Synthesis of Polycyclic Fused Indoline Scaffolds through a Substrate-Guided Reactivity Switch

Abstract

Zn(II)-catalyzed divergent synthesis of functionalized polycyclic indolines through formal [3 + 2] and [4 + 2] cycloadditions of indoles with 1,2-diaza-1,3-dienes (DDs) is reported. The nature and type of substituents of substrates are found to act as a chemical switch to trigger two distinct reaction pathways and to obtain two different types of products upon the influence of the same catalyst. The mechanism of both [4 + 2] and [3 + 2] cycloadditions was investigated and fully rationalized by density functional theory (DFT) calculations.

Hetero-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies

“…A large number of new reviews [ 26 , 27 , 56 , 57 ] and original publications [ 31 , 58 , 59 , 60 , 61 , 62 ], which appeared in the last four years, demonstrates the growing interest in the chemistry of azoalkenes and their applications in hetero -Diels-Alder reactions. The presented study showed important mechanistic aspects and demonstrated that scarcely known 3,6-dihydro-2 H -1,3,4-thiadiazines can efficiently be prepared by regioselective hetero -Diels-Alder reactions of thioketones with in situ-generated azoalkenes, bearing an electron-withdrawing substituent at the terminal N-atom.…”

Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis

“…Using ZnCl 2 as a Lewis Acid catalyst, 1,2-diaza-1,3-dienes 138 can react with indoles 139 at room temperature to give cycloaddition products [ 57 ]. This reaction can follow two reaction pathways to provide two different heterocycles; tetrahydro-1 H -pyridazino-[3,4-b]indoles 140 and tetrahydropyrrolo[2,3-b]indoles 141 ( Scheme 29 ).…”

Syntheses of Heterocycle-2,3-Fused Indoline and Azaindoline ­Derivatives

“…The structure of 1a was determined by 1 H, 13 C, and twodimensional NMR analyses (HMQC, HMBC) in CDCl 3 and DMSO-d 6 . The 1 H and 13 C NMR investigations of 1a suggested the presence of rotamers due to the Boc protecting groups, but equilibrating species were most often distinguished by variable-temperature NMR. The cis-configuration was confirmed by comparison with the H C(2) -H C(3) coupling constant and from the results of an NOE experiment.…”

“…10 Palacios and co-workers reported a [4+2]-cycloaddition between indoles and nitrosoalkenes, 11 and the Larionov group reported the first example of a copper-catalyzed asymmetric [4+2]-cycloaddition of nitrosoalkenes. 12 In 2020, the Favi group developed a Zn(II)-catalyzed [4+2]-cycloaddition of indoles with 1,2-diaza-1,3-dienes, 13 and Li and co-workers reported dearomative [4+2]-annulations of 3-nitroindoles and enals. 14 Although these methods for synthesizing sixmembered-ring-fused indolines are relatively well developed, the range of heterocyclic structures is often limited by hypervalent iodine oxidation.…”