Decarboxylative Sulfinylation Enables a Direct, Metal‐Free Access to Sulfoxides from Carboxylic Acids

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.

Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids

“…We hypothesized that such a tricomponent direct decarboxylative triazolation could be accomplished by a triple catalytic process that entails direct decarboxylative azidation and subsequent cycloaddition with alkynes. However, the combination of the two processes into one multicatalytic process is challenging because of the mismatch between the oxidatively mediated azidation and the oxidant-intolerant Cu I -catalyzed cycloaddition that is instead diverted to a Glaser-type alkyne dimerization. − Additionally, an efficient photocatalytic system would be needed that can both facilitate direct decarboxylation of difficult-to-oxidize carboxylic acids to bypass the typically required preactivation to more reactive carboxylic acid derivatives − and also be compatible with the organoazide- and triazole-forming catalytic cycles. Importantly, the successful development of direct, tricomponent conversion of carboxylic acids to triazoles necessitates a broad-scope, direct decarboxylative azidation of carboxylic acids that is tolerant to oxidation-sensitive processes and is mediated by a simple inorganic azide source.…”

“… 56 Importantly, while the same chemical space can potentially be accessed by a sequence of several reactions, PARSE studies are limited to the comparison of direct transformations, which is in line with the main goal of such studies, that is, to inform and guide the development of more efficient synthetic methodologies for direct functional group interconversions. 58 Additionally, PARSE studies are intrinsically limited to the investigation of the product chemical space that can be accessed by direct transformations from the known reactant chemical space regardless of individual experimental conditions that are used to mediate the transformation. Given the focus on the underlying chemical transformation as a main design feature, PARSE does not provide information on the efficiencies of individual synthetic methods (i.e., specific sets of reaction conditions enabling the transformation), or outcomes of reactions with specific substrates.…”

Exploring the synthetic application of sulfinyl radicals

“…16C). 95 The use of the cross-coupling reaction of the sulfinyl radical and carbon-centered radical in this field allows sulfoxide synthesis to avoid relying on the oxidation of sulfides and provides an alternative route to the preparation of sulfoxides.…”

NIS-initiated photo-induced oxidative decarboxylative sulfoximidation of cinnamic acids

“…3 Visible-light-induced decarboxylative cross-coupling reactions have emerged as one of the powerful synthetic methodologies for various C–C and C-heteroatom bond formations. 4 Cai et al disclosed a decarboxylative cross-coupling reaction of cinnamic acids with sulfonyl hydrazides under visible-light irradiation in the presence of eosin Y, oxygen, and base (Scheme 1a). 5…”

“…1 Photo-induced decarboxylation provides an eco-safe and effective pathway; however, they mostly rely on transition metals or organic dye-based catalysts. 4 As a consequence, many C–C and C-heteroatom bond-forming decarboxylative reactions are still out of reach in conventional chemistry. Considering all these aspects, we aimed to design a photoinduced decarboxylative sulfoximidation of cinnamic acid under metal and base-free conditions.…”