CN113173862B - A method for the selective desaturation of inert carbon-carbon bonds to synthesize alkenes - Google Patents

Abstract

This case involves a method for the selective desaturation of inert carbon-carbon bonds to synthesize olefins. Using chlorinated amides as raw materials, they are synthesized in the presence of visible light, ruthenium catalysts and ligands, and the reaction solution is post-treated to obtain remote alkenyl amides. compound. In the present invention, in the presence of ruthenium catalysts and phenylpyridine ligands, the intramolecular carbon-hydrogen bond activation of amide compounds is successfully realized, and remote olefin compounds are synthesized; the method uses simple and easy-to-obtain chlorinated amides as raw materials, and the substrate has a wide range of applications , the reaction efficiency is high; in the process of free radical migration, 1,5 migration always occurs and is accompanied by β-H elimination, and the terminal alkenes and the formation of conjugated double bonds are the main products, which have good regioselectivity; the resulting alkenes The highest E/Z value of the compound is greater than 20:1, and the stereoselectivity is good. Moreover, the double bond of this type of compound can be further converted into other functional groups, and the conversion process is simple and one-step, and the obtained derivatives can be used as pharmaceutical intermediates, with high potential application value.

Description

A method for the selective desaturation of inert carbon-carbon bonds to synthesize alkenes

technical field

The invention relates to the technical field of organic compound synthesis, in particular to a method for synthesizing olefins through selective desaturation of inert carbon-carbon bonds.

Background technique

Alkenes are one of the most widely used functional groups in organic synthesis. They are widely found in various bioactive molecules and natural products. As powerful precursors for the construction of other functional group compounds, olefins are versatile synthetic materials and their derivatives. As a precursor, alkenes have many applications in biochemistry and other fields, and at the same time, they are also a stable, effective and cheap raw material. Different alkenes have specific skeletons, and the chemical units (C=C double bond, aryl group at the C-1 position of the double bond or other substituents) provide favorable conditions for participating in the construction of heterocyclic compounds of different sizes. Furthermore, its asymmetric synthesis provides convenience for the direct assembly of chiral heterocycles.

Unfortunately, the synthesis of alkenes via direct desaturation of aliphatic chains has been poorly explored. This is mainly due to the inherent difficulty in activating the kinetically inert C( ^sp3 )-H bond. Although considerable progress has been made in transition metal-catalyzed conversion of unactivated C-H bonds to valuable C-C and C-heteroatom bonds, selective site-controlled desaturation of aliphatic hydrocarbons into alkenes Still needs development. Among the modern catalyzed approaches that usually operate via a direct transfer-hydrogenation process or a directed cooperative metallation-deprotonation pathway, the latter approach is more advantageous because of its higher stability. However, this method suffers from low selectivity and efficiency, limited substrate range, and harsh reaction conditions.

Contents of the invention

Aiming at the deficiencies in the prior art, the purpose of the present invention is to utilize ruthenium catalyst, use chlorinated amide as a substrate, and accurately excavate the hydrogen atom on the δ-carbon through the 1,5-HAT process promoted by visible light, and generate the The free radical intermediate is further eliminated by β-H under the action of ruthenium, and finally alkene compounds are obtained. This method has high regioselectivity and stereoselectivity.

To achieve the above object, the present invention provides the following technical solutions:

A method for the selective desaturation of inert carbon-carbon bonds to synthesize olefins. In an organic solvent system, the chlorinated amides compound shown in formula 1) is used as a raw material and synthesized under the conditions of visible light, a ruthenium catalyst and a ligand. The reaction After post-treatment of the liquid, the remote alkenyl amide compound shown in formula 2) is obtained;

In the above scheme, the dotted line of formula 1) and formula 2) represents a carbon-carbon bond, according to the situation whether the dotted line bond exists in the described formula 1), the two structural formulas of formula 1) have two kinds of situations respectively, thereby respectively Alkenes with two different double bond positions can be obtained, which can be represented by the following four sets of equations:

Wherein, R _is arbitrarily selected from tert-butyl, adamantyl, haloalkyl, benzyl, cyclohexyl, ester group, cycloalkyl, heterocycloalkyl, tert-butoxycarbonyl or macromolecule alkyl;

R is _arbitrarily selected from 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl or thiophene;

_R3 is arbitrarily selected from hydrogen, alkenyl or alkyl, and the alkyl can be connected with the benzene ring to form a closed ring;

n=0, 1 or 2.

Further, the ruthenium catalyst is [RuCl ₂ (p-cymene)] ₂ , RuCl(p-cymene)(ppy), RuOAc(p-cymene)(ppy) or Ru(MeCN) ₄ (ppy)PF ₆ , more preferably [RuCl ₂ (p-cymene)] ₂ ; the ligand is a phenylpyridine compound, preferably 2-phenylpyridine, 2-phenyl-4-tert-butylpyridine or 2-phenyl -4 methylpyridine.

Further, the specific synthesis conditions are as follows: add chlorinated amide compound, ruthenium catalyst, ligand, alkali, water and organic solvent into a sealed tube, and react for 48 hours under an inert gas atmosphere.

Further, the molar ratio of the chloroamide, ruthenium catalyst, ligand, base, and water is 1:1:0.05～0.1:0.1～0.2:1.5-2:0-20.

Further, the organic solvent is 1,2-dichloroethane, tetrahydrofuran, acetonitrile or dichloromethane, more preferably 1,2-dichloroethane; the base is preferably potassium acetate.

Further, the post-processing method is thin layer chromatography, column chromatography or recrystallization method for purification.

