Nickel-catalyzed allylic carbonylative coupling of alkyl zinc reagents with tert-butyl isocyanide

Abstract

Transition metal-catalyzed carbonylation with carbon nucleophiles is one of the most prominent methods to construct ketones, which are highly versatile motifs prevalent in a variety of organic compounds. In comparison to the well-established palladium catalytic system, the nickel-catalyzed carbonylative coupling is much underdeveloped due to the strong binding affinity of CO to nickel. By leveraging easily accessible tert-butyl isocyanide as the CO surrogate, we present a nickel-catalyzed allylic carbonylative coupling with alkyl zinc reagent, allowing for the practical and straightforward preparation of synthetically important β,γunsaturated ketones in a linear-selective fashion with excellent trans-selectivity under mild conditions. Moreover, the undesired polycarbonylation process which is often encountered in palladium chemistry could be completely suppressed. This nickel-based method features excellent functional group tolerance, even including the active aryl iodide functionality to allow the orthogonal derivatization of β,γ-unsaturated ketones. Preliminary mechanistic studies suggest that the reaction proceeds via a π-allylnickel intermediate.

Nickel‐Catalyzed Allylic Substitution Reactions: An Evolving Alternative

“…[25] Interestingly, Qu, Chen and coworkers demonstrated an elegant use of tert-butyl isocyanide as a CO surrogate in the Nicatalyzed allylic carbonylative Negishi coupling between allylic acetate and alkyl zinc reagents to furnish β,γ-unsaturated ketones under mild conditions (Scheme 12). [26] This process is highly regio-and chemoselective, and avoids the parasitic formation of undesired alkene isomerization and poly-carbonylation products. Preliminary mechanistic control experiments indicated the intermediacy of a π-allyl-Ni species in the catalytic cycle.…”

Quinim Ligand-Enabled Ni-Catalyzed Asymmetric 1,2-Carbamoyl-Alkylation of Unactivated Alkenes

“…该类化合物的手性合成传统上依赖 于步骤繁琐的手性辅基策略, 近期张万斌 [2] 和丁奎岭 [3] 课题组分别报道了不对称氢化的策略构建其中一类 α-苄基取代的 γ-内酰胺, Cramer 课题组 [4] 报道了镍催化的 不对称氢胺甲酰策略构建其中一类 α-甲基取代的 γ-内 酰胺, 然而通用的不对称催化策略到目前为止仍然没有 实现. 华东理工大学化学与分子工程学院陈宜峰和曲景 平团队 [5] 致力于烯烃的双官能团化, 在他们课题组发展 的系列镍催化羰基化反应基础上 [6] , 通过新型手性配体 的理性设计, 发展一类全新的手性 Quinim 配体骨架, 从 廉价易得的高烯丙胺衍生的胺酰氯出发, 通过镍催化还 原偶联策略, 成功实现了烯烃不对称胺甲酰基-烷基双 官能团化反应 [7]…”

Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes

“…As a catalyst complementary to palladium, the use of nickel as an inexpensive catalyst in such processes has recently received much attention, especially in carbonylation reactions involving a C­(sp 3 ) fragment . To avoid the formation of deactivated nickel/carbonyl species such as Ni­(CO) 4 in the presence of excess CO, pioneering studies by Gosmini and Hu have demonstrated that, in the presence of zinc reductant and cobalt or nickel catalyst, , ethyl chloroformate can generate CO in situ and is a safe and effective surrogate for CO.…”