Citation: Xiao Li, Li Jiaheng, Wang Ting. Visible-Light-Induced N-Radical Directed Remote Functionalization of sp³ C-H Bonds[J]. Acta Chimica Sinica, ;2019, 77(9): 841-849. doi: 10.6023/A19050183 shu

Visible-Light-Induced N-Radical Directed Remote Functionalization of sp³ C-H Bonds

Xiao Li ^a,, ,
Li Jiaheng ^b ,
Wang Ting ^b,,

a.
Biogen, 115 Broadway, Cambridge, Massachusetts 02142, United States
b.
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, New York 12222, United States

Corresponding author: Xiao Li, xiao.221@buckeyemail.osu.edu Wang Ting, twang3@albany.edu
Received Date: 15 May 2019
Available Online: 14 September 2019

Figures(21)

The selective functionalization of unactivated sp³ carbon-hydrogen (C-H) bond is an attractive strategy in modern organic transformation. The hydrogen atom transfer (HAT) catalysis has recently shown its advances in remotely selective activation of an inert C-H bond with great functional group compatibility, generating new carbon-carbon (C-C) bonds and carbon-heteroatom (C-O, C-N, C-X) bonds. Therefore, the remote sp³ C-H functionalization has become an intensively investigated research area, drawing extensive attention in synthetic community. Particularly, the 1, 5-hydrogen atom abstraction of nitrogen radicals, the key step of the Hoffman-L ffler-Freytag (HLF) reaction, has been widely applied in the preparation of heterocycles. Comparing to the well-studied area of nucleophilic N-species, N-centered radical based reactions are still underdeveloped. The limited utility is partially due to the required use of hazardous radical initiators, elevated temperatures, or high-energy UV irradiation for the generation of N-radicals. Recently, visible-light photoredox catalysis has been leading efficient accesses to Nitrogen-radicals under mild conditions. The visible-light-induced nitrogen radical formation has also stimulated the development of the remote sp³ C-H functionalization by photoredox catalysis. The classic HLF reaction requires pre-functionalization at N-center in the substrate to promote the formation of N-radical. Recently, a direct N-H single electron transfer (SET) oxidation was realized by photoredox catalysis in Knowles and Rovis's group, generating N-radicals efficiently. The processes significantly simplified the preparation of the HLF reaction substrates and broaden the application of this classic reaction. In addition, the visible-light-induced nitrogen radical-directed reaction on modified imines provided possibilities for the remote sp³ C-H functionalization of ketones, as ketone is the product of imine hydrolysis. Moreover, the application of chiral Lewis acid catalysis combined with visible-light photoredox catalysis enabled the asymmetric alkylation of the unactivated remote sp³ C-H position, which achieves both regioselective and stereoselective functionalization. In conclusion, this strategy takes advantage of mild generation of N-radicals upon visible-light excitation. Subsequent 1, 5-hydrogen atom transfer (1, 5-HAT) and intermolecular radical coupling would realize the remote functionalization of unactivated sp³ C-H bonds. The strategies have been successfully applied in remote C(sp³)-H amidation, fluorination, chlorination, iodination, alkylation, vinylation, allylation, oxygenation, thioetherification, cyanation and alkynylation. In this review, we focus on visible-light-induced nitrogen radical directed functionalization of remote sp³ C-H bonds, summarized the methodologies, and briefly reviewed their synthetic applications in pharmaceuticals and natural products.
- visible-light,
- radical,
- remote functionalization
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沈阳化工大学材料科学与工程学院沈阳 110142

Visible-Light-Induced N-Radical Directed Remote Functionalization of sp3 C-H Bonds

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通讯作者: 陈斌, bchen63@163.com

Visible-Light-Induced N-Radical Directed Remote Functionalization of sp³ C-H Bonds