Further, when the post-processing method is thin layer chromatography or column chromatography purification method, the developer used is a mixed solvent of ethyl acetate-petroleum ether; when the post-processing method is recrystallization purification method, the used The solvent is dichloromethane-n-hexane mixed solvent.

Further, the visible light can be an incandescent lamp or a blue light, preferably a 38W 460nm blue light.

The beneficial effects of the present invention are: the present invention successfully realizes the intramolecular carbon-hydrogen bond activation of amide compounds in the presence of ruthenium catalysts and phenylpyridine ligands, and synthesizes remote olefin compounds; the method uses simple and easy-to-obtain chlorinated amides as Raw materials and substrates have a wide range of applications and high reaction efficiency; in the process of free radical migration, 1,5 migration always occurs with β-H elimination, and the main products are terminal alkenes and the formation of conjugated double bonds, which have good Regioselectivity; the highest E/Z value of the obtained olefin compound is greater than 20:1, and the stereoselectivity is good; and, the double bond in the compound prepared by this method can be further converted into other functional groups, such as monohydroxylation and dihydroxylation , cyclopropanation, etc. In this case, through the method of first desaturation and then combined with addition, other functional groups can be easily modified on inert saturated hydrocarbons. The conversion process is simple, and the obtained derivatives can be used as pharmaceutical intermediates, with potential application value high.

Detailed ways

The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as there is no conflict with each other.

The chemical reagents and drugs used in this case can be purchased from the market unless otherwise specified.

The synthesis method of chloroamide compounds used in the following examples refers to the document J.Am.Chem.Soc.2019, 141, 19941-19949. In this case, chloroamide compounds with the following specific structural formulas were synthesized.

The ruthenium catalyst used in the following examples was synthesized with reference to the literature, [RuCl ₂ (p-cymene)] ₂ (CAS: 100928-22-1), RuCl (p-cymene) (ppy) (Chang, S.Org.Lett.2014 ,16,2022–2025), RuOAc(p-cymene)(ppy)(Jutand,AJAm.Chem.Soc.2011,133,10161–10170) and Ru(MeCN) ₄ (ppy)PF ₆ (Ackermann,L. Angew. Chem. Int. Ed. 2020, 59, 18103–18109).

In the following examples, the structural formula of the ligand is as follows:

The specific synthesis process of the remote olefin compound of the present invention is: add 0.2mmol chloroamide 1, ruthenium catalyst (10mol%, 12.8mg), ligand L (20mol%), KOAc (0.4mmol, 40mg), H ₂ O (1mmol, 18mg), was added with 1,2-dichloroethane (4mL) for lyophilization and deoxygenation, under nitrogen protection. Seal the tube, and react for 48 hours under the irradiation of 38W 460nm blue light unless otherwise specified. After the reaction, the reaction mixture was concentrated to obtain a crude product, which was purified by column chromatography to obtain olefinic compound 2.

Depend on synthesis

Example 1: Add 0.2mmol chloroamide 1a, [RuCl ₂ (p-cymene)] ₂ (10mol%, 12.8mg) to a 10mL Schlenk type sealed tube equipped with a magnetic stirrer, ligand L1 (20mol%) , KOAc (0.4mmol, 40mg), H ₂ O (1mmol, 18mg), and 1,2-dichloroethane (4mL) were added for lyophilization and deoxygenation, under nitrogen protection. Seal the tube, and react under the irradiation of 38W 460nm blue light for 48 hours unless otherwise specified. After the reaction, the reaction mixture was concentrated to obtain a crude product, which was purified by column chromatography to obtain olefinic compound 2a. The yield is 58% yield, E/Z≧20/1, and the E/Z ratio is obtained from the integral ratio of the isomer olefin hydrogen atom characteristic signal peaks in the H NMR spectrum of the crude product.

¹ H NMR (400MHz, CDCl ₃ ) δ7.38(d, J=7.4Hz, 2H), 7.32(t, J=7.4Hz, 2H), 7.23(d, J=7.2Hz, 1H), 6.50(d ,J=15.9Hz,1H),6.29(dt,J=15.8,7.3Hz,1H),5.42(s,1H),3.07(d,J=8.4Hz,2H),1.35(s,9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.9, 136.7, 134.1, 128.6, 127.6, 126.3, 123.0, 51.3, 41.9, 28.8.

IR(film):ν(cm ^-1 )3310,2972,2926,1668,1640,1546,1452,1389,1252, 1177,963,757,691.

HRMS(ESI,m/z)calcd for C ₁₄ H ₁₉ NONa[M+Na] ⁺ :240.1359,found: 240.1364.

Example 2: On the basis of Example 1, L1 (20 mol%) was replaced by L2 (20 mol%), and the rest were the same as in Example 1 to synthesize compound 2a with a yield of 26%, E/Z≧20 /1.

Example 3: On the basis of Example 1, L1 (20 mol%) was replaced by L3 (20 mol%), and the rest were the same as in Example 1 to synthesize compound 2a with a yield of 49%, E/Z≧20 /1.

Example 4: On the basis of Example 1, L1 (20 mol%) was replaced with L4 (20 mol%), and the rest were the same as Example 1 to synthesize compound 2a (0% yield).

Example 5: On the basis of Example 1, L1 (20 mol%) was replaced by L5 (20 mol%), and the rest were the same as Example 1 to synthesize compound 2a (0% yield).

Example 6: On the basis of Example 1, L1 (20 mol%) was replaced by L6 (20 mol%), and the rest were the same as in Example 1 to synthesize compound 2a (0% yield).

Example 7: On the basis of Example 1, L1 (20 mol%) was replaced with L7 (20 mol%), and the rest were the same as Example 1 to synthesize compound 2a (0% yield).

