Synthesis of Functionalized Thieno[2,3-b]indoles via One-Pot Reaction of Indoline-2-thiones with Morita–Baylis–Hillman and Rauhut–Currier Adducts of Nitroalkenes

Abstract

A straightforward protocol for the synthesis of functionalized thieno[2,3- b ]indoles by base-mediated [3 + 2]-annulation of indoline-2-thione with Morita–Baylis–Hillman and Rauhut–Currier adducts of nitroalkenes is described. Complete regioselectivity, broad substrate scope, and mild reaction conditions make this strategy very valuable. Moreover, the thieno[2,3- b ]indoles comprising functional groups such as hydrazine and ketoalkyl moieties are amenable for further synthetic elaboration.

Recent advances in the synthesis of thienoindole analogs and their diverse applications

“…Mane et al 52 also reported an alternative efficient approach for the synthesis of thieno[2,3- b ]indole derivatives. They treated substituted RC adduct 78 with N-protected indoline-2-thione 79 in K 2 CO 3 (1.0 eq.)…”

“….9 One-pot approach for synthesizing thieno[2,3-b]indole starting from indoline-2-thiones and nitroalkene-based adducts Mane et al52 reported a novel approach for the synthesis of thieno[2,3-b]indoles via the base-assisted[3 + 2]annulation of indoline-2thione involving nitroalkene adducts, i.e., Morita-Baylis-Hillman (MBH)53,54 76 and Rauhut-Currier (RC)55 78 adduct. The a-hydrazino-a,b-unsaturated nitroalkene intermediate was synthesized in excellent yields from imidazole or DMAP directed Morita-Baylis-Hillman reaction of nitroalkene and azodicarboxylates 56.…”

Construction of Indole‐Fused Heterocycles Starting from 2‐Thioxoindolines, Iminoindolines, and Their Derivatives

“…Namboothiri and co‐workers utilized indoline‐2‐thiones 58 to participate the base‐mediated [3+2] annulations with Morita‐Baylis‐Hillman (MBH) and Rauhut‐Currier adducts of nitroalkenes. The resulting indole‐annulated thiophenes 122 and 124 bearing hydrazine, ketoalkyl, and other functional groups provided opportunities for further synthetic applications (Scheme 32a) [47] . Subsequently, the same group reported a formal [3+3] cyclization of indoline‐2‐thiones 58 and MBH acetate 125 in the presence of DBU.…”

“…The resulting indole-annulated thiophenes 122 and 124 bearing hydrazine, ketoalkyl, and other functional groups provided opportunities for further synthetic applications (Scheme 32a). [47] Subsequently, the same group reported a formal [3 + 3] cyclization of indoline-2thiones 58 and MBH acetate 125 in the presence of DBU. The functionalized tetrahydrothiopyrano [2,3-b] indoles 126 were obtained in high yields (72%-94% yields) with good diastereoselectivities (60:40 to > 95:5 dr, Scheme 32b).…”

Synthesis of Densely Substituted Sulfonylfurans and Dihydrofurans via Cascade Reactions of α-Functionalized Nitroalkenes with β-Ketosulfones

“…In particular, nitroalkene-derived secondary MBH acetates have been employed primarily as 1,2-bielectrophiles by us and others for the synthesis of fused and functionalized heterocycles using various 1,3-binucleophiles. − These include O-heterocycles such as furans and pyrans using 1,3-dicarbonyls/phenols; N-heterocycles such as pyrroles, imidazoles, imidazopyridines, picolinate, diazepines, and indolizines using 1,3-dicarbonyls, amidines, 2-aminopyridines, sulfamidate imines, thiourea, and 2-mercaptopyridne, respectively; S-heterocycles, for example, benzimidazothiazines using 2-mercaptobenzimidazole; as well as other multiheteroatom-containing ones, for example, benzoxacinones using 2-aminophenol. Similarly, reactions of α-hydrazinonitroalkenes with 1,3-binucleophiles such as phenols/naphthols and 1,3-dicarbonyls for the synthesis of (dihydro)­furans, as well as with thioindoles for the synthesis of thienoindoles, have been reported. The 1,2-bielectrophilic reactivity of α-bromonitroalkenes with 1,3-binucleophiles such as 1,3-dicarbonyls and amidines, respectively, has been exploited for the synthesis of dihydrofurans and imidazoles …”