Recent Advances in Polychloromethylation Reactions

Abstract

Molecules with di‐ or trichloromethyl group are widely existed in natural products and man‐made structures that represent special activities in pharmaceuticals and agrochemicals. Besides, polychloromethyl‐containing compounds are also high valuable intermediates in organic synthesis and also can be used as functional materials. Therefore, significant efforts have been made toward the incorporation of polychloromethyl groups into certain structures. In this field, a variety of polychloromethyl reagents, such as CH2Cl2, HCCl3, CCl4, TMSCCl3, TMSCCl2H, etc. have been utilized as the di‐ or trichloromethyl sources toward polychloromethylated structures through radical, nucleophilic, and other reaction patterns. In this review, we summarized and discussed the recent achievements in the synthesis of polychloromethylated compounds, mainly focused on the employment of different polychloromethyl reagents. Most of the works we investigated were reported after 2010. Mechanism discussions and outlooks were also given.

Recent advances in C–H functionalization of 2H-indazoles

“…In light of the relatively mild reaction conditions and high atom economy, radical reactions have become very popular for the construction of carbon–carbon bonds and carbon–hetero bonds, and have been successfully utilized in the total synthesis and late-stage modification of natural products. 25…”

Visible light-mediated polychlorination of alkenes via the dichloromethyl radical generated by chloroform and chlorides

“…3 Moreover, chloroform and chlorides are commercially available bulk chemicals, and are the ideal chlorination sources for polychlorination of alkenes. 4…”

“…The generality of this catalytic platform was further evaluated by developing a series of new chlorides toward the synthesis of polychloroalkanes. 4 Deuterium was readily incorporated into the products by using commercially available CDCl 3 ( 32 ). 11 Meanwhile, α-chlorinated esters, hexachloroacetone, trichloroacetonitrile, hexachloroethane and tetrachloromethane were all competent chloride agents and provided the target products in respectable yields ( 33–37 ), which demonstrated the excellent functional group tolerance in the presence of the photocatalyst Ir(ppy) 3 .…”

Metal-free polychloromethyl radical-initiated cyclization of unactivated N-allylindoles towards pyrrolo[1,2-a]indoles

“…2 As a result, the development of convenient protocols for the formation of useful structures with polychloromethyl groups is an important research topic. 3,4 Dichloromethane and chloroform are common feedstocks in the laboratory and are usually used as solvents in organic reactions. Nevertheless, they are undeniably ideal di- and trichloromethyl radical precursors.…”

“…Nevertheless, they are undeniably ideal di- and trichloromethyl radical precursors. 4 In this area, Li, Liu, Loh, Zhao and others have achieved the di- and/or trichloromethylation of substituted alkenes for the construction of many structures with diversity and complexity. 5 Our group also described the di- and trichloromethylation of unactivated alkenes for the construction of heterocyclic compounds.…”