Example 8: On the basis of Example 1, L1 (20 mol%) was replaced by L8 (20 mol%), and the rest were the same as in Example 1 to synthesize compound 2a (0% yield).

When the catalyst and other conditions are constant and only the ligand structure is changed, the phenylpyridines of Examples 1-3 can be used to synthesize compound 2a, while Examples 4-8 fail to obtain compound 2a, indicating that compounds L4-L8 are not suitable as Ligands were used for the synthesis of this case.

Example 9: On the basis of Example 1, 1,2-dichloroethane (2 mL) was replaced with tetrahydrofuran (2 mL), and the rest was the same as Example 1 to obtain compound 2a with a yield of 27%, E /Z≧20/1.

Example 10: On the basis of Example 1, 1,2-dichloroethane (2 mL) was replaced by acetonitrile (2 mL), and the rest was the same as Example 1 to obtain compound 2a with a yield of 26%, E /Z≧20/1.

Example 11: On the basis of Example 1, 1,2-dichloroethane (2 mL) was replaced with 1,2-dichloroethane (4 mL), and the rest was the same as in Example 1 to obtain compound 2a , yield 75%, E/Z≧20/1.

Comparing Example 1 and Examples 9-10, it can be found that general organic solvents are suitable for the synthesis method of this case, but when 1,2-dichloroethane is used, the yield of compound 2a is higher.

Example 12: On the basis of Example 11, replace [RuCl ₂ (p-cymene)] ₂ (10mol%, 14mg) with RuCl(p-cymene) (ppy) (10mol%, 8.5mg), The rest was the same as in Example 11 to obtain compound 2a with a yield of 65% and E/Z≧20/1.

Example 13: On the basis of Example 11, [RuCl ₂ (p-cymene)] ₂ (10mol%, 14mg) was replaced by RuOAc(p-cymene) (ppy) (10mol%, 9.0mg), The rest was the same as in Example 11 to obtain compound 2a with a yield of 74% and E/Z≧20/1.

Example 14: On the basis of Example 11, replace [RuCl ₂ (p-cymene)] ₂ (10mol%, 14mg) with Ru(MeCN) ₄ (ppy)PF ₆ (10mol%, 9.1mg) , the rest were the same as in Example 11 to obtain compound 2a with a yield of 17% and E/Z≧20/1.

Example 15: On the basis of Example 11, replace [RuCl ₂ (p-cymene)] ₂ (10mol%, 14mg) with CpIrCl ₂ (5mol%, 6.6mg), and the rest are the same as Example 11, Compound 2a was synthesized (0% yield).

Example 16: On the basis of Example 11, replace [RuCl ₂ (p-cymene)] ₂ (10mol%, 14mg) with fac-Ir(ppy) ₃ (2mol%, 2.6mg), and the rest with Same as in Example 11, compound 2a was synthesized (0% yield).

Comparing Examples 15 and 16, it can be found that non-ruthenium catalysts cannot be used in the synthesis method of this case, and cannot play a catalytic role.

By contrasting examples 1-16, the best synthetic conditions that can be drawn are: add chloramide 1 (0.2mmol) in the 10mL Schlenk type sealed tube that magnetic stirring bar is housed, [RuCl ₂ (p-cymene)] ₂ ( 10 mol%, 12.8mg), L1 (20mol%), KOAc (0.4mmol, 40mg), H ₂ O (1mmol, 18mg), add 1,2-dichloroethane (4mL) to freeze-dry and deoxygenate, nitrogen protection . The tube was sealed and reacted for 48 hours under the irradiation of 38W 460nm blue light. After the reaction, the reaction mixture was concentrated to obtain a crude product, which was purified by thin layer chromatography (petroleum ether/ethyl acetate=10:1, Rf=0.3) to obtain compound 2.

Taking compound 2a as an example, its synthesis mechanism is as follows:

Ruthenium p-cymene ([RuCl ₂ (p-cymene)] ₂ ) and phenylpyridine form a composite catalyst in situ under alkaline conditions. The composite catalyst acts as a photocatalyst and donates electrons to form nitrogen radicals. Nitrogen free radicals have high energy and can undergo intramolecular 1,5-hydrogen transfer; they also play a role in the dehydrogenation step, eliminating β-H to form carbon-carbon double bonds, and mainly to form terminal double bonds or conjugated double bonds products with good regioselectivity.

By changing the structural formula of chloroamide 1, remote alkenyl amide compounds with specific structural formulas of P2-P26 can be obtained.

P2

Synthesized from 1b

A white solid was obtained, 36.8 mg, 0.142 mmol, yield: 71%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.37(d, J=7.0Hz, 2H), 7.32(dd, J=8.2, 6.7Hz, 2H), 7.28-7.23(m, 3H), 7.16(t, J＝8.6Hz, 3H), 6.50(d, J＝15.8Hz, 1H), 6.30-6.19 (m, 1H), 5.62(s, 1H), 3.30(q, J＝6.9Hz, 2H), 3.11( dd,J=7.3,1.1Hz,2H),2.64(t,J=7.6Hz,2H),1.84(q,J=7.4Hz,2H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.52, 141.33, 136.51, 134.74, 128.61, 128.44, 128.30, 127.79, 126.28, 125.99, 122.38, 40.88, 39.35, 33.29, 31.06.

IR(film):ν(cm ^-1 )3310,3029,2969,2923,1634,1546,1493,1358,1248, 1181,963,748,691.

HRMS(ESI,m/z)calcd for C ₁₉ H ₂₁ NONa[M+Na] ⁺ :302.1515,found: 302.1516.

