Exploring the Reactivity of Rigid 1-Azadienes Derived from Methylene γ-Lactams. Applications to the Stereoselective Synthesis of γ-Spirolactams.

A study on the reactivity of rigid 1-azadienes derived from methylene γ-lactams is reported. Through the functionalization of 1-amino α,β-unsaturated γ-lactam derivatives, easily available from a multicomponent reaction of amines, aldehydes and pyruvates it is possible to in situ generate rigid 1-azadienes locked by a γ-lactam core. The 4π-system of those rigid 1-azadienes can behave as both diene and dienophile species, through a spontaneous cyclodimerization reaction, or exclusively as dienes or dienophiles if they are trapped with imines or cyclopentadiene, respectively. The use of chiral rigid 1-azadienes as dienophiles in the cycloaddition reaction with cyclopentadiene leads to the formation of γ-spirolactams bearing four stereogenic centers in a highly stereospecific manner, reporting the first example of the use of methylene-γ-lactams in the synthesis of spirocycles.