Photocatalytic Hydrogenation of Quinolines to Form 1,2,3,4‐Tetrahdyroquinolines Using Water as the Hydrogen Atom Donor
Jingjing Zhang, Nico Spreckelmeyer, Jessika Lammert, Maxim‐Aleksa Wiethoff, Matthew J. Milner, Christian Mück‐Lichtenfeld, Armido Studer
Abstract
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.