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. 2021 Apr 13;12(18):6429-6436.
doi: 10.1039/d1sc01389k.

Photocatalytic decarboxylative amidosulfonation enables direct transformation of carboxylic acids to sulfonamides

Vu T Nguyen  1 , Graham C Haug  1 , Viet D Nguyen  1 , Ngan T H Vuong  1 , Hadi D Arman  1 , Oleg V Larionov  1
Affiliations

Photocatalytic decarboxylative amidosulfonation enables direct transformation of carboxylic acids to sulfonamides

Vu T Nguyen et al. Chem Sci. .

Abstract

Sulfonamides feature prominently in organic synthesis, materials science and medicinal chemistry, where they play important roles as bioisosteric replacements of carboxylic acids and other carbonyls. Yet, a general synthetic platform for the direct conversion of carboxylic acids to a range of functionalized sulfonamides has remained elusive. Herein, we present a visible light-induced, dual catalytic platform that for the first time allows for a one-step access to sulfonamides and sulfonyl azides directly from carboxylic acids. The broad scope of the direct decarboxylative amidosulfonation (DDAS) platform is enabled by the efficient direct conversion of carboxylic acids to sulfinic acids that is catalyzed by acridine photocatalysts and interfaced with copper-catalyzed sulfur-nitrogen bond-forming cross-couplings with both electrophilic and nucleophilic reagents.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Decarboxylative amidosulfonation as an enabling synthetic tool for the direct conversion of carboxylic acids to sulfonamides.
Fig. 2
Fig. 2. Tricomponent synthesis of sulfonamides and sulfonyl azides by the dual catalytic direct decarboxylative amidosulfonation.
Scheme 1
Scheme 1. Scope of the direct decarboxylative amidosulfonation with O-benzylhydoxylamines. Reaction conditions: carboxylic acid (0.15–0.3 mmol), DABSO (0.33 mmol), A1 (10 mol%), CuF2 (10 mol%) O-benzoylhydroxylamine (0.6 mmol), CH2Cl2 (6 mL), LED light (400 nm).
Scheme 2
Scheme 2. Scope of the direct decarboxylative amidosulfonation of anilines. Reaction conditions: aniline (0.3 mmol), carboxylic acid (0.6–0.75 mmol), CuOTf·½PhMe (10 mol%), A2 (7 mol%), DABSO (0.45 mmol), tBuO2Bz (0.36–0.45 mmol), CH2Cl2 (3 mL), LED light (400 nm). aA1 (7 mol%). bA3 (10 mol%), Cu(acac)2 (10 mol%).
Scheme 3
Scheme 3. Scope of the direct decarboxylative azidosulfonation. Reaction conditions: carboxylic acid (0.3 mmol), copper 2-thiophenecarboxylate (CuTC) (10 mol%), A1 (10 mol%), DABSO (0.45 mmol), tBuO2Bz (0.75 mmol), NaN3 (0.9 mmol), PhCF3/MeCN (3 : 1, 3 mL), LED light (400 nm), 12 h.
Fig. 3
Fig. 3. Direct decarboxylative amidosulfonation and azidosulfonation of natural products and active pharmaceutical ingredients.
Fig. 4
Fig. 4. Computed energy profiles of the acridine catalyst turnover in the sulfinic acid formation and the Cu-catalyzed N-alkyl and N-aryl amidosulfonation and azidosulfonation, ΔG, kcal mol−1.
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