Radical Hydro‐Fluorosulfonylation of Unactivated Alkenes and Alkynes

Abstract

Recently, radical fluorosulfonylation is emerging as an appealing approach for the synthesis of sulfonyl fluorides, which are highly in demand in various disciplines, particularly in chemical biology and drug discovery. Here, we report the first establishment of radical hydro‐fluorosulfonylation of alkenes, which is enabled by using 1‐fluorosulfonyl 2‐aryl benzoimidazolium (FABI) as an effective redox‐active radical precursor. This method provides a new and facile approach for the synthesis of aliphatic sulfonyl fluorides from unactivated alkenes, and can be further applied to the late‐stage modifications of natural products and peptides, as well as ligation of drugs in combination with click chemistry. Remarkably, this system could enable the radical hydro‐fluorosulfonylation of alkynes, affording valuable alkenylsulfonyl fluoride products with a rare, high Z‐selectivity, which are normally less stable and more challenging to synthesize in comparison with the E‐configured products.

EnT-Mediated N–S Bond Homolysis of a Bifunctional Reagent Leading to Aliphatic Sulfonyl Fluorides

“…While the synthesis of unsaturated ((hetero)­aryl, alkinyl, alkenyl) sulfonyl fluorides has been extensively studied, the synthesis of aliphatic sulfonyl fluorides with high flexibility of substitution pattern remains underdeveloped. , Employing our developed EnT-mediated hydro-fluorosulfonylation conditions (Figure C), we turned toward investigating the alkene scope (Figure ).…”

“…We further concluded that switching the reactivity mode by introducing a hydrogen atom donor could enable the rapid synthesis of the aliphatic sulfonyl fluorides. Notably, while our studies were underway, Wang and co-workers as well as Song and Liao and co-workers reported the hydro-fluorosulfonylation of alkenes by utilization of benzimidazolium salts as sulfonyl fluoride radical precursors and cyclohexadiene as hydrogen source by photoredox catalysis.…”

“…Liao and co-workers applied sulfuryl chloride fluoride under mild photoredox conditions to furnish alkenyl sulfonyl fluorides from alkenes, while alkynes underwent chloro-fluorosulfonylation . Very recently, benzimidazolium-based reagents (Figure A) were simultaneously uncovered by Wang and Liao , group independently to serve as sulfonyl fluoride radical precursors by photoredox catalysis, enabling the synthesis of alkenyl sulfonyl fluorides and β-alkoxy sulfonyl fluorides, among other functionalities. Weng and co-workers formed carbon-centered radicals by proton-coupled electron transfer (PCET) to amides and intramolecular 5- exo -trig cyclization with alkenes or by energy transfer (EnT)-mediated decarboxylation of oxime esters .…”

Radical Fluorosulfonyl Arylation of Alkenes: Accessing FSO2-Functionalized Chromanes via Formal Endo and Exo Cyclization

“…On the basis of these results and related mechanistic studies in the literature, , we outline a possible mechanism (Figure C). Under blue LED irradiation, the organic photocatalyst (ODA) can be excited [ E 1/2 (ODA*/ODA •+ ) = −1.76 V vs SCE] and then reduce redox-active radical precursor 2a ( E 1/2 = −1.07 V vs SCE) via a single-electron transfer (SET) process. Consequently, a homolytic fission of the N–S bond in 2a′ delivers the desired FSO 2 radicals.…”

“…As a continuation of our interest in radical fluorosulfonylation, , herein, we report the development of a radical fluorosulfonylation of alkenes/intramolecular arylation sequence for the synthesis of FSO 2 -functionalzied chromanes (Figure C), based on the fluorosulfonyl radical precursor, FABI, newly developed in our laboratory , with ODA as an organic photoredox catalyst. Notably, both endo and exo cyclization can be adopted to access different structures.…”