Synthesis of Enantiopure 3-Butyn-2-ol

The methyl and ethynyl residues of 3-butyn-2-one (23a) show similar steric demands, making it difficult for reducing reagents to distinguish between the two enantiofacial sides of the substrate. Thus, all methods for reducing 23a fail to afford the enantiopure alcohol 24 [42]. 

The synthesis of enantiomerically pure (S)-3-butyn-2-ol [(S)-24j was achieved via CPCR-catalyzed reduction by introducing a silyl group with an aromatic substituent into the substrate (compound 23c) [41]. 

When recLBADH was tested with n-alkyl ethynyl ketones it was observed that the preferred stereochemistry of the resulting propargylic alcohol depends on the 

All of these oxidoreductases reduce aromatic and aliphatic a-chloropropargyhc ketones (27a-27c) with high activity. a-Bromopropargylic ketone 27d is also accepted as a substrate however, the enzymatic activity of TBADH and recLBADH decreases, probably for steric reasons. Due to the low solubility of substrate 27a about 25% of a short-chained alcohol was added. The large excess of short-chained alcohol shifted the substrate/product equilibrium toward the desired propargylic alcohol 28a, resulting in almost quantitative conversions with high total turnover numbers (TTN) of the cofactor. 

millimolar quantities of substrate 27a were converted using as little as 0.005 mol% cofactor and small amounts of enzyme (100 U recLBADH per g substrate 200 U HLADH per g substrate, respectively). The analytically pure products (S)- and (R)-28a were obtained easily by extraction in an isolated yield of 95%. HPLC analysis revealed 99% conversion and, additionally, only a single enantiomer could be detected (ee 99%). 

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