A highly selective
asymmetric synthesis of a potent anti-TB drug
(−)-bedaquiline is accomplished using sulfur ylide asymmetric
epoxidation, employing (+)-isothiocineole as an inexpensive and readily
available chiral sulfide. Excellent enantioselectivity (er 96:4) and
diastereoselectivity (dr 90:10) were obtained for the construction
of the key diaryl epoxide, which was subsequently subjected to a highly
regioselective ring opening (96:4). The synthesis was completed in
nine steps starting from commercially available aldehyde in 8% overall
yield.