A Concise, Enantioselective Approach for the Synthesis of Yohimbine Alkaloids

We report a concise, enantioselective
synthesis of the yohimbine
alkaloids (−)-rauwolscine and (−)-alloyohimbane. The
key transformation involves a highly enantio- and diastereoselective
NHC-catalyzed dimerization and an amidation/N-acyliminium
ion cyclization sequence to furnish four of the five requisite rings
and three of the five stereocenters in two operations. This route
also provides efficient access to all four diastereomeric arrangements
of the core stereotriad of the yohimbine alkaloids from a common intermediate.
This platform approach in combination with the ability to access both
enantiomers from the carbene-catalyzed reaction is a powerful strategy
that can produce a wide range of complex alkaloids and related structures
for future biomedical investigations.