Exploring the Reactivity of Rigid 1-Azadienes Derived from Methylene γ-Lactams. Applications to the Stereoselective Synthesis of Spiro-γ-Lactams
Adrián López-Francés, Zuriñe Serna-Burgos, Xabier del Corte, Jesús M. de los Santos, Abel de Cózar, Javier Vicario
TL;DR
This paper explores how rigid 1-azadienes from methylene γ-lactams can be used to create spiro-γ-lactams with high stereospecificity.
Contribution
The first example of using methylene-γ-lactams to synthesize spirocycles with four stereogenic centers is presented.
Findings
Rigid 1-azadienes can act as both diene and dienophile in cyclodimerization.
Chiral rigid 1-azadienes enable stereospecific synthesis of spiro-γ-lactams.
A multicomponent reaction efficiently produces the starting 1-amino α,β-unsaturated γ-lactam derivatives.
Abstract
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-electron 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 spiro-γ-lactams 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.
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Taxonomy
TopicsSynthesis of β-Lactam Compounds · Asymmetric Synthesis and Catalysis · Synthesis and Catalytic Reactions