Highly Enantioselective Iridium-Catalyzed Hydrogenation of 2-Benzylquinolines and 2-Functionalized and 2,3-Disubstituted Quinolines

Abstract

The enantioselective hydrogenation of 2-benzylquinolines and 2-functionalized and 2,3-disubstituted quinolines was developed by using the [Ir(COD)Cl](2)/bisphosphine/I(2) system with up to 96% ee. Moreover, mechanistic studies revealed the hydrogenation mechanism of quinoline involves a 1,4-hydride addition, isomerization, and 1,2-hydride addition, and the catalytic active species may be a Ir(III) complex with chloride and iodide.

Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

“…We also revealed that the hydrogenation process involves 1,4-hydride addition to quinoline, isomerization and 1,2-hydride addition, and the catalytically active species may be Ir(III) complex [39].…”

“…In consistency with our former study, the absolute configuration of the product was also determined by the central chirality and 49f), the hydrogenation products with opposite absolute configuration were obtained in moderate enantioselectivity. Considering high enantioselectivity of catalytic system [Ir(COD)Cl] 2 /MeOBiPhep/I 2 , we extended this catalytic system to challenge 2-benzylquinolines 50 and 2-functionalized quinolines 52 [39]. Under the former optimized conditions, all the 2-benzylquinoline derivatives were reduced smoothly to the corresponding 1,2,3,4-tetrahydro-benzylquinolines with excellent enantioselectivities and high yields regardless of the electronic and steric properties of the substituent groups (Scheme 11).…”

“…As summarized in Table 8, a variety of 2-functionalized quinoline derivatives could be successfully hydrogenated [39]. For the substrates bearing alkyl or aryl ketones, the tetrahydroquinoline derivatives were obtained with good to excellent enantioselectivities.…”

“…Imine intermediate G could coordinate with Ir(III)-H species B to form the intermediate H, followed by the insertion and sigma-bond metathesis to release the product 1,2,3,4-tetrahydroquinolines P and regenerate B to complete the catalytic cycle [39]. 335 …”

“…We reasoned that the hydrogenation mechanism of 2,3-disubstituted quinolines was somewhat different from that of 2-substituted quinolines [39]. For the hydrogenation of 2-substituted quinolines, the hydrogenation of C=N bond is the enantioselectivity-control step (Scheme 16, H to I), while the enantioselectivity-control step of the former is the isomerization of enamine to imine combined with the hydrogenation of C=N bond, which is in fact a dynamic kinetic resolution process.…”