A Concise, Enantioselective Approach for the Synthesis of Yohimbine Alkaloids
Eric R. Miller, M. Todd Hovey, Karl A. Scheidt
Abstract
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.