯(E-19b)
1H NMR(CDCl3,400MHz)(E-isomer)δ:7.94–7.88(m,2H),7.64–7.58(m,1H),7.56–7.50(m,2H),6.46(t,J＝7.8Hz,1H),3.80(s,3H),2.10(dd,J＝7.7,6.8Hz,2H),1.75(hept,J＝6.7Hz,1H),and0.92(d,J＝6.7Hz,6H).13C NMR(CDCl3,101MHz)δ:154.08,139.27,133.50,129.09,128.21,126.18,63.11,34.46,28.12,and22.41.IR(thin film,cm-1):3070,2956,2870,1446,1322,1305,1160,1137,1092,1067,764,750,687,and 646cm-1.HRMS(DART-TOF)calculated for C13H18NaO3S+[M+Na]+m/z 277.0869,found277.0873.
(Z)-(1-甲氧基-4-甲基-1-戊烯基)-砜基苯(Z-19b)
1H NMR(CDCl3,400MHz)(Z-isomer)δ:7.97–7.90(m,2H),7.66–7.59(m,1H),7.57–7.50(m,2H),5.31(t,J＝8.0Hz,1H),3.59(s,3H),2.59(dd,J＝8.0,6.9Hz,2H),1.71(hept,J＝6.7Hz,1H),and0.95(d,J＝6.7Hz,6H).13C NMR(CDCl3,101MHz)δ:152.97,140.05,133.60,129.00,128.20,114.83,58.77,33.91,29.39,and22.29.IR(thin film,cm-1):2956,2869,1635,1464,1447,1319,1307,1142,1121,1084,975,758,732,and 687cm-1.HRMS(DART-TOF)calculated for C13H18NaO3S+[M+Na]+m/z 277.0869,found277.0871.
(3)化合物19c的制备
参照标准操作步骤，利用4-三异丙基硅氧基丁醛(3.0mmol,733mg)和甲氧基甲基苯基砜(3.3mmol)作为原料。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝15:1，得到化合物19c，E/Z＝1.1:1，无色油状840mg，产率68％。
(E)-(1-甲氧基-5-三异丙基硅氧基-1-戊烯基)-砜基苯(E-19c)
1H NMR(CDCl3,400MHz)(E-isomer)δ:7.95–7.87(m,2H),7.65–7.57(m,1H),7.56–7.48(m,2H),6.47(t,J＝7.7Hz,1H),3.82(s,3H),3.70(t,J＝6.1Hz,2H),2.34(q,J＝7.6Hz,2H),1.72–1.64(m,2H),1.12–1.06(m,3H),and1.04(d,J＝4.6Hz,18H).13C NMR(CDCl3,101MHz)δ:153.93,139.24,133.52,129.11,128.33,126.92,63.23,62.43,31.87,22.37,18.08,and12.04.IR(thin film,cm-1):2941,2864,1318,1307,1275,1260,1156,1102,1063,881,764,750,723,and 685cm-1.HRMS(DART-TOF)calculated forC21H36NaO4SSi+[M+Na]+m/z435.1996,found 435.2001.
(Z)-(1-甲氧基-5-三异丙基硅氧基-1-戊烯基)-砜基苯(Z-19c)
1H NMR(CDCl3,400MHz)(Z-isomer)δ:7.97–7.89(m,2H),7.66–7.59(m,1H),7.55–7.49(m,2H),5.35(t,J＝8.0Hz,1H),3.75(t,J＝6.4Hz,2H),3.58(s,3H),2.76(q,J＝7.8Hz,2H),1.75–1.67(m,2H),1.13–1.08(m,3H),and1.07(d,J＝4.6Hz,18H).13C NMR(CDCl3,101MHz)δ:152.67,140.09,133.60,129.04,128.16,115.33,62.88,58.61,33.55,22.14,18.15,and12.11.IR(thin film,cm-1):2940,2864,1447,1325,1275,1260,1144,1099,882,764,750,and 687cm-1.HRMS(DART-TOF)calculated for C21H36NaO4SSi+[M+Na]+m/z 435.1996,found 435.2000.
(4)化合物19d的制备
参照标准操作步骤，利用4-三异丙基硅氧基丁醛(3.0mmol,463mg)和甲氧基甲基苯基砜(3.3mmol)作为原料。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝15:1，得到化合物19d，E/Z＝1.9:1，无色油状811mg，产率84％。
(R,E)-(1-甲氧基-4,8-二甲基-1,7-壬二烯基)-砜基苯(E-19d)
1H NMR(CDCl3,400MHz)(E-isomer)δ:7.96–7.86(m,2H),7.66–7.57(m,1H),7.56–7.48(m,2H),6.46(t,J＝7.7Hz,1H),5.04(tp,J＝6.9,1.2Hz,1H),3.81(s,3H),2.21(ddd,J＝14.5,7.5,5.8Hz,1H),2.13–2.04(m,1H),2.02–1.89(m,2H),1.67(s,3H),1.66–1.59(m,1H),1.58(s,3H),1.38–1.27(m,1H),1.25–1.13(m,1H),and0.90(d,J＝6.7Hz,3H).13C NMR(CDCl3,101MHz)δ:154.14,139.35,133.51,131.65,129.13,128.26,126.29,124.31,63.14,36.80,32.72,32.47,25.80,25.54,19.70,and17.73.IR(thin film,cm-1):3006,2961,2914,1446,1318,1305,1275,1260,1154,1065,764,750,687,and 645cm-1.HRMS(DART-TOF)calculated for C18H26NaO3S+[M+Na]+m/z 345.1495,found 345.1499.
(R,Z)-(1-甲氧基-4,8-二甲基-1,7-壬二烯基)-砜基苯(Z-19d)
1H NMR(CDCl3,400MHz)(Z-isomer)δ:7.97–7.90(m,2H),7.65–7.59(m,1H),7.56–7.50(m,2H),5.30(t,J＝8.0Hz,1H),5.12–5.05(m,1H),3.60(s,3H),2.68(ddd,J＝15.1,7.8,5.9Hz,1H),2.58(dt,J＝15.3,7.9Hz,1H),2.01(tp,J＝22.0,7.2Hz,2H),1.69(s,3H),1.60(s,3H),1.60–1.52(m,1H),1.39(dddd,J＝13.3,9.4,6.5,5.4Hz,1H),1.22(dddd,J＝13.6,9.3,7.9,6.0Hz,1H),and0.93(d,J＝6.7Hz,3H).13C NMR(CDCl3,101MHz)δ:153.02,140.07,133.59,131.48,129.00,128.22,124.64,114.92,58.82,36.72,33.71,32.22,25.82,25.66,19.44,and17.78.IR(thin film,cm-1):2962,2912,2850,1635,1447,1322,1307,1275,1260,1143,1084,974,763,750,and 688cm-1.HRMS(DART-TOF)calculated forC18H26NaO3S+[M+Na]+m/z 345.1495,found 345.1498.
实施例2、不同工艺参数对Suzuki-Miyaura偶联反应的影响
1、配体对Suzuki-Miyaura偶联反应的影响
以如下反应路线为基本反应路线，研究不同的配体对Suzuki-Miyaura偶联反应的影响。
反应结果如表1所示，表中L1、L2、L3和L4的结构式如下：
表1配体对Suzuki-Miyaura偶联反应的影响
aReaction conditions(unless otherwise specified)：8a(0.05mmol，1.0equiv)，9(0.10mmol，2.0equiv)，THF(0.4mL).Yield and conversion weredetermined by1H NMR using 1，3，5-trimethoxybenzene as internal standard.bNi(cod)2instead of Ni(OTf)2
由表1的结果可知：配体为Cy3P·HBF4(即表1中的Cy3PHBF4)时，所得化合物的产率最高，即Cy3P·HBF4为本申请的最优配体。
2、溶剂对Suzuki-Miyaura偶联反应的影响
以如下反应路线为基本反应路线，研究不同的溶剂对Suzuki-Miyaura偶联反应的影响。
反应结果如表2所示：
表2溶剂对Suzuki-Miyaura偶联反应的影响
aReaction conditions(unless otherwiise specified):8a(0.05mmol,1.0equiv),9(0.10mmol,2.0equiv),THF(0.4mL).Yield and conversion weredetermined by 1H NMR using 1,3,5-trimethoxybenzene as internal standard.
由表2可知：叔丁醇和四氢呋喃利于反应的进行。其中，优选为四氢呋喃。
3、催化剂对Suzuki-Miyaura偶联反应的影响
以如下反应路线为基本反应路线，研究不同的催化剂对Suzuki-Miyaura偶联反应的影响。
反应结果如表3所示：
表3不同催化剂对Suzuki-Miyaura偶联反应的影响
aReaction conditions(unless otherwise specified):8a(0.05mmol,1.0equiv),9(0.10mmol,2.0equiv),THF(0.4mL).Yield and conversion weredetermined by 1H NMR using 1,3,5-trimethoxybenzene as internalstandard.bReactions were stirred at 80℃ 13h then 100℃10h.
由表3可知：与其他催化剂相比，含Ni的催化剂有利于反应的进行。其中，优选的催化剂为Ni(COD)2。
4、碱对Suzuki-Miyaura偶联反应的影响
以如下反应路线为基本反应路线，研究不同的碱对Suzuki-Miyaura偶联反应的影响。
反应结果如表4所示：
表4不同碱对Suzuki-Miyaura偶联反应的影响
aReaction conditions(unless otherwise specified)：8a(0.05mmol，1.0equiv)，9(0.10mmol，2.0equiv)，THF(0.4mL).Yield and conversion weredetermined by1H NMR using1，3，5-trimethoxybenzene as internal standard.
由表4可知：该反应最佳的碱为KOH。
5、温度、时间对Suzuki-Miyaura偶联反应的影响
以如下反应路线为基本反应路线，研究不同的温度、时间对Suzuki-Miyaura偶联反应的影响。
反应结果如表5所示：
表4不同温度、时间对Suzuki-Miyaura偶联反应的影响
aReaction conditions(unless otherwise specified)：8a(0.05mmol，1.0equiv)，9(0.10mmol，2.0equiv)，THF(0.4mL).Yield and conversion weredetermined by1H NMR using 1，3，5-trimethoxybenzene as internal standard.
由表5可知：该反应最佳的温度为60-80℃，反应时间为8-16小时。
通过上述反应条件的优化可知，利用本发明亲电试剂α-O烯基砜实现Suzuki-Miyaura偶联反应的最优条件为：金属催化剂为Ni(COD)2，配体为Cy3P·HBF4，溶剂为四氢呋喃或叔丁醇，碱为KOH，反应温度为60-80℃，反应时间为8-16h。
实施例3、利用本发明α-O-烯基砜作为Suzuki-Miyaura偶联反应的亲电试剂制备芳基糖苷和开链烯基醚
将实施例1制备的α-O-烯基砜(1当量)，商业可得的芳基硼酸或硼酸酯(2当量)，Cy3P·HBF4(0.2当量)加入到装入磁力搅拌子的螺旋盖瓶子中，将瓶盖拧松后进入手套箱。加入Ni(COD)2(0.1当量)、KOH(2当量)、THF(0.2M，即α-O-烯基砜在THF中的浓度为0.2M)。将小反应瓶拧紧后，移出手套箱，用黑胶带将瓶口处封紧。将混合体系在60-80℃下搅拌8-16小时。随后将反应液冷却到室温，用乙酸乙酯(10ml)稀释和饱和NH4Cl洗涤后，用乙酸乙酯萃取(10mL x3)。有机层用无水Na2SO4干燥，减压蒸馏，硅胶色谱柱纯化得到目标产物。其中THF可以替换为叔丁醇。
(1)1-苯基-3，4，6-三苄氧基-D-葡萄糖烯(10)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol，111mg)，苯硼酸(0.40mmol，48.8mg)，Ni(COD)2(0.02mmol，5.5mg)，Cy3PHBF4(0.04mmol，14.7mg)和KOH(0.40mmol，22.4mg)的THF(1.0mL)混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8∶1，分离纯化得到黄色油状化合物10(92.6mg，0.19mmol，收率为94％).1HNMR(CDCl3，400MHz)δ：7.64-7.58(m，2H)，7.39-7.23(m，18H)，5.43(d，J＝3.2Hz，1H)，4.86(d，J＝11.2Hz，1H)，4.71(d，J＝11.6Hz，1H)，4.64(d，J＝11.6Hz，1H)，4.63(d，J＝12.4Hz，1H)，4.63(d，J＝11.6Hz，1H)，4.60(d，J＝12.4Hz，1H)，4.38(dd，J＝6.4，2.8Hz，1H)，4.26(ddd，J＝8.1，4.8，3.0Hz，1H)，3.98(dd，J＝8.4，6.0Hz，1H)，3.93(dd，J＝11.0，4.8Hz，1H)，and 3.88(dd，J＝10.9，3.0Hz，1H).13C NMR(CDCl3，101MHz)δ：152.87，138.65，138.42，134.68，128.81，128.55，128.52，128.48，128.25，128.06，127.86，127.84，127.79，127.76，127.69，125.41，96.18，77.48，76.76，74.55，73.66，73.61，70.62，and68.77.IR(thinfilm，cm-1)：3029，2930，2859，1652，1452，1276，1090，750，and 695cm-1.HRMS(DART-TOF)calculated for C33H32NaO4 +[M+Na]+m/z 515.2193，found 515.2187.
