Catalyst- and Silane- Controlled Enantioselective Hydrofunctionalization of Alkenes by TM-HAT and RPC Mechanism

Abstract

The catalytic enantioselective synthesis of tetrahydrofurans, found in the structures of many biologically active natural products, via a transition-metal-catalyzed hydrogen atom transfer (TM-HAT) and radical-polar crossover (RPC) mechanism is described. Hydroalkoxylation of non-conjugated alkenes proceeded efficiently with excellent enantioselectivity (up to 97:3 er) using a suitable chiral cobalt catalyst, <i>N</i>-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, and a diethylsilane. Surprisingly, absolute configuration of the product was highly dependent on the bulkiness of the silane. Mechanistic studies suggested a HAT mechanism and multiple enantiodetermining steps via an organocobalt(III) intermediate. DFT calculations suggested the presence of a cationic organocobalt intermediate, and that a critical factor of the enantioselectivity is the thermodynamic stability of the organocobalt(III) intermediate.

Cobalt-Catalyzed Intermolecular Markovnikov Hydroamination of Nonactivated Olefins: N2-Selective Alkylation of Benzotriazole

“…Co–H complex D reacts with the olefin substrates 1 through the HAT mechanism to afford branched alkylcobalt­(III) intermediate E regioselectively. The cationic cobalt­(III) complex C generated earlier goes back to the cobalt­(II) catalytic cycle via oxidation of alkylcobalt­(III) E to cationic alkylcobalt­(IV) complex F . , Finally, an S N 2-like displacement of F with silylated-BT G takes place to give the hydroamination product 3 and regenerate cobalt­(II) catalyst A .…”

Synthesis and Mechanistic Interrogation of Ginkgo biloba Chemical Space en route to (–)-Bilobalide

“…This discouraging selectivity exposed the inherent limitation of MHAT reactions: substrate dependent stereoselectivity in almost all cases. 58 Solvent screens were possible using cobalt catalysis, 59 but Mn and Fe catalysts typically required an alcoholic solvent to function. Our lab found that these catalysts required alcohol because the standard reductant, PhSiH3, performed poorly compared to its mono-alcoholysis product, isopropoxy(phenyl)silane, a highly efficient reductant that functions in numerous solvents.…”

Catalytic Direct Cyclization of Alkenyl Thioester

“…Previously, our laboratory reported that the addition of an N -fluoropyridinium salt to the TM-HAT cobalt catalysis gave rise to a radical-polar crossover (RPC) mechanism that generated a formal cationic species, enabling the functionalization of alkenes with a nucleophile under nearly neutral conditions . Thus, our original plan for hydrothiolation was to use a thiol group as a nucleophile.…”