Nickel-Catalyzed Reductive Cross-Coupling of Aryl Halides with Alkyl Halides

Abstract

The direct reductive cross-coupling of alkyl halides with aryl halides is described. The transformation is efficient (equimolar amounts of the starting materials are used), generally high-yielding (all but one between 55 and 88% yield), highly functional-group-tolerant [OH, NHBoc, NHCbz, Bpin, C(O)Me, CO(2)Et, and CN are all tolerated], and easy to perform (uses only benchtop-stable reagents, tolerates small amounts of water and oxygen, changes color when complete, and uses filtration workup). The reaction appears to avoid the formation of intermediate organomanganese species, and a synergistic effect was found when a mixture of two ligands was employed.

Recent advances in homogeneous nickel catalysis

“…75 By coupling an aryl iodide ( 49 ) and an alkyl iodide ( 50 ) electrophile with NiI 2 ·xH 2 O and a bipyridyl and phosphine ligand, as well as a stoichiometric manganese reducing agent, high reactivity and selectivity for cross-coupled products were observed. Later, a range of aryl bromides and chlorides and alkyl bromides were shown to be reactive with zinc as the reducing agent.…”

Nickel-Catalyzed Reductive Couplings

“…Unlike these in situ nucleophile/electrophile coupling processes, the recent Ni-catalyzed reductive arylation of alkyl electrophiles possesses distinctive mechanisms, which has sparkled important novel dual catalytic arylation/vinylation modes. 1 Ni-catalyzed arylation of primary and secondary alkyl halides Weix first reported a Ni-catalyzed reductive coupling of alkyl and aryl halides in the presence of 10 mol% pyridine using Mn as the reductant, wherein in situ generation of organometallic reagents is not involved (Scheme 14, left) [43]. A wide range of alkyl and aryl halides are suitable under mild reaction conditions.…”

Nickel-catalyzed cross coupling of non-activated alkyl halides: a mechanistic perspective

“…60 A combination of a bipyridine ligand, a bis(phosphine) ligand, and pyridine gave optimized yields. 2 equiv.…”