Photocatalytic Hydrogenation of Quinolines to Form 1,2,3,4-Tetrahdyroquinolines Using Water as the Hydrogen Atom Donor.

The design of a sequential process combining hydrogenation and a subsequent stereomutation is an attractive strategy for the stereoselective reduction of cyclic disubstituted π-systems to access the thermodynamically more stable trans isomer, which would be the minor compound considering a kinetically controlled cis hydrogenation process. Herein, we demonstrate stereoselective photocatalytic phosphine-mediated quinoline reductions with water as the hydrogen atom source under mild conditions to afford the corresponding 1,2,3,4-tetrahydroquinolines with complete selectivity towards reduction of the heteroaromatic part. The method shows broad functional group tolerance and provides access to trans-2,3-disubstituted tetrahydroquinolines with moderate to excellent diastereoselectivity. These trans isomers are not readily obtained using established methods, as transition-metal-catalyzed regioselective quinoline hydrogenations provide the corresponding cis-2,3-disubstituted isomers with high selectivity. Mechanistic studies reveal that the hydrogenation of the 2,3-disubstituted quinolines proceeds through a cascade process comprising an initial cis selective photocatalytic hydrogenation of the heteroarene core of the quinoline, followed by a trans selective photoisomerization.