Stereodivergent Synthesis of Substituted N,O-Containing Bicyclic Compounds by Sequential Addition of Nucleophiles to N-Alkoxybicyclolaetams

摘要

The functionalization of amides by the direct addition of two successive nucleophiles to the carbonyl group for the synthesis of cyclic or acyclic amines is a topic of growing interest. Usually the amide is activated as a chloro or triflyloxyiminium intermediate, a thioamide, or an imide before the successive addition of organometallic reagents, hydride, or other nucleophiles. However, the direct addition of Grignard reagents with heating, or organolithium compounds at room temperature, to bicyclic lactams followed by hydride reduction has been reported.' The same sequence with amides or N-alkyl monocyclic lactams is less common but has prece-dent.