The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data‐guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides. The reaction is facilitated by a kinetically favored sulfoxide formation from the intermediate sulfinyl sulfones, despite the strong thermodynamic preference for the sulfone formation, unveiling the previously unknown and chemoselective radicalophilic sulfinyl sulfone reactivity.
Functional group divergence and the structural basis of acridine photocatalysis revealed by direct decarboxysulfonylation
The reactivity of the sulfonyl group varies dramatically from nucleophilic sulfinates through chemically robust sulfones to electrophilic sulfonyl halides—a feature that has been used extensively in medicinal chemistry, synthesis, and materials science, especially as bioisosteric replacements and structural analogs of carboxylic acids and other carbonyls. Despite the great synthetic potential of the carboxylic to sulfonyl functional group interconversions, a method that can convert carboxylic acids directly to sulfones, sulfinates and sulfonyl halides has remained out of reach. We report herein the development of a photocatalytic system that for the first time enables direct decarboxylative conversion of carboxylic acids to sulfones and sulfinates, as well as sulfonyl chlorides and fluorides in one step and in a multicomponent fashion. A mechanistic study prompted by the development of the new method revealed the key structural features of the acridine photocatalysts that facilitate the decarboxylative transformations and provided an informative and predictive multivariate linear regression model that quantitatively relates the structural features with the photocatalytic activity.
more »
« less
- NSF-PAR ID:
- 10335970
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 13
- Issue:
- 14
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 4170 to 4179
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
more » « less
Abstract The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data‐guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides. The reaction is facilitated by a kinetically favored sulfoxide formation from the intermediate sulfinyl sulfones, despite the strong thermodynamic preference for the sulfone formation, unveiling the previously unknown and chemoselective radicalophilic sulfinyl sulfone reactivity.
-
null (Ed.)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.more » « less
-
Recently, dual catalytic strategies towards the decarboxylative elimination of carboxylic acids have gained attention. Our lab previously reported a photoredox/cobaloxime dual catalytic method that allows the synthesis of enamides and enecarbamates directly from N ‐acyl amino acids that avoids the use of any stoichiometric reagents. Further development, detailed herein, has improved upon this transformation’s utility and further experimentation has provided new insights into the reaction mechanism. These new developments and insights are anticipated to aid in the expansion of photoredox/cobalt dual catalytic systems.more » « less
-
Direct installation of the sulfinate group by the functionalization of unreactive aliphatic C–H bonds can provide access to most classes of organosulfur compounds, because of the central position of sulfinates as sulfonyl group linchpins. Despite the importance of the sulfonyl group in synthesis, medicine, and materials science, a direct C(sp 3 )–H sulfination reaction that can convert abundant aliphatic C–H bonds to sulfinates has remained elusive, due to the reactivity of sulfinates that are incompatible with typical oxidation-driven C–H functionalization approaches. We report herein a photoinduced C(sp 3 )–H sulfination reaction that is mediated by sodium metabisulfite and enables access to a variety of sulfinates. The reaction proceeds with high chemoselectivity and moderate to good regioselectivity, affording only monosulfination products and can be used for a solvent-controlled regiodivergent distal C(sp 3 )–H functionalization.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D2SC00789D
