JPS62158222A - Production of optically active homoallyl alcohol - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for synthesizing macrolide antibiotics, etc., in high yield and selectively, by reacting a specific aluminum compound with an aldehyde in the presence of a stannous compound and a pyrrolidine compound in an organic solvent. CONSTITUTION:A compound shown by formula I (R<1>-R<5> are H, 1-10C alkyl, aryl or aralkyl) is reacted with a compound shown by formula R<6>-CHO (R<6> is 1-10C alkyl, aryl or aralkyl) in the presence of a compound shown by formula II (X and Y are halogen or sulfonic acid residue) and a compound shown by formula III [R<7> is H or 1-5C alkyl; R<8> and R<9> are 1-10C alkyl, aryl or mutually bonded to give 2-5C alkylene chain; steric configuration of asymmetric carbon shown by * is (S)] in an organic solvent (e.g., toluene, THF or methylene chloride) at -100-25 deg.C to give the aimed compound shown by formula IV. The aimed compound is obtained by a short process in high yield and high selectivity without using an optically active allylating agent which already contain an asymmetric source.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel method for producing optically active homoallyl alcohol.

(Problems to be Solved by the Prior Art and the Invention) The optically active homoallyl alcohol obtained by the present invention is useful as a synthetic unit for organic compounds, and is also useful for the production of macrolide antibiotics such as famycin. Combined i (“J,
Am, 0hern, 8oc, J/02, 7ri62 (lrito) noya iono7a (1onopho
re) Synthesis of antibiotics such as monensin ([J, Am
, Ohem, Soc, J102.2//lr(/
It is used as an important synthetic intermediate in the production of resins and horns.

Conventionally, as a method for producing optically active homoallylic alcohol, an optically active allylporan represented by the following formula (■] is added to an optically active allylporane represented by the following formula (■) -
OHO (11 optically inactive aldehyde compounds (in the formula, R is an alkyl group) are reacted to form a total compound, and then the covalent bond between the oxygen atom and the boron atom in the compound of formula (■) When the bond is cleaved by hydrolysis, the following formula (■S (in the formula, Rfl has the same meaning as above, water has the asymmetric carbon configuration C8) or the optical structure of F, which shows that the configuration is H (IL)) A process is known which consists in producing active homoallylic alcohols (rJ, km, Ohem.

See Soc, Jlor, 20ri2 (/rir3). In this conventional method, the allylation reagent is an optically active allylborane of the formula , since the configuration of the asymmetric carbon of the homoallylic alcohol in the final target product is determined, the optical activity is determined, and thus, the conventional method contains all covalent bonds of the asymmetric source. This requires the use of allylated reagents.

For this reason, it is necessary to prepare in advance the allyl f H reagent in which the asymmetric source is introduced in the conventional method H, (+) described above, and after the reaction (11), the intermediate product with the formula (■
It is necessary to carry out all the reaction operations to remove the chiral source from the fH compound of J, and also to remove the chiral source from the
There are drawbacks such as the need for twice the amount of asymmetric source, the operation is complicated, and the efficiency is low.

(Means to Solve All Problems) The present inventors achieved the following by using an optically active allylation reagent that already contains an asymmetric source as in the above-mentioned conventional method.
In order to develop a method for producing optically active homoallylic alcohol that is easy to operate and efficient, we have conducted extensive research, and as a result, we have used an optically active diamine compound represented by the following formula (fVJ) as an asymmetric source.

An optically inactive allyl f-hyaluminum f-arsenic compound represented by the following formula (I) is used as an allyl f-hyaluminum reactant, and a tin of the formula [phase] containing a stannous atom as the central metal of the coordinate bond is used. Using Compound 16, these three f-H compounds are dissolved in an organic solvent, and when the aldehyde compound described below is further reacted with the solution, an optically active homozygous compound of formula (1) is obtained. We have discovered that allyl alcohol can be selectively produced. Moreover, it was also recognized that the desired homoallyl alcohol could be easily extracted from the reaction solution by extraction with an appropriate organic solvent.

Therefore, the present invention relates to the linear formula (1) (where ul, R2, R3, Ba, and BS may be the same or different from each other, and each of them is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an aryl group) Or an aluminum 16 compound represented by 2 representing an aralkyl group and the following formula (2
) % formula % () (wherein, R represents the number of carbon atoms/, IQ represents an alkyl group, aryl group, or aralkyl group) and an aldehyde f compound represented by the following formula [phase] (wherein, x, yh may be the same or different from each other.

n represents a halogen atom or a sulfonic acid residue) and a stannous compound of the following formula (IVJ (wherein, R represents hydrogen or an alkyl group having carbon number/-j, and R and R may be the same as each other) May be different,
Each represents an alkyl group or an aryl group having 1 to 10 carbon atoms, or R8 and R9 are bonded to each other and carbon e, 2~! The following is characterized by reacting in an organic solvent in the presence of a pyrrolidine compound which may form an alkylene chain and has an asymmetric carbon configuration (S) t-ff shown by *. Formula (V) (In the formula, R1, R2, R3, B6 have the same meanings as above, and the configuration of the asymmetric carbon indicated by * is 几1R21R6
The gist of this invention is a method for producing an optically active homoallylic alcohol represented by (8) or (Kawa) depending on the method.

