Michael addition of a-azido ketones on iminocoumarin derivatives: an efficient access to new functionalized azido chromenes Thelagathoti Hari Babu, Jayabal Kamalraja, Doraiswamy Muralidharan, Paramasivan T. Perumal ⇑ Organic Chemistry Division, Central Leather Research Institute (CSIR), Adyar, Chennai 600 020, India article info Article history: Received 28 April 2011 Revised 18 May 2011 Accepted 22 May 2011 Available online 6 June 2011 Keywords: Michael addition a-Azido ketones Azido chromenes Triazolyl chromenes abstract A facile one-pot synthesis of functionalized azido chromenes was achieved by Michael addition of a-azido ketones on iminocoumarin derivatives obtained from salicylaldehydes and malononitrile. Syn- thesized azido chromenes were successfully transformed into triazolyl chromenes by the [3+2] cycload- dition reaction. Ó 2011 Elsevier Ltd. All rights reserved. a-Azido ketones 1 are a synthetically valuable group of azides that exhibit double reactivity in C–C bond formation. The electro- philic carbonyl function provides a target for the attack of carba- nions leading to adducts such as compounds 2 and the chemistry has been utilized by Langer et al. 1 (Scheme 1). On the other hand, a-azido ketones possessing an a-hydrogen show enhanced C–H acidity due to the anion stabilizing effect of the azido group. The controlled generation of carbanions 3 followed by trapping with various carbon electrophiles results in the formation of aldol-type products 4 (Scheme 1). a-Azido ketones represent useful precursors of the synthetically important 1,2-amino alcohols, 2 2-azido alcohols, 3 a-amino ke- tones 4 by the reduction process. The reaction of phenacyl azides with trivalent phosphorous compounds (phosphines, phosphites, etc.) leads to iminophosphoranes which upon hydrolysis provides amines. 5 Addition of carbanion of a-azidoacetophenone to highly stabilized Michael acceptors, such as methyl 2-arylidenecyanoace- tate, 2-arylidene-2-cyanoacetophenone, or 2-arylidenemalononit- rile was reported to give polysubstituted pyrroles via the attack of the carbanion to electron-deficient C-b carbon of the Michael acceptor followed by deprotonation-induced formation of an imino anion by loss of nitrogen. Finally, an intramolecular nucleophilic addition to the ester, ketone, or cyano function leads to pyrroles. 6 Although a-azidoketones are widely employed in reduction, oxida- tion reactions, but their applicability as nucleophilic species in multicomponent reactions to synthesize heterocycles has not been explored to any great extent. As part of our program aimed at developing new methods for the preparation of heterocyclic com- pounds in one-pot, multicomponent reactions, 7 we report an effi- cient and simple synthesis of highly functionalized azido chromene derivatives. 2-Aminochromenes are employed as pigments, 8 cosmetics, agrochemicals, 9 and are major constituents of many natural prod- ucts. In continuation of our work involving three component reac- tion of salicylaldehydes, malononitrile and various other nucleophiles, 10 we herein introduce phenacyl azides as new nucle- ophiles in these three-component reactions. 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.05.101 ⇑ Corresponding author. Tel.: +91 44 24913289; fax: +91 44 24911589. E-mail address: ptperumal@gmail.com (P.T. Perumal). O N 3 RCH=X O XH N 3 R 1 R 2 R O O R 3 R 4 R 5 O O O H N 3 R 3 R 4 R 1 R 2 R 5 O N 3 R 1 R 2 electrophilic center nucleophilic center B : 3 4 2 1 R 1 R 2 - Scheme 1. Reactivity of a-azido ketones in C–C bond formation reactions. Tetrahedron Letters 52 (2011) 4093–4096 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet