Microwave-Assisted Tandem Cross Metathesis Intramolecular Aza-Michael Reaction: An Easy Entry to Cyclic β-Amino Carbonyl Derivatives

摘要

We have developed the first cross metathesis intramolecular aza-Michael tandem reaction, catalyzed by a Hoveyda —Grubbs second generation catalyst (Ⅱ)/BF_3·OEt_2 system, that allows rapid access to protected 2,5-substituted pyrrolidine and 2-substituted piperidine heterocyles with excellent overall yields. Microwave irradiation effectively accelerates the tandem process, producing an inversion of the selectivity when α-substituted amines were used as starting materials. These β-amino carbonyl units are very interesting building blocks for the synthesis of several alkaloids. In addition, the tandem protocol constitutes one of the few intramolecular aza-Michael reactions of Cbz-protected amines reported in the literature, thus becoming a straightforward methodology to access such compounds. New applications of this methodology are currently under study.