Synthesis of enantiomerically enriched (R)- and (S)-benzofuranyl- and benzo[b]thiophenyl-1,2-ethanediols via enantiopure cyanohydrins as intermediates

The chemoenzymatic synthesis of highly enantiopure (R)- and (S)-benzofuranyl- and benzo[b]thiophenyl-cyanohydrins and their chemical transformation into the corresponding heteroaryl-1,2-ethanediols is described.

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(S)-2-(Benzofuran-2-yl)-2-hydroxyacetonitrileC10H7NO2Ee = 99% on Chiralpak IA HPLC column[α]D25=+55.7 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (S)

(S)-2-(Benzo[b]thiophen-2-yl)-2-hydroxiacetonitrileC10H7NOSEe >99.5% on Chiralcel OJ-H HPLC column[α]D25=+27.9 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (S)

(R)-2-(Benzofuran-3-yl)-2-hydroxyacetonitrileC10H7NO2Ee = 99% on Chiralcel IA HPLC column[α]D25=+40.5 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)

(R)-2-(Benzo[b]thiophen-3-yl)-2-hydroxiacetonitrileC10H7NOSEe >99.5% on Chiralpak IB column[α]D25=+51.5 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)

(S)-(Benzofuran-2-yl)(cyano)methyl acetateC12H9NO3Ee = 98% on Chiralpak IA HPLC column[α]D25=-54.9 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (S)

(S)-(Benzo[b]thiophen-2-yl)(cyano)methyl acetateC12H9NO2SEe = 98% on Chiralcel OJ-H HPLC column[α]D25=-30.8 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (S)

(R)-Benzofuran-3yl)(cyano)methyl acetateC12H9NO3Ee = 98% on Chiralpak IA HPLC column[α]D25=+11.9 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)

(R)-(Benzo[b]thiophen-3-yl)(cyano)methyl acetateC12H9NO2SEe = 97% on Chiralpak IB HPLC column[α]D25=+24.8 (c 1, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)