Reduction of Quinoxalines: A Convergent Disproportionation Reaction

Significance

The authors report an elegant transition metal/Brønsted acid relay catalytic system for the asymmetric reduction of quinoxalines 1, where a convergent disproportionation reaction of the dihydroquinoxaline intermediates 4 is involved. With Ru(II) as the catalyst for the initial reduction of 1 to dihydroquinoxalines 4 with H₂ and phosphoric acid catalyst 3 for subsequent asymmetric disproportionation reactions of 4, tetrahydroquinoxaline products 2 were obtained generally in high yields and enantioselectivities. The detection of dihydroquinoxaline intermediates 4 in the hydrogenation of 1 without the addition of the Brønsted acid suggested that the first hydrogenation process catalyzed by Ru(II) was the rate-determining step. The higher reaction rate of the chiral acid catalyzed reaction (k ₁) compared to the undesired side ­reaction (k ₂) catalyzed by Ru(II) is crucial to the observed high enantioselectivities.