NHC-Catalyzed Synthesis of α-Sulfonyl Ketones via Radical-Mediated Sulfonyl Methylation of Aldehydes

Abstract

An N-heterocyclic carbene (NHC)-catalyzed facile assembly of α-sulfonyl ketones has been successfully developed through a radical-mediated sulfonyl methylation of readily available aldehydes. This protocol involves the effective single-electron transfer reduction of α-iodosulfones by NHC-bound Breslow intermediates, thus allowing a subsequent radical−radical coupling to afford the target compounds. Moreover, the catalytic system was found to be equally effective for difunctionalization of styrenes and 1,3-enynes via a three-component radical relay process.α-Sulfonyl ketones (or β-keto sulfones), as an important type of building block, have been widely applied in synthesizing various organic functional materials and pharmaceuticals (Scheme 1A). 1 In particular, some α-sulfonyl ketones exhibit important biological activities, such as antipyretic and anticholinesterase activity 2 and antibacterial activity, 3 and these compounds have also been used as inhibitors of hydroxysteroid dehydrogenase type I. 4 Thus, substantial effort

N‐Heterocyclic Carbenes (NHCs)‐Catalyzed Coupling Reactions of Aldehydes and Organic Halides

“…In 2021, the group of Ohmiya [8] developed a strategy that crosscoupling between aldehydes 1 and α-bromoesters or αbromoamides 10 generates β-ketocarbonyl compounds 11 with a quaternary carbon center at the α-position (yields up to 97 %), undergoing a pathway of NHCs-catalyzed SET reduction (Scheme 3a). Later, α-sulfonyl ketones 10 was generated by the coupling of aldehydes 1 and α-iodosulfone 13, described by Du's group, [15] using A2 as the catalyst, Na 2 CO 3 as the base in the solvent DMF (Scheme 3b). This reaction system features mild reaction conditions and high compatibility for various substrates (including bioactive fragments of diacetone-D-galactose-derived aldehyde 13 b).…”

Recent advances in ring-opening of cyclobutanone oximes for capturing SO2, CO or O2via a radical process

“…β-Keto sulfones are valuable structural moieties widely found in natural products and functional materials, and as important synthetic intermediates in the synthesis of bioactive molecules and pharmaceutical molecules. 47–49 Very recently, Wei's group reported an iron-catalyzed multi-component reaction employing terminal alkynes 25 , cyclobutanone oximes 1 and eco-friendly sulfur dioxide source Na 2 S 2 O 5 for the synthesis of β-keto sulfones under mild reaction conditions (Scheme 10). 50 In this method, naturally abundant and readily available FeCl 2 was used as the catalyst and additional oxidants and ligands were not required.…”

NHC-catalyzed radical acylation of cycloalkyl silyl peroxides to access 1,6-,1,7-, and 1,8-diketones

“…12 In particular, the enolate form of NHC-bound Breslow intermediates possessing high reductive potential and fast electron transfer properties could match well with radical precursors with certain oxidizing ability, thus allowing radical–radical couplings through a single-electron transfer (SET) process. 13 In line with our interest in NHC radical chemistry, 14 we posited to form the reactive carbonyl-containing alkyl radical Int-1 and NHC-bound ketyl radical Int-2 through a SET process between CSP 1 and the NHC-bound Breslow intermediate formed by the combination of NHC with aldehydes 2 . The subsequent radical–radical coupling between Int-1 and Int-2 may afford the long-chain 1, n -diketones 3 (Scheme 1C).…”