Enantioselective Synthesis of (R)- and (S)-1-2H-1-Octanol and Their Corresponding Amines

Abstract

Both enantiomers of 1-2H-1-octanol were obtained by the enzymatic reduction of deuterated octanal in the presence of alcohol dehydrogenases (ADH) (ADH-T or ADH-LB) as the biocatalyst in good yield, purity, and enantiomeric excess (>95%). The cofactor nicotinamide adenine dinucleotide phosphate was regenerated by the addition of isopropanol. To simplify the synthetic route, the direct reduction of octanal using the same enzymes and the same cofactor but adding deuterated isopropanol was evaluated. This provided a one-step procedure from a commercially available starting compound to both enantiomers of 1-2H-1-octanol in good yields (>80%) and good enantiomeric excess (∼97%). The (S)-alcohols were converted to their corresponding (R)-amines, which showed ee's around 90%.