(2)1-对甲氧基苯基-3，4，6-三苄氧基-D-葡萄糖烯(13a)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对甲氧基苯硼酸(0.40mmol,60.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的THF(1.0mL)混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到无色油状化合物13a(85.7mg,0.16mmol,收率为82％).1HNMR(CDCl3,400MHz)δ:7.56–7.52(m,2H),7.36–7.25(m,15H),6.87–6.82(m,2H),5.31(d,J＝3.2Hz,1H),4.85(d,J＝11.2Hz,1H),4.71(d,J＝11.2Hz,1H),4.68(d,J＝11.6Hz,1H),4.64(d,J＝12.0Hz,1H),4.62(d,J＝11.6Hz,1H),4.60(d,J＝12.0Hz,1H),4.37(dd,J＝6.0,3.2Hz,1H),4.25(ddd,J＝8.0,4.8,2.8Hz,1H),3.96(dd,J＝8.4,6.0Hz,1H),3.92(dd,J＝11.0,4.9Hz,1H),3.87(dd,J＝10.9,3.0Hz,1H),and3.79(s,3H).13C NMR(CDCl3,101MHz)δ:160.17,152.72,138.72,138.43,128.52,128.50,128.46,128.05,127.84,127.81,127.77,127.71,127.67,127.34,126.80,113.60,94.50,77.37,76.79,74.59,73.57,70.48,68.80,and55.38.IR(thin film,cm-1):3439,3028,3006,1599,1275,1259,1089,1070,1026,833,764,749,and 696cm-1.HRMS(DART-TOF)calculated for C34H35O5 +[M+H]+m/z 523.2479,found 523.2485.
(3)1-对二甲氨基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13b)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对二甲氨基苯硼酸频哪醇酯(0.40mmol,98.9mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到无色油状化合物13b(79.3mg,0.15mmol,收率为74％).1H NMR(CDCl3,400MHz)δ:7.53–7.46(m,2H),7.37–7.24(m,15H),6.68–6.62(m,2H),5.26(d,J＝3.2Hz,1H),4.86(d,J＝11.2Hz,1H),4.71(d,J＝11.2Hz,1H),4.68(d,J＝10.4Hz,1H),4.66(d,J＝12.0Hz,1H),4.63(d,J＝10.4Hz,1H),4.61(d,J＝12.0Hz,1H),4.39(dd,J＝5.9,3.2Hz,1H),4.23(ddd,J＝8.1,4.7,3.1Hz,1H),3.95(dd,J＝10.8,4.8Hz,1H),3.95(dd,J＝11.2,3.2Hz,1H),and2.95(s,6H).13C NMR(CDCl3,101MHz)δ:153.37,150.90,138.88,138.54,138.54,128.49,128.47,128.44,128.04,127.84,127.76,127.63,127.60,126.42,122.73,111.81,92.84,77.33,77.09,74.78,73.59,73.52,70.27,68.95,and40.50.IR(thin film,cm-1):3061,3028,2860,1609,1522,1359,1276,1260,1088,820,764,749,and 696cm-1.HRMS(DART-TOF)calculated for C35H38NO4 +[M+H]+m/z536.2795,found 536.2791.
(4)1-对氟苯基-3,4,6-三苄氧基-D-葡萄糖烯(13c)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对氟苯硼酸(0.40mmol,56.0mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到黄色油状化合物13c(80.7mg,0.16mmol,收率为79％).1H NMR(CDCl3,400MHz)δ:7.59–7.54(m,2H),7.36–7.25(m,15H),7.04–6.96(m,2H),5.35(d,J＝3.2Hz,1H),4.85(d,J＝11.6Hz,1H),4.70(d,J＝11.6Hz,1H),4.68(d,J＝12.0Hz,1H),4.62(d,J＝12.0Hz,1H),4.62(d,J＝12.0Hz,1H),4.59(d,J＝12.0Hz,1H),4.36(dd,J＝5.6,3.2Hz,1H),4.26(ddd,J＝8.0,4.8,2.8Hz,1H),3.96(dd,J＝8.4,6.0Hz,1H),3.91(dd,J＝10.9,5.0Hz,1H),and3.86(dd,J＝10.9,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:163.19(d,J＝249.5Hz),151.99,138.58,138.32,130.86(d,J＝3.0Hz),128.56,128.53,128.49,128.06,127.88,127.85,127.79,127.74,127.32(d,J＝8.1Hz),115.26(d,J＝21.2Hz),95.94,77.43,76.53,74.43,73.62,73.58,70.70,and68.67.19F NMR(CDCl3,376MHz)δ:–112.88.IR(thin film,cm-1):3461,3030,2864,1508,1275,1260,1228,1093,1027,839,764,749,and 697cm-1.HRMS(DART-TOF)calculated for C33H31FNaO4 +[M+Na]+m/z533.2099,found 533.2104.
(5)1-对三氟甲基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13d)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对三氟甲基苯硼酸(0.40mmol,76.0mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到白色固体化合物13d(83.0mg,0.15mmol,收率为74％).1H NMR(CDCl3,400MHz)δ:7.69(d,J＝8.4Hz,2H),7.57(d,J＝8.4Hz,2H),7.36–7.25(m,15H),5.50(d,J＝2.8Hz,1H),4.85(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.69(d,J＝11.6Hz,1H),4.64(d,J＝11.6Hz,1H),4.63(d,J＝12.0Hz,1H),4.59(d,J＝12.0Hz,1H),4.37(dd,J＝6.0,3.2Hz,1H),4.28(ddd,J＝8.0,4.8,2.8Hz,1H),3.98(dd,J＝8.4,6.0Hz,1H),3.92(dd,J＝10.9,4.9Hz,1H),and3.86(dd,J＝10.9,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:151.45,138.45,138.26,138.04,130.57(q,J＝32.5Hz),128.60,128.56,128.52,128.07,127.93,127.87,127.80,127.79,125.62,125.22(q,J＝3.8Hz),124.24(q,J＝272.7Hz),98.20,77.55,76.40,74.33,73.71,73.61,70.96,and68.56.19F NMR(CDCl3,376MHz)δ:–62.55.IR(thin film,cm-1):3031,2864,1322,1164,1109,1066,1027,1014,848,732,and 695cm-1.HRMS(DART-TOF)calculated for C34H31F3NaO4 +[M+Na]+m/z583.2067,found 583.2069.熔点:58.4–60.6℃.
(6)1-(3,4-二甲氧基苯基)-3,4,6-三苄氧基-D-葡萄糖烯(13e)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),3,4-二甲氧基苯硼酸(0.40mmol,72.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到白色固体化合物13e(90.6mg,0.16mmol,收率为82％).1H NMR(CDCl3,400MHz)δ:7.38–7.25(m,15H),7.19(dd,J＝8.4,2.0Hz,1H),7.11(d,J＝2.0Hz,1H),6.82(d,J＝8.4Hz,1H),5.31(d,J＝3.2Hz,1H),4.85(d,J＝11.6Hz,1H),4.72(d,J＝11.6Hz,1H),4.69(d,J＝11.2Hz,1H),4.65(d,J＝11.2Hz,1H),4.63(d,J＝12.4Hz,1H),4.62(d,J＝12.4Hz,1H),4.37(dd,J＝6.0,3.2Hz,1H),4.28(ddd,J＝8.4,4.8,3.2Hz,1H),3.96(dd,J＝7.6,4.8Hz,1H),3.92(dd,J＝10.8,5.2Hz,1H),3.88(dd,J＝10.8,3.2Hz,1H),3.87(s,3H),and3.85(s,3H).13C NMR(CDCl3,101MHz)δ:152.64,149.70,148.67,138.72,138.41,138.36,128.53,128.52,128.45,128.06,127.85,127.83,127.73,127.70,127.68,118.33,110.78,108.76,94.92,77.36,76.66,74.58,73.55,73.53,70.65,68.78,56.02,and55.98.IR(thin film,cm-1):3464,3005,2863,1513,1453,1274,1261,1088,1070,1023,764,750,and 696cm-1.HRMS(DART-TOF)calculated for C35H37O6 +[M+H]+m/z553.2585,found 553.2587.熔点:100.7–102.1℃.
(7)1-间甲基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13f)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),间甲基苯硼酸(0.40mmol,54.4mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到白色固体化合物13f(76.0mg,0.15mmol,收率为75％).1H NMR(CDCl3,400MHz)δ:7.43–7.39(m,2H),7.37–7.25(m,15H),7.23–7.18(m,1H),7.13–7.09(m,1H),5.41(d,J＝2.8Hz,1H),4.85(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.69(d,J＝11.6Hz,1H),4.64(d,J＝12.0Hz,1H),4.62(d,J＝11.6Hz,1H),4.60(d,J＝12.0Hz,1H),4.38(dd,J＝6.0,3.2Hz,1H),4.25(ddd,J＝8.0,4.4,3.2Hz,1H),3.97(dd,J＝8.8,6.4Hz,1H),3.92(dd,J＝11.0,4.9Hz,1H),3.88(dd,J＝11.1,3.3Hz,1H),and2.34(s,3H).13C NMR(CDCl3,101MHz)δ:153.00,138.68,138.42,137.77,134.61,129.57,128.52,128.49,128.45,128.14,128.03,127.83,127.81,127.76,127.72,127.66,126.08,122.58,96.03,77.43,76.77,74.56,73.60,73.53,70.53,68.73,and21.57.IR(thin film,cm-1):3028,2862,1453,1275,1261,1089,1026,764,749,and 695cm-1.HRMS(DART-TOF)calculated for C34H34NaO4 +[M+Na]+m/z 529.2349,found 529.2350.熔点:43.5–46.6℃.
(8)1-邻氟苯基-3,4,6-三苄氧基-D-葡萄糖烯(13g)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),邻氟苯硼酸(0.40mmol,56.0mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到白色固体化合物13g(73.5mg,0.14mmol,收率为72％).1H NMR(CDCl3,400MHz)δ:7.64(t,J＝7.6Hz,1H),7.39–7.23(m,16H),7.12(t,J＝7.6Hz,1H),7.05(dd,J＝11.6,8.4Hz,1H),5.62(d,J＝3.2Hz,1H),4.87(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.70(d,J＝11.6Hz,1H),4.64(d,J＝12.0Hz,1H),4.62(d,J＝11.6Hz,1H),4.59(d,J＝12.0Hz,1H),4.41(dd,J＝6.4,2.4Hz,1H),4.24(ddd,J＝8.6,4.8,2.0Hz,1H),3.99(dd,J＝8.6,6.2Hz,1H),3.99(dd,J＝10.8,4.8Hz,1H),and 3.89(dd,J＝10.8,2.0Hz,1H).13C NMR(CDCl3,101MHz)δ:160.12(d,J＝252.5Hz),147.87(d,J＝4.0Hz),138.52,138.40,138.36,129.94(d,J＝9.1Hz),128.87(d,J＝3.0Hz),128.51,128.49,128.45,128.03,127.89,127.81,127.77,127.72,127.67,123.94(d,J＝3.0Hz),122.77(d,J＝11.1Hz),116.07(d,J＝23.2Hz),101.70(d,J＝11.1Hz),77.55,76.80,74.30,73.68,73.55,70.45,and68.70.19F NMR(CDCl3,376MHz)δ:–112.84.IR(thin film,cm-1):3087,2918,2863,1492,1452,1091,1049,1026,732,and 695cm-1.HRMS(DART-TOF)calculatedfor C33H31FNaO4 +[M+Na]+m/z 533.2099,found 533.2101.熔点:59.1–62.3℃.
(9)1-(1-萘基)-3,4,6-三苄氧基-D-葡萄糖烯(13h)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),1-萘硼酸(0.40mmol,68.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到无色油状化合物13h(97.6mg,0.18mmol,收率为90％).1H NMR(CDCl3,400MHz)δ:8.25(dd,J＝8.4,1.4Hz,1H),7.84–7.78(m,2H),7.54(dd,J＝7.2,1.4Hz,1H),7.46–7.38(m,3H),7.37–7.24(m,15H),5.22(d,J＝3.2Hz,1H),4.92(d,J＝11.2Hz,1H),4.77(d,J＝11.2Hz,1H),4.71(d,J＝12.0Hz,1H),4.63(d,J＝11.6Hz,1H),4.60(d,J＝12.0Hz,1H),4.56(d,J＝12.0Hz,1H),4.44(dd,J＝6.4,3.2Hz,1H),4.41(ddd,J＝8.0,4.8,2.4Hz,1H),4.13(dd,J＝8.4,6.4Hz,1H),3.99(dd,J＝10.8,4.8Hz,1H),and3.89(dd,J＝10.8,2.8Hz,1H).13C NMR(CDCl3,101MHz)δ:154.51,138.54,138.50,138.40,133.78,133.74,131.37,129.42,128.55,128.53,128.43,128.26,128.03,127.89,127.84,127.77,127.69,127.62,126.92,126.34,126.13,125.93,125.12,100.77,77.75,76.76,74.60,73.78,73.55,70.72,and68.81.IR(thin film,cm-1):3028,3006,2861,1453,1275,1260,1071,1026,764,749,and 695cm-1.HRMS(DART-TOF)calculated forC37H34NaO4 +[M+Na]+m/z565.2349,found 565.2358.
(10)1-邻甲基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13i)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),邻甲基苯硼酸(0.40mmol,54.4mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到无色油状化合物13i(81.1mg,0.16mmol,收率为80％).1H NMR(CDCl3,400MHz)δ:7.37–7.23(m,16H),7.22–7.18(m,1H),7.16–7.11(m,2H),5.01(d,J＝2.9Hz,1H),4.87(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.68(d,J＝11.6Hz,1H),4.61(d,J＝11.6Hz,1H),4.58(d,J＝12.0Hz,1H),4.53(d,J＝12.0Hz,1H),4.38(dd,J＝6.2,2.9Hz,1H),4.23(ddd,J＝8.8,4.8,2.6Hz,1H),4.01(dd,J＝8.8,6.2Hz,1H),3.91(dd,J＝10.8,4.8Hz,1H),3.84(dd,J＝10.8,2.7Hz,1H),and2.37(s,3H).13C NMR(CDCl3,101MHz)δ:155.36,138.60,138.51,138.35,136.81,135.58,130.44,129.16,128.79,128.52,128.48,128.41,127.97,127.87,127.77,127.73,127.72,127.62,125.55,99.60,77.49,76.99,74.62,73.73,73.54,70.56,68.90,and20.37.IR(thin film,cm-1):3006,2989,2862,1275,1260,1086,1041,1027,764,747,and 695cm-1.HRMS(DART-TOF)calculated for C34H34NaO4 +[M+Na]+m/z 529.2349,found 529.2355.
