Alkyl halides as both hydride and alkyl sources in catalytic regioselective reductive olefin hydroalkylation

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

Xianxiao Chen


Scholarcy highlights

  • 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
  • The abundance, low cost and distinct reactivity profiles of alkenes have enabled these feedstock molecules to be widely utilized in olefin functionalization reactions for various chemical synthesis applications
  • Disubstituted/trisubstituted alkenes and primary haloalkanes through a Mn/Ni dual catalytic metal-hydride hydrogen atom transfer approach, or with olefins linked to a tridendate directing group and 1,3-dicarbonyl nucleophiles using a Pd-based catalyst
  • There is compelling motivation to develop a complementary catalytic regime that accomplishes efficient and branched-selective hydroalkylation of unactivated acyclic olefins with exceptional control of regioselectivity in the presence of commonly occurring functionalities
  • Attempts to carry out reductive hydroalkylation using neopentyl bromide as alkyl donor and isopropyl bromide as hydride donor gave the desired hydroalkylation adduct 9w in 32% yield, along with side products derived from dialkylation with neopentyl bromide as well as reductive hydroalkylation with isopropyl bromide. β,γ-Unsaturated amides with 1,2disubstitiuted C=C bonds underwent reaction to form the corresponding β-alkylated products, but those with 1,1-disubstituted and trisubstituted olefins were ineffective substrates
  • Γ,δ-unsaturated amides bearing terminal and internal C=C bonds were found to participate in remote hydroalkylation with primary and secondary haloalkanes, affording products 18a–e in 47–82% yield as single β regioisomers through single double-bond migrations
  • To shed light on the importance of the alkyl halide partner in our catalytic system, we carried out deuterium labeling studies with 7a in the presence of two equivalents of d-20 under the standard reaction conditions

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