Thermal [3þ2] cycloaddition reaction of azomethine imines with allenoates for dinitrogen-fused heterocycles Risong Na a , Honglei Liu a , Zhen Li a , Bo Wang a , Jun Liu a, b , Ming-An Wang a , Min Wang a , Jiangchun Zhong a , Hongchao Guo a, * a Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, PR China b Chemical Industry Press,13 Qingnianhu South St., Beijing 100011, PR China article info Article history: Received 15 November 2011 Received in revised form 29 December 2011 Accepted 13 January 2012 Available online 20 January 2012 Keywords: Azomethine imine [3þ2] Cycloaddition Allenoate Thermal Dinitrogen-fused heterocycle abstract The thermal [3þ2] cycloaddition reactions of two classes of azomethine imines with allenoates have been investigated. The reactions are operationally simple and proceed smoothly under mild reaction conditions to provide a variety of dinitrogen-fused heterocycles in moderate to excellent yields. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction 1,3-Dipolar cycloaddition reaction has emerged as one of the most powerful tools for the construction of a variety of hetero- cycles from simpler starting materials. 1 Various 1,3-dipoles such as nitrone, azomethine ylide, azomethine imine, nitrile oxide, carbonyl ylide, azide, nitrile imine, carbonyl oxide, diazoalkane, and diazoacetate have been used for all kinds of target hetero- cycles. 1 Among these 1,3-dipoles, azomethine imine is a highly attractive one due to its salient features such as easy preparation, stability, and the potential application of the corresponding cycloadduct. 2 It has been employed as efficient 1,3-dipole in various thermal, metal-catalyzed, and organocatalytic cycload- ditions. 2,3 Various dipolarophiles such as alkenes and alkynes could undergo [3þ2] cycloaddition with azomethine imines to furnish the useful heterocycles. 2,3 Although the allenes have similar reaction mode as alkenes and alkynes and have been extensively studied in the cycloaddition reactions with numerous 1,3-dipoles, 4 the cycloaddition of allenoates with azomethines has been overlooked for so many years. Most recently, we re- ported first phosphine-catalyzed [3þ2], [3þ3], [4þ3], and [3þ2þ3] annulation reactions of allenoates with azomethine imines, providing generally applicable routes toward dinitrogen- fused heterocycles, such as tetrahydropyrazolo-pyrazolone, -pyridazinone, -diazepinone, and -diazocinone, 5 which are key units in or building blocks of many pharmaceuticals, agrochem- icals, biologically active compounds, and other useful chemicals. 6 In the study of the phosphine-catalyzed cycloadditions, when the reaction temperature was higher than room temperature, the thermal cycloaddition product was often observed and isolated as side-product. It prompted us to investigate thermal cycload- dition reaction of azomethine imines with allenoates in detail. Herein, we describe first thermal [3þ2] cycloaddition of azome- thine imines with allenoates to furnish functionalized dinitrogen-fused heterocycles (Scheme 1). 2. Results and discussion The two classes of azomethine imines, C,N-cyclic azomethine imines 1 and N,N 0 -cyclic azomethine imines 2, were investigated in our research and prepared according to the reported procedur- e. 3j,m,n,cc,7 We first tried the reaction of C,N-cyclic azomethine imine 1a with the allenoate 2a in dichloromethane at room temperature. The reaction was sluggish to give the corresponding annulation product as a diastereomeric mixture of 4aa and 4 0 aa in 40% yield, which couldn’t be separated by silica gel chromatography (Table 1 , entry 1). 8 Using the NMR spectroscopy and X-ray crystallography 9 (Fig. 1), the structures of 4aa and 4 0 aa were established to be [3þ2] cycloaddition products, and the product 4aa was the major * Corresponding author. Tel.: þ86 10 62731356; fax: þ86 10 62820325; e-mail address: hchguo@cau.edu.cn (H. Guo). Contents lists available at SciVerse ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2012.01.029 Tetrahedron 68 (2012) 2349e2356