(11)1-(3,4-亚甲二氧基苯基)-3,4,6-三苄氧基-D-葡萄糖烯(13j)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),3,4-亚甲二氧基苯硼酸(0.40mmol,66.4mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝8:1，分离纯化得到白色固体化合物13j(87.9mg,0.16mmol,收率为82％).1H NMR(CDCl3,400MHz)δ:7.36–7.27(m,15H),7.13(dd,J＝8.4,1.6Hz,1H),7.07(d,J＝1.6Hz,1H),6.75(d,J＝8.4Hz,1H),5.93(s,2H),5.28(d,J＝3.2Hz,1H),4.85(d,J＝11.6Hz,1H),4.70(d,J＝11.6Hz,1H),4.67(d,J＝11.6Hz,1H),4.63(d,J＝12.0Hz,1H),4.61(d,J＝11.6Hz,1H),4.59(d,J＝12.0Hz,1H),4.35(dd,J＝6.0,3.2Hz,1H),4.23(ddd,J＝8.0,4.8,3.2Hz,1H),3.95(dd,J＝8.4,6.0Hz,1H),3.90(dd,J＝10.9,4.9Hz,1H),and3.85(dd,J＝10.9,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:152.55,148.14,147.69,138.65,138.39,138.37,129.02,128.54,128.51,128.48,128.05,127.85,127.84,127.79,127.74,127.70,119.54,108.02,106.07,101.27,95.09,77.43,76.76,74.54,73.60,73.58,70.56,and68.71.IR(thin film,cm-1):3063,2867,1488,1444,1095,1037,1028,932,732,and 695cm-1.HRMS(DART-TOF)calculated for C34H32NaO6 +[M+Na]+m/z 559.2091,found 559.2095.熔点:52.2–55.4℃.
(12)1-乙烯基-3,4,6-三苄氧基-D-葡萄糖烯(13k)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),乙烯基硼酸频哪醇酯(0.40mmol,61.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13k(42.4mg,0.01mmol,收率为48％).1H NMR(CDCl3,400MHz)δ:7.35–7.25(m,15H),6.07(dd,J＝17.2,10.8Hz,1H),5.63(dd,J＝17.2,1.6Hz,1H),5.16(dd,J＝10.8,1.7Hz,1H),4.92(d,J＝3.1Hz,1H),4.83(d,J＝11.4Hz,1H),4.68(d,J＝11.4Hz,1H),4.63(d,J＝11.6Hz,1H),4.61(d,J＝12.0Hz,1H),4.58(d,J＝12.0Hz,1H),4.56(d,J＝11.6Hz,1H),4.28(dd,J＝6.1,3.1Hz,1H),4.13(ddd,J＝8.1,4.7,3.0Hz,1H),3.90(dd,J＝8.6,6.1Hz,1H),3.86(dd,J＝11.0,4.8Hz,1H),3.82(dd,J＝11.0,3.1Hz,1H).13C NMR(CDCl3,101MHz)δ:151.71,138.54,138.47,138.40,131.36,128.53,128.51,128.47,128.07,127.85,127.76,127.67,115.64,100.98,77.21,76.65,74.54,73.74,73.60,70.63,68.72.IR(thin film,cm-1):3032,2917,2861,1689,1264,1228,1111,1097,908,729,and 697cm-1.HRMS(DART-TOF)calculated for C49H51N2O6 +[M+H]+m/z 763.3742,found 763.3745.
(13)1-烯丙基-3,4,6-三苄氧基-D-葡萄糖烯(13l)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg)，烯丙基硼酸频哪醇酯(0.40mmol,67.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13l(77.6mg,0.17mmol,收率为85％).1H NMR(CDCl3,400MHz)δ:7.44–7.23(m,15H),5.84(ddt,J＝16.9,10.1,6.8Hz,1H),5.18–5.00(m,2H),4.80(d,J＝11.5Hz,1H),4.70(d,J＝2.9Hz,1H),4.68–4.48(m,5H),4.20–4.13(m,1H),4.10(ddd,J＝8.1,5.0,3.1Hz,1H),3.84(dd,J＝8.1,5.8Hz,1H),3.81(dd,J＝10.9,5.0Hz,1H),3.75(dd,J＝10.8,3.0Hz,1H),2.84(d,J＝6.8Hz,2H).13C NMR(CDCl3,101MHz)δ:154.71,138.64,138.42,138.39,133.84,128.48,128.44,128.02,127.82,127.80,127.78,127.67,117.25,95.71,77.07,76.10,74.36,73.54,73.49,70.44,68.71,and 38.06.IR(thin film,cm-1):3029,2864,1673,1453,1261,1095,1027,916,743,and696cm-1.HRMS(DART-TOF)calculated for C30H32NaO4 +[M+Na]+m/z 479.2193,found479.2196.
(14)1-对氰基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13m)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对氰基苯硼酸(0.40mmol,58.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13m(72.5mg,0.14mmol,收率为70％).1H NMR(CDCl3,400MHz)δ:7.67(d,J＝8.0Hz,2H),7.59(d,J＝8.8Hz,2H),7.35–7.27(m,15H),5.53(d,J＝3.2Hz,1H),4.84(d,J＝11.2Hz,1H),4.70(d,J＝11.2Hz,1H),4.69(d,J＝11.6Hz,1H),4.64(d,J＝11.6Hz,1H),4.61(d,J＝12.0Hz,1H),4.58(d,J＝12.0Hz,1H),4.35(dd,J＝6.0,3.2Hz,1H),4.28(ddd,J＝8.0,4.8,2.8Hz,1H),3.97(dd,J＝8.4,6.0Hz,1H),3.91(dd,J＝10.9,5.0Hz,1H),and3.85(dd,J＝10.9,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:150.86,138.83,138.31,138.14,138.12,132.07,128.59,128.55,128.50,128.47,128.04,127.94,127.90,127.84,127.80,127.77,125.79,118.87,112.08,99.27,77.53,76.19,74.17,73.70,73.57,71.05,and68.43.IR(thin film,cm-1):3006,2989,2864,1275,1260,1097,764,749,and 698cm-1.HRMS(DART-TOF)calculated forC34H31NNaO4 +[M+Na]+m/z540.2145,found 540.2146.熔点:103.5–106.6℃.
(15)1-对甲氧羰基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13n)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对甲氧羰基苯硼酸(0.40mmol,72.0mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13n(89.1mg,0.16mmol,收率为81％).1H NMR(CDCl3,400MHz)δ:8.00(d,J＝8.4Hz,2H),7.66(d,J＝8.4Hz,2H),7.40–7.24(m,15H),5.53(d,J＝3.2Hz,1H),4.85(d,J＝11.2Hz,1H),4.71(d,J＝11.2Hz,1H),4.70(d,J＝11.6Hz,1H),4.64(d,J＝11.6Hz,1H),4.62(d,J＝12.4Hz,1H),4.59(d,J＝12.4Hz,1H),4.37(dd,J＝6.4,2.8Hz,1H),4.27(ddd,J＝8.4,4.8,3.2Hz,1H),3.98(dd,J＝8.4,6.0Hz,1H),3.87(dd,J＝10.6,4.8Hz,1H),3.90(s,3H),and 3.87(dd,J＝10.6,2.8Hz,1H).13C NMR(CDCl3,101MHz)δ:166.89,151.76,138.85,138.46,138.26,130.15,129.57,128.57,128.53,128.49,128.05,127.89,127.85,127.83,127.78,127.75,125.21,98.32,77.51,76.49,74.32,73.70,73.57,70.87,68.54,and52.22.IR(thin film,cm-1):3029,2862,1718,1274,1099,1026,1016,732,and 695cm-1.HRMS(DART-TOF)calculated forC35H34NaO6 +[M+Na]+m/z 573.2248,found 573.2249.熔点:65.9–68.1℃.
(16)1-(4-(2-羟基丙烷-2-基)苯基)-3,4,6-三苄氧基-D-葡萄糖烯(13o)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),4-(2-羟基丙烷-2-基)苯硼酸(0.40mmol,72.0mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13o(78.2mg,0.14mmol,收率为71％).1H NMR(CDCl3,400MHz)δ:7.57(d,J＝8.4Hz,2H),7.44(d,J＝8.4Hz,2H),7.37–7.27(m,15H),5.41(d,J＝3.2Hz,1H),4.86(d,J＝11.2Hz,1H),4.71(d,J＝11.2Hz,1H),4.70(d,J＝12.0Hz,1H),4.63(d,J＝12.0Hz,1H),4.62(d,J＝12.0Hz,1H),4.60(d,J＝12.0Hz,1H),4.38(dd,J＝6.0,2.8Hz,1H),4.26(ddd,J＝8.4,4.8,3.2Hz,1H),3.97(dd,J＝8.4,6.0Hz,1H),3.92(dd,J＝10.9,4.8Hz,1H),3.88(dd,J＝11.0,3.1Hz,1H),1.82–1.74(br s,1H),and1.57(s,6H).13C NMR(CDCl3,101MHz)δ:152.70,149.80,138.67,138.43,133.16,128.57,128.53,128.50,128.07,127.89,127.86,127.80,127.78,127.71,125.34,124.35,96.00,77.48,76.77,74.58,73.66,73.62,72.62,70.63,68.79,and31.83.IR(thin film,cm-1):3414,3030,2972,2865,1275,1261,1088,1071,1026,1015,748,733,and 696cm-1.HRMS(DART-TOF)calculated for C36H38NaO5 +[M+Na]+m/z 573.2611,found573.2615.
(17)1-对乙酰基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13p)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对乙酰基苯硼酸(0.40mmol,65.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13p(78.1mg,0.15mmol,收率为73％).1H NMR(CDCl3,400MHz)δ:7.94–7.89(m,2H),7.71–7.66(m,2H),7.37–7.28(m,15H),5.55(d,J＝3.2Hz,1H),4.85(d,J＝11.2Hz,1H),4.72(d,J＝11.2Hz,1H),4.70(d,J＝11.6Hz,1H),4.66(d,J＝11.6Hz,1H),4.63(d,J＝12.4Hz,1H),4.60(d,J＝12.4Hz,1H),4.38(dd,J＝6.0,3.2Hz,1H),4.28(ddd,J＝8.4,4.8,3.2Hz,1H),3.98(dd,J＝8.4,6.0Hz,1H),3.92(dd,J＝10.9,4.9Hz,1H),3.88(dd,J＝10.9,3.0Hz,1H),and2.59(s,3H).13C NMR(CDCl3,101MHz)δ:197.73,151.68,138.97,138.44,138.26,138.24,137.02,128.58,128.54,128.50,128.36,128.06,127.91,127.86,127.78,127.76,125.40,98.55,77.53,76.48,74.32,73.71,73.60,70.93,68.57,and26.76.IR(thin film,cm-1):3006,2989,2861,1680,1604,1275,1260,1089,1026,764,749,and 696cm-1.HRMS(DART-TOF)calculated for C35H34NaO5 +[M+Na]+m/z 557.2298,found 557.2300.熔点:88.2–90.3℃.
(18)1-对二甲氨基甲酰基苯基-3,4,6-三苄氧基-D-葡萄糖烯(13q)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),对二甲氨基甲酰基苯硼酸(0.40mmol,77.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13q(50.7mg,0.09mmol,收率为45％).1H NMR(CDCl3,400MHz)δ:7.63(d,J＝8.4Hz,2H),7.40–7.37(m,2H),7.36–7.26(m,15H),5.47(d,J＝3.2Hz,1H),4.86(d,J＝11.2Hz,1H),4.72(d,J＝11.2Hz,1H),4.69(d,J＝12.0Hz,1H),4.65(d,J＝12.0Hz,1H),4.62(d,J＝12.0Hz,1H),4.60(d,J＝12.0Hz,1H),4.38(dd,J＝6.0,3.6Hz,1H),4.27(ddd,J＝8.4,4.8,3.2Hz,1H),3.98(dd,J＝8.4,6.0Hz,1H),3.92(dd,J＝10.9,4.9Hz,1H),3.87(dd,J＝10.9,3.0Hz,1H),3.10(s,3H),and2.95(s,3H).13C NMR(CDCl3,101MHz)δ:171.38,152.01,138.50,138.29,138.29,136.45,135.77,128.55,128.51,128.47,128.04,127.86,127.84,127.80,127.77,127.72,127.13,125.29,97.19,77.48,76.57,74.41,73.67,73.58,70.78,68.64,39.64,and35.49.IR(thin film,cm-1):3006,2989,2862,1629,1275,1261,1079,764,749,and696cm-1.HRMS(DART-TOF)calculated for C36H37NNaO5 +[M+Na]+m/z 586.2564,found586.2572.
(19)1-(二苯并噻吩-4-基)-3,4,6-三苄氧基-D-葡萄糖烯(13r)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),二苯并噻吩-4-硼酸(0.40mmol,91.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13r(99.3mg,0.17mmol,收率为83％).1H NMR(CDCl3,400MHz)δ:8.14–8.08(m,2H),7.82–7.76(m,1H),7.66(dd,J＝7.6,1.2Hz,1H),7.45–7.24(m,18H),5.61(d,J＝2.8Hz,1H),4.91(d,J＝11.6Hz,1H),4.76(d,J＝11.6Hz,1H),4.75(d,J＝11.6Hz,1H),4.70(d,J＝11.6Hz,1H),4.67(d,J＝12.0Hz,1H),4.64(d,J＝12.0Hz,1H),4.48(dd,J＝6.4,3.2Hz,1H),4.37(ddd,J＝8.8,6.4,3.2Hz,1H),4.11(dd,J＝8.6,6.4Hz,1H),4.04(dd,J＝11.2,4.0Hz,1H),and 4.01(dd,J＝11.2,4.0Hz,1H).13C NMR(CDCl3,101MHz)δ:152.91,140.32,138.63,138.45,138.40,137.12,136.61,135.11,130.12,128.57,128.52,128.45,128.07,127.93,127.85,127.78,127.65,126.90,125.23,124.43,124.33,122.44,122.03,121.56,99.23,77.97,77.10,74.56,73.86,73.69,70.64,and68.76.IR(thin film,cm-1):3028,3006,2859,1275,1260,1089,1041,1026,764,749,and 695cm-1.HRMS(DART-TOF)calculated for C39H34NaO4S+[M+Na]+m/z621.2070,found621.2079.熔点:75.6–78.1℃.
