Synthesis of Polysubstituted Maleimides via Metal-Free Cascade Reaction of Isocyanides and α-Diazoketones

Abstract

In this paper, synthesis of polysubstituted maleimides was described via cascade reaction of isocyanides and α-diazoketones. This strategy features readily available substrates, high atom-economy and metal-free conditions. A variety of valuable polysubstituted maleimides are assembled in good yields.

Catalyst-free formal [4+1]/[4+2] cyclization cascade sequence of isocyanides with two molecules of acylketene formed in situ from thermal-induced Wolff rearrangement of 2-diazo-1,3-diketones

“…Based on the aforementioned results and previous reports [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][57][58][59], a possible reaction mechanism was proposed in Scheme 4. Initially, the thermal-induced decomposition of 2diazo-1,3-diketone 2 leads to the formation of acylketene intermediate Int-I by Wolff rearrangement, followed by the intermolecular nucleophilic attack of isocyanides 1 yielding the highly reactive nitrilium ion intermediate Int-II.…”

“…They can react as versatile C4 synthons with different nucleophiles and dienophiles. In most cases, these reactions give rise to products of formal [4+1] [38][39][40][41][42][43] or [4+2] [44][45][46][47] cycloaddition. In particular, reactions of acylketenes with the C@N double bond of imines leads to derivatives of 1,3-oxazines [48][49][50].…”

Highly diastereoselective cascade dearomatization of 3-(2-isocyanoethyl)indoles with nitrile imines: a facile access to unexpected polycyclic indolines

“…Alternatively, 3-(2-isocyanoethyl) indole, 5 emerged as an extremely appropriate candidate, has been successfully applied in the rapid assembly of numerous potentially bioactive and important indoline alkaloids. In recent years, the dearomative cascade annulation of 3-(2-isocyanoethyl)indole derivatives with Michael acceptors, 6 imines, 7 isocyanates, 8 diazo esters 9 and azomethine imines 10 has been independently developed to build these intriguing polycyclic indoline skeletons (Scheme 1B). However, in some cases, due to high steric congestion, the concise and efficient formation of complex polycyclic scaffolds in one pot remains a challenging task in organic synthesis.…”

“…12 Mechanistically, 3-(2-isocyanoethyl)indole-based cascade reactions generally involve the nucleophilic addition of isocyanides to electrophilic partners, which subsequently underwent an intramolecular dearomative annulation, followed by the trapping of another potential nucleophilic terminus, and eventually facilitated the cascade process (Scheme 1B). [6][7][8][9][10] Accordingly, nitrile imines seem to be particularly promising partners to react with 3-(2-isocyanoethyl)indoles to achieve a novel and challenging cascade cyclization sequence.…”