posted on 2019-03-14, 19:43authored byMarie
L. J. Wong, James J. Mousseau, Steven J. Mansfield, Edward A. Anderson
Bicyclo[1.1.1]pentanes
(BCPs), useful surrogates for para-substituted arenes,
alkynes, and tert-butyl groups
in medicinal chemistry, are challenging to prepare when featuring
stereogenic centers adjacent to the BCP. We report the development
of an efficient route to α-chiral BCPs, via highly diastereoselective
asymmetric enolate functionalization. We also describe the application
of this chemistry to the synthesis of BCP analogues of phenylglycine
and tarenflurbil, the single enantiomer of the NSAID flurbiprofen.