Nickel‐Catalyzed Enantioselective Reductive Alkyl‐Carbamoylation of Internal Alkenes

Abstract

Herein, we leverage the Ni-catalyzed enantioselective reductive dicarbofunctionalization of internal alkenes with alkyl iodides to enable the synthesis of chiral pyrrolidinones bearing vicinal stereogenic centers. The application of newly developed 1-Nap Quinim is critical for formation of two contiguous stereocenters in high yield, enantioselectivity, and diastereoselectivity. This catalytic system also improves both the yield and enantioselectivity in the synthesis of α,α-dialkylated γlactams. Computational studies reveal that the enantiodetermining step proceeds with a carbamoyl-Ni I intermediate that is reduced by the Mn reductant prior to intramolecular migratory insertion. The presence of the t-butyl group of the Quinim ligand leads to an unfavorable distortion of the substrate in the TS that leads to the minor enantiomer. Calculations also support an improvement in enantioselectivity with 1-Nap Quinim compared to p-tol Quinim.

Ni-catalyzed carbamoylation of unactivated alkenes for stereoselective construction of six-membered lactams

“…Combined with the above experiments and our previous results, a plausible catalytic cycle could be speculated (Fig. 7c ): 35 Firstly, the low-valent nickel species A undergoes oxidative addition of carbamoyl chloride to form carbamoyl-Ni(II) species B . Then the carbamoyl-Ni(I) C is formed by the reduction of Mn, which then proceeds with an enantiodetermining migratory insertion into alkene to forge the intermediate D .…”

“…2 ). The Quinim ligands ( L1 and L2 ) exploited in our lab 34 , 35 , were first examined, but only trace of target product 3a was obtained with less than 30% ee. To our delight, the corrected GC yield of 3a significantly increased to 76% with the utilization of Quinox L3 36 , 37 , 67 instead of Quinim, though the er value was only 58.5:41.5.…”

Recent Advances in Nickel Catalyzed Asymmetric Acylation Reactions

“…进一步, 陈宜峰课题组 [25] 将烯基底物拓展到 1,6-二 烯结构, 实现了镍催化氨甲酰氯取代的 [26] . 该反应一步构建两个连续的 立体中心, 表现出优秀的产率、对映选择性和非对映选 择性.…”

Ni-Catalyzed Enantioselective Intramolecular Mizoroki–Heck Reaction for the Synthesis of Phenanthridinone Derivatives

“…A second perhaps more surprising deficiency in the recent reports of intramolecular nickel-catalyzed Heck reactions, including alkene difunctionalization, is an example of six-membered ring formation with high levels of enantioselectivity. There is an abundance of reports with excellent enantioselectivity to form five-membered rings, − with indolinone or oxindole structures being the most common product formed by far. In contrast, there is only one recent report with a collection of six-membered substrates with excellent enantioselectivity and two additional reports citing just one successful enantioselective six-membered ring example. , Otherwise, communications to date have reported modest enantioselectivities below 50% enantiomeric excess (e.r.…”