Diastereoselective Synthesis of Spiro[indoline‐3,7′‐pyrrolo[1,2‐a]azepines] via Sequential [3+2] Cycloaddition and Ring Expansion Reaction

Abstract

Spiro[indoline-3,7'-pyrrolo[1,2-a]azepines] were conveniently synthesized in satisfactory yields and with high diastereoselectivity from three-component reaction of L-proline, isatins and chalcones and sequential reaction with dimethyl but-2-ynedioate or methyl propiolate in refluxing methanol. The ferrocenyl-chalcones and dibenzylideneace-tones were also successfully used in this one-pot two-step reaction to give novel ferrocenyl and styryl-substituted spiro compounds. The reaction mechanism included domino [3 + 2] cycloadddtition reaction of azomethine ylide with chalcone and ring-expansion reaction of in situ generated spiro[indoline-3,3'-pyrrolizine] with electron-deficient alkynes.

One‐Pot Sequential [3+2] Cycloaddition and Ring‐Expansion Reaction for Selective Synthesis of Polycyclic Spirooxindole

“…According to the previously reported one‐pot two‐step reaction conditions of L‐proline, isatin and chalcone, [11c,d] the three‐component reaction of L‐proline 1 , N ‐alkylisatin 2 and o ‐hydroxychalcone 3 was carried out in refluxing methanol for two hours, the expected 1,3‐dipolar cycloaddition product, spiro[indoline‐3,3′‐pyrrolizines], were actually formed in good yields. Without isolation, further reaction with excess amount of methyl propiolate 4 in refluxing methanol for eight hours resulted in the functionalized spiro[chromane‐2,3′‐indoline]‐2′,4‐diones 5 a‐5 h as major products and spiro[chromeno[3,2‐ d ]azocine‐2,3′‐indolin]‐3‐yl)acrylate 6 a‐6 h as minor products (Table 1).…”

“…1 in Scheme 1). On the other hand, the similar ring expansion reaction with methyl propiolate in refluxing acetonitrile afforded hexahydro‐ and octahydropyrrolo[1′,2′:1,2]azocino[4,5‐c]quinolines depending on the N ‐alkyl group in isatins [11d] (Eq. 2 in Scheme 1).…”

Use of Dialkyl Acetylenedicarboxylates in the Multicomponent Synthesis of Heterocyclic Structures

“…. [82] A five-component reaction for synthesis of (5Z, 8Z)-7Hperido[2,3-d]azepine derivatives 130 is reported by Kohestani and co-workers in 2021 by using first step materials such as: isatine 126, dimethyl acetylenedicarboxylate 1, 4-methoxcyphenacyl bromide 67, ammonium acetate 16 and activated acetylenic compounds 129 in present of Fe 3 O 4 /TiO 2 /MWCNT MNCs as an efficient catalyst. (Scheme 54).…”

“…pyrrolo[1,2‐a]azepine is one of the special N‐heterocycle that found in the large group of alkaloids which includes more than one hundred different natural products, for this reason, synthesis of these substances are particularly important. [82] …”

Selective construction of spiro[indoline-3,5′-pyrrolo[3,4-b]azepines] and spiro[indoline-3,3′-pyrroles] via a [4 + 3]/[3 + 2] cycloaddition reaction of α,β-unsaturated aldimines and MBH adducts of isatins

“…1 Thus, the development of effective synthetic protocols for multifunctionalized azepine derivatives has attracted growing interest from synthetic chemists. 2 For this purpose, various efficient synthetic methodologies such as [4 + 3] cycloaddition, 3 [5 + 2] cycloaddition, 4 ring-opening of vinylaziridines 5 and others 6 have been successfully developed. The [4 + 3] cycloaddition reaction has emerged as one of the most powerful strategies for the construction of various azepine systems.…”