P3

synthesized from 1c

A yellow solid was obtained, 23.3 mg, 0.104 mmol, yield: 52%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ )δ7.41-7.35(dd,2H),7.35-7.29(dd,2H), 7.27-7.25(m,1H),6.56(d,J=15.9Hz,1H), 6.28(dt,J=15.8,7.3Hz,1H),6.06(s,1H),3.61(t,J=3.4Hz,2H),3.18(dd,J=7.3,1.2Hz,2H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.90, 136.47, 135.02, 128.63, 127.87, 126.33, 121.90, 43.89, 41.29, 40.67.

IR(film):ν(cm ^-1 )3310,3055,2921,2621,1740,1644,1544,1450,1407, 1358,1218,1175,1150,1087,1026,999,916,742,691.

HRMS(ESI,m/z)calcd for C ₁₂ H ₁₄ NONa[M+Na-Cl] ⁺ :206.1176,found: 206.1172.

P4

synthesized from 1d

A white solid was obtained, 28.0 mg, 0.084 mmol, yield: 42%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.76(dd, J=5.3, 3.2Hz, 2H), 7.67(dd, J=5.5, 3.0Hz, 2H), 7.35(d, J=7.2Hz, 2H) ,7.29(t,J=7.3Hz,2H),7.23(t,J=3.2Hz,1H),6.48(d,J=15.9Hz,1H),6.20(dd,J=15.8,7.4Hz,1H) ,6.11(s,1H),3.86(dd, J=6.4,4.4Hz,2H),3.58-3.53(m,2H),3.09(d,J=7.4Hz,2H).

¹³ C NMR (101MHz, CDCl ₃ ) δ171.18, 168.51, 136.70, 134.52, 134.03, 132.00, 128.48, 127.59, 126.33, 123.30, 122.33, 40.69, 39.10, 37.45.

IR(film):ν(cm ^-1 )3547,3306,3036,1740,1699,1644,1577,1450,1383, 1281,1209,1187,1105,1065,985,912,850,763,689.

HRMS(ESI,m/z)calcd for C ₂₀ H ₁₈ N ₂ O ₃ Na[M+Na] ⁺ :357.1022, found:357.1025.

P5

synthesized from 1e

A white solid was obtained, 40.1 mg, 0.136 mmol, yield: 68%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.39-7.34(m, 2H), 7.30(t, J=7.5Hz, 2H), 7.25-7.20(m, 1H), 6.49(d, J=15.9Hz, 1H), 6.27(dt, J＝15.8, 7.2Hz, 1H), 5.27(s, 1H), 3.05(dd, J＝7.2, 1.2Hz, 2H), 2.05(s, 3H), 1.98(d, J ＝2.6Hz,6H),1.66(s,6H).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.68, 136.79, 134.10, 128.57, 127.62, 126.27, 123.12, 51.98, 42.03, 41.60, 36.31, 29.41.

IR(film):ν(cm ^-1 )3299,2906,2851,1689,1638,1540,1450,1362,1307, 1275,1238,1167,1142,965,734,693.

HRMS(ESI,m/z)calcd for C ₂₀ H ₂₅ NONa[M+Na] ⁺ :318.1828, found:318.1829.

P6

synthesized from 1f

A white solid was obtained, 34.6 mg, 0.101 mmol, yield: 50%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ )δ7.64-7.47(m,1H),7.32-7.26(m,2H),7.24(d, J=7.8Hz,1H),7.21-7.14(m,1H), 6.44(d, J=15.8Hz, 1H), 6.23(dt, J=15.8, 7.2 Hz, 1H), 6.11(d, J=7.8Hz, 1H), 3.97(s, 2H), 3.91–3.87(dp ,J=11.2,3.7Hz,1H),3.08(dd,J=7.2,1.4Hz,2H),2.78(t,J=11.8Hz,2H),1.89-1.77(m,2H),1.39(s,9H ), 1.30-1.19 (ddd, J=26.16, 12.32, 3.88 2H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.13, 154.61, 136.61, 134.13, 132.05, 128.56, 127.67, 126.24, 122.60, 79.58, 46.75, 42.46, 40.79, 31.92, 28.39.

IR(film):ν(cm ^-1 )3267,2932,1687,1640,1546,1475,1424,1364,1311, 1275,1236,1167,1081,969,763,698

HRMS(ESI,m/z)calcd for C ₂₀ H ₂₅ NONa[M+Na] ⁺ :367.1992, found:367.1995.

P7

Synthesized from 1g

A yellow oil was obtained, 32.7 mg, 0.135 mmol, yield: 67%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.37(d, J=7.8Hz, 2H), 7.31(dd, J=7.5Hz, 2H), 7.25(dd, J=4.2Hz, 1H), 6.52(d ,J=15.9Hz,1H),6.27(dt,J=14.9,7.3Hz,1H),5.56(s,1H),4.00(ddt,J=14.8,7.1,3.6Hz,1H),3.92(dt, J＝11.4Hz, 2H), 3.50-3.40(dt, 2H), 3.13(d, J＝7.3Hz, 2H), 1.91-1.83(dd, 2H), 1.43(qd, J＝11.9, 4.3Hz, 2H ).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.96, 136.52, 134.68, 128.64, 127.84, 126.30, 122.25, 66.74, 45.82, 40.94, 33.09.

