Combined lipase-catalyzed resolution/Mitsunobu esterification for the production of enantiomerically enriched arylalkyl carbinols

Several arylalkyl carbinols [1-indanol, 1-tetralol, 1-phenylethanol, 1-(1-naphthyl)ethanol, 1-(2-naphthyl)ethanol, 1-(4-methoxyphenyl)ethanol, 1-acenaphthenol] were deracemized through sequential combinations of lipase-catalyzed resolution and Mitsunobu inversion. The corresponding (R)-acetates were obtained in 72–83% yield and 89–99% ee.

Seven other arylalkyl secondary alcohols were obtained as their (R)-acetates in 70–83% yield and 89–99% ee.Figure optionsDownload as PowerPoint slide

(S)-(+)-1-IndanolC9H10OEe >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+16.7 (c 1, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(+)-1,2,3,4-Tetrahydro-1-naphthalenolC10H12OEe >99% by HPLC on (Chiralcel® OB-H) column[α]D20=+28.1 (c 2, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(−)-1-(2-Naphthyl)ethanolC12H12OEe >99% by HPLC on (Chiralcel® OD-H) column[α]D20=-36.5 (c 1, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(−)-1-(6-Methoxy-2-naphthyl)ethanolC13H14O2Ee >99% by HPLC on (Chiralcel® OD-H) column[α]D20=-36.4 (c 0.8, EtOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(−)-1-(1-Naphthyl)ethanolC12H12OEe >99% by HPLC on (Chiralcel® OD-H) column[α]D20=-66.5 (c 1, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(+)-1-AcenaphthenolC12H10OEe >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+1.4 (c 2.6, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(−)-1-PhenylethanolC8H10OEe >99% by HPLC on (Chiralcel® OB-H) column[α]D20=-41.5 (c 0.8, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-(−)-1-(4-Methoxyphenyl)ethanolC9H12O2Ee >99% by HPLC on (Chiralcel® OB-H) column[α]D20=-43.5 (c 0.7, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: S

(R)-(+)-Indan-1-yl acetateC11H12O2Ee >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+110.1 (c 2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1,2,3,4-Tetrahydro-1-naphthalenol acetateC12H14O2Ee >99% by HPLC on (Chiralcel® OB-H) column[α]D20=+112.8 (c 2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1-(2-Naphthyl)ethyl acetateC14H14O2Ee >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+110.2 (c 1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1-[2-(6-Methoxynaphthyl)]ethyl acetateC15H16O3Ee >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+110 (c 1, EtOH)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1-(1-Naphthyl)ethyl acetateC14H14O2Ee >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+49.5 (c 1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1-Acenaphthylenol-1,2-dihydro acetateC14H12O2Ee >99% by HPLC on (Chiralcel® OD-H) column[α]D20=+85.9 (c 2.4, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1-Phenylethyl acetateC10H12O2Ee >99% by HPLC on (Chiralcel® OB-H) column[α]D20=+135.9 (c 1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R

(R)-(+)-1-(4-Methoxyphenyl)ethyl acetateC11H14O3Ee = 91% by HPLC on (Chiralcel® OB-H) column[α]D20=+123.6 (c 1.2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: R