Enantioselective Synthesis of Polycyclic γ‑Lactams with Multiple Chiral Carbon Centers via Ni(0)-Catalyzed Asymmetric Carbonylative Cycloadditions without Stirring

γ-Lactam derivatives with multiple
contiguous stereogenic
carbon centers are ubiquitous in physiologically active compounds.
The development of straightforward and reliable synthetic routes to
such chiral structural motifs in a stereocontrolled manner should
thus be of importance. Herein, we report a strategy to construct polycyclic
γ-lactam derivatives that contain more than two contiguous stereogenic
centers in an enantioselective as well as atom-economic manner. Moreover,
we have achieved the first enantioselective synthesis of strigolactam
derivative GR-24, a racemic variant of which is a potential seed germination
stimulator and plant-growth regulator. A key of the procedure presented
here is a nickel(0)/chiral phosphoramidite-catalyzed asymmetric [2+2+1]
carbonylative cycloaddition between readily accessible ene-imines
and carbon monoxide, which proceeded enantioselectively to furnish
up to 90% ee (>99% ee after recrystallization). The results of
mechanistic
studies, including the isolation of a chiral heteronickelacycle, support
that the enantioselectivity on the two contiguous carbon atoms of
the γ-lactams is determined during the oxidative cyclization
on nickel(0).