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. 25,27 Employing our developed EnT-mediated hydro-fluorosulfonylation conditions (Figure 2C), we turned toward investigating the alkene scope (Figure 6).…”

“…Liao and co-workers applied sulfuryl chloride fluoride under mild photoredox conditions to furnish alkenyl sulfonyl fluorides from alkenes, 23 while alkynes underwent chlorofluorosulfonylation. 24 Very recently, benzimidazolium-based reagents (Figure 1A) were simultaneously uncovered by Wang 25 and Liao 26,27 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 28 or by energy transfer (EnT)mediated decarboxylation of oxime esters.…”

Fluorosulfonyl radicals: new horizons for the synthesis of sulfonyl fluorides

“…Soon after, using the same 1-fluorosulfonyl benzoimidazolium triflate salt as the fluorosulfonyl radical precursor, the Liao group further developed a radical hydro-fluorosulfonylation of alkenes by employing oxygen-doped anthanthrene (ODA) as the photocatalyst and 1,4-cyclohexadiene (1,4-CHD) as a hydrogen donor (Scheme 7). 18 This method enabled the synthesis of various aliphatic sulfonyl fluorides 40 under mild and metal-free conditions, which could be applied to the late-stage functionalization of natural products, peptides and drugs. Moreover, with (TMS) 3 SiH as a hydrogen donor, the application of this photocatalytic system to the radical hydro-fluorosulfonylation of alkynes was also demonstrated, allowing the formation of alkenylsulfonyl fluorides 41 with high Z -selectivity.…”

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

“…As a continuation of our interest in radical fluorosulfonylation, 41,42 herein, we report the development of a radical fluorosulfonylation of alkenes/intramolecular arylation sequence for the synthesis of FSO 2 -functionalzied chromanes (Figure 1C), based on the fluorosulfonyl radical precursor, FABI, newly developed in our laboratory 51,52 with ODA as an organic photoredox catalyst. Notably, both endo and exo cyclization can be adopted to access different structures.…”

“…On the basis of these results and related mechanistic studies in the literature, 49,50 we outline a possible mechanism (Figure 3C). Under blue LED irradiation, the organic photocatalyst (ODA) can be excited [E 1/2 (ODA*/ODA •+ ) = −1.76 V vs SCE] 52 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.…”