Evaluation of Amino Substituents as Nucleofugal Controllers of Regioselectivity and as Chelate Modulators of Stereoselectivity in Squarate Ester Cascades.

TLDR: In this article, the tandem addition of an alkenyllithium reagent and a 2-lithioally-lamine to squarate esters has been systematically examined, and the effect of the sequencing of this twofold addition has been investigated.

Abstract: The tandem addition of an alkenyllithium reagent and a 2-lithioallylamine to squarate esters has been systematically examined. The effect of the sequencing of this twofold addition has been investigated. The extent to which the amino group is eliminated was found to be dependent on the structural features of the companion nucleophile. Also assessed was the comparative ease with which the amino and methoxy groups experience competitive β-elimination from the highly reactive, medium-ring dianionic intermediates. Attempts were made to curtail the level of competing 1,4-addition, and success was achieved by increasing the effective size of the O-alkyl groups in the squarate ester. The highly stereocontrolled transformations described represent a notably direct means for producing highly fused polycyclic compounds. Mechanistic considerations surrounding these reactions, which are characterized by an impressive enhancement of molecular scaffolding, are discussed.