Rhodium-Catalyzed Double Hydroboration of Quinolines

Abstract

Selective double hydroelementation of N-heteroarenes can be one of the most straightforward and atom-economic routes toward dearomatized N-heterocycles bearing a (chiral) sp3 C–E bond (E = B, Si, etc.) at a specific site. Herein, we describe the development of a one-pot, site- and stereoselective borylative reduction of quinolines leading to a series of tetrahydroquinolines that possess an (enantioenriched) C(sp3)–B bond in the 4-position. A cationic Rh precatalyst [Rh(cod)2]OTf with a phosphine ligand DPEPhos enabled the borylative reduction of a range of quinolines with HBpin to provide the C4-borylated tetrahydroquinolines (THQ) in good to high yields under mild conditions. Mechanistic studies elucidated the Rh-mediated stepwise dearomative reduction cascade: (i) moderately regioselective hydroboration of quinoline resulting in a mixture of 1,2- and 1,4-dihydroquinolines (DHQ), (ii) regioselective hydroboration of the 1,2-DHQ intermediate to give the C4-borylated THQ, (iii) slow isomerization of the 1,4-DHQ to the 1,2-DHQ, and (iv) formation of the cationic Rh-quinoline adduct as a catalytic resting species. The C4-selective asymmetric borylative reduction within the cationic Rh/(S)-BINAP system was accomplished albeit with moderate enantioselectivity on average in moderate to good yields. The installed C(sp3)–Bpin unit in the 4-position was transformed to various functional groups through simple organic reactions.