Prof. WANG Xiaoming group of the State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry focuses on the study of catalytic systems involving multi-metal species, including the realization of challenging conversions by bimetallic catalysis and bi (multi)-nuclear metal catalysis (Angew. Chem. Int. Ed. 2023, 10.1002/anie.202307973; Angew. Chem. Int. Ed. 2022, 61, e202115497; Angew. Chem. Int.Ed. 2021, 60, 26604; Angew. Chem. Int. Ed. 2021, 60, 17088; ACS Cent. Sci. 2022, 8, 581; J. Am. Chem. Soc. 2021, 143, 11799; ACS Catal. 2021, 11, 13696; Nat. Commun. 2021, 12, 3813, etc.). Recently, they demonstrates the first nickel-titanium bimetallic system catalyzed asymmetric reductive aryl-benzylation of alkenes using benzyl alcohols, affording a series of biologically important benzene-fused cyclic compounds in good yields with high ee values.

Difunctionalization of alkenes can rapidly construct complex molecules, especially, Ni-catalyzed asymmetric reductive dicarbofunctionalization of tethered alkenes is one of the most effective methods for the rapid assembly of various chiral cyclic frameworks. As alcohols are ubiquitous in nature and medicine, the direct use of alcohols as coupling partners via homolytic C-OH bond cleavage remains formidable challenges with great opportunities to achieve new and useful transformations. Moreover, low-valent titanium complexes have been considered particularly effective for radical deoxygenation of free alcohols due to their strong oxophilicity, high reduction potential, and cost-efficiency, which plays an important role in the direct deoxygenation of alcohols. In this context, the combination of inexpensive Ti reagent for direct activation of alcohols with Ni-catalyzed asymmetric reductive difunctionalization of tethered alkenes may offer great opportunities for the synthesis of useful chiral building blocks using free alcohols.

Recently, the WANG group developed an unprecedented nickel-titanium bimetallic system mediated asymmetric reductive aryl-benzylation of alkenes. Using the radicals generated in situ by titanium-mediated homolytic C-O bond cleavage of benzyl alcohols as the key species, this nickel-catalyzed transformation proceeds under mild reaction conditions, with a broad substrate scope, and high tolerance of functional groups, providing easy access to various chiral benzene-fused cyclic compounds including oxindoles, dihydrobenzofurans, tetralins, indane and isochroman bearing an all-carbon quaternary center with enantioselectivities of up to more than 99% ee in one step. The synthetic utility of the protocol was showcased in the late-stage modification of pharmaceuticals and streamlined synthesis of the structural scaffolds of natural products. Preliminary mechanistic investigations suggest that the reaction is most likely to proceed via a Ti-mediated direct homolysis of alcoholic C-O bond, followed by the interception of the benzyl radical with σ-alkyl-Ni(II)X species in Ni-catalyzed asymmetric cross-coupling process.

The research outcome has been reported on (Cell Rep. Phys. Sci. 2023, 10.1016/j.xcrp.2023.101474) and this work was financially supported by China Postdoctoral Science Foundation, National Natural Science Foundation of China, UCAS, Hangzhou Institute for Advanced Study, SIOC and State Key Laboratory of Organometallic Chemistry.

Figure 1. Enantioselective Reductive Aryl-Benzylation of Alkenes by a Nickel-Titanium Bimetallic System (Image by WANG Xiaoming) 

WANG Xiaoming Ph.D.Professor

Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

Ling Ling Road 345 Shanghai 200032 China

Tel: 0086-21-54925578

Email: xiaoming@sioc.ac.cn