Recent Advances in the Synthesis of Cyclic Sulfoximines via C–H Bond Activation

Abstract

Sulfoximines, a ubiquitous class of structural motifs, are widely present in bioactive molecules and functional materials that have received considerable attention from modern organic chemistry, pharmaceutical industries, and materials science. Sulfoximines have proved to be an effective directing group for C–H functionalization which was widely investigated for the synthesis of cyclic sulfoximines. Within the last decade, great progress has been achieved in the synthesis of cyclic sulfoximines. Thus, this review highlights the recent advances in the synthesis of cyclic sulfoximines via the C–H activation strategy and is classified based on the substrate types.

Electrochemical oxidative cross coupling of NH-sulfoximines with disulfides

“…[9][10][11][12][13][14][15][16] NH-sulfoximines as an analogue of sulfones are widely present in many drug molecules, and they can be directly N-H functionalized to synthesize complicated scaffolds with potential applications. [17][18][19][20][21][22][23] In recent years, N-H arylation, alkylation (Scheme 1(Aa)), and removal of SQN-directed groups (Scheme 1(Ab)) of NHsulfoximines under electrochemical conditions have been reported successively. [24][25][26][27][28] For instance, in 2021, Mei's group first developed a Ni-catalyzed electrochemical N-arylation reaction of aryl halides and NH-sulfoximines.…”

Electrochemically Enable N-Sulfenylation/Phosphinylation of Sulfoximines via Oxidative Dehydrocoupling Reaction

“…Sulfoximines moiety are widely in medicinal and agricultural . As a result, increasing attention has been paid to the synthesis of N -substituted sulfoximine derivatives, and significant progress has been achieved in the field. , Among them, N -sulfenylsulfoximines are one important class of sulfoximines. Traditional approaches for the synthesis of N -sulfenylsulfoximines suffered from the usage of hazardous chloride (Scheme a) .…”

Computational Insights into the Formation and Structure of S–N Containing Cyclic Peptides

“…Despite the prevalence of thiols and amines in nature, S–N bonds are among the most uncommon types of inter- or intramolecular cross-links . In contrast, it has long been known that synthetically, such bonds can be formed under relatively gentle conditions and are widespread in industry and pharmaceuticals. − At present, while only approximately 100 S–N containing biomolecules are known, there is increasing evidence for their diverse and biologically important roles. , In fact, such species are now known to play critical roles in the extracellular matrix (e.g., collagen IV), cellular signaling (e.g. S-Nitrosothiols), as neurotoxins (e.g., methionine sulfoximine), anti-inflammatory drugs, or antibiotics .…”

“…These stereogenic centers are underexplored as pharmacophores even though they can significantly increase the structural diversity and complexity of drug candidates . Given the potential chemistry available via S–N bonds, e.g., reversible formation and functionalization, coupled with the biological and pharmaceutical current and potential uses of cyclic peptides, ,, there is a need to understand the factors that may be important for the formation of cyclic peptides via such bonds . These insights would also be important for aiding experimental identification and isolation of such S–N containing macrocyclic species beyond the limited examples so far experimentally known.…”