Chemoenzymatic synthesis of (R)- and (S)-1-heteroarylethanols

A chemoenzymatic methodology for the synthesis of highly enantiomerically enriched (S)- and (R)-1-heteroarylethanols by enantioselective bioreduction with baker’s yeast of the corresponding 1-heteroarylethanones followed by three racemization free chemical steps including a Mitsunobu reaction was developed.

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(S)-1-(Benzo[d]thiazol-2-yl)ethanolC9H9NOSEe = 98% on Astec B-DM GC column[α]D20=-18.5 (c 1, CHCl3)Source of chirality: bioreduction by baker’s yeastAbsolute configuration: (S)

(S)-1-(Benzo[b]thiophen-2-yl)ethanolC10H10OSEe = 99% on on Astec B-DM GC column[α]D20=-21.2 (c 1, CHCl3)Source of chirality: bioreduction by baker’s yeastAbsolute configuration: (S)

(R)-1-(Benzo[b]thiophen-2-yl)ethanolC10H10OSEe = 99% on on Astec B-DM GC column[α]D20=+21.2 (c 1, CHCl3)Source of chirality: bioreduction by baker’s yeastAbsolute configuration: (S)

(S)-1-(Benzo[b]thiophen-3-yl)ethanolC10H10OSEe = 99% on on Astec B-DM GC column[α]D20=-27.1 (c 1, CHCl3)Source of chirality: bioreduction by baker’s yeastAbsolute configuration: (S)

(S)-1-(Benzofuran-3-yl)ethanolC10H10O2Ee = 99% on Astec B-DM GC column[α]D20=-18.95 (c 1, CHCl3)Source of chirality: bioreduction by baker’s yeastAbsolute configuration: (S)