A novel synthetic route to 6‐azabicyclo[3.2.1]oct‐3‐enes via silicon directed N‐Acyliminium chemistry: Synthesis of (±)‐gabaculine

Abstract

AbstractAlkylation of the lithium enolate, derived from 5‐ethoxy‐2‐pyrrolidone 1 (Scheme 1), using alkyl halides containing either the vinylsilane or 2‐propynylsilane moiety, provides substrates 3 for cyclization studies passing through N‐acyliminium intermediates 4 toward the 6‐azabicyclo[3.2.1]‐octanes 5 and 7. These ring‐closure experiments are unsuccessful in the case of vinylsilanes, and an explanation for this failure is presented. Ring closures of 2‐propynylsilanes lead, in high yield, to bicyclic allenes 5, which, in a few steps (ozonolysis, Shapiro reaction), are transformed into 7. This methodology constitutes the basis of a total synthesis of (±)‐gabaculine (10). The synthesis is completed from 52 by lactam hydrolysis and sulfoxide elimination.