MgI₂-Catalyzed Nucleophilic Ring-Opening Reactions of Donor–Acceptor Cyclopropanes with Indoline-2-thiones

Abstract

MgI2-catalyzed nucleophilic ring-opening reactions of donor–acceptor cyclopropanes with indoline-2-thiones as easy-to-handle sulfur nucleophiles were investigated. A series of functionalized γ-indolylthio butyric acid derivatives were synthesized in good to excellent yields under mild reaction conditions. Furthermore, the thioether functionalized ring-opening products could be transformed to sulfone and methionine analogues.

Synthesis of Indole-Fused Dihydrothiopyrano Scaffolds via (3 + 3)-Annulations of Donor–Acceptor Cyclopropanes with Indoline-2-Thiones

“…1 H NMR (400 MHz, CDCl 3 ): δ 7. 2H),3H),1H),1H),1H),1H),4.53 (dd,J = 12.0,1.8 Hz,1H),4H),3.36 (dd,J = 13.8,1.9 Hz,1H),2.91 (dd,J = 13.8,12.0 Hz, 1H), 1.24 (t, J = 5.3 Hz, 3H), 1.21 (t, J = 5.3 Hz, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ): δ 168. 1, 167.3, 138.3, 138.2, 132.2, 130.7, 129.3, 128.9, 127.8, 121.8, 121.5, 119.6, 111.7, 70.3, 63.5, 63.1, 58.3, 41.3, 41.1, 14.09, 14.05; HRMS: m/z calculated for C 23 H 22 NO 4 SI [M + H] + 536.0391, found 536.0392; IR (neat) (v): 2926(v): , 2852(v): , 1743(v): , 1448(v): , 1254(v): , 1227(v): , 1082indole -4,4(9H)-dicarboxylate (3ab).…”

“…Isolated by chromatography on silica gel (n-hexane/EA = 10/1) 165 mg, 50% yield, brown solid; mp = 124−126 °C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.37−7.34 (m, 2H), 7.31 (d,J = 7.8 Hz,1H),7.21 (d,J = 7.9 Hz,2H),1H),1H),7.06 (d,J = 8.0 Hz,1H),4.49 (dd,J = 12.0,1.9 Hz,1H),4H),3.33 (dd,J = 13.9,2.0 Hz,1H),2.89 (dd,J = 13.8,12.1 Hz, 1H), 2.37 (s, 3H), 1.22−1.17 (m, 6H); ■ ASSOCIATED CONTENT…”

“…In 2020, Namboothiri and his team engineered and characterized the formation of tetrahydrothiopyrano­[2,3- b ]­indoles from (3 + 3)-annulation of nitroallylic acetates and indoline-2-thiones in the presence of base under mild conditions (Scheme b) . While preparing the present manuscript, Jiang et al reported nucleophilic ring-opening reactions of D–A cyclopropanes with indoline-2-thiones in the presence of MgI 2 as a catalyst (Scheme c) . Keeping the potential of indole-fused thiopyrano compounds in mind, we hypothesized the reaction route in which initially DACs will be attacked by indoline-2 thione to open the ring.…”

“…11 While preparing the present manuscript, Jiang et al reported nucleophilic ring-opening reactions of D−A cyclopropanes with indoline-2-thiones in the presence of MgI 2 as a catalyst (Scheme 1c). 12 Keeping the potential of indole-fused thiopyrano compounds in mind, we hypothesized the reaction route in which initially DACs will be attacked by indoline-2 thione to open the ring. Once nucleophilic ring opening is done, the C-center attached to the ester groups needs to change its nucleophilic character to electrophilic character for further cyclization to furnish the indole-fused sulfur-containing six-membered ring.…”

Benzotriazole-Triggered Three-Component Lewis Acid-Catalyzed Ring-Opening 1,3-Aminofunctionalization of Donor–Acceptor Cyclopropanes

“…Functionalized cyclopropanes with donor and acceptor moieties at the vicinal positions, known as donor–acceptor (D–A) cyclopropanes, are valuable three-carbon building blocks. , Using mild Lewis acids, these strained and polarized three-membered rings can be opened up, thus generating 1,3-dipolar intermediates that can be subsequently intercepted with various coupling partners, resulting in versatile (3 + 2), (3 + 3), and (3 + 4) annulation reactions to construct five- to seven-membered rings. , Another class of reactivity is the D–A cyclopropane ring-opening triggered by nucleophiles, and a variety of acyclic molecules can be synthesized using this technique. For instance, diverse heteroatom nucleophiles including amines, thiols, phenols, carbazoles, and carbon nucleophiles can trigger the D–A cyclopropane ring-rupture, leading to the monofunctionalization of the cyclopropane ring.…”