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.

Divergent regioselective Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides

“…Whereas no better results were obtained, and when TfOH was added, the reaction system became messy with partial recovery of the alkene substrate (30%). It was noteworthy that treatment of alkenes bearing other bi-or monodentate auxiliaries rather than AQ amide [58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75] , 4-phenylbutene, or γ-δ unsaturated AQ amide under the conditions A-C all failed to give either coupling or reductive elimination products. The presence of AQ as a bidentate auxiliary could not only simulate the intermolecular reaction as an intramolecular variant to enhance the reactivity of nonactivated olefins, but also stabilize the high-valent copper species via a [5,5]-metallabicyclic intermediate to allow for further hydride elimination or reductive elimination.…”