The alkyl groups of R1, R2, and 3° in the compounds of the general formula (I) and the above may be linear or branched, such as methyl, ethyl, propyl, butyl, and hexyl.

A-/f-loudecyl group is mentioned. B1, B,
2. An example of a case where B5 is an aryl group is phenyl.

A naphthyl group is mentioned, and an example of a case where R', R2, and R3 are a 7ralkyl group is a benzyl group.
Ru. 84. in the compound of general formula (I). The alkyl group of R5 may be linear or branched, and examples thereof include methyl, ethyl, propyl, n-butyl, isobutyl, tertiary butyl, and octyl groups.

As an example, when R4, R, and 5 are 7-aryl groups.

Examples include phenyl and tolyl groups, and examples of aralkyl groups include benzyl groups.

R4 and FL5 are never hydrogen atoms at the same time.

The alkyl group of R6 in the compounds of formula I and Fungi can be straight-chain or branched, examples being:

Examples include methyl, ethyl, hexenyl, and octyl groups. As an example when R6 is an aryl group.

Examples include phenyl, tolyl, methoxyphenyl, nitrophenyl, chlorophenyl, and heptyl groups.

Examples of aralkyl groups include benzyl, 7enethyl, phenyl, propyl or cinnamyl groups.

When X and Y are halogens in the tin f-h compound of the above general formula, examples thereof include chloro, bromo, and fluoro groups, with n-fluoro group being preferred. When X and Y are sulfonic acid residues, for example, methanesulfone) (-8030
H3), trifluoromethanesulfonate (-8030
F5) , ) sylate (-8o306H4-cH3J
.

Benzene sulfonate (-803-06H5) is mentioned.

Examples of the alkyl group represented by 7 in the pyrrolidine compound of the general formula CM) include methyl, ethyl, propyl, and butyl groups, and may be linear or branched. When R and R are alkyl groups, f′L may be linear or branched, and examples of this alkyl group include methyl,
Examples include ethyl and butyl groups. Examples of the alkylene chain formed by R and R bonding to each other include one example. The alkylene chain may be interrupted by a nitrogen atom. An example of R8 and R9 being an aryl group is a phenyl group.

The preparation of compound 16 of general formula (I) is described in the literature "J, Orga
nomet.

It can be produced by the method disclosed in Ohem, J 2J, 02, 70.

For general formulas σm and (■λ f and manufacturing of hardware, ro
hem, Lett, J, /riJJ, 7gg7
It can be manufactured by the method disclosed on page n.

In the method of the present invention, the 16 compound of formula (I), the 16 compound of formula (IVJ), the 16 compound of the weapon, and the 16 compound of formula (IVJ) are reacted with each other. However, preferably, the formula (IV
16 compound of J is added, then the compound of formula (I) is added, and finally the aldehyde of formula (■) is added. Plus a reaction? It is good to do this. The reaction is generally carried out in an organic solvent, such as toluene, hexane, petroleum ether, ether, tetrahydrofuran, salts of himethylene, chloroform.

Examples include carbon tetrachloride and dichloroethane. Preferably, a non-coordinating solvent is used. The type of solvent affects the yield of the desired optically active homoallylic alcohol, so
The choice of solvent is best determined by preliminary tests. The reaction temperature was -700-2J℃, and the reaction time was Ho3~
! It's time.

f H compound GID, (the number of moles used for IVJ is 16 compound (I
), and the number of moles of f arsenic compound used is o3 to 1 mole relative to compound m. It is used in an amount sufficient to completely dissolve the vine and within the range normally used.After the reaction is completed, the desired homoallyl alcohol (V)' is extracted from the reaction solution, and after normal post-treatment, it is distilled or The target compound can be isolated by purification using column chromatography.

In the method of the present invention, the tin atom of the tin compound of formula (2) becomes the center of the coordination bond in a solution dissolved in an organic solvent,
The pyrrolidine compound of formula (IVJ), the aluminum f-hyde compound of formula (I), and the aldehyde compound of formula (ID) coordinate to form a coordination compound represented by the following formula (1). !'L1 then.

The allyl group of the aluminum r arsenium compound approaches and bonds to the aldehyde group carbon of the aldehyde compound (R'0HOJ) in this coordination compound from a certain direction determined by the steric form of the entire coordination compound. It is estimated that by stereoselectively adding allyl alcohol, an optically active homoallylic alcohol is formed.

The method of the present invention consists of allyl aluminum (I) and aldehyde (n).
Optically active homoallyl alcohol is selectively synthesized by a simple operation of reacting the compound surface with the compound (rVJ) all at once in the presence of rVJ.

