Oxidative Thioesterification of Alkenes Mediated by 1,3‐Dibromo‐5,5‐dimethylhydantoin and DMSO for the Synthesis of α‐Ketothioesters

Abstract

A simple and mild approach for the synthesis of α‐ketothioesters via 1,3‐Dibromo‐5,5‐dimethylhydantoin (DBH)/DMSO mediated oxidative thioesterification of alkenes has been developed. Various of α‐ketothioesters products were produced in moderate to good yields under metal‐free conditions. And this method features readily available starting materials and broad substrate scope. Moreover, a plausible mechanism was proposed based on the methyl bromide captured experiment.

Recent Advances in the Synthesis and Applications of α‐Ketothioesters

“…Fang, Guo, and co‐workers in 2019 developed a mild 1,3‐dibromo‐5,5‐dimethylhydantoin (DBH, 29 )/DMSO mediated oxidative thioesterification of alkenes 28 (Scheme 13). [42] Different bases were tested and the best results were obtained using 1.0 equivalent of sodium bicarbonate (NaHCO 3 ). The protocol is a versatile approach to access a wide range of α‐ketothioesters 4 ao – 4 at , including aliphatic and heteroaromatic substituted derivatives.…”

“…[7] Later in 2015, Benaglia, Gaggero, and co-workers disclosed a method for the synthesis of α-ketothioesters containing a chiral centre using a cinchona-derived bifunctional catalyst 43 (Scheme 25). [50] The asymmetric conjugate addition of 2-carboxythioester-1,3-dithiane (42) to nitrostyrenes 41 in the presence of 20 mol% of catalyst 43 gave the addition products 44 a-c in moderate to good yields and with enantioselectivities up to 92%. The products 44 thus obtained were quantitatively transformed into α-ketothioesters 4 bh-4 bj via oxidative hydrolysis of 1,3-dithinae to ketone group using N-bromosuccinimide (NBS) in acetone at 0°C, without affecting the stereochemical integrity of the starting materials 44.…”

“…Recently, various other oxidative thioesterification methods from easily available and cheap starting materials such as methyl ketones, alkenes, alkynes, or 2‐oxoaldehydes in the presence of DMSO, thiols, or disulfides have been developed to access α‐ketothioesters with a range of appended functionalities (Section 2.4.) [39–42] . The oxidative thioesterification approach belongs to the most‐studied synthetic methods till date.…”

“…[8,[29][30][31][32][33] Apart from the nucleophilic acyl substitution and Pummerer-type rearrangement, significant progress has recently been made for the synthesis of α-ketothioesters via oxidative thioesterification approach. [34][35][36][40][41][42][43] A major breakthrough in the chemistry of α-ketothioesters was the seminal work by Das and co-workers, [36] who synthesized its unsaturated analogues in moderate to good yields from α,βunsaturated methylketones via oxidative bromination and Kornblum oxidation [37] sequence (Section 2.4.). Dimethyl sulfoxide (DMSO) as a low-toxic and easyto-handle reagent, has been utilized as a source of the pendant sulphur moiety in α-ketothioesters, instead of the thiols.…”

“…Recently, various other oxidative thioesterification methods from easily available and cheap starting materials such as methyl ketones, alkenes, alkynes, or 2-oxoaldehydes in the presence of DMSO, thiols, or disulfides have been developed to access α-ketothioesters with a range of appended functionalities (Section 2.4.). [39][40][41][42] The oxidative thioesterification approach belongs to the most-studied synthetic methods till date. Among other methods, simple aerobic oxidation of α hydroxythioesters, [43][44] goldcatalyzed [45] and electrochemical oxidation [46] of alkynes have been used to access these valuable scaffolds (Section 2.4.).…”