γ-Lactam derivatives with contiguous multiple stereogenic carbon centers are ubiquitous in physiologically active compounds. The development of a straightforward and reliable synthetic method that affords such chiral structural motifs in a stereocontrolled manner should be thus of importance. The transition-metal-catalyzed [2+2+1] carbonylative cycloaddition of imine, alkene, and carbon monoxide should represent an efficient method for the synthesis of the chiral γ-lactam motif; however, such an asymmetric process has not been developed so far. Recently, we have developed the nickel-catalyzed carbonylative cycloaddition between ene-imines and CO gas, which proceeded in a completely diastereoselective manner to construct a tricyclic γ-lactam motif with two contiguous stereogenic carbon centers. Herein, we demonstrate the first nickel-catalyzed asymmetric carbonylative cycloaddition between ene-imines and CO. In the presence of a catalytic amount of Ni(cod)2 and chiral phosphoramidite L*, the carbonylative cycloaddition between ene-imine 1a and CO proceeded to afford polycyclic γ-lactam 2a as a sole diastereomer with 90% ee (Scheme 1). The synthetic utility of the present nickel-catalyzed process was demonstrated by the first enantioselective synthesis of Strigolactam GR-24 from enantiopure 2a, which was prepared by the present nickel-catalyzed reaction followed by recrystallization. The further synthetic utilities were demonstrated by the derivatizations of 2a into versatile chiral N-heterocycles.

Enantioselective formation of γ-lactams with multiple chiral carbon centers by Ni(0)-catalyzed asymmetric carbonylative cycloaddition

2019 Fall National Meeting

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