(20)1-(噻吩-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13s)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),噻吩-3-硼酸(0.40mmol,51.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到黄色油状化合物13s(89.8mg,0.18mmol,收率为90％).1H NMR(CDCl3,400MHz)δ:7.47(dd,J＝3.2,1.2Hz,1H),7.36–7.25(m,15H),7.24–7.21(m,1H),7.20–7.17(m,1H),5.30(d,J＝3.2Hz,1H),4.84(d,J＝11.6Hz,1H),4.70(d,J＝11.6Hz,1H),4.67(d,J＝12.0Hz,1H),4.63(d,J＝12.0Hz,1H),4.60(d,J＝12.0Hz,1H),4.59(d,J＝12.0Hz,1H),4.35(dd,J＝6.0,3.2Hz,1H),4.25(ddd,J＝8.2,4.8,3.2Hz,1H),3.95(dd,J＝8.4,6.0Hz,1H),3.90(dd,J＝10.9,4.9Hz,1H),and 3.85(dd,J＝11.0,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:149.52,138.62,138.37,138.35,136.88,128.53,128.51,128.47,128.05,127.84,127.76,127.74,127.69,125.70,124.99,122.36,95.87,77.30,76.41,74.39,73.60,73.56,70.60,and68.70.IR(thin film,cm-1):3434,3028,3006,2864,1275,1260,1087,1071,1026,764,749,and 695cm-1.HRMS(DART-TOF)calculated forC31H30NaO4S+[M+H]+m/z 521.1757,found 521.1765.
(21)1-(苯并呋喃-5-基)-3,4,6-三苄氧基-D-葡萄糖烯(13t)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),苯并呋喃-5-硼酸(0.40mmol,64.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13t(91.5mg,0.17mmol,收率为86％).1H NMR(CDCl3,400MHz)δ:7.86(d,J＝1.6Hz,1H),7.59(d,J＝2.0Hz,1H),7.55(dd,J＝8.4,1.6Hz,1H),7.45–7.41(m,1H),7.37–7.26(m,15H),6.74(dd,J＝2.0,0.8Hz,1H),5.42(d,J＝3.2Hz,1H),4.87(d,J＝11.2Hz,1H),4.72(d,J＝11.2Hz,1H),4.71(d,J＝12.0Hz,1H),4.65(d,J＝12.0Hz,1H),4.63(d,J＝12.0Hz,1H),4.61(d,J＝12.0Hz,1H),4.40(dd,J＝6.0,3.2Hz,1H),4.30(ddd,J＝8.4,4.8,2.8Hz,1H),3.99(dd,J＝8.4,5.6Hz,1H),3.95(dd,J＝10.9,4.9Hz,1H),and 3.90(dd,J＝10.9,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:155.34,153.23,145.62,138.69,138.41,129.85,128.54,128.51,128.47,128.06,127.85,127.83,127.80,127.74,127.69,127.41,122.24,118.59,111.05,106.99,95.59,77.48,76.80,74.60,73.60,73.58,70.54,and68.79.IR(thin film,cm-1):3030,2865,1264,1110,1091,1027,730,and 696cm-1.HRMS(DART-TOF)calculated forC35H32NaO5 +[M+Na]+m/z 555.2142,found 555.2151.熔点:65.4–67.8℃.
(22)1-(苯并呋喃-3-yl)-3,4,6-三苄氧基-D-葡萄糖烯(13u)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),苯并呋喃-3-硼酸(0.40mmol,64.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13u(80.0mg,0.15mmol,收率为75％).1H NMR(CDCl3,400MHz)δ:7.83(s,1H),7.70–7.66(m,1H),7.49–7.45(m,1H),7.39–7.28(m,15H),7.28–7.21(m,2H),5.41(d,J＝2.8Hz,1H),4.88(d,J＝11.2Hz,1H),4.73(d,J＝11.2Hz,1H),4.71(d,J＝12.0Hz,1H),4.67(d,J＝12.0Hz,1H),4.63(d,J＝12.0Hz,1H),4.60(d,J＝12.0Hz,1H),4.41(dd,J＝6.0,3.0Hz,1H),4.29(ddd,J＝8.2,4.8,2.8Hz,1H),4.00(dd,J＝8.4,6.0Hz,1H),3.93(dd,J＝10.9,5.1Hz,1H),and 3.87(dd,J＝10.9,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:155.74,147.50,143.84,138.72,138.36,138.32,128.61,128.55,128.51,128.08,127.91,127.89,127.82,127.75,124.81,124.64,123.19,121.22,117.02,111.79,97.64,77.29,76.72,74.50,73.71,73.60,70.83,and68.76.IR(thinfilm,cm-1):3028,3006,2861,1665,1451,1275,1260,1095,1040,1026,764,749,and695cm-1.HRMS(DART-TOF)calculated for C35H32NaO5 +[M+Na]+m/z 555.2142,found555.2147.熔点:63.2–65.9℃.
(23)1-(二苯并呋喃-4-基)-3,4,6-三苄氧基-D-葡萄糖烯(13v)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),二苯并呋喃-4-硼酸(0.40mmol,84.8mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13v(100.2mg,0.17mmol,收率为86％).1H NMR(CDCl3,400MHz)δ:7.96–7.91(m,1H),7.90–7.87(m,1H),7.84–7.79(m,1H),7.60–7.55(m,1H),7.48–7.41(m,3H),7.39–7.25(m,15H),6.34(d,J＝2.8Hz,1H),4.92(d,J＝11.6Hz,1H),4.80(d,J＝11.6Hz,1H),4.77(d,J＝11.6Hz,1H),4.74(d,J＝11.6Hz,1H),4.69(d,J＝12.0Hz,1H),4.64(d,J＝12.0Hz,1H),4.56(dd,J＝6.0,3.2Hz,1H),4.33(ddd,J＝8.4,4.4,3.2Hz,1H),4.08(dd,J＝8.4,6.0Hz,1H),3.99(dd,J＝11.0,4.7Hz,1H),and3.94(dd,J＝11.1,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:156.07,152.83,148.38,138.75,138.48,138.45,128.56,128.53,128.49,128.11,128.00,127.84,127.82,127.76,127.70,127.26,125.05,124.01,123.04,122.71,120.77,120.68,119.74,111.92,101.82,77.60,77.18,74.42,73.74,73.64,70.50,and68.86.IR(thin film,cm-1):3062,3029,2861,1450,1189,1086,1045,1026,746,732,and 695cm-1.HRMS(DART-TOF)calculated for C39H34NaO5 +[M+Na]+m/z 605.2298,found 605.2303.熔点:113.4–115.5℃.
(24)1-间吡啶-3,4,6-三苄氧基-D-葡萄糖烯(13w)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),3-吡啶硼酸(0.40mmol,49.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到黄色油状化合物13w(58.2mg,0.12mmol,收率为59％).1H NMR(CDCl3,400MHz)δ:8.84(d,J＝2.2Hz,1H),8.53(dd,J＝4.9,1.6Hz,1H),7.85(dt,J＝8.0,2.0Hz,1H),7.36–7.25(m,15H),7.25–7.22(m,1H),5.47(d,J＝3.2Hz,1H),4.85(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.68(d,J＝12.0Hz,1H),4.65(d,J＝12.0Hz,1H),4.62(d,J＝12.0Hz,1H),4.59(d,J＝12.0Hz,1H),4.36(dd,J＝5.9,3.2Hz,1H),4.28(ddd,J＝8.1,4.9,2.9Hz,1H),3.98(dd,J＝8.3,5.9Hz,1H),3.92(dd,J＝10.9,4.9Hz,1H),and 3.86(dd,J＝11.0,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:150.42,149.68,146.93,138.39,138.21,138.19,132.66,130.36,128.57,128.53,128.49,128.04,127.90,127.85,127.76,123.05,97.68,77.52,76.24,74.27,73.69,73.60,70.94,and68.50.IR(thin film,cm-1):3029,3006,2989,2862,1275,1260,1090,1043,1025,764,750,and695cm-1.HRMS(DART-TOF)calculated for C32H32NO4 +[M+H]+m/z 494.2326,found494.2325.
(25)1-(喹啉-6-基)-3,4,6-三苄氧基-D-葡萄糖烯(13x)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),喹啉-6-硼酸(0.40mmol,69.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13x(96.7mg,0.18mmol,收率为89％).1H NMR(CDCl3,400MHz)δ:8.87(dd,J＝4.0,1.6Hz,1H),8.11(dd,J＝8.4,1.6Hz,1H),8.07(d,J＝2.0Hz,1H),8.05(d,J＝8.8Hz,1H),7.90(dd,J＝9.2,2.0Hz,1H),7.39–7.25(m,16H),5.61(d,J＝3.2Hz,1H),4.87(d,J＝11.2Hz,1H),4.73(d,J＝11.2Hz,1H),4.70(d,J＝11.6Hz,1H),4.66(d,J＝11.6Hz,1H),4.65(d,J＝12.0Hz,1H),4.62(d,J＝12.0Hz,1H),4.42(dd,J＝5.9,3.2Hz,1H),4.34(ddd,J＝8.0,4.9,3.0Hz,1H),4.02(dd,J＝8.3,5.9Hz,1H),3.97(dd,J＝10.9,5.0Hz,1H),and3.92(dd,J＝10.9,3.1Hz,1H).13C NMR(CDCl3,101MHz)δ:151.90,150.68,148.47,138.49,138.28,138.26,136.59,132.50,129.26,128.55,128.51,128.47,128.03,127.86,127.84,127.80,127.76,127.72,126.74,124.41,121.53,97.74,77.49,76.48,74.41,73.62,73.53,70.80,and68.62.IR(thinfilm,cm-1):3031,2865,1264,1091,1027,764,731,and 697cm-1.HRMS(DART-TOF)calculated for C36H34NO4 +[M+H]+m/z 544.2482,found 544.2484.熔点:106.7–108.9℃.
(26)1-(喹啉-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13y)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),喹啉-3-硼酸(0.40mmol,102.1mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13y(94.5mg,0.17mmol,收率为87％).1H NMR(CDCl3,400MHz)δ:9.10(d,J＝2.4Hz,1H),8.33(d,J＝1.6Hz,1H),8.09(d,J＝8.4Hz,1H),7.80(dd,J＝8.0,1.3Hz,1H),7.68(ddd,J＝8.4,6.4,1.2Hz,1H),7.53(ddd,J＝8.4,6.4,1.2Hz,1H),7.40–7.25(m,15H),5.63(d,J＝3.2Hz,1H),4.88(d,J＝11.2Hz,1H),4.75(d,J＝11.6Hz,1H),4.72(d,J＝12.0Hz,1H),4.68(d,J＝11.6Hz,1H),4.64(d,J＝12.0Hz,1H),4.63(d,J＝12.0Hz,1H),4.41(dd,J＝6.0,3.2Hz,1H),4.35(ddd,J＝8.4,4.8,3.2Hz,1H),4.03(dd,J＝8.4,6.0Hz,1H),3.96(dd,J＝10.9,5.0Hz,1H),and3.91(dd,J＝10.9,3.0Hz,1H).13C NMR(CDCl3,101MHz)δ:150.41,147.96,147.89,138.40,138.20,132.08,129.78,129.29,128.59,128.53,128.49,128.38,128.05,127.90,127.88,127.88,127.77,127.77,127.54,127.39,127.05,98.14,77.53,76.28,74.31,73.68,73.58,71.04,and68.51.IR(thin film,cm-1):3029,2861,1650,1495,1452,1361,1291,1090,1025,788,748,733,and 695cm-1.HRMS(DART-TOF)calculated for C36H34NO4 +[M+H]+m/z 544.2482,found 544.2482.熔点:106.3–109.5℃.
(27)1-(N-苯基吲哚-5-基)-3,4,6-三苄氧基-D-葡萄糖烯(13z)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),N-苯基吲哚-5-硼酸(0.40mmol,133.3mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13z(84.6mg,0.14mmol,收率为68％).1H NMR(CDCl3,400MHz)δ:7.94(d,J＝1.6Hz,1H),7.43(dd,J＝8.7,1.7Hz,1H),7.39–7.23(m,18H),7.19(d,J＝8.7Hz,1H),7.09(d,J＝3.2Hz,1H),7.05(dd,J＝7.8,1.7Hz,2H),6.54(d,J＝3.1Hz,1H),5.39(d,J＝3.1Hz,1H),5.27(s,2H),4.87(d,J＝11.6Hz,1H),4.73(d,J＝11.6Hz,1H),4.70(d,J＝11.6Hz,1H),4.68(d,J＝12.0Hz,1H),4.63(d,J＝11.6Hz,1H),4.62(d,J＝12.0Hz,1H),4.42(dd,J＝6.0,3.1Hz,1H),4.28(ddd,J＝8.1,4.7,3.0Hz,1H),4.00(dd,J＝8.5,6.0Hz,1H),3.96(dd,J＝11.0,4.9Hz,1H),and3.92(dd,J＝11.0,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:154.20,138.86,138.55,137.50,136.75,128.96,128.87,128.60,128.51,128.48,128.45,128.05,127.85,127.79,127.76,127.74,127.65,127.61,126.81,126.52,119.79,118.57,109.42,102.55,94.47,77.48,77.16,74.81,73.59,73.58,70.31,68.96,and50.27.IR(thin film,cm-1):3062,2920,2856,1648,1452,1094,1027,731,and 696cm-1.HRMS(DART-TOF)calculated forC42H40NO4 +[M+H]+m/z 622.2952,found 622.2956.
