Chemoenzymatic method for the preparation of γ-amino alcohols from phenylfuran-based aldehydes; lipase-catalyzed kinetic resolution of β-hydroxy nitriles

The chemoenzymatic preparation of novel enantiopure phenylfuran-based γ-amino alcohols with N-Boc-protection starting from the corresponding aldehydes is described. Enantiopurity (ee 98–99%) is introduced using Thermomyces lanuginosus lipase as the IMMTLL-T1-1500 preparation with β-hydroxy nitriles in an acylation/alcoholysis sequence in tert-butylmethyl ether.

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(R)-3-[5-(3-Chlorophenyl)furan-2-yl]-3-hydroxypropanenitrileC13H10ClNO2Ee = 99%[α]D25=+46.7 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (3R)

(R)-3-[5-(2-Chlorophenyl)furan-2-yl]-3-hydroxypropanenitrileC13H10ClNO2Ee = 99%[α]D25=+44.7 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (3R)

(R)-3-[5-(4-Chlorophenyl)furan-2-yl]-3-hydroxypropanenitrileC13H10ClNO2Ee = 99%[α]D25=+45.5 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (3R)

(R)-3-[5-(4-Bromophenyl)furan-2-yl]-3-hydroxypropanenitrileC13H10BrNO2Ee = 99%[α]D25=+39.4 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (3R)

(R)-3-Hydroxy-3-[5-(4-nitrophenyl)furan-2-yl]-propanenitrileC13H10N2O4Ee = 99%[α]D25=+55.4 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (3R)

(R)-1-[5-(3-Chlorophenyl)furan-2-yl]-2-cyanoethyl acetateC15H12ClNO3Ee = 89%[α]D25=+181.6 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (1R)

(R)-1-[5-(2-Chlorophenyl)furan-2-yl]-2-cyanoethyl acetateC15H12ClNO3Ee = 88%[α]D25=+171.0 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (1R)

(R)-1-[5-(4-Chlorophenyl)furan-2-yl]-2-cyanoethyl acetateC15H12ClNO3Ee = 93%[α]D25=+198.8 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (1R)

(R)-1-[5-(4-Bromophenyl)furan-2-yl]-2-cyanoethyl acetateC15H12BrNO3Ee = 82%[α]D25=+167.4 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (1R)

(R)-1-[5-(4-Nitrophenyl)furan-2-yl]-2-cyanoethyl acetateC15H12N2O5Ee = 93%[α]D25=+221.9 (c 1, CHCl3)Source of chirality: lipase catalysisAbsolute configuration: (1R)

(S)-3-N-Boc-amino-1-[5-(3-chlorophenyl)furan-2-yl]-propan-1-olC18H22ClNO4Ee = 99%[α]D25=+1.4 (c 1, CHCl3)Source of chirality: lipase catalysis/retention of configurationAbsolute configuration: (1S)

(S)-3-N-Boc-amino-1-[5-(2-chlorophenyl)furan-2-yl]-propan-1-olC18H22ClNO4Ee = 98%[α]D25=+0.2 (c 2, CHCl3)Source of chirality: lipase catalysis/retention of configurationAbsolute configuration: (1S)

(S)-3-N-Boc-amino-1-[5-(4-chlorophenyl)furan-2-yl]-propan-1-olC18H22ClNO4Ee = 99%[α]D25=+1.9 (c 2, CHCl3)Source of chirality: lipase catalysis/retention of configurationAbsolute configuration: (1S)

(S)-3-N-Boc-amino-1-[5-(4-bromophenyl)furan-2-yl]propan-1-olC18H22BrNO4Ee = 95%[α]D25=+1.2 (c 2, CHCl3)Source of chirality: lipase catalysis/retention of configurationAbsolute configuration: (1S)