Green methodology for enzymatic hydrolysis of acetates in non-aqueous media via carbonate salts

Herein we report a new approach to enantiomerically enriched acetates using a lipase-catalyzed hydrolysis in non-aqueous media by alkaline carbonate salts. The use of sodium carbonate in the enzymatic hydrolysis with Candida antarctica lipase B (CAL-B) of racemic acetates shows a large enhancement of the reactivity and selectivity of this lipase. The role of the carbonate salts, the amount and the nature of the alkaline earth metal on the efficiency of this new pathway are investigated. The enzymatic kinetic resolution of acetates 1a–9a, by enzymatic-carbonate hydrolysis under mild conditions is described. In all cases, the resulting alcohols and remaining acetates were obtained in high ee values (up to >99%) while the selectivities reached E >500.

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(S)-(−)-1-Phenylethyl acetateC10H12O2ee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=-136 (c 0.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(+)-1-PhenylethanolC8H10Oee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=+53 (c 0.2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-1-(4-Methoxyphenyl)ethyl acetateC11H14O3ee = 96%. By GC on CHIRALSIL-DEX CB column[α]D20=-13 (c 0.3, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(+)-1-(4-Methoxyphenyl) ethanolC9H12O2ee = 97%. By GC on CHIRALSIL-DEX CB column[α]D20=+40 (c 0.2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-1-(4-Ethoxyphenyl)ethyl acetateC12H16O3ee = 95%. By GC on CHIRALSIL-DEX CB column[α]D20=-110 (c 0.5, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(+)-1-(4-Ethoxyphenyl)ethanolC10H14O2ee = 97.6%. By GC on CHIRALSIL-DEX CB column[α]D20=+41 (c 0.5, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-1-(Naphthalen-2-yl)ethyl acetateC14H14O2ee = 98%. By GC on CHIRALSIL-DEX CB column[α]D20=-110.7 (c 0.12, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(+)-1-(2-Naphthyl) ethanolC12H12Oee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=+38.3 (c 0.25, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-1-(6-Methoxynaphthalen-2-yl) ethyl acetateC15H16O3ee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=-110 (c 0.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(+)-1-(6-Methoxynaphthalen-2-yl) ethanolC13H14O2ee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=+39.8 (c 0.15, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-2,3-Dihydro-1H-indenyl acetateC11H12O2ee = 97%. By GC on CHIRALSIL-DEX CB column[α]D20=-101 (c 0.8, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(−)-IndanolC91H10Oee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=-16 (c 0.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-1,2,3,4-Tetrahydronaphthalen-1-yl acetateC12H14O2ee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=-107 (c 0.7, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(−)-1,2,3,4-Tetrahydronaphthalen-1-olC10H12Oee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=-28 (c 0.5, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(S)-(−)-1-Acenaphthyl acetateC14H12O2ee = 90%. By HPLC on (Chiralcel® ODH) column[α]D20=-78 (c 0.15, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)

(R)-(−)-1-AcenaphthenolC12H10Oee = 98.2%. By HPLC on (Chiralcel® ODH) column[α]D20=-1.4 (c 0.5, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(RFc)-(+)-2-Hydroxymethyl-1-phenylthioferroceneC17H16FeOSee >99%. By HPLC on (Chiralpak® AD) column[α]D20=+56 (c 1, CH2Cl2)Source of chirality: asymmetric catalysisAbsolute configuration: (R)