(28)1-(1-苯基-1H-吡咯[2,3-b]吡啶-5-基)-3,4,6-三苄氧基-D-葡萄糖烯(13aa)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),1-苯基-1H-吡咯[2,3-b]吡啶-5-硼酸(0.40mmol,133.7mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13aa(107.1mg,0.17mmol,收率为86％).1H NMR(CDCl3,400MHz)δ:8.62(d,J＝2.0Hz,1H),8.13(d,J＝2.1Hz,1H),7.38–7.23(m,18H),7.20–7.16(m,2H),7.15(d,J＝3.5Hz,1H),6.47(d,J＝3.5Hz,1H),5.47(s,2H),5.42(d,J＝3.2Hz,1H),4.87(d,J＝11.2Hz,1H),4.73(d,J＝11.2Hz,1H),4.70(d,J＝11.6Hz,1H),4.67(d,J＝11.6Hz,1H),4.64(d,J＝11.6Hz,1H),4.61(d,J＝11.6Hz,1H),4.41(dd,J＝6.0,3.2Hz,1H),4.31(ddd,J＝8.0,4.9,2.9Hz,1H),4.01(dd,J＝8.4,5.9Hz,1H),3.96(dd,J＝11.0,4.9Hz,1H),and3.90(dd,J＝11.0,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:152.33,147.98,141.39,138.64,138.41,138.38,137.77,128.81,128.70,128.56,128.52,128.48,128.06,127.89,127.84,127.80,127.76,127.73,127.69,127.53,126.17,123.37,119.85,100.81,95.39,77.53,76.74,74.59,73.65,73.63,70.62,68.78,and48.07.IR(thin film,cm-1):3029,2927,2862,1275,1261,1086,1026,906,764,749,729,and 695cm-1.HRMS(DART-TOF)calculated for C41H39N2O4 +[M+H]+m/z 623.2904,found623.2911.
(29)1-(5-甲氧基吡啶-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13ab)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),5-甲氧基吡啶-3-硼酸频哪醇酯(0.40mmol,61.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13ab(88.0mg,0.17mmol,收率为84％).1H NMR(CDCl3,400MHz)δ:8.45(d,J＝1.6Hz,1H),8.24(d,J＝2.8Hz,1H),7.37–7.36(m,1H),7.36–7.27(m,15H),5.47(d,J＝3.2Hz,1H),4.85(d,J＝11.2Hz,1H),4.72(d,J＝11.6Hz,1H),4.69(d,J＝12.0Hz,1H),4.65(d,J＝11.6Hz,1H),4.62(d,J＝12.4Hz,1H),4.58(d,J＝12.0Hz,1H),4.35(dd,J＝6.0,3.2Hz,1H),4.29(ddd,J＝8.4,4.8,2.8Hz,1H),3.97(dd,J＝8.4,6.0Hz,1H),3.91(dd,J＝10.9,5.0Hz,1H),3.86(dd,J＝10.9,3.0Hz,1H),and3.83(s,3H).13C NMR(CDCl3,101MHz)δ:155.49,150.19,139.32,138.40,138.21,138.20,137.64,131.13,128.59,128.55,128.50,128.06,127.92,127.88,127.77,127.74,117.12,98.06,77.52,76.17,74.28,73.67,73.59,70.99,68.49,and55.70.IR(thin film,cm-1):3028,3006,2863,1453,1275,1260,1204,1089,1026,764,749,and 695cm-1.HRMS(DART-TOF)calculated for C33H34NO5 +[M+H]+m/z 524.2431,found524.2434.
(30)1-(6-甲氧基吡啶-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13ac)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),6-甲氧基吡啶-3-硼酸频哪醇酯(0.40mmol,61.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13ac(94.3mg,0.18mmol,收率为90％).1H NMR(CDCl3,400MHz)δ:8.42(d,J＝2.4Hz,1H),7.74(dd,J＝8.7,2.5Hz,1H),7.36–7.26(m,15H),6.69(d,J＝8.7Hz,1H),5.30(d,J＝3.1Hz,1H),4.85(d,J＝11.2Hz,1H),4.71(d,J＝11.2Hz,1H),4.68(d,J＝11.6Hz,1H),4.64(d,J＝11.6Hz,1H),4.61(d,J＝12.4Hz,1H),4.58(d,J＝12.4Hz,1H),4.35(dd,J＝5.9,3.1Hz,1H),4.26(ddd,J＝8.0,4.9,2.9Hz,1H),3.96(dd,J＝8.4,6.0Hz,1H),3.94(s,3H),3.90(dd,J＝10.9,2.9Hz,1H),and3.85(dd,J＝10.9,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:164.44,150.84,144.37,138.53,138.31,138.29,135.88,128.58,128.54,128.50,128.08,127.89,127.88,127.82,127.79,127.74,123.99,110.30,95.52,77.47,76.46,74.41,73.67,73.66,70.78,68.65,and53.71.IR(thin film,cm-1):3029,2861,1601,1493,1453,1379,1284,1091,1023,831,748,733,and 696cm-1.HRMS(DART-TOF)calculated for C33H34NO5 +[M+H]+m/z524.2431,found 524.2434.
(31)1-(6-三氟甲基吡啶-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13ad)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),6-三氟甲基吡啶-3-硼酸(0.40mmol,76.4mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物13ad(105.5mg,0.19mmol,收率为94％).1H NMR(CDCl3,400MHz)δ:8.90(d,J＝2.0Hz,1H),8.00(dd,J＝8.4,2.0Hz,1H),7.63(d,J＝8.0Hz,1H),7.37–7.27(m,15H),5.55(d,J＝3.2Hz,1H),4.85(d,J＝11.6Hz,1H),4.72(d,J＝11.6Hz,1H),4.69(d,J＝12.0Hz,1H),4.65(d,J＝12.0Hz,1H),4.60(d,J＝12.0Hz,1H),4.59(d,J＝12.0Hz,1H),4.35(dd,J＝6.0,3.2Hz,1H),4.31(ddd,J＝8.4,4.8,2.8Hz,1H),3.98(dd,J＝8.4,6.0Hz,1H),3.91(dd,J＝10.9,5.0Hz,1H),and3.85(dd,J＝10.9,2.9Hz,1H).13C NMR(CDCl3,101MHz)δ:149.09,147.75(q,J＝34.8Hz),146.99,138.22,138.08,133.82,133.09,128.65,128.59,128.54,128.07,128.00,127.91,127.86,127.80,121.64(q,J＝275.2Hz),120.00(q,J＝6.0Hz),99.83,77.65,75.96,74.09,73.77,73.65,71.31,and68.36.19F NMR(CDCl3,376MHz)δ:–67.83.IR(thin film,cm-1):3029,3006,2989,2865,1334,1275,1260,1085,1025,764,749,and695cm-1.HRMS(DART-TOF)calculated for C33H31F3NO4 +[M+H]+m/z 562.2200,found562.2208.熔点:73.2–75.1℃.
(32)1-(6-吗啡啉吡啶-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13ae)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),6-吗啡啉吡啶-3-硼酸(0.40mmol,83.2mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13ae(102.9mg,0.18mmol,收率为89％).1H NMR(CDCl3,400MHz)δ:8.45(d,J＝2.0Hz,1H),7.68(dd,J＝8.6,2.4Hz,1H),7.35–7.26(m,15H),6.56(d,J＝9.2Hz,1H),5.26(d,J＝3.2Hz,1H),4.85(d,J＝11.2Hz,1H),4.71(d,J＝11.2Hz,1H),4.67(d,J＝12.0Hz,1H),4.64(d,J＝12.0Hz,1H),4.61(d,J＝12.0Hz,1H),4.60(d,J＝12.0Hz,1H),4.36(dd,J＝6.0,3.2Hz,1H),4.24(ddd,J＝8.0,4.8,2.8Hz,1H),3.96(dd,J＝8.4,6.0Hz,1H),3.91(dd,J＝10.9,4.9Hz,1H),3.85(dd,J＝11.0,2.9Hz,1H),3.82–3.78(m,4H),and3.55–3.50(m,4H).13C NMR(CDCl3,101MHz)δ:159.46,151.28,145.51,138.62,138.36,134.72,128.55,128.52,128.48,128.07,127.86,127.77,127.70,120.60,105.89,94.19,77.38,76.62,74.52,73.66,73.61,70.64,68.74,66.80,and45.62.IR(thin film,cm-1):3449,3005,2856,1595,1496,1275,1260,1238,1112,1068,1026,942,764,749,and 696cm-1.HRMS(DART-TOF)calculated forC36H39N2O5 +[M+H]+m/z 579.2853,found 579.2862.
(33)1-(6-(4-叔丁氧羰基哌嗪-1-基)吡啶-3-基)-3,4,6-三苄氧基-D-葡萄糖烯(13af)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),6-(4-叔丁氧羰基哌嗪-1-基)吡啶-3-硼酸频哪醇酯(0.40mmol,122.9mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13af(108.4mg,0.16mmol,收率为80％).1H NMR(CDCl3,400MHz)δ:8.44(d,J＝2.4Hz,1H),7.67(dd,J＝8.9,2.4Hz,1H),7.39–7.26(m,15H),6.57(d,J＝8.9Hz,1H),5.26(d,J＝3.1Hz,1H),4.85(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.67(d,J＝11.6Hz,1H),4.63(d,J＝12.0Hz,1H),4.62(d,J＝11.6Hz,1H),4.59(d,J＝12.0Hz,1H),4.35(dd,J＝5.9,3.2Hz,1H),4.24(ddd,J＝8.0,4.9,3.0Hz,1H),3.95(dd,J＝8.3,5.8Hz,1H),3.91(dd,J＝11.0,4.9Hz,1H),3.85(dd,J＝11.0,3.0Hz,1H),3.58–3.50(m,8H),and1.48(s,9H).13C NMR(CDCl3,101MHz)δ:159.12,154.91,151.26,145.52,143.75,138.60,138.34,134.76,128.53,128.51,128.46,128.05,127.85,127.75,127.68,120.39,106.11,94.13,80.09,77.36,76.60,74.51,73.64,73.59,70.62,68.72,45.08,28.55,and24.93.IR(thin film,cm-1):3461,2977,2861,1691,1594,1407,1364,1236,1164,996,931,749,733,and 697cm-1.HRMS(DART-TOF)calculated for C41H48N3O6 +[M+H]+m/z 678.3538,found 678.3544.
(34)1-(2,4-二甲氧基嘧啶-5-基)-3,4,6-三苄氧基-D-葡萄糖烯(13ag)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),2,4-二甲氧基嘧啶-5-硼酸(0.40mmol,73.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13ag(79.5mg,0.15mmol,收率为73％).1H NMR(CDCl3,400MHz)δ:8.56(s,1H),7.36–7.25(m,15H),5.71(d,J＝3.2Hz,1H),4.86(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.67(d,J＝12.0Hz,1H),4.64(d,J＝12.0Hz,1H),4.61(d,J＝12.0Hz,1H),4.58(d,J＝12.0Hz,1H),4.38(dd,J＝6.4,3.2Hz,1H),4.20(ddd,J＝8.0,4.8,2.8Hz,1H),4.01(s,3H),4.00(s,3H),3.97(dd,J＝8.4,6.4Hz,1H),3.90(dd,J＝10.9,4.7Hz,1H)and3.84(dd,J＝11.0,2.8Hz,1H).13C NMR(CDCl3,101MHz)δ:167.83,164.47,157.36,146.42,138.59,138.32,138.23,128.49,128.47,128.04,127.85,127.83,127.74,127.71,109.95,101.07,77.41,76.97,74.23,73.69,73.62,70.62,68.63,54.99,and54.26.IR(thin film,cm-1):3006,2989,2864,1590,1556,1470,1400,1276,1260,1076,1011,803,764,749,and 696cm-1.HRMS(DART-TOF)calculatedfor C33H35N2O6 +[M+H]+m/z 555.2490,found 555.2491.
(35)1-(11-(1-乙氧羰基哌啶-4-基烯基)-6,11-二氢-5H-苯并[5,6]环庚[1,2-b]吡啶-8-基)-3,4,6-三苄氧基-D-葡萄糖烯(13ah)
根据标准操作，实施例1制备的α-O-烯基砜8a(0.20mmol,111mg),11-(1-乙氧羰基哌啶-4-基烯基)-6,11-二氢-5H-苯并[5,6]环庚[1,2-b]吡啶-8-硼酸(0.40mmol,189.7mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物13ah(83.9mg,0.11mmol,收率为55％).1HNMR(CDCl3,400MHz)δ:8.39(dd,J＝4.8,1.7Hz,1H),7.44–7.38(m,3H),7.37–7.25(m,15H),7.16(d,J＝7.9Hz,1H),7.07(dd,J＝7.7,4.8Hz,1H),5.40(d,J＝3.1Hz,1H),4.84(d,J＝11.6Hz,1H),4.71(d,J＝11.6Hz,1H),4.68(d,J＝12.0Hz,1H),4.64(d,J＝12.0Hz,1H),4.62(d,J＝12.4Hz,1H),4.59(d,J＝12.4Hz,1H),4.34–4.39(m,1H),4.27–4.21(m,1H),4.13(q,J＝7.1Hz,2H),3.95(dd,J＝8.4,5.9Hz,1H),3.92–3.85(m,2H),3.84–3.74(m,2H),3.47–3.30(m,2H),3.19–3.09(m,2H),2.90–2.78(m,2H),2.55–2.45(m,1H),2.40–2.28(m,3H),and1.25(t,J＝7.1Hz,3H).13C NMR(CDCl3,101MHz)δ:157.42,157.31,155.62,152.61,152.56,146.68,139.94,139.84,138.63,138.39,138.37,137.64,137.59,137.53,137.11,135.13,133.80,133.71,129.27,129.21,128.52,128.48,128.44,127.99,127.81,127.73,127.66,126.04,126.02,123.20,123.17,122.23,96.09,96.04,77.42,76.65,76.61,74.53,73.57,73.53,70.56,70.53,68.74,61.39,44.98,32.04,32.01,31.91,31.85,30.90,30.66,and14.81.IR(thin film,cm-1):3032,2917,2861,1689,1264,1228,1111,1097,908,729,and 697cm-1.HRMS(DART-TOF)calculated for C49H51N2O6 +[M+H]+m/z763.3742,found 763.3745.