P8

Synthesized from 1h

A white solid was obtained, 33.8 mg, 0.140 mmol, yield: 70%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.37(d, J=7.3Hz, 2H), 7.31(dd, J=7.6Hz, 2H), 7.23(dd, J=7.6Hz, 1H), 6.51(d ,J=15.9Hz,1H),6.27(dt,J=15.6,7.3Hz,1H),5.48(s,1H),3.77(ddt,J=14.4,6.3,3.6Hz,1H),3.11(dd, J＝7.3,1.3Hz,2H),1.89(dt,J＝12.6,4.0Hz,2H),1.73-1.53(m,4H),1.33(tt,J＝24.7,10.9Hz,3H), 1.19-1.02 (tt,3H).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.64, 136.65, 134.48, 128.61, 127.74, 126.29, 122.64, 48.31, 41.07, 33.13, 25.47, 24.84.

IR(film):ν(cm ^-1 )3547,3306,3036,1740,1699,1644,1577,1450,1383, 1281,1209,1187,1105,1065,985,912,850,763,689.

HRMS(ESI,m/z)calcd for C ₁₆ H ₂₁ NONa[M+Na] ⁺ :266.1515, found:266.1514.

P9

synthesized from 1i

A yellow solid was obtained, 19.9 mg, 0.082 mmol, yield: 41%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.40-7.36(m, 2H), 7.34-7.29(m, 2H), 7.26(d, J=1.6Hz, 1H), 6.53(d, J=15.8Hz, 1H), 6.30(dt, J=15.8, 7.3Hz, 1H), 5.74(s, 1H), 3.17-3.09(m, 4H), 0.93(ddt, J=12.4, 7.6, 3.7Hz, 1H), 0.51 -0.46(m,2H),0.18(q, J＝5.6,5.1Hz,2H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.51, 136.63, 134.56, 128.61, 127.76, 126.30, 122.51, 44.50, 40.89, 10.64, 3.38.

IR(film):ν(cm ^-1 )3236,3073,3036,1740,1699,1644,1577,1450,1383, 1281,1209,1187,1105,1065,985,912,850,763,689.

HRMS(ESI,m/z) calcd for C ₁₄ H ₁₇ NONa[M+Na] ⁺ :238.1202, found:238.1201.

P10

synthesized from 1j

A white solid was obtained, 41.0 mg, 0.990 mmol, yield: 50%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.35(d, J=7.6Hz, 2H), 7.29(t, J=7.5Hz, 2H), 7.22(t, J=7.2Hz, 1H), 6.50(d ,J=15.9Hz,1H),6.28(dt,J=15.3,7.3Hz,1H),5.85(s,1H),5.50-5.21(m,2H),3.24-3.18(m,2H),3.13( d,J=7.2Hz,2H),1.98(ddt,J=15.7,12.1,5.8Hz,4H),1.45(dt,J=14.6,7.3Hz,3H),1.33-1.20(m,28H),0.86 (q,J=5.9Hz,5H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.57, 136.62, 134.45, 129.93, 129.75, 128.59, 127.72, 126.26, 122.63, 40.88, 39.74, 31.89, 29.76, 29.73, 29.69, 29. 67,29.65,29.59,29.53,29.51,29.43 ,29.31,29.26,29.21,27.18,26.90,22.67,14.11.

IR(film):ν(cm ^-1 )3250,3069,2919,2851,1628,1560,1466,1422,1248, 963,753,716,689.

HRMS(ESI,m/z) calcd for C ₂₈ H ₄₅ NONa[M+Na] ⁺ :434.3393, found:434.3386.

P11

Synthesized from 1k

A white solid was obtained, 30.0 mg, 0.104 mmol, yield: 57%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.35(d, J=7.3Hz, 2H), 7.28(dd, J=7.3Hz, 2H), 7.24-7.17(dd, 1H), 6.51(d, J= 15.8Hz, 1H), 6.38(s, 1H), 6.28(dt, J=15.4, 7.2Hz, 1H), 4.59(q, J=7.1Hz, 1H), 3.70(s, 3H), 3.16(d, J＝7.1Hz, 2H), 1.38(d, J＝7.1Hz, 3H).

¹³ C NMR (101MHz, CDCl ₃ ) δ173.47, 170.34, 136.64, 134.52, 128.56, 127.69, 126.32, 122.10, 52.44, 48.06, 40.49, 18.34.

IR(film):ν(cm ^-1 )3547,3306,3255,3036,2957,1740,1644,1577,1497, 1434,1383,1209,1081,985,912,850,763,689.

HRMS(ESI,m/z)calcd for C ₁₅ H ₁₉ NO ₃ Na[M+Na] ⁺ :286.1047, found:286.1045.

P12

Synthesized from 1l

A yellow oil was obtained, 44.0 mg, 0.122 mmol, yield: 61%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ )δ7.38-7.33(m,2H),7.29(td,J=6.7,6.2,1.6Hz,2H),7.24-7.19(m,1H),6.54(d,J =15.9Hz, 1H), 6.34-6.26(td, J=15.88, 7.2 1H), 6.24(s, 1H), 4.59(dd, J=8.6, 4.9Hz, 1H), 4.21-4.12(m, 2H) ,1.88(dqd,J=9.4,4.8,2.6Hz,1H),1.46-1.39(m,1H),1.25(t,J=7.1Hz,3H),1.19-1.11(m,1H),0.90(t ,J＝7.2Hz,6H).

¹³ C NMR (101MHz, CDCl ₃ ) δ171.95, 170.40, 136.68, 134.50, 128.56, 127.67, 126.31, 122.24, 61.21, 56.37, 40.65, 37.98, 25.24, 15.37, 14.17, 11.5 8.

IR(film):ν(cm ^-1 )3301,2961,2901,31736,1642,1540,1454,1371,1244, 1191,1095,1024,965,736,691.

HRMS(ESI,m/z)calcd for C ₁₇ H ₂₃ NO ₃ Na[M+Na] ⁺ :312.1570,found: 312.1570.

