Alkyl Halides as Both Hydride and Alkyl Sources in Catalytic Regioselective Reductive Olefin Hydroalkylation

Abstract

Among the plethora of catalytic methods developed for hydrocarbofunctionalization of olefins to date, reactions that regioselectively install a functionalized alkyl unit at the 2-position of a terminal unactivated C=C bond to afford branched products are scarce. Here, we show that a Ni-based catalyst in conjunction with a stoichiometric reducing agent promote Markovnikov-selective hydroalkylation of unactivated alkenes tethered to a recyclable 8-aminoquinaldine directing auxiliary. These mild reductive processes employ readily available primary and secondary haloalkanes as both the hydride and alkyl donor, obviating the need for additional hydrosilane, acidic or basic additives. Reactions of alkenyl amides with ≥five-carbon chain length regioselectively afforded β-alkylated products through remote hydroalkylation, underscoring the fidelity of the catalytic process and the directing group's capability in stabilizing five-membered nickelacycle intermediates. The operationally simple protocol exhibits exceptional functional group tolerance and is amenable to the synthesis of bioactive molecules as well as regioconvergent transformations.

Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines

“…1a) [36][37][38][39][40][41][42] . In 2020, Koh's group developed an aminoquinaldine-directed hydroalkylation reaction, in which one alkyl halide molecule provides an alkyl motif and another delivers a hydride via β-H elimination 46 . In addition to alkyl halides, imines or aldehyde can also be used as coupling partners for hydroalkylation reactions of tetrafluoroethylene with silanes 47,48 .…”