Compared to the conventional method for producing an optically active form of homoallylic alcohol (1), there is no need to prepare an optically active allylation reagent containing a chiral source (1%), and a general allylation reagent (1) is not required. )t- using optically active homoallyl alcohol (v
) It has the advantage of being able to be completely synthesized, and (after one reaction).

It has advantages such as not requiring any operation to remove the chiral source from the product. The method of the present invention has a short number of steps and high yield.

This is an extremely advantageous method for producing the desired optically active homoallylic alcohol in a highly selective manner.

Hereinafter, the present invention will be explained in detail by showing all examples, but the present invention is not limited to these examples.

Example 1 J 24L p of stannous trifluoromethanesulfonate 8n (0-802-cF5)2 under argon flow
Dissolve q f in methylene chloride and add (S) -/-methyl-2-(piperidinomethyl)pyrrolidine represented by the following formula [in formula (■), R7-methyl group, C13
and R9 combine with each other to form a +C)H29 chain] Glue 7. Add Mg to 2-salt r
Add the solution dissolved in himethylene at N temperature and use the same eccentric position for 3 minutes.
Stir for 0 minutes. Then, cool the mixture to 17t''.

Next, a hismethylene solution of a salt of the following formula (where t-Bu represents an inbutyl group) containing an allyl aluminum t-arsenic metal t-O, OM+7)alf and Iwl were added. The resulting nine mixtures total-7
After stirring at r°C for 30 minutes, add penzaldehyde 42,
A solution of salt f himethylene (2d) containing jav'i was added dropwise.

After reacting for 1 hour at -7t°C, the reaction solution was added with an ammonium solution /jlIE/, /N -HC# /
, 0#! / was added, the temperature was raised to room temperature, and then extracted with methylene chloride (-tsgxg). After drying the extracted fi with anhydrous sulfuric acid), it was isolated and purified by TLC (development #tMn-hexane-ether (7:3)) to obtain the desired homoallylic alcohol of formula 37. -2 Misaki was obtained. Yield: 5'/% The feed configuration of the asymmetric carbon of this compound was (8).

[α] D −32, rill (c 2.4!t, C
6H6) The above homoallyl alcohol compound obtained by all conventional methods (r J, Org, Chem, Jj&, 2
! (a)-α-trifluoromethyl-α-methoxy-phenylacetic acid ester,!
= L7tM% "FNMR is used to determine the optical yield using the following formula. The optical yield is zg% (e, a
,) Deatsutomo.

Similarly to Example 1, formula (1) shown in Table 1 below
Compound 1 The compound of formula (II), the compound of formula (!Il), and the 16 compound of formula (F) are reacted with each other in amounts of t molar ratio shown in Table 1 to obtain homoallylic alcohol of Bacterium nigra. The order in which the compounds are obtained and reacted with each compound is as follows: the tin compound (In') is reacted with the aluminum compound (1), then the pyrrolidine compound (IV) is reacted with the aldehyde compound (in') In the same manner as in Example 1, the tin compound (■) was treated with a pyrrolidine compound (Ink anti-oxidant), and then the aluminum compound (1
) and then reacted with aldehyde P compound (II). The solvent used as the reaction medium was petroleum ether in Example j, and tetrahydrofuran (IHF' in Example 6).
Other than that, methylene chloride (CH2C#2'l
Met. "The reaction temperature when reacting the pyrrolidine compound (fV) was -zs°C in Example 7 and -Jj in Example 1.
The reaction temperature when reacting the Mayu aldehyde compound was all 17t°C,
The reaction time was 1 hour.

Regarding the Kozo formula of the 9%1 compound shown in Table 1, Me is a methyl group, Et is an ethyl group, t-Bu is an isobutyl group, and P
h represents a phenyl group, and O'rf represents a trifluoromethylsulfonic acid residue -0-SO□-CF5.

Claims (1)

[Claims] The following formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R^1, R^2, R^3, R^4, and R^5 are the same as each other) or a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, an aryl group, or an aralkyl group) and an aluminum compound represented by the following formula (I
I) An aldehyde compound represented by R^6-CHO(II) (in the formula, R^6 represents an alkyl group, an aryl group, or an aralkyl group having 1 to 10 carbon atoms) and the following formula (III) ▲ Formula, There are chemical formulas, tables, etc. ▼(III) (In the formula, X and Y may be the same or different, and each represents a halogen atom or a sulfonic acid residue) and the following formula (IV) ▲Mathematical formula , chemical formulas, tables, etc.▼(IV) (In the formula, R^7 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R^8 and R^9 may be the same or different from each other, and each represents an alkyl group or aryl group having 1 to 10 carbon atoms, or R^8 and R^9
may be bonded to each other to form an alkylene chain having 2 to 5 carbon atoms, and the asymmetric carbon configuration represented by * represents (S)) in an organic solvent in the presence of a pyrrolidine compound represented by The following formula (V) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(V) (In the formula, R^1, R^2, R^3, and R^6 have the same meanings as above. and the configuration of the asymmetric carbon indicated by * is R^1
, R^2 and R^6 are (S) or (R)).