P13

Synthesized from 1m

A white solid was obtained, 36.5 mg, 0.126 mmol, yield: 63%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.37-7.32 (m, 2H), 7.28 (t, J = 7.5Hz, 2H), 7.21 (td, J = 6.0, 4.9, 3.1Hz, 1H), 6.54 ( dt,J=15.8,1.5Hz,1H),6.33-6.28(m,1H),6.26(s,1H),4.48(d,J=9.4Hz,1H),3.69(s,3H),3.18(dd ,J＝7.2,1.2Hz,2H),0.94(s, 9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ172.07, 170.37, 136.66, 134.55, 128.57, 127.69, 126.29, 122.23, 59.88, 51.79, 40.64, 34.72, 26.52.

IR(film):ν(cm ^-1 )3314,2967,1740,1648,1532,1475,1438,1368,1216, 1158,981,738,693.

HRMS(ESI,m/z) calcd for C ₁₇ H ₂₃ NO ₃ Na[M+Na] ⁺ :312.1570, found:312.1570.

P14

synthesized from 1n

A yellow solid was obtained, 39.4 mg, 0.122 mmol, yield: 61%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.38-7.34(m, 2H), 7.34-7.31(m, 2H), 7.30 (dd, J=6.1, 2.8Hz, 4H), 7.26(dt, J=4.4 ,1.6Hz,1H),6.51(d,J=15.9Hz,1H),6.29(dt,J=15.8,7.2Hz,1H),5.97(s,1H),5.15(q,J=7.0Hz,1H ),3.17-3.12(m,2H), 1.48(s,3H).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.74, 143.06, 136.62, 134.53, 128.69, 128.61, 127.75, 127.38, 126.32, 126.14, 122.40, 48.80, 40.89, 21.76.

IR(film):ν(cm ^-1 )3301,3034,2950,1740,1646,1536,1499,1440,1366, 1273,1175,969.

HRMS(ESI,m/z)calcd for C ₂₀ H ₂₁ NO ₃ Na[M+Na] ⁺ :346.1414, found:346.1416.

P15

synthesized from 1o

A yellow solid was obtained, 48.5 mg, 0.183 mmol, yield: 92%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.35(d, J=7.3Hz, 2H), 7.28(t, J=7.3Hz, 2H), 7.24-7.18(m, 1H), 6.51(d, J= 15.8Hz, 1H), 6.38(s, 1H), 6.28(dt, J=15.4, 7.2Hz, 1H), 4.59(q, J=7.1Hz, 1H), 3.70(s, 3H), 3.16(d, J＝7.1Hz, 2H), 1.38(d, J＝7.1Hz, 3H).

¹³ C NMR (101MHz, CDCl ₃ ) δ173.47, 170.34, 136.64, 134.52, 128.56, 127.69, 126.32, 122.10, 52.44, 48.06, 40.49, 18.34.

IR(film):ν(cm ^-1 )3296,3032,2918,1634,1540,1491,1444,1428,1160, 969.

HRMS(ESI,m/z)calcd for C ₁₈ H ₁₉ NONa[M+Na] ⁺ :288.1359, found:288.1359.

P16

synthesized from 1p

A yellow solid was obtained, 19.8 mg, 0.080 mmol, yield: 40%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.30(d, J=8.7Hz, 2H), 6.84(d, J=8.7Hz, 2H), 6.43(dt, J=15.7, 1.5Hz, 1H), 6.11 (dt,J=15.7,7.3Hz,1H),5.39(s,1H),3.79(s,3H),3.03(dd,J=7.3,1.2Hz,2H),1.33(s,9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.22, 159.24, 133.66, 129.55, 127.44, 120.65, 113.98, 55.27, 51.24, 41.91, 28.76.

IR(film):ν(cm ^-1 )3318,2972,1670,1642,1607,1544,1509,1454,1419, 1391,1362,1297,1248,1224,1175,1032,963,830,808.

HRMS(ESI,m/z) calcd for C ₁₅ H ₂₁ NO ₂ Na[M+Na] ⁺ :270.1465, found:270.1463.

P17

synthesized from 1q

A yellow solid was obtained, 25.2 mg, 0.121 mmol, yield: 55%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.26(d, J=8.2Hz, 2H), 7.12(d, J=8.0Hz, 2H), 6.46(d, J=15.8Hz, 1H), 6.21(dt ,J=15.8,7.3Hz,1H),5.43(s,1H),3.05(dd,J=7.3,1.2Hz,2H),2.32(s,3H),1.33(s,9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ170.13, 137.53, 134.15, 129.27, 126.19, 125.32, 121.85, 51.27, 41.94, 28.76, 21.16.

IR(film):ν(cm ^-1 )3310,2976,2921,1670,1640,1546,1454,1391,1360, 1252,1224,1177,965,940,799.

HRMS(ESI,m/z) calcd for C ₁₅ H ₂₁ NONa[M+Na] ⁺ :254.1515, found:254.1514.

P18

synthesized from 1r

A white solid was obtained, 53.9 mg, 0.182 mmol, yield: 91%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.42(dt, J=9.1, 2.4Hz, 2H), 7.22(dd, J=8.7, 2.2Hz, 2H), 6.42(d, J=15.9Hz, 1H) ,6.28(dt,J=15.8,7.1Hz,1H),5.35(s,1H),3.04(dd,J=7.1,1.2Hz,2H),1.33(s,9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.60, 135.72, 132.73, 131.66, 127.79, 123.94, 121.36, 51.38, 41.76, 28.77.

