A general method for the synthesis of enantiopure aliphatic chain alcohols with established absolute configurations. Part 2, via catalytic reduction of acetylene alcohol MαNP esters

A general method for synthesizing enantiopure (100% ee) aliphatic alcohols with established absolute configurations has been developed and applied to alcohols CH3(CH2)n–CH(OH)–(CH2)mCH3, the enantiomeric discrimination of which is the most difficult, if m = n + 1 and n is large. Racemic saturated alcohols with short chains could be directly enantioresolved as (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid) esters by HPLC on silica gel, and their absolute configurations were simultaneously determined by 1H NMR diamagnetic anisotropy. However, the application of this powerful MαNP ester method to alcohols with long chains was difficult, because of smaller values of the separation factor α. In such cases, the use of the corresponding acetylene alcohol MαNP esters was crucial. Acetylene alcohol MαNP esters were largely separated by HPLC on silica gel, and their absolute configurations were unambiguously determined by 1H NMR as reported in the Part 1 paper. The MαNP esters obtained with established absolute configurations were catalytically hydrogenated to yield saturated alcohol MαNP esters. It was evidenced that no racemization occurred at the stereogenic center of the alcohol moiety during catalytic hydrogenation, by the coinjection of MαNP esters in HPLC. From the MαNP esters obtained, enantiopure (100% ee) aliphatic chain alcohols with established absolute configurations were recovered. Although the [α]D values of these alcohols were too small for the identification of the enantiomers, it was clarified that the analytical HPLC of MαNP esters is useful for identification in most cases.

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(R)-3-Hexyl (S)-2-methoxy-2-(1-naphthyl)propionateC20H26O3Ee = 100%[α]D24 = −15.6 (c 1.11, CHCl3)Source of chirality: enantioresolutionAbsolute configuration: (R,S) determined by 1H NMR

(S)-3-Hexyl (S)-2-methoxy-2-(1-naphthyl)propionateC20H26O3Ee = 100%[α]D23 = −4.6 (c l.08, CHCl3)Source of chirality: enantioresolutionAbsolute configuration: (S,S) determined by 1H NMR

(R)-4-Octyl (S)-2-methoxy-2-(l-naphthyl)propionateC22H30O3Ee = 100%[α]D24 = −11.3 (c 1.28, CHCl3)Source of chirality: enantioresolutionAbsolute configuration: (R,S) determined by 1H NMR

(S)-4-Octyl (S)-2-methoxy-2-(1-naphthyl)propionateC22H30O3Ee = 100%[α]D24 = −7.1 (c 1.34, CHCl3)Source of chirality: enantioresolutionAbsolute configuration: (S,S) determined by 1H NMR

(R)-9-Octadecyl (S)-2-methoxy-2-(1-naphthyl)propionateC32H50O3Ee = 100%[α]D28 = −5.3 (c 1.22, CHCl3)Source of chirality: enantioresolution of precursorAbsolute configuration: (R,S)

(S)-9-Octadecyl (S)-2-methoxy-2-(1-naphthyl)propionateC32H50O3Ee = 100%[α]D23 = −5.0 (c 1.56, CHCl3)Source of chirality: enantioresolution of precursorAbsolute configuration: (S,S)

(S)-10-Nonacosyl (S)-2-methoxy-2-(l-naphthyl)propionateC43H72O3Ee = 100%[α]D26 = −2.2 (c 1.05, CHCl3)Source of chirality: enantioresolution of precursorAbsolute configuration: (S,S)

(R)-19-Octatriacontyl (S)-2-methoxy-2-(1-naphthyl)propionateC52H90O3Ee = 100%[α]D28 = −2.6 (c 1.20, CHCl3)Source of chirality: enantioresolution of precursorAbsolute configuration: (R,S)

(S)-19-Octatriacontyl (S)-2-methoxy-2-(1-naphthyl)propionateC52H90O3Ee = 100%[α]D24 = −2.4 (c 5.96, CHCl3)Source of chirality: enantioresolution of precursorAbsolute configuration: (S,S)

(R)-4-OctanolC8H18OEe = 100%[α]D35 = −0.50 (ρ 0.819, neat)Source of chirality: precursorAbsolute configuration: (R)

(S)-9-OctadecanolC18H38OEe = 100%[α]D23 = +0.1 (c 6.09, cyclohexane)Source of chirality: precursorAbsolute configuration: (S)

(R)-19-OctatriacontanolC38H78OEe = 100%[α]D53 = −0.038 (σ 0.56, c 1.04, CHCl3)Source of chirality: precursorAbsolute configuration: (R)