Highly enantioselective synthesis, crystal structure, and circular dichroism spectroscopy of (R)‐bambuterol hydrochloride

The present article describes the asymmetric synthesis of (R)-bambuterol hydrochloride based on 1-(3,5-dihydroxyphenyl)ethanone as starting material, which was esterified by dimethylcarbamic chloride, and brominated by copper (II) bromide. Then the carbonyl group was reduced efficiently using (−)-B-chlorodiisopinocamphenylborane [(−)-DIP-chloride™] as an asymmetrical reducing agent. Followed by epoxide ring closure with NaOH and ring expansion with tert-butylamine led to the desired product (R)-bambuterol with e.e. up to 99%. The optical properties and absolute configuration of (R)-bambuterol hydrochloride were further investigated using circular dichroism spectroscopy and X-ray single crystal analysis. Chirality, 2008. © 2008 Wiley-Liss, Inc.