Strain-Enabled S-Arylation and S-Alkenylation of Sulfinamides

Abstract

Converting commercially available and affordable chiral sulfinamides to pharmaceutically important chiral sulfoximines via SIV-functionalization is synthetically appealing, however, remains little developed due to the competing N-functionalization pathway. To address this challenge, we disclose a strain-enabled stereospecific and chemoselective S-arylation and S-alkenylation of sulfinamides using arynes and cyclic alkynes. The origin of high SIV-selectivity is elucidated by density functional theory (DFT) calculations, which reveals the potential involvement of a novel concerted mechanism. This method affords unprecedented chemical diversity on groups attached to the nitrogen center (N-R) that is valuable for diversity-oriented drug discovery

Synthesis of Sulfoximines by Copper-Catalyzed Oxidative Coupling of Sulfinamides and Aryl Boronic Acids

“…One challenge in preparing intermediates 5d and 5h was the compatibility of the aniline group during sulfoximine synthesis. A “–NHBoc” motif could hardly be tolerated in previous S-arylation methods using the hypervalent iodine reagent or aryne precursor. , However, aryl boronic acid bearing a para “–NHBoc” motif was commercially available and could be directly converted to the corresponding sulfoximines in satisfactory yield using our method ( 5a , 5e ). Following the conventional N- modification and deprotection, , the target intermediates were obtained in four steps.…”

“…For the preparation of aryl sulfoximines, a copper-catalyzed S-arylation of sulfinamides using hypervalent iodine reagents has been developed (Figure A) . We have also discovered a novel metal-free S-arylation and alkenylation reaction enabled by strain-containing molecules (Figure B) . These two methods successfully addressed the challenge of S/N chemoselectivity using different strategies.…”

“…In addition to the commercially available sulfinamides used above, optically pure sulfinamides with different functional groups could be prepared from reported protocols. For instance, removing the tert- butyl group from the sulfoxmine products obtained in Scheme would give optically pure sulfinamide. ,, These compounds were also studied in our reaction. As shown in Scheme , both electron-rich and electron-deficient aryl sulfinamides reacted with aryl boronic acid 2b to afford the desired diaryl sulfoximines in good yields and optically pure form.…”

Targeted isolation of 1,1‐diphenyl‐2‐picrylhydrazyl inhibitors from Saxifraga atrata and their antioxidant activities

“…Exogenous free radical inhibitors are not synthesized by the human body and must be obtained from external sources, primarily from natural products (NPs) such as vitamins [13], polyphenols, and flavonoids [14]. Some exogenous free radical inhibitors, such as tert-butyl hydroquinone, are artificially synthesized [15]. NPs have long been considered promising exogenous antioxidant candidates [16].…”

Advances and Challenges of Epidemic Outbreaks in the Post-COVID-19 Era in China

“…The total number of intensive care unit beds was 181,000, equating to 12.8 beds per 100,000 individuals. [7] Moreover, the combined expertise and skill of experts and medical staff have been used to coordinate a better response to the current epidemic. Government authorities have approved 13 vaccine candidates for emergency use, including 5 inactivated vaccines, 5 recombinant protein vaccines, and 3 vector-based vaccines.…”