Hydriodic Acid‐Mediated Cyclization of α‐Substituted Secondary 2‐Ethenylbenzamides: Synthesis of 2‐Substituted 2,3‐Dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones and 3,3‐Disubstituted (E)‐1‐(Arylimino)‐1,3‐dihydroisobenzofurans

Abstract

A new and facile method for the preparation of 2-substituted 2,3-dihydro-3,3-dimethyl-1H-isoindol-1-ones 3 and 3,3-disubstituted (E)-1-(arylimino)-1,3-dihydroisobenzofurans 6 has been developed. Thus, treatment of N-alkyl(or aryl)-2-(1-methylethen-1-yl)benzamides 2 with concentrated hydriodic acid (HI) in MeCN at room temperature afforded 3. Similar treatment of N-aryl-2-(1-phenylethen-1-yl)benzamide 5 with concentrated HI at 08 afforded 6.Introduction. -We previously reported a synthesis of 3,3-disubstituted-2,3-dihydro-1H-isoindol-1-ones based on iodoamination of a-substituted secondary 2-ethenylbenzamides, which could be prepared by the reaction of a-substituted 2-lithiostyrenes with isocyanates [1]. As an extension of this work, we herein describe the results of our study on HI-mediated cyclization of a-substituted secondary 2-ethenylbenzamides, which provide concise and efficient synthetic routes to 2-substituted 2,3-dihydro-3,3-dimethyl-1H-isoindol-1-ones and 3,3-disubstituted (E)-1-(arylimino)-1,3-dihydroisobenzofurans depending on the a-substituents of a-substituted secondary 2-ethenylbenzamides. The synthesis of 2,3-dihydro-1H-isoindol-1-ones has recently attracted considerable attention owing to the occurrence of biological active compounds containing this heterocyclic system [2]. A number of methods for the synthesis of this system have been developed [3]. However, most of these methods require several steps and/or involve tedious reaction conditions. On the other hand, a few general methods have been reported for the preparation of 1-(alkyl(or aryl)imino)-1,3-dihydroisobenzofuran derivatives [4]. For example, Kunai and co-workers have reported a synthesis of 3,3-disubstituted 1-(tert-octylimino)-1,3-dihydroisobenzofurans by three-component coupling using arynes and tert-octyl isocyanide [4a] [4c]. This class of molecules may be of biological interest, because a number of molecules, which have a related isobenzofuran-1(3H)-one (phthalide) structure, have exhibited a variety of biological activities [5].

Bidentate cycloimidate palladium complexes with aliphatic and aromatic anagostic bonds

“…18,19 Numerous methods are known for the synthesis of iminoisobenzofurans from readily accessible substrates: (1-alkynyl)benzamides can be cyclized to imidates either by synergetic Pd/Cu catalysis 20 or by electrophilic cyclization. 21,22 The fluoride-induced three component coupling of an isocyanate, a carbonyl compound and a TMS-substituted phenyl triflate was performed; an aryne is the reactive intermediate in this reaction. 23,24 Our attempts to synthesize ortho-oxazolinyl-functionalized triarylmethyl alcohols 2 from 2-bromophenyloxazolines 16, 25 1 following established procedures 26 more or less surprisingly resulted in the isolation of the benzannulated imidoyl lactones 3 in excellent yields (Fig.…”