A palladium-catalyzed aryl C-H bonds activation/acetoxylation reaction utilizing a bidentate system has been explored. This transformation has been applied to a wide array of pyridine and 8-aminoquinoline derivatives and it exhibits excellent functional group tolerance.

A series of C 3 *-TunePhos chiral diphosphine ligands has been successfully applied in the iridium-catalyzed enantioselective hydrogenation of quinolines, and this methodology provided an efficient access to a variety of optically active tetrahydroquinolines with up to 93% ee. Furthermore, attempts on the asymmetric hydrogenation of quinoline N-oxide are also discussed.Keywords: asymmetric catalysis; enantioselectivity; hydrogenation; iridium; quinolines The direct catalytic asymmetric hydrogenation of quinolines constitutes the most convenient route to enantiomerically pure tetrahydroquinolines, [1] which are not only useful synthetic intermediates [2] but also structural moieties in alkaloids which are natural products and biologically active compounds.[3] The first example of asymmetric hydrogenation of quinolines was reported by Zhou [4a] and co-workers, and some progresses has been achieved thereafter. [4][5][6] However, the challenges of developing easily accessible, air-stable, chiral ligands and their application in the direct asymmetric hydrogenation of highly substituted quinolines still remain.In previous communications, we have developed a practical and convenient synthetic route to prepare a series of air-stable, modular, biaryl chiral diphosphine ligands C 3 *-TunePhos (Scheme 1).[7] These ligands were designed to achieve superior enantioselectivities for asymmetric hydrogenations utilizing the highly modular nature of their unique steric and electronic properties and they have been demonstrated to be highly effective in the hydrogenation N-substituted allylphthalimides, [7g] b-keto esters [7h] and unfunctionalized ketones.[7i] Chan et al. demonstrated the catalytic capability of (S),A C H T U N G T R E N N U N G (S,S)-1b for the iridium-catalyzed reduction of some heteroaromatic compounds, [7j] however, hard modifications on P-aryl groups restrict their potential applications, since for atropisomeric biaryldiphosphines, a small variation of the dihedral angle of the ligands can have a significant impact on the reactivity and selectivity of the reaction. Thus, to screen the catalytic performance of C 3 *-TunePhos families and illustrate their potential utilities, we summarized our efforts in the iridium-catalyzed asymmetric hydrogenation of highly substituted quinoline derivatives.Our initial study began with hydrogenation of 2-methylquinoline 1a as the model substrate and a brief screening of the performance of different catalysts.

Indene derivatives including an allene functional group are readily prepared in moderate to excellent yields with high regioselectivity under very mild reaction conditions by the Pd/C-catalyzed reaction of propargylic compounds. The resulting products can be further elaborated using Pd-catalyzed annulation reactions.