Multicomponent Reductive Cross‐Coupling of an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Diversely Functionalized Sulfones

Abstract

Conventionally, sulfones are prepared by oxidation of sulfides with strong oxidants. Now, a multicomponent reductive cross‐coupling involving an inorganic salt (sodium metabisulfite) for the straightforward construction of sulfones is disclosed. Both intramolecular and intermolecular reductive cross‐couplings were comprehensively explored, and diverse sulfones were accessible from the corresponding alkyl and aryl halides. Intramolecular cyclic sulfones were systematically obtained from five‐ to twelve‐membered rings. Naturally occurring aliphatic systems, such as steroids, saccharides, and amino acids, were highly compatible with the SO2‐insertion reductive cross‐coupling. Four clinically applied drug molecules, which include multiple heteroatoms and functional groups with active hydrogens, were successfully prepared via a late‐stage SO2 insertion. Mechanistic studies show that alkyl radicals and sulfonyl radicals were both involved as intermediates in this transformation.

A palladium-catalyzed cross-electrophile coupling reaction involving sulfur dioxide for the direct synthesis of diversely functionalized sulfones

“…The inherent low reactivity of electrophiles and poor control of cross-coupling selectivity along with the difficulty in the activation of SO 2 bring serious challenges that need to be addressed. A significant advancement was reported in 2020 by Jiang, 14 in which diverse aryl-alkyl sulfones could be effectively synthesized from aryl iodides and alkyl bromides (Fig. 1c).…”

Recent Advances in Asymmetric Organomulticatalysis

“…Thus, it can recognize the non‐ionic nitroolefin 115 [66d–h] through the H‐bond interaction to control the enantioselectivity. The catalyst of 2,6‐lutidine as Brønsted base can deprotonate the acidic nucleophile of thiol 116 , and then leading to realizing the asymmetric sulfa‐Michael addition and affording the desired sufide 117 [66i–t] . The diverse derivatization finally transfers the sulfide 117 to the bioactive molecules of taurine derivative 118 and 4‐monosubstituted β ‐sultam 119 .…”

Catalyst-free photoinduced radical sulfonylation/cyclization of unactivated alkenes toward sulfone-containing quinazolinones

“…In contrast, the radical sulfur dioxide insertion strategy increases the versatility and flexibility in building sulfone-containing compounds due to the atom and step economy of this type of multicomponent coupling reaction and is considered an emerging and powerful technique with great potential. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The radical-induced difunctionalization of alkenes allows for the expedited establishment of two vicinal carbon-carbon and/or carbon-heteroatom chemical bonds with easily accessible feedstocks under mild conditions and has thus attracted a great deal of attention from the synthetic community. [33][34][35][36][37][38][39][40] In this context, remarkable progress have been made in developing sulfonyl radical-initiated alkene difunctionalization by means of a sulfur dioxide insertion process.…”