Asymmetric Linear-Selective Reductive Allylic Addition of Imines

Transition metal-catalyzed enantioselective allylic transformations with allylic electrophiles are widely recognized as a reliable method for synthesizing chiral small organic molecules, significantly impacting natural product synthesis and pharmaceutical development. In contrast to well-established linear-selective or branch-selective allylic substitution through the judicious choice of transition metal catalyst, the current allylic addition of carbonyls is primarily focused on the γ-selective allylation. Achieving linearselective allylative addition remains challenging due to the inversion of the six-membered Zimmerman−Traxler type transition state. Herein, we present a cobalt-catalyzed asymmetric reductive α-selective allyl addition of ketimines with the leveraging stereoselective radical addition, allowing expedient access to highly linear-selective homoallylic amino esters with excellent enantioselectivity and high functional group tolerance. This protocol also enables the threecomponent enantioselective reductive allylic addition of α-imino ester with the in-situ formation of allyl radical intermediate by integration of alkyl bromides and dienes, providing a more versatile approach for the assembly of diversified linear-selective homoallylic α- tetrasubstituted amino acid derivatives. Moreover, this reductive catalytic system shows high compatibility towards the cascade asymmetric linear-selective allyl addition and C-N coupling reaction with utilizing diallyl phosphate as a bis-electrophilic reagent, delivering the pipecolinic acid derivatives.