(36)1-苯基-3,4,6-三-叔丁基二甲基硅氧基-D-葡萄糖烯(16a)
根据标准操作，实施例1制备的α-O-烯基砜15a(0.15mmol,94.3mg),苯硼酸(0.30mmol,36.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16a(69.5mg,0.12mmol,收率为82％).1H NMR(CDCl3,400MHz)δ:7.65–7.61(m,2H),7.36–7.30(m,3H),5.28(d,J＝4.0Hz,1H),4.20–4.16(m,2H),4.00(dd,J＝11.2,7.0Hz,1H),3.92–3.85(m,2H),0.93(s,9H),0.91(s,9H),0.90(s,9H),0.15(s,6H),0.14(s,6H),0.06(s,3H),and0.03(s,3H).13C NMR(CDCl3,101MHz)δ:150.81,135.72,128.50,128.18,125.44,98.16,80.67,70.52,69.17,61.78,26.15,26.10,26.06,18.53,18.30,18.27,-3.79,-3.89,-3.99,-4.49,-5.10,and-5.15.IR(thin film,cm-1):2954,2929,2886,2857,1472,1462,1256,1104,1081,833,772,and 750cm-1.HRMS(DART-TOF)calculated for C39H34NaO5 +[M+Na]+m/z 587.3379,found587.3384.
(37)1-苯基-3-O-三异丙基硅氧基-4,6-O-二叔丁基硅基-D-葡萄糖烯(16b)
根据标准操作，实施例1制备的α-O-烯基砜15b(0.10mmol,58.3mg),苯硼酸(0.20mmol,24.4mg),Ni(COD)2(0.01mmol,2.8mg),Cy3PHBF4(0.02mmol,7.4mg),和KOH(0.20mmol,11.2mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16b(31.2mg,0.06mmol,收率为60％).1H NMR(CDCl3,400MHz)δ:7.54–7.49(m,2H),7.35–7.29(m,3H),5.23(d,J＝2.3Hz,1H),4.59(dd,J＝6.7,2.4Hz,1H),4.32(dd,J＝10.4,4.8Hz,1H),4.12(dd,J＝10.0,1.2Hz,1H),4.09(dd,J＝9.6,2.8Hz,1H),3.99(ddd,J＝10.1,4.8,2.8Hz,1H),1.18–1.12(m,21H),1.08(s,9H),and1.01(s,9H).13C NMR(CDCl3,101MHz)δ:151.17,134.35,128.77,128.34,125.20,101.42,77.68,73.16,71.92,66.29,27.63,27.13,22.93,20.05,18.37,18.35,and12.68.IR(thin film,cm-1):2933,2862,1654,1470,1339,1279,1260,1161,1110,1086,1021,889,825,760,and 752cm-1.HRMS(DART-TOF)calculated for C29H50NaO4Si2 +[M+Na]+m/z 541.3140,found 541.3141.
(38)1-苯基-3,4,6-三苄氧基-D-半乳糖烯(16c)
根据标准操作，实施例1制备的α-O-烯基砜15c(0.15mmol,83.4mg),苯硼酸(0.30mmol,36.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16c(53.2mg,0.11mmol,收率为72％).1H NMR(CDCl3,400MHz)δ:7.62–7.57(m,2H),7.37–7.23(m,18H),5.41(dd,J＝3.2,0.8Hz,1H),4.88(d,J＝12.0Hz,1H),4.71–4.66(m,3H),4.52(d,J＝12.0Hz,1H),4.48(d,J＝12.0Hz,1H),4.37–4.41(m,1H),4.35–4.31(m,1H),4.06–4.03(m,1H),3.90(dd,J＝10.4,5.6Hz,1H),and3.82(dd,J＝10.4,5.6Hz,1H).13C NMR(CDCl3,101MHz)δ:151.96,138.73,138.60,138.30,134.83,128.67,128.51,128.50,128.41,128.17,127.92,127.77,127.74,127.67,127.62,125.34,96.29,76.24,73.53,73.30,71.82,71.28,71.23,and68.48.IR(thin film,cm-1):3061,3028,2922,2859,1451,1275,1260,1083,1026,764,749,and694cm-1.HRMS(DART-TOF)calculated for C33H32NaO4 +[M+Na]+m/z 515.2193,found515.2200.
(39)1-苯基-3,4-二苄氧基-D-岩藻糖烯(16d)
根据标准操作，实施例1制备的α-O-烯基砜15d(0.15mmol,67.5mg),苯硼酸(0.30mmol,36.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16d(40.6mg,0.11mmol,收率为70％).1H NMR(CDCl3,400MHz)δ:7.64–7.57(m,2H),7.43–7.24(m,13H),5.40(dd,J＝2.8,1.2Hz,1H),4.96(d,J＝12.0Hz,1H),4.76(d,J＝12.0Hz,1H),4.74(d,J＝12.0Hz,1H),4.71(d,J＝12.0Hz,1H),4.40(ddd,J＝4.3,3.0,1.2Hz,1H),4.25(qdd,J＝6.7,2.0,1.1Hz,1H),3.78(ddd,J＝4.4,2.0,1.2Hz,1H),and1.41(d,J＝6.4Hz,3H).13C NMR(CDCl3,101MHz)δ:152.43,138.86,138.79,135.14,128.55,128.37,128.35,128.16,127.70,127.65,125.30,95.75,73.55,73.30,73.09,71.16,and16.61.IR(thin film,cm-1):3028,2929,2853,1495,1450,1276,1261,1100,1063,1025,765,749,730,and 693cm-1.HRMS(DART-TOF)calculatedfor C26H26NaO3 +[M+Na]+m/z 409.1774,found 409.1781.
(40)1-苯基-3,4-二苄氧基-L-鼠李糖烯(16e)
根据标准操作，实施例1制备的α-O-烯基砜15e(0.15mmol,67.5mg),苯硼酸(0.30mmol,36.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到白色固体化合物16e(49.8mg,0.13mmol,收率为86％).1H NMR(CDCl3,400MHz)δ:7.60–7.55(m,2H),7.41–7.27(m,13H),5.42(d,J＝2.8Hz,1H),4.91(d,J＝11.6Hz,1H),4.74(d,J＝11.6Hz,1H),4.73(d,J＝11.6Hz,1H),4.66(d,J＝11.6Hz,1H),4.40(dd,J＝6.5,2.8Hz,1H),4.13(dq,J＝9.0,6.4Hz,1H),3.59(dd,J＝9.1,6.5Hz,1H),and1.50(d,J＝6.4Hz,3H).13C NMR(CDCl3,101MHz)δ:153.08,138.71,138.46,134.73,128.76,128.56,128.54,128.26,128.12,127.90,127.88,127.76,125.31,96.41,79.74,77.70,74.54,74.07,70.68,and17.74.IR(thin film,cm-1):3028,3005,2989,2931,2862,1276,1260,1099,1063,764,750,and 694cm-1.HRMS(DART-TOF)calculated for C26H26NaO3 +[M+Na]+m/z 409.1774,found 409.1778.熔点:73.5–74.9℃
(41)1-苯基-3,4-二苄氧基-D-阿拉伯糖烯(16f)
根据标准操作，实施例1制备的α-O-烯基砜15f(0.15mmol,65.4mg),苯硼酸(0.30mmol,36.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的叔丁醇(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16f(43.0mg,0.12mmol,收率为77％).1H NMR(CDCl3,400MHz)δ:7.57–7.53(m,2H),7.43–7.27(m,13H),5.43(d,J＝5.2Hz,1H),4.77(s,2H),4.72(d,J＝12.0Hz,1H),4.65(d,J＝12.4Hz,1H),4.27(dd,J＝10.4,10.4Hz,1H),4.21–4.16(m,2H),and3.84(ddd,J＝10.4,3.8,3.8Hz,1H).13C NMR(CDCl3,101MHz)δ:154.38,139.04,138.24,134.82,128.93,128.58,128.50,128.27,128.01,127.93,127.89,127.68,125.40,95.02,73.38,71.27,71.14,67.82,and63.91.IR(thinfilm,cm-1):3027,3005,2988,2927,2854,1275,1260,1088,1026,764,749,and 693cm- 1.HRMS(DART-TOF)calculated for C25H24NaO3 +[M+Na]+m/z 395.1618,found 395.1624.
(42)1-苯基-3,4-二苄氧基-D-木糖烯(16g)
根据标准操作，实施例1制备的α-O-烯基砜15g(0.15mmol,65.4mg),苯硼酸(0.30mmol,36.6mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16g(46.3mg,0.12mmol,收率为83％).1H NMR(CDCl3,400MHz)δ:7.65–7.59(m,2H),7.38–7.26(m,13H),5.49(dd,J＝4.8,1.2Hz,1H),4.69(d,J＝12.4Hz,1H),4.67(d,J＝12.4Hz,1H),4.65(d,J＝12.0Hz,1H),4.59(d,J＝12.0Hz,1H),4.32(ddd,J＝12.0,4.8,1.2Hz,1H),4.15(dd,J＝11.6,2.0Hz,1H),4.06(ddd,J＝4.8,3.2,1.2Hz,1H),and3.78–3.74(m,1H).13C NMR(CDCl3,101MHz)δ:154.38,138.63,138.19,135.05,128.85,128.61,128.58,128.23,127.95,127.91,127.87,127.81,125.40,95.14,72.85,71.34,71.00,70.34,and64.85.IR(thin film,cm-1):3028,3006,2988,2924,2863,1451,1276,1260,1095,1055,1026,764,749,and 693cm-1.HRMS(DART-TOF)calculated for C25H24NaO3 +[M+Na]+m/z 395.1618,found 395.1620.
(43)1-苯基-六苄氧基-D-麦芽糖烯(16h)
根据标准操作，实施例1制备的α-O-烯基砜15h(0.10mmol,98.8mg),苯硼酸(0.20mmol,24.4mg),Ni(COD)2(0.02mmol,5.5mg),Cy3PHBF4(0.04mmol,14.7mg),和KOH(0.40mmol,22.4mg)的四氢呋喃(1.0mL)溶液混合物在60℃搅拌12小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯＝10:1，分离纯化得到无色油状化合物16h(85.1mg,0.09mmol,92％).1H NMR(CDCl3,400MHz)δ:7.63–7.57(m,2H),7.35–7.22(m,31H),7.12(m,2H),5.55(d,J＝3.6Hz,1H),5.44(d,J＝3.6Hz,1H),4.93(d,J＝10.8Hz,1H),4.80(d,J＝10.8Hz,1H),4.78(d,J＝10.8Hz,1H),4.66(d,J＝11.2Hz,1H),4.65(s,2H),4.57(s,1H),4.56(d,J＝12Hz,1H),4.53(d,J＝11.6Hz,1H),4.47(d,J＝10.8Hz,1H),4.48–4.40(m,2H),4.35(d,J＝12Hz,1H),4.32(dd,J＝7.2,5.2Hz,1H),3.95(dd,J＝11.2,5.2Hz,1H),3.92(dd,J＝9.6,8.8Hz,1H),3.91-3.86(m,1H),3.85(dd,J＝11.2,3.6Hz,1H),3.67(dd,J＝10.0,9.2Hz,1H),3.61(dd,J＝10.8,2.8Hz,1H,H6b),3.57(dd,J＝9.6,3.6Hz,1H),and3.49(dd,J＝10.8,2.0Hz,1H,H6a).13C NMR(CDCl3,101MHz)δ:153.23,139.05,138.61,138.58,138.45,138.28,138.14,134.65,128.90,128.55,128.50,128.45,128.43,128.40,128.30,128.07,128.02,127.99,127.98,127.84,127.73,127.72,127.70,127.67,127.61,127.60,127.59,125.37,96.21,95.73,81.99,79.82,77.75,77.22,76.17,75.70,75.11,73.57,73.52,72.89,70.94,70.13,68.98,68.45,and68.41.IR(thin film,cm-1):3028,3006,2989,2862,1452,1275,1260,1068,1027,764,749,and 695cm-1.HRMS(DART-TOF)calculated for C60H60NaO9 +[M+Na]+m/z 947.4130,found947.4128.
当原料α-O-烯基砜是E/Z两种异构体的混合物，当使用单纯的E或者Z异构体时，反应得到的产物是相同的。
(44)1-(1-甲氧基-2-苯乙烯基)-4-甲基苯(21a)
参照标准操作步骤，实施例1制备的α-O-烯基砜19a(0.30mmol,82.3mg,1.0equiv),对甲苯硼酸(0.60mmol,81.6mg,2.0equiv),Ni(COD)2(0.03mmol,8.25mg,0.1equiv),Cy3PHBF4(0.06mmol,22.0mg,0.2equiv),和KOH(0.60mmol,33.6mg,2.0equiv)的混合物在四氢呋喃(1.5mL)中60℃搅拌8小时。.柱层析分离，洗脱剂为石油醚/乙酸乙酯＝25:1，得到无色油状化合物21a(56mg,0.25mmol,收率为83％,无法分离的E和Z两种异构体的混合物).1H NMR(CDCl3,400MHz)δ:7.72–7.66(m,1.32H),7.47–7.41(m,1.32H),7.33(t,J＝7.6Hz,1.36H),7.26–7.16(m,2.40H),7.13–6.95(m,2.60H),6.05(s,0.64H,E-isomer),5.78(s,0.36H,Z-isomer),3.77(s,1.08H,Z-isomer),3.61(d,J＝1.0Hz,1.92H,E-isomer),2.37(s,1.92H,E-isomer),and2.31(s,1.08H,Z-isomer).13C NMR(CDCl3,101MHz)δ:157.47,156.51,138.52,138.41,137.24,136.20,133.64,133.44,129.31,129.29,129.01,128.95,128.66,128.48,128.06,126.68,126.52,125.24,112.18,101.33,57.98,55.57,21.47,and21.38.IR(thin film,cm-1):3021,2933,2835,1631,1510,1446,1276,1199,1119,1063,819,764,750,and694cm-1.HRMS(DART-TOF)calculated for C16H16NaO+[M+Na]+m/z 247.1093,found247.1098.
