Nickel-catalyzed intermolecular oxidative Heck arylation driven by transfer hydrogenation

Abstract

The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the PdII/Pd0/PdII catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking. Herein, we demonstrate that the regioselectivity (γ-selectivity vs. δ-selectivity) and pathway selectivity (hydroarylation vs. oxidative Heck coupling) of a directed Ni-catalyzed alkene arylation can be controlled by judicious tuning of the coordination environment around the nickel catalyst via optimization of an appropriate phosphine ligand and directing group. In this way, the Ni(0)-catalyzed oxidative Heck arylation that relies on transfer hydrogenation of an acceptor olefin is developed with excellent E/Z selectivity and regioselectivity. Mechanistic investigations suggest that the addition of the acceptor is crucial for lowering the energy for carbometalation and for enabling catalytic turnover.

Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines

“…In this respect, advances in nickel-complex-catalyzed hydrocarbonation of olefins have expanded the chemical space of accessible structures and enabled new synthetic disconnections [17][18][19][20][21] . Compared with hydroarylation [22][23][24][25][26][27][28][29][30][31][32][33][34] and hydroalkenylation 26,32,35 , hydroalkylation produces molecules that are richer in sp 3 -hybridized carbon centers and contain more stereogeometric information [36][37][38][39][40][41][42] , a feature that may improve biological activity 43,44 . In the 1990s, Mori disclosed intramolecular C(sp 3 )-C(sp 3 ) bond formation reactions between conjugated dienes and carbonyl groups with catalysis by a nickel hydride complex generated by treatment of Ni(cod) 2 with Et 3 SiH 45 .…”

Low-Valent Tungsten Redox Catalysis Enables Controlled Isomerization and Carbonylative Functionalization of Alkenes

“…1c) with high regioselectivity (31). The development of a W(0)-catalyzed directed migratory carbonylation would complement other substrate-directed tandem alkene isomerization/functionalization reactions, such as oxidative arylation and hydroalkylation catalyzed by nickel (32)(33).…”

Palladium-Catalyzed Regioselective Arylation of Unprotected Allylamines

“… 10 − 13 A powerful approach for the arylation of olefins is the Mizoroki–Heck (MH) reaction, 14 , 15 though internal olefin substrates often require directing groups to achieve reasonable regioselectivity. 16 − 19 In the case of allylamine substrates, protection of the amine has been required ( Scheme 1 a) to achieve these reactions, 20 − 24 and the reactions are limited to a single arylation except in a few circumstances ( Scheme 1 b). 25 − 27 We therefore decided that the direct arylation of unprotected or free cinnamylamines, and subsequently diarylation of terminal allylamines, would provide rapid access to new therapeutic targets which had previously been challenging to directly access via conventional methods.…”