Direct dehydrogenative alkyl Heck-couplings of vinylarenes with umpolung aldehydes catalyzed by nickel

Abstract

Alkenes are fundamental functionalities in nature and highly useful intermediates in organic synthesis, medicinal chemistry and material sciences. Transition-metal-catalyzed Heck couplings with organic halides as electrophiles have been established as a powerful protocol for the synthesis of this valuable building block. However, the requirement of organic halides and the generation of stoichiometric hazardous halide wastes may cause significant sustainable concerns. The halide-free oxidative Heck alkenylations involving organometallics or arenes as the coupling partners provide a facile and alternative pathway. Nonetheless, stoichiometric amounts of extra oxidant are essential in most cases. Herein, we present a direct dehydrogenative alkyl Heck-coupling reaction under oxidant-free conditions, liberating hydrogen, nitrogen and water as the side products. Excellent regioselectivity is achieved via neighboring oxygen atom coordination. Broad substrate scope, great functional group (ketone, ester, phenol, free amine, amide etc) tolerance and modification of pharmaceutical candidates and biological molecules exemplified its generality and practicability.

C(sp3)−C(sp3) bond formation via nickel-catalyzed deoxygenative homo-coupling of aldehydes/ketones mediated by hydrazine

“…Based on the above experimental results and our previously reported works 34 , 35 , we proposed a plausible reaction mechanism, as depicted in Fig. 5 .…”

“…5 . Initially, the active nickel (II) species A potentially coordinates with hydrazone anion to form nickel (II) complex B , which rapidly releases N 2 gas through Wolff−Kishner reaction-like process and an intramolecular benzyl migration to obtain intermediate C 35 . Next, intermediate C combines with another hydrazone anion to form the intermediate E via the nickel (II) complex D .…”

Emerging Nickel Catalysis in Heck Reactions: Recent Developments

“…Considering the mechanistic point of view, the reaction proceeded through usual oxidative addition of nickel(0) into the weak C-OTf bond of triflates to produce protocol. [42] With the optimal reaction condition the substrate scope were investigated revealing that vinyl arenes 18 containing both electron withdrawing groups (F, CF 3 ) or electron donating groups (Me, Ph, OMe, t Bu, OH, NH 2 ) on addition to hydrazone derivatives 52 yielding the desired Heck product 53 in moderate to excellent yields (Scheme 29). Moreover, alkenes tolerating sensitive functional groups such as amine, ester, hydroxyl, and amide could effective participate in this transformation in presence of organometallic reagent.…”

“…In a recent report Lv et al . discussed halide‐free oxidative Heck alkenylations with excellent regioselectivity in dehydrogenative way of vinyl arenes with aryl aldehydes 49 under nickel‐catalyzed oxidant‐free conditions as strong alternative to common Heck reaction protocol [42] . With the optimal reaction condition the substrate scope were investigated revealing that vinyl arenes 18 containing both electron withdrawing groups (F, CF 3 ) or electron donating groups (Me, Ph, OMe, t Bu, OH, NH 2 ) on addition to hydrazone derivatives 52 yielding the desired Heck product 53 in moderate to excellent yields (Scheme 29).…”

Nickel-catalyzed intermolecular oxidative Heck arylation driven by transfer hydrogenation

“…Despite significant advances during the past several decades 1–10 , Heck-type reactions still suffer from significant limitations, including a difficulty controlling selectivity with internal alkyl-substituted alkenes due to the lack of steric and electronic differentiation in the key migratory insertion step and issues of C=C bond isomerization due to chain-walking 17 . Additionally, though notable exceptions exist 18,19 , oxidative Heck reactions with arylmetal species have traditionally required use of comparatively expensive palladium catalysts with specially tailored reoxidation systems 20–26 . Recently, Zhou reported a highly selective Ni-catalyzed hydroarylation of styrenes and 1,3-dienes with arylboron compounds, which was proposed to proceed via oxidation addition of Ni(O) to an alcohol O–H bond to form a Ni–H species, hydrometallation across the alkene, transmetalation with the organoboron reagents, and C–C reductive elimination (Fig.…”