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) sp 3 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(sp 3 )−B bond in the 4position. 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 1,2and 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(sp 3 )−Bpin unit in the 4-position was transformed to various functional groups through simple organic reactions.

Cobalt‐Catalyzed Bis‐Borylation of Quinolines: The Importance of the Cobalt Triplet State

“…Finally, the 2-methylquinolines, also called quinaldines, work very smoothly in our conditions at room temperature, whereas using Park's rhodium complex required an increase of the temperature. [17] This result proves that the first hydroboration is not sensitive to the steric hindrance, contrary to our previously published hydrosilylation. [12] Thus, quinaldines 1 s, 1 t, 1 u, 1 v, 1 w were selectively converted into the desired products without formation of side-products and borylated tetrahydroquinolines 5 s-5 w were isolated in yield range of a 46-67 %.…”

“…During our investigation Park reported an elegant work based on a similar strategy using a rhodium catalyst with an excess of pinacolborane. [17] Herein we describe a sustainable cascade consisting of a bis-borylation of quinolines using the simple well-defined low valent cobalt complex Co-1 at low temperature in a short reaction time with no excess of pinacol borane.…”

Cobalt-catalyzed double hydroboration of pyridines

“…Mechanistic studies have revealed critical steps of catalyst and substrate activations and deep insight into the coordination chemistry at cobalt. 26–28 Structural variation of the modular 2-pyridonate ligand enabled high activities of the iso-propyl derivative. The presumably formed cobalt( ii ) hydride complex Co2b underwent disproportionation to give cobalt( iii ) hydride complex Co6 that was found to be catalytically active.…”

“…The more challenging double hydroboration of pyridines to tetrahydropyridines, however, has remained mostly unsuccessful. Double hydro-boration of quinolines was achieved both in the presence of catalytic amounts of B(C 6 F 5 ) 3 , 25 with Rh 26 or Co 27 catalysts. To the best of our knowledge, there is only a single report on the catalytic double hydroboration of pyridine ( Scheme 1c ).…”