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

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, N-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.