Copper‐Catalyzed Aminothiolation of 1,3‐Dienes via a Dihydrothiazine Intermediate

Abstract

Heteroatom-containing organic molecules are of particular interest to medicinal chemists and materials scientists.Astrategy to reach these architectures via direct difunctionalization of abundant 1,3-dienes is especially attractive. Herein, we describe the development of ar egio-and diastereoselective 1,4-aminothiolation of 1,3-dienes with as ulfur diimide reagent, acopper catalyst, and alkylGrignardreagents. This unique protocol provides remote nitrogen and sulfur functionalities with high levels of stereocontrol. The reaction proceeds via at andem hetero-Diels-Alder cycloaddition of N,N'-bis(benzenesulfonyl)sulfur diimide with 1,3-diene followed by copper-catalyzed Grignardsubstitution. Mechanistic studies support ac opper catalyzed formation of an unprecedented [10-S-4] sulfurane that reductively eliminates to afford a3 ,6-dihydrothiazine,w hich is selectively converted to 1,4aminothiols. Scheme 5. A) Mechanism of aminothiolation of 1,3-dienes. B) Exploration of aryl Grignard scope. Reaction conditions: Dimethyl intermediate 26 (0.2 mmol, 1equiv), THF (0.2 m), cool to À78 8 8C, Ar-MgBr (1 equiv), then 23 8 8Cf or 30 min. [a] Isolated yield.

Metal‐Free, PhI(OAc)2‐Promoted Oxidative C(sp2)−H Difunctionalization: Synthesis of Thioaminated Naphthoquinones

“…We observed that the reaction with benzenethiol, 2 a did not produce the targeted product 6 while reacting with pyrrolidine, the aminated product 7 was formed with 90% yield. With these convincing results, we were interested to perform another reaction by taking the aminated product (7) reacting with benzenethiol, 2 a under the standard condition and interestingly, the desired thioaminated product 4 a was obtained with 81% yield (Scheme 2c). However, the reaction with diphenyl disulfide (8) under the same reaction condition produced no desired product 4 a (Scheme 2d).…”

“…[1][2][3][4][5] According to the recent literature, the construction of CÀ N and CÀ S bond has been achieved through the direct thioamination of alkene, alkyne and aryne systems. [6][7][8][9][10][11][12] In this context, unsaturated dione-based organic molecules have come into consideration in the periphery of the difunctionalization reaction. Particularly, 1,4-naphthoquinones have been utilized for difunctionalization by oxidative coupling with anilines and sulfonyl azide considering only a single CÀ H bond to participate.…”