(45)1-(1-甲氧基-4-甲基戊基-1-烯基)-4-甲基苯(21b)
参照标准操作步骤,实施例1制备的α-O-烯基砜19b(0.30mmol,76.2mg,1.0equiv),对甲苯硼酸(0.60mmol,81.6mg,2.0equiv),Ni(COD)2(0.03mmol,8.25mg,0.1equiv),Cy3PHBF4(0.06mmol,22.0mg,0.2equiv),和KOH(0.60mmol,33.6mg,2.0equiv)的混合物在四氢呋喃(1.5mL)中60℃搅拌8小时。.柱层析分离，洗脱剂为石油醚/乙酸乙酯＝25:1，得到无色油状化合物21b(43mg,0.21mmol,收率为70％).1H NMR(CDCl3,400MHz)δ:7.37–7.32(m,1.5H),7.26–7.23(m,0.5H),7.17–7.12(m,2.0H),5.26(t,J＝7.2Hz,0.74H,E-isomer),4.71(t,J＝7.2Hz,0.26H,Z-isomer),3.62(s,0.78H,Z-isomer),3.50(s,2.22H,E-isomer),2.34(s,3H),2.15(t,J＝7.2Hz,1.48H,E-isomer),1.95(t,J＝7.1Hz,0.52H,Z-isomer),1.69(hept,J＝6.7Hz,0.74H,E-isomer),1.59(hept,J＝6.7Hz,0.26H,Z-isomer),0.95(d,J＝6.7Hz,4.44H,E-isomer),and0.87(d,J＝6.7Hz,1.56H,Z-isomer).13C NMR(CDCl3,101MHz)δ:155.77,155.19,137.71,137.55,133.87,133.44,129.16,128.80,128.72,126.01,112.87,99.14,58.49,55.09,36.53,34.68,29.90,28.96,22.66,22.42,21.41,and21.29.IR(thin film,cm-1):2953,2868,1275,1260,1118,1078,822,764,and 750cm-1.HRMS(DART-TOF)calculated for C14H20NaO+[M+Na]+m/z 227.1406,found227.1411.
(46)1-(1-甲氧基-5-三异丙基硅氧基-1-烯基)-4-甲基苯(21c)
参照标准操作步骤,实施例1制备的α-O-烯基砜19c(0.30mmol,124mg,1.0equiv),对甲苯硼酸(0.60mmol,81.6mg,2.0equiv),Ni(COD)2(0.03mmol,8.25mg,0.1equiv),Cy3PHBF4(0.06mmol,22.0mg,0.2equiv),和KOH(0.60mmol,33.6mg,2.0equiv)的混合物在四氢呋喃(1.5mL)中60℃搅拌8小时。.柱层析分离，洗脱剂为石油醚/乙酸乙酯＝25:1，得到无色油状化合物21c(98mg,0.27mmol,收率为90％).1H NMR(CDCl3,400MHz)δ:7.36–7.30(m,1.3H),7.28–7.24(m,0.7H),7.16–7.11(m,2H),5.28(t,J＝7.2Hz,0.62H,E-isomer),4.70(t,J＝7.2Hz,0.38H,Z-isomer),3.75(t,J＝6.5Hz,1.24H,E-isomer),3.66(t,J＝6.5Hz,0.76H,Z-isomer),3.61(s,1.14H,Z-isomer),3.51(s,1.86H,E-isomer),2.34(s,3H),2.32(q,J＝7.5Hz,1.24H,E-isomer),2.15(q,J＝7.5Hz,0.76H,Z-isomer),1.72–1.65(m,1.24H,E-isomer),1.65–1.60(m,0.76H,Z-isomer),1.07(m,13.02H,E-isomer),and1.03(m,7.98H,Z-isomer).13C NMR(CDCl3,101MHz)δ:155.56,154.99,137.77,137.56,133.67,133.34,129.15,128.73,128.62,125.95,113.60,99.82,63.31,63.04,58.62,55.07,34.68,33.40,24.00,22.12,21.39,21.29,18.20,18.16,12.21,and12.17.IR(thin film,cm-1):2941,2864,1742,1462,1102,1071,882,821,680,and 657cm-1.HRMS(DART-TOF)calculated for C22H38NaO2Si+[M+Na]+m/z 385.2533,found 385.2538.
(47)(R)-1-(1-甲氧基-4,8-二甲基壬基-1,7-二烯基)-4-甲基苯(21d)
参照标准操作步骤,实施例1制备的α-O-烯基砜19d(0.30mmol,97mg,1.0equiv),对甲苯硼酸(0.60mmol,81.6mg,2.0equiv),Ni(COD)2(0.03mmol,8.25mg,0.1equiv),Cy3PHBF4(0.06mmol,22.0mg,0.2equiv),和KOH(0.60mmol,33.6mg,2.0equiv)的混合物在四氢呋喃(1.5mL)中60℃搅拌8小时。.柱层析分离，洗脱剂为石油醚/乙酸乙酯＝25:1，得到无色油状化合物21d(65mg,0.24mmol,78％).1H NMR(CDCl3,400MHz)δ:7.36–7.31(m,1.5H),7.26–7.22(m,0.5H),7.17–7.11(m,2H),5.25(t,J＝7.2Hz,0.76H,E-isomer),5.15–5.09(m,0.76H,E-isomer),5.08–5.04(m,0.24H,Z-isomer),4.70(t,J＝7.2Hz,0.24H,Z-isomer),3.62(s,0.72H,Z-isomer),3.50(s,2.28H,E-isomer),2.35(s,3H),2.32–2.21(m,1H),2.18–2.08(m,1H),2.05–1.89(m,2H),1.68(s,3H),1.61(s,3H),1.55–1.45(m,1H),1.44–1.31(m,1H),1.26–1.14(m,1H),0.94(d,J＝6.6Hz,2.28H,E-isomer),and0.86(d,J＝6.7Hz,0.72H,Z-isomer).13C NMR(CDCl3,101MHz)δ:155.81,155.28,137.71,137.55,133.85,133.44,131.20,131.17,129.15,128.79,128.72,126.01,125.10,125.08,112.65,98.86,58.47,55.10,37.04,36.75,34.58,34.26,33.33,32.76,25.87,25.85,25.75,21.41,21.30,19.86,19.61,17.79,and17.75.IR(thin film,cm-1):2956,2919,1275,1260,1075,822,764,and 750cm-1.HRMS(DART-TOF)calculated for C19H28NaO+[M+Na]+m/z295.2032,found 295.2033.
实施例4、利用本发明制备的开链烯基醚制备酮
将实施例3制备的开链烯基醚(化合物21a～21d)溶解在二氯甲烷中，冷却到0℃，加入三氟乙酸(TFA，10.0equiv)。搅拌2小时。TLC检测反应至完全，饱和碳酸氢钠淬灭，二氯甲烷萃取，无水硫酸钠干燥，减压蒸馏，柱层析分离得到产物酮。
(1)1-对甲苯基-2-苯基乙酮(22a)
参照标准操作步骤,利用实施例3制备的开链烯基醚21a(0.22mmol,49mg)和三氟乙酸(2.2mmol,250mg)溶解在二氯甲烷(1.6mL)中，室温搅拌2小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯15:1，得到无色油状化合物22a(23mg,0.13mmol,收率为50％).1H NMR(CDCl3,400MHz)δ:7.95–7.86(m,2H),7.34–7.28(m,2H),7.28–7.20(m,5H),4.25(s,2H),and2.39(s,3H).13C NMR(CDCl3,101MHz)δ:197.38,144.08,134.92,134.28,129.56,129.44,128.89,128.76,126.92,45.55,and21.76.IR(thin film,cm-1):3027,3005,2905,1682,1333,1275,1260,814,764,750,and 696cm-1.HRMS(DART-TOF)calculated forC15H14NaO+[M+Na]+m/z 233.0937,found 233.0944.
(2)4-甲基-1-对甲苯基戊酮(22b)
参照标准操作步骤,利用实施例3制备的开链烯基醚21b(0.18mmol,37mg)和三氟乙酸(1.8mmol,205mg)溶解在二氯甲烷(1.6mL)中，室温搅拌2小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯15:1，得到无色油状化合物22b(24mg,0.126mmol,收率为70％).1H NMR(CDCl3,400MHz)δ:7.91–7.82(m,2H),7.28–7.21(m,2H),2.98–2.89(m,2H),2.40(s,3H),1.71–1.64(m,1H),1.64–1.59(m,2H),and0.94(d,J＝6.0Hz,6H).13C NMR(CDCl3,101MHz)δ:199.55,142.68,133.76,128.35,127.32,35.66,32.53,27.03,21.58,and20.73.IR(thinfilm,cm-1):3005,2988,2956,1682,1275,1260,764,and 750cm-1.HRMS(DART-TOF)calculated for C13H18NaO+[M+Na]+m/z 2813.1250,found 213.1251.
(3)5-羟基-1-对甲苯基戊酮(22c)
参照标准操作步骤,利用实施例3制备的烯基醚21c(0.18mmol,65mg)和三氟乙酸(1.8mmol,205mg)溶解在二氯甲烷(1.6mL)中，室温搅拌2小时。减压蒸馏，加入四丁基氟化铵的四氢呋喃溶液(5mL，1M)，室温搅拌2小时，饱和氯化铵溶液淬灭，乙酸乙酯萃取，无水Na2SO4干燥，减压蒸馏。柱层析分离，洗脱剂为石油醚/乙酸乙酯15:1，得到无色油状化合物22c(两步产率73％).1H NMR(CDCl3,400MHz)δ:7.89–7.82(m,2H),7.27–7.22(m,2H),3.67(t,J＝6.4Hz,2H),2.99(t,J＝7.1Hz,2H),2.41(s,3H),1.93(br s,1H),1.87–1.79(m,2H),and1.69–1.61(m,2H).13C NMR(CDCl3,101MHz)δ:200.21,143.91,134.58,129.37,128.29,62.47,38.10,32.40,21.73,and20.41.IR(thin film,cm-1):3408,2931,2868,1674,1606,1449,1407,1275,1260,1229,1180,1057,1010,978,804,764,and 749cm-1.HRMS(DART-TOF)calculated for C12H16NaO2 +[M+Na]+m/z 215.1043,found215.1029.
(4)(R)-4,8-二甲基-1-对甲苯基壬基-7-烯-1-酮(22d)
参照标准操作步骤,利用实施例3制备的开链烯基醚21d(0.108mmol,28mg)和三氟乙酸(1.08mmol,123mg)溶解在二氯甲烷(1.6mL)中，室温搅拌2小时。柱层析分离，洗脱剂为石油醚/乙酸乙酯15:1，得到无色油状化合物22d(26mg,0.102mmol,收率为95％).1H NMR(CDCl3,400MHz)δ:7.89–7.82(m,2H),7.28–7.23(m,2H),3.01–2.94(m,1H),2.94–2.86(m,1H),2.41(s,3H),1.86–1.72(m,3H),1.54(s,6H),1.52–1.47(m,1H),1.42–1.30(m,3H),1.25–1.14(m,1H),and0.93(d,J＝6.2Hz,3H).13C NMR(CDCl3,101MHz)δ:200.43,143.79,134.73,129.39,128.31,89.43,40.69,37.01,36.27,32.53,31.53,25.70,21.75,21.22,and19.47.IR(thin film,cm-1):3004,2952,2871,1774,1681,1370,1275,1260,1214,1159,1137,764,and 750cm-1.HRMS(DART-TOF)calculated for C18H26NaO2 +[M+Na]+m/z281.1876,found 281.1881.
实施例5、利用本发明制备的芳基糖苷制备糖尿病药物
该方法成为制备二型糖尿病药物依格列净和2-去氧依格列净的新方法，步骤如下：
步骤1：
1-(3-(苯并[b]噻吩-2-甲基)-4-氟苯基)-3,4,6-三叔丁基二甲基硅氧基-D-葡萄糖烯(25)
参照标准步骤,将实施例1制备的α-O烯基砜15a(0.30mmol,189mg,1.0equiv),硼酸脂24(0.45mmol,166mg,1.5equiv),Ni(COD)2(0.03mmol,8.25mg,0.1equiv),Cy3PHBF4(0.06mmol,22.0mg,0.2equiv),和KOH(0.60mmol,33.6mg,2.0equiv)在四氢呋喃(1.5mL)中，60℃搅拌12小时。柱层析分离(石油醚/乙酸乙酯8:1)得到产物25，白色固体。(192mg,0.264mmol,88％).1H NMR(CDCl3,400MHz)δ:7.76–7.71(m,1H),7.68–7.63(m,1H),7.56(dd,J＝7.3,2.3Hz,1H),7.50(ddd,J＝8.6,5.0,2.3Hz,1H),7.32–7.28(m,1H),7.27–7.22(m,1H),7.04(t,J＝9.2Hz,1H),7.02(s,1H),5.17(d,J＝4.4Hz,1H),4.25(s,2H),4.17–4.14(m,1H),4.15–4.11(m,1H),3.98(dd,J＝11.2,6.9Hz,1H),3.88–3.85(m,1H),3.84(dd,J＝11.6,3.6Hz,1H),0.91–0.87(m,27H),0.12(s,6H),0.11(s,3H),0.10(s,3H)0.02(s,3H),and0.01(s,3H).13C NMR(CDCl3,101MHz)δ:161.06(d,J＝248.0Hz),149.93,143.47,140.17,139.94,132.01(d,J＝3.5Hz),128.15(d,J＝4.3Hz),126.29(d,J＝16.2Hz),125.84(d,J＝8.2Hz),124.26,123.82,123.14,122.27,121.99,115.30(d,J＝22.4Hz),98.18,80.74,70.49,69.25,61.75,30.27(d,J＝3.3Hz),26.12,26.07,26.06,18.50,18.28,18.27,-3.83,-3.88,-3.97,-4.52,-5.11,and-5.16.19F NMR(CD3OD,376MHz)δ:–118.19.IR(thin film,cm-1):2953,2929,2857,1726,1471,1275,1259,1102,835,764,and749cm-1.HRMS(DART-TOF)calculated for C39H63FNaO5SSi3 +[M+Na]+m/z 769.3580,found769.3582.熔点：156.3–157.9℃.
