Mechanistic Characterization of (Xantphos)Ni(I)-Mediated Alkyl Bromide Activation: Oxidative Addition, Electron Transfer, or Halogen-Atom Abstraction

Abstract

Ni­(I)-mediated single-electron oxidative activation of alkyl halides has been extensively proposed as a key step in Ni-catalyzed cross-coupling reactions to generate radical intermediates. There are four mechanisms through which this step could take place: oxidative addition, outer-sphere electron transfer, inner-sphere electron transfer, and concerted halogen-atom abstraction. Despite considerable computational studies, there is no experimental study to evaluate all four pathways for Ni­(I)-mediated alkyl radical formation. Herein, we report the isolation of a series of (Xantphos)­Ni­(I)–Ar complexes that selectively activate alkyl halides over aryl halides to eject radicals and form Ni­(II) complexes. This observation allows the application of kinetic studies on the steric, electronic, and solvent effects, in combination with DFT calculations, to systematically assess the four possible pathways. Our data reveal that (Xantphos)­Ni­(I)-mediated alkyl halide activation proceeds via a concerted halogen-atom abstraction mechanism. This result corroborates previous DFT studies on (terpy)­Ni­(I)- and (py)­Ni­(I)-mediated alkyl radical formation, and contrasts with the outer-sphere electron transfer pathway observed for (PPh3)4Ni­(0)-mediated aryl halide activation. This study of a model system provides insight into the overall mechanism of Ni-catalyzed cross-coupling reactions and offers a basis for differentiating electrophiles in cross-electrophile coupling reactions.

The Persistent Radical Effect in Organic Synthesis

“…The stereoconvergence clearly supported the radical nature of the oxidative addition of the active Ni complex into the C alkyl −X bond. In a recent study addressing the oxidative addition of nickel to alkyl‐X, Diao showed that the alkyl radical is generated by halogen atom abstraction by a nickel(I) complex (inner‐sphere electron transfer) …”

“…In ar ecent study addressing the oxidative addition of nickel to alkyl-X, Diao showed that the alkyl radical is generated by halogen atom abstraction by anickel(I) complex (inner-sphere electron transfer). [214] Schley and Fu carried out mechanistic investigations on the enantioconvergent arylation of propargylic bromides and proposed the catalytic cycle depicted in Figure 38. [215] ANi I Br complex reductively cleaves the C À Br bond in the activated halide to generate ap ropargylic Cradical and aN i II Br 2 complex, which is converted by transmetalation with the aryl donor into a[LNi II -Ar]Br complex.…”

Der “Persistent Radical Effect” in der organischen Chemie

“…In aktuellen Studien wird die oxidative Addition von Nickel an Alkyl‐X adressiert. Diao zeigte, dass Alkyl‐Radikale über eine Halogen‐Atom‐Abstraktion durch einen Nickel(I)‐Komplex generiert werden können (intramolekularer Elektronentransfer) …”

“…Diao zeigte,d ass Alkyl-Radikale über eine Halogen-Atom-Abstraktion durch einen Nickel(I)-Komplex generiert werden kçnnen (intramolekularer Elektronentransfer). [214] Schley und Fu führten mechanistische Untersuchungen zur enantiokonvergenten Arylierung von chiralen Propargylbromiden durch und postulierten den in Abbildung 38 dargestellten Katalysezyklus. [215] Ein Ni I Br-Komplex spaltet reduktiv die C-Br-Bindung des aktivierten Halogenids,w odurch ein propargylisches C-Radikal und ein Ni II Br 2 -Komplex generiert wird.…”

Gegensätzliche Reaktionsweisen magnesium‐ und zinkbasierter Germaniumnukleophile in der C(sp3)‐Ge‐Kreuzkupplung mit Alkylelektrophilen

“…[14] In Übereinstimmung mit der großen Mehrzahl nickelkatalysierter Negishi-Kupplungsreaktionen von Alkylhalogeniden [15] ist ein plausibler Ni I /Ni III -Katalysecyclus in den Hintergrundinformationen gezeigt. Die Ringçffnung zu den Alkenregioisomeren 10 j und 11 j trat tatsächlich ein, und das cyclopropylmethylsubstituierte German 8j wurde in geringerer Menge gefunden (vgl.…”