Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Abstract

Catalytic C(sp 3 )−H functionalization has provided enormous opportunities to construct organic molecules, facilitating the derivatization of complex pharmaceutical compounds. Within this framework, direct hydrogen atom transfer (HAT) photocatalysis becomes an appealing approach to this goal. However, the viable substrates utilized in these protocols are limited, and the site selectivity shows preference to activated and thermodynamically favored C(sp 3 )−H bonds. Herein, we describe the development of undirected iron-catalyzed C(sp 3 )−H borylation, thiolation, and sulfinylation reactions enabled by the photoinduced ligand-to-metal charge transfer (LMCT) process. These reactions exhibit remarkably broad substrate scope (>150 examples in total), and most importantly, all of these three reactions show unconventional regioselectivity, with the occurrence of C(sp 3 )−H borylation, thiolation, and sulfinylation preferentially at the distal methyl position. The procedures are operationally simple and readily scalable and provide access to high-value products from simple hydrocarbons in one step. Mechanistic studies and control experiments indicate that the afforded site selectivity is not only relevant to the HAT species but also largely affected by the use of boron-and sulfone-based radical acceptors.

An iron-catalyzed C–S bond-forming reaction of carboxylic acids and hydrocarbons via photo-induced ligand to metal charge transfer

“…As part of our ongoing interest in developing novel photochemical transformations, 16 we herein report an iron LMCT catalytic strategy that allows for the decarboxylative thiolation reaction of alkyl and (hetero)aryl carboxylic acids, as well as C(sp 3 )–H thiolation and sulfinylation of unreactive hydrocarbons. In contrast to our previously developed protocol of C–H thiolation and sulfinylation that utilized sodium sulfinate as the coupling counterpart and identified water as a key determinant of chemoselectivity, 15 this work reveals that the reaction atmosphere (under N 2 or air) results in the formation of two different types of products, thioether and sulfoxide. Furthermore, the photo-induced iron-catalyzed C(sp 3 )–H sulfonyl fluorination reaction has also been established.…”

“…Inspired by our previous work on photo-induced C(sp 3 )–H thiolation and sulfinylation using sodium sulfinate as the coupling counterpart, 15 we wondered whether an air atmosphere could serve as an efficient oxygen source to oxidize the generated thioethers to sulfoxides, thereby providing a novel synthetic route for decarboxylative sulfinylation. 14 b ,17 Regrettably, the decarboxylative sulfinylation reaction of alkyl carboxylic acids failed, probably because the generated alkyl radical species through decarboxylation are highly susceptible to oxidative degradation by atmospheric oxygen.…”

“…Inspired by our previous work, 15 we wondered whether air could serve as an oxygen source to oxidize the generated thioethers to sulfoxides, thereby providing a photochemical protocol for C(sp 3 )–H sulfinylation. To confirm our hypothesis, the reaction of cyclohexane and S -phenyl benzenethiosulfonate ( 2 ) took place under an atmosphere of air.…”

“…Building on previous seminal work 14 and our recent effort on C–S bond construction (Scheme 1a), 15 we hypothesized that the Fe-LMCT strategy could be used to achieve the decarboxylative thiolation reaction for both aliphatic and aromatic carboxylic acids. Additionally, we anticipated that the reaction atmosphere can serve as a distinguishing factor for the chemoselectivity, selectively achieving thiolation and sulfinylation (Scheme 1b).…”

Iron-Catalyzed Photoredox Intermolecular Dearomatization of Benzothiazoles with Alkanes

“…Because iron has the ability to exhibit intense visible-light absorption and ligand-to-metal charge transfer (LMCT), it is a theoretically feasible candidate for the requirement of photoactive metal complexes. The various strategies for using iron as a photoredox catalyst have been developed to achieve C­(sp 3 )–H bond activation − and functionalization of ethane. , In line with our ongoing interests in visible light-induced synthetic reactions, − we envisioned that the FeCl 3 could play a dual role in generating a chlorine radical by LMCT and in achieving dearomatization of substrates as a reducing agent (Scheme c). We disclose herein an efficient dearomatization strategy of benzothiazoles that could offer a novel method for the synthesis of benzothiazoline with stereochemical diversity and multiple functions.…”