Selective Cascading Hydroboration of N-Heteroarenes via Cobalt Catalysis

Abstract

Selective cascading hydroelementation of N-heteroarenes represented by pyridines can provide diverse accesses to not only dihydro products but also tetrahydro products and piperidines bearing an sp(3) C-E bond (E = B, Si, etc.). Herein, we describe the Co-catalyzed cascading hydroboration of quinolines and pyridines. A precatalyst Co(acac)(2) with a (PN)-N-boolean AND ligand (R-Fc-PHOX; R = Bu-t, Ph, or Pr-i) enabled stepwise hydroboration of quinolines with HBpin (1 or 3 equiv) to exclusively give 1,2-DHQ and C4-borylated tetrahydroquinolines in high efficiency (TON up to 2000/[Co] in a gram scale and TOF up to 500/h). A similar system but using a monodentate phosphine ligand efficiently catalyzed the regio- and stereoselective double hydroboration of pyridines to furnish a range of 1,3-diboryl-1,2,3,4-tetrahydropyridines, which were in situ hydrogenated to the corresponding piperidines bearing an sp(3) C-B bond beta to the nitrogen atom. Experimental mechanistic studies on the Co-catalyzed hydroboration of quinoline suggested a range of insights as follows: (1) A precursor of an active ((PN)-N-boolean AND)Co hydride species is ((PN)-N-boolean AND)Co(acac)(2), which is involved in the catalyst initiation step with an induction period. (2) The first hydroboration phase is highly 1,2-selective. (3) C(sp(3))-B bond formation in the second hydroboration phase is the turnover-limiting step of the overall catalytic process. (4) The cascading hydroboration of quinolines is under kinetic differentiation.