IR(film):ν(cm ^-1 )3310,2979,1670,1638,1544,1481,1454,1393,1360, 1222,1175,1069,1005,963,940,822.

HRMS(ESI,m/z)calcd for C ₁₄ H ₁₈ BrNONa[M+Na] ⁺ :318.0464, found:318.0464.

P19

Synthesized from 1s

A white solid was obtained, 24.1 mg, 0.108 mmol, yield: 54%, E/Z>20:1.

¹ H NMR (400MHz, CDCl ₃ ) δ7.16-7.09(m, 1H), 6.94(d, J=4.7Hz, 2H), 6.61(d, J=15.7Hz, 1H), 6.09(dt, J= 15.6,7.3Hz,1H),5.39(s,1H),3.02(dd,J＝7.3,1.3Hz,2H),1.33(s,9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ169.67, 141.76, 127.31, 127.23, 125.51, 124.22, 122.49, 51.34, 41.64, 28.75.

IR(film):ν(cm ^-1 )3318,2972,2928,1640,1609,1544,1454,1419,1391, 1360,1322,1297,1250,1222,1175,1034,963,810.

HRMS(ESI,m/z) calcd for C ₁₂ H ₁₇ NOSNa[M+Na] ⁺ :246.0923, found:246.092.

P20

Synthesized from 1t

A white solid was obtained, 30.4 mg, 0.140 mmol, yield: 70%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.45-7.41(m, 2H), 7.36-7.31(m, 2H), 7.31-7.27(m, 1H), 5.60(d, J＝1.1Hz, 1H), 5.49( s,1H),5.24(d,J=1.0Hz,1H),3.36(s,2H),1.20(s,9H).

13C NMR (101MHz, CDCl3) δ169.48, 142.88, 139.22, 128.55, 128.10, 125.79, 116.49, 51.05, 45.31, 28.44.

IR(film):ν(cm-1)3284,2921,1638,1550,1450,1356,1258,1226,897,799,777,700,602.

HRMS(ESI,m/z)calcd for C14H19NONa[M+Na]+:240.1359,found:240.1354.

P21

Synthesized from 1u

A yellow solid was obtained, 17.1 mmg, 0.084 mmol, yield: 42%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.53(d, J＝7.8Hz, 1H), 7.42–7.31(m, 2H), 7.27(d, J＝8.5Hz, 1H), 7.01(dd, J＝17.5, 11.0Hz, 1H), 5.70(dd, J=17.5, 1.0Hz, 1H), 5.58(s, 1H), 5.34(dd, J=11.0, 1.0Hz, 1H), 1.45(s, 9H).

13C NMR (101MHz, CDCl3) δ168.8, 136.7, 135.43, 134.52, 129.73, 127.67, 127.21, 126.12, 116.46, 51.95, 28.81.

IR(film):ν(cm-1)3310,2969,2926,1644,1544,1452,1391,1360,1222, 895,777,700.

HRMS(ESI,m/z)calcd for C13H17NONa[M+Na]+:226.1202,found:226.1197.

P22

Synthesized from 1v

A white solid was obtained, 25.7 mg, 0.125 mmol, yield: 56%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.18(dd, J＝7.1, 1.6Hz, 1H), 7.13-7.06(m, 2H), 6.79(d, J＝9.9Hz, 1H), 6.12(dt, J＝ 9.3,4.5Hz,1H),5.55(s,1H),2.77(t,J=8.2Hz,2H),2.28(tdd,J=7.9,4.5,1.8Hz,2H),1.45(s,9H).

13C NMR (101MHz, CDCl3) δ169.18, 136.55, 134.59, 131.12, 130.33, 128.78, 126.43, 124.87, 124.62, 51.83, 28.85, 27.93, 22.60.

IR(film):ν(cm-1)3310,2923,1640,1521,1452,1389,1358,1307,1287,1220,771.

HRMS(ESI,m/z)calcd for C15H19NONa[M+Na]+:254.1515,found:254.1512.

P23

Synthesized from 1w

A white solid was obtained, 31.7 mg, 0.147 mmol, yield: 73%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.60 (dd, J = 7.5, 1.5Hz, 1H), 7.30 (dtd, J = 20.5, 7.4, 1.5Hz, 2H), 7.16 (dd, J = 7.3, 1.5Hz, 1H), 6.04(s,1H), 5.21-5.18(m,1H), 5.05(s,1H), 2.07(s,3H), 1.39(s,9H).

13C NMR (101MHz, CDCl3) δ168.20, 146.71, 141.50, 135.12, 129.93, 128.75, 128.44, 127.44, 115.63, 51.57, 28.45, 24.50.

IR(film):ν(cm-1)3259,2965,1628,1540,1479,1450,1362,1322,1222, 895,761.

HRMS(ESI,m/z)calcd for C14H19NONa[M+Na]+:240.1359,found:240.1356.

P24

Synthesized from 1x

A yellow solid was obtained, 18.4 mg, 0.080 mmol, yield: 40%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.54(d, J＝7.8Hz, 1H), 7.42-7.29(m, 2H), 7.22(d, J＝7.5Hz, 1H), 6.85(d, J＝15.7Hz ,1H),6.72(dd,J=15.6,10.2Hz,1H),6.50(dt,J=16.9,10.1Hz,1H),5.55(s,1H),5.34(d,J=16.9Hz,1H) ,5.19(d, J＝10.0Hz,1H),1.45(s,9H).

13C NMR (101MHz, CDCl3) δ168.93, 137.08, 134.69, 132.04, 129.89, 129.64, 127.35, 125.96, 118.45, 51.96, 28.83.