步骤2：
化合物25(72.9mg,0.1mmol,1.0equiv)溶解在THF(2mL)中，冷却到0℃，缓慢加入BH3·THF(1.0M,0.3mL,0.3mmol,3.0equiv)，搅拌12小时。加入30％H2O2(3.0mL)再加入3M的NaOH水溶液(3.0ml)。室温搅拌24小时。用二氯甲烷(25mL)稀释，依次用20％NaHSO3(25mL),饱和NH4Cl(25mL),水(25mL),和饱和食盐水(25mL)洗涤。有机层用无水Na2SO4干燥，过滤，减压蒸馏。粗产物溶于THF(2mL),加入四丁基氟化铵(TBAF，1.0M in THF,0.33mL,3.3eq.)，室温搅拌2小时。浓缩，柱层析分离(DCM/MeOH 20:1)得到白色固体依格列净26a(19.8mg,49％for three steps).1H NMR(CD3OD,400MHz)δ:7.72(d,J＝7.9Hz,1H),7.64(d,J＝7.7Hz,1H),7.42(dd,J＝7.4,2.2Hz,1H),7.35(ddd,J＝7.7,5.1,2.2Hz,1H),7.27(t,J＝7.4Hz,1H),7.25–7.18(m,1H),7.09(d,J＝9.2Hz,1H),7.05(d,J＝4.7Hz,1H),4.31–4.19(m,2H),4.11(d,J＝9.4Hz,1H),3.91–3.82(m,1H),3.68(dd,J＝12.0,4.7Hz,1H),and3.49–3.32(m,4H).13C NMR(CD3OD,101MHz)δ:162.28(d,J＝245.0Hz),145.47,141.99,141.61,137.73(d,J＝3.5Hz),132.28(d,J＝4.4Hz),129.84(d,J＝8.2Hz),127.94(d,J＝16.0Hz),125.70,125.27,124.49,123.46,123.35,116.39(d,J＝22.4Hz),83.35,82.70,80.26,77.01,72.38,63.60,and31.19(d,J＝3.4Hz).19F NMR(CD3OD,376MHz)δ:–121.56.IR(thin film,cm-1):3361,2925,1501,1457,1275,1260,1086,764,and 750cm-1.HRMS(DART-TOF)calculated for C21H21FNaO5S+[M+Na]+m/z 427.0986,found427.0984.熔点:146.2–147.9℃.
步骤3：
化合物25(72.9mg,0.1mmol,1.0eq.)溶解在混合溶剂AcOEt/MeOH(5:1,36mL)中，加入10％Pd/C(150mg)，氢气环境下搅拌24小时。利用硅藻土过滤，减压蒸馏。粗产物溶解在THF(2mL)中,加入四丁基氟化铵(TBAF，1.0M in THF,0.33mL,3.3eq.)。室温下搅拌2小时，减压蒸馏，柱层析分离(DCM/MeOH 20:1)得到白色固体2-去氧依格列净26b(33.1mg,85％for two steps).1H NMR(CD3OD,400MHz)δ:7.71(d,J＝7.8Hz,1H),7.64(d,J＝7.6Hz,1H),7.39(d,J＝7.2Hz,1H),7.37–7.30(m,1H),7.30–7.17(m,2H),7.12–7.04(m,1H),7.02(s,1H),4.48(d,J＝11.4Hz,1H),4.24(s,2H),3.90(d,J＝11.6Hz,1H),3.79–3.62(m,2H),3.38–3.21(m,2H),2.14(d,J＝12.9Hz,1H),and1.68–1.50(m,1H).13C NMR(CD3OD,101MHz)δ:161.95(d,J＝244.7Hz),145.51,141.93,141.56,139.96(d,J＝3.6Hz),130.48(d,J＝4.3Hz),128.23(d,J＝5.5Hz),128.11(d,J＝2.3Hz),125.72,125.29,124.49,123.47,123.28,116.58(d,J＝22.4Hz),82.66,78.49,74.53,73.74,63.74,43.25,and31.20(d,J＝3.3Hz).19F NMR(CD3OD,376MHz)δ:–121.95.IR(thin film,cm-1):3348,2921,2847,1501,1275,1260,1064,1026,824,764,and 749cm-1.HRMS(DART-TOF)calculated forC21H21FNaO4S+[M+Na]+m/z 411.1037,found 411.1042.
实施例6、利用本发明制备的芳基糖苷制备糖尿病药物
1-(3-(苯并[b]噻吩-2-甲基)-4-氟苯基)-3-O-三异丙基硅氧基-4,6-O-二叔丁基硅基-D-葡萄糖烯
参照标准步骤,将实施例1制备的α-O烯基砜15b(0.30mmol,175mg,1.0equiv),硼酸脂24(0.45mmol,166mg,1.5equiv),Ni(COD)2(0.03mmol,8.25mg,0.1equiv),Cy3PHBF4(0.06mmol,22.0mg,0.2equiv),和KOH(0.60mmol,33.6mg,2.0equiv)在四氢呋喃(1.5mL)中，60℃搅拌12小时。柱层析分离(石油醚/乙酸乙酯8:1)得到产物27。(102mg,0.15mmol,50％).1H NMR(CDCl3,400MHz)δ:7.76–7.70(m,1H),7.65–7.63(m,1H),7.35–7.43(m,2H)，7.31–7.22(m,2H)，7.02(t,J＝9.6Hz,1H),7.00(s,1H),5.12(d,J＝2.3Hz,1H),4.54(dd,J＝2.3,6.8Hz,1H),4.30–4.25(m,1H),4.23(s,2H),4.10–4.05(m,2H),3.99–3.92(m,1H),1.17–1.08(m,21H),1.07(s,9H),and1.00(s,9H).IR(thin film,cm-1):2943,2860,1726,1471,1276,1259,1152,828,762,and 750cm-1.HRMS(DART-TOF)calculated forC38H55FNaO4SSi2 +[M+Na]+m/z 682.3344,found 682.3340。
化合物27(68.3mg,0.1mmol,1.0equiv)溶解在THF(2mL)中，冷却到0℃，缓慢加入BH3·THF(1.0M,0.3mL,0.3mmol,3.0equiv)，搅拌12小时。加入30％H2O2(3.0mL)再加入3M的NaOH水溶液(3.0ml)。室温搅拌24小时。用二氯甲烷(25mL)稀释，依次用20％NaHSO3(25mL),饱和NH4Cl(25mL),水(25mL),和饱和食盐水(25mL)洗涤。有机层用无水Na2SO4干燥，过滤，减压蒸馏。粗产物溶于THF(2mL),加入四丁基氟化铵(TBAF，1.0M in THF,0.33mL,3.3eq.)，室温搅拌2小时。浓缩，柱层析分离(DCM/MeOH 20:1)得到白色固体依格列净26a(18.2mg,45％for three steps).1H NMR(CD3OD,400MHz)δ:7.72(d,J＝7.9Hz,1H),7.64(d,J＝7.7Hz,1H),7.42(dd,J＝7.4,2.2Hz,1H),7.35(ddd,J＝7.7,5.1,2.2Hz,1H),7.27(t,J＝7.4Hz,1H),7.25–7.18(m,1H),7.09(d,J＝9.2Hz,1H),7.05(d,J＝4.7Hz,1H),4.31–4.19(m,2H),4.11(d,J＝9.4Hz,1H),3.91–3.82(m,1H),3.68(dd,J＝12.0,4.7Hz,1H),and3.49–3.32(m,4H).13C NMR(CD3OD,101MHz)δ:162.28(d,J＝245.0Hz),145.47,141.99,141.61,137.73(d,J＝3.5Hz),132.28(d,J＝4.4Hz),129.84(d,J＝8.2Hz),127.94(d,J＝16.0Hz),125.70,125.27,124.49,123.46,123.35,116.39(d,J＝22.4Hz),83.35,82.70,80.26,77.01,72.38,63.60,and31.19(d,J＝3.4Hz).19F NMR(CD3OD,376MHz)δ:–121.56.IR(thin film,cm-1):3361,2925,1501,1457,1275,1260,1086,764,and 750cm-1.HRMS(DART-TOF)calculated for C21H21FNaO5S+[M+Na]+m/z 427.0986,found427.0984.熔点:146.2–147.9℃.
步骤3：
化合物27(68.3mg,0.1mmol,1.0eq.)溶解在混合溶剂AcOEt/MeOH(5:1,36mL)中，加入10％Pd/C(150mg)，氢气环境下搅拌24小时。利用硅藻土过滤，减压蒸馏。粗产物溶解在THF(2mL)中,加入四丁基氟化铵(TBAF，1.0M in THF,0.33mL,3.3eq.)。室温下搅拌2小时，减压蒸馏，柱层析分离(DCM/MeOH 20:1)得到白色固体2-去氧依格列净26b(31.1mg,80％for two steps).1H NMR(CD3OD,400MHz)δ:7.71(d,J＝7.8Hz,1H),7.64(d,J＝7.6Hz,1H),7.39(d,J＝7.2Hz,1H),7.37–7.30(m,1H),7.30–7.17(m,2H),7.12–7.04(m,1H),7.02(s,1H),4.48(d,J＝11.4Hz,1H),4.24(s,2H),3.90(d,J＝11.6Hz,1H),3.79–3.62(m,2H),3.38–3.21(m,2H),2.14(d,J＝12.9Hz,1H),and1.68–1.50(m,1H).13C NMR(CD3OD,101MHz)δ:161.95(d,J＝244.7Hz),145.51,141.93,141.56,139.96(d,J＝3.6Hz),130.48(d,J＝4.3Hz),128.23(d,J＝5.5Hz),128.11(d,J＝2.3Hz),125.72,125.29,124.49,123.47,123.28,116.58(d,J＝22.4Hz),82.66,78.49,74.53,73.74,63.74,43.25,and31.20(d,J＝3.3Hz).19F NMR(CD3OD,376MHz)δ:–121.95.IR(thin film,cm-1):3348,2921,2847,1501,1275,1260,1064,1026,824,764,and 749cm-1.HRMS(DART-TOF)calculated forC21H21FNaO4S+[M+Na]+m/z 411.1037,found 411.1042.
综上，本发明利用α-O-烯基砜作为亲电试剂进行Suzuki-Miyaura偶联反应时，反应原料α-O-烯基砜制备简单、结构稳定，能够克服利用有机卤化物和磺酸作为Suzuki-Miyaura偶联反应的亲电试剂时存在的不稳定、制备困难等缺点。同时，该反应的反应条件温和，能够兼容范围很广的杂环和各类官能团，同时产率高，能够实现大规模工艺生产。同时，本发明利用α-O-烯基砜作为亲电试剂进行Suzuki-Miyaura偶联反应可以以高产率生成芳基糖苷和开链烯基醚，还可以制备二型糖尿病药物依格列净和2-去氧依格列净，应用广泛。
Claims (10)
1.一种利用α-O-烯基砜作为亲电试剂的Suzuki-Miyaura偶联反应，其特征在于：它包括如下步骤：取α-O-烯基砜、有机硼试剂、配体、碱、催化剂于溶剂反应，即可；
所述偶联反应中α-O-烯基砜、有机硼试剂、配体、碱、催化剂的摩尔比为1:1～5:0.1～0.5:1～5:0.05～0.25；所述α-O-烯基砜与溶剂的摩尔体积比mol/L为0.1～10:1；
所述α-O-烯基砜为如下结构式之一：
所述有机硼试剂选自芳基硼酸或硼酸酯；所述配体选自Ph3P或Cy3P·HBF4；所述碱选自KOH或NaOH；所述催化剂为含Ni的催化剂；所述溶剂为四氢呋喃或叔丁醇。
2.根据权利要求1所述的Suzuki-Miyaura偶联反应，其特征在于：
所述偶联反应中α-O-烯基砜、有机硼试剂、配体、碱、催化剂的摩尔比为1:1.5～2:0.1～0.2:2:0.1；所述α-O-烯基砜与溶剂的摩尔体积比mol/L为0.1～0.2:1。
3.根据权利要求2所述的Suzuki-Miyaura偶联反应，其特征在于：所述偶联反应中α-O-烯基砜、有机硼试剂、配体、碱、催化剂的摩尔比为1:2:0.2:2:0.1；所述α-O-烯基砜与溶剂的摩尔体积比mol/L为0.2:1。
4.根据权利要求1～3任一项所述的Suzuki-Miyaura偶联反应，其特征在于：
所述配体为Cy3P·HBF4；所述碱为KOH；所述催化剂为Ni(COD)2；所述溶剂为四氢呋喃。
5.根据权利要求1～3任一项所述的Suzuki-Miyaura偶联反应，其特征在于：所述反应温度为60～80℃；所述反应时间为8-16h。
6.根据权利要求5所述的Suzuki-Miyaura偶联反应，其特征在于：反应时间为12-16h。
7.根据权利要求1所述的Suzuki-Miyaura偶联反应，其特征在于：所述亲电试剂为如下结构式之一：
8.一种芳基糖苷，其特征在于：所述芳基糖苷为利用权利要求1～7任一项所述的Suzuki-Miyaura偶联反应制备得到的芳基糖苷，其中，所述芳基糖苷为如下结构式之一：
9.一种开链烯基醚，其特征在于：所述开链烯基醚为利用权利要求1～7任一项所述的Suzuki-Miyaura偶联反应制备得到的开链烯基醚，其中，
所述开链烯基醚为如下结构式之一：
10.权利要求1～7任一项所述的Suzuki-Miyaura偶联反应在制备二型糖尿病药物依格列净和/或2-去氧依格列净中的应用。
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