IR(film):ν(cm-1)3247,2967,2921,1632,1597,1536,1473,1391,1360, 1320,1260,1222,1005,893.

HRMS(ESI,m/z)calcd for C15H19NONa[M+Na]+:252.1359,found:252.1357.

P25

synthesized from 1y

A white solid was obtained, 28.2 mg, 0.130 mmol, yield: 65%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.43-7.37 (m, 2H), 7.32 (t, J = 7.3Hz, 2H), 7.27 (d, J = 6.9Hz, 1H), 5.28 (s, 1H), 5.14 (s,1H),5.09(s,1H),2.83(t,J＝7.6Hz, 2H),2.25-2.15(m,2H),1.29(s,9H).

13C NMR (101MHz, CDCl3) δ171.53, 147.21, 140.49, 128.40, 127.57, 126.16, 113.16, 51.11, 36.27, 31.28, 28.78.

IR(film):ν(cm-1)3310,2969,1644,1544,1452,1391,1360,1222,895,777,700.

HRMS(ESI,m/z)calcd for C15H21NONa[M+Na]+:254.1515,found:254.1512.

P26

Synthesized from 1z

A white solid was obtained, 13.9 mg, 0.060 mmol, yield: 30%, E/Z>20:1.

1H NMR (400MHz, CDCl3) δ7.31 (d, J = 7.0Hz, 2H), 7.28 (s, 2H), 7.21-7.16 (m, 1H), 6.42 (d, J = 15.8Hz, 1H), 6.19 (dt,J=15.7,6.9Hz,1H),5.27(s,1H),2.51(q,J=7.3Hz,2H),2.24(t,J=7.4Hz,2H),1.32(s,9H) .

13C NMR (101MHz, CDCl3) δ171.43, 137.41, 130.93, 128.93, 128.49, 127.07, 125.98, 51.18, 37.25, 28.83.

IR(film):ν(cm-1)3297,2963,2921,1640,1550,1448,1387,1360,1269, 1220,963,738,604.

HRMS(ESI,m/z)calcd for C15H21NONa[M+Na]+:254.1515,found:254.1512.

The P1-P26 compound obtained above can be further converted into -Hydroxyamides. Taking P18 as an example, using the literature method (Pollrich, A.Org.Biomol.Chem., 2004, 2, 1116-1124), in the presence of Co(acac) ₂ and SiH ₃ , 2r can be converted in 56% yield for 3.

¹ H NMR (400MHz, CDCl ₃ ) δ7.43(d, J=8.4Hz, 2H), 7.23(s, 2H), 5.44(s, 1H), 4.71(dd, J=7.8, 3.8Hz, 1H) ,4.51(s,1H),2.23(t,J=6.5Hz,2H),1.94(td,J=13.7,6.7Hz,2H),1.32(s,9H).

¹³ C NMR (101MHz, CDCl ₃ ) δ173.01, 143.80, 131.33, 127.50, 120.83, 72.94, 51.48, 34.20, 33.68, 28.70.

IR(film):ν(cm ^-1 )3312,2925,1642,1548,1487,1454,1424,1395,1362, 1222,1136,1105,1069,1008.

HRMS(ESI,m/z)calcd for C ₁₄ H ₂₀ NO ₂ BrNa[M+Na] ⁺ :336.057, found:336.0566.

Although the embodiment of the present invention has been disclosed as above, it is not limited to the use listed in the specification and implementation, it can be applied to various fields suitable for the present invention, and it can be easily understood by those skilled in the art Therefore, the invention is not limited to the specific details without departing from the general concept defined by the claims and their equivalents.

Claims (4)

1. A method for the selective desaturation of inert carbon-carbon bonds to synthesize olefins, characterized in that, in an organic solvent system, the chlorinated amides compound shown in formula 1) is used as a raw material, under visible light, a ruthenium catalyst and a ligand Synthesized under existing conditions, the reaction solution is post-treated to obtain a remote alkenyl amide compound shown in formula 2), and the reaction process is selected from any one of the following reaction formulas; Wherein, _R is arbitrarily selected from any one of tert-butyl, adamantyl, haloalkyl, benzyl, ester group, cycloalkyl, heterocycloalkyl, tert-butoxycarbonyl; _R is arbitrarily selected as 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl or thiophene; _R is optionally selected as hydrogen, alkenyl or alkyl; n=0, 1 or 2; The ruthenium catalyst is [RuCl ₂ (p-cymene)] ₂ , RuCl (p-cymene) (ppy), RuOAc (p-cymene) (ppy) or Ru(MeCN) ₄ (ppy) PF ₆ ; the The ligand is a phenylpyridine compound, the structural formula is selected from One of them; the visible light is blue light; the specific condition is to add chlorinated amide compounds, ruthenium catalyst, ligand, alkali, water and organic solvent in a sealed tube, and react for 48h under an inert gas atmosphere. 2. The method for selective desaturation of inert carbon-carbon bonds to synthesize olefins as claimed in claim 1, wherein the organic solvent is 1,2-dichloroethane, tetrahydrofuran, acetonitrile or dichloromethane. 3. The method for selective desaturation of inert carbon-carbon bonds to synthesize olefins as claimed in claim 1, wherein the post-treatment method is purification by thin layer chromatography, column chromatography or recrystallization. 4. the method for selective desaturation of inert carbon-carbon bond as claimed in claim 3 and synthetic olefin, it is characterized in that, when the method for described aftertreatment is thin-layer chromatography or column chromatography purification method, used developing agent is A mixed solvent of ethyl acetate-petroleum ether; when the method of the post-treatment is the recrystallization purification method, the solvent used is a mixed solvent of dichloromethane-n-hexane.