Regioselective 1,3-dipolar cycloaddition of nitrilimines to 2-methyl-2-vinyl oxirane Muhammet Yıldırım, Yas ¸ ar D € ur € ust * Department of Chemistry, Abant _ Izzet Baysal University, TR-14280, Bolu, Turkey article info Article history: Received 26 November 2010 Received in revised form 16 February 2011 Accepted 7 March 2011 Available online 12 March 2011 Keywords: Nitrilimine Vinyl oxirane Regioselective Pyrazole abstract 1,3-Dipolar cycloaddition of in situ generated C,N-diaryl nitrilimines to 2-methyl-2-vinyl oxirane gives rise to the regioselective formation of novel 5-(2-methyloxiranyl)-4,5-dihydropyrazole derivatives in moderate to good yields. The structures and stereochemistries of the new cycloadducts were confirmed by spectroscopic/physical methods including X-ray diffraction data. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction 1,3-Dipolar cycloaddition reactions occupy a significant place due to their versatility in the construction of five-membered het- erocylic systems. 1 Most especially, nitrilimines have been utilized in many cycloaddition reactions (generated in situ) and thus, pyrazole- and pyrazoline-containing heterocycles have been intensively syn- thesized for many years by using ethylenic, heterocyclic dipolarophiles 2e9 in the presence of different catalysts. 10,11 In general, 1,3-dipolar cycloaddition reactions of nitrilimines with a dipolarophile having nonidentical terminal p-centers, such as monosubstituted ethylenes can lead theoretically to the 5- and 4- substituted 2-pyrazolines (regioisomers). Many examples reported in the literature showed that the orientation observed for alkenes substituted with electron-donor, conjugating, and moderate elec- tron-acceptor substituents is the 5-substituted regioisomer. 12,13 The rationalization of such regiochemical results became evident in terms of the frontier molecular orbital theory of Fukui. 14e16 In addition, vinyl oxiranes are simple 2-alkenyl substituted ep- oxides, which are attractive precursors for the construction of functionalized four- and five-membered or larger rings by Pd-cat- alyzed or intramolecular FriedeleCraft reactions. 17e19 The only reported cycloaddition reaction of vinyl oxiranes in- volved heterocumulenes; isocyanates and carbodiimides were used as reagents. 20 In this regard, to the best of our knowledge, since there is no example of nitrilimine cycloaddition reactions to vinyl oxirane derivatives, we have been interested in the present work to study 1,3-dipolar cycloaddition of diaryl substituted nitrilimines to 2- methyl-2-vinyl oxirane. 2. Results and discussion We performed the cycloaddition reaction of nitrilimines obtained initially in situ from the treatment of C,N-diaryl substituted a-chloro hydrazones with the excess triethylamine in dry dichloromethane then with the addition of excess 2-methyl-2-vinyl oxirane at room temperature. The progress of the reaction was fol- lowed by TLC until all diarylnitrilimine has been consumed. The overall reaction yielded a mixture of diastereomers (RR,RS) in moderate to good yields (40e92%) with low diastereoselectivity (Scheme 2). 5R,2 0 R-6 and 5R,2 0 S-7 diastereomers have been obtained in the ratios between 62:38 and 36:64 (Table 1 and Scheme 1). Table 1 Diastereomeric ratios and yields of title compounds 6e7(aeh) Compd R 1 R 2 Reaction time (h) Et 3 N (equiv) 2M2VO (equiv) Yield (%) a Diastereomeric ratio (5R,2R-6:5R,2S-7) 6ae7a H H 24 10 3 92 54:46 (i) b 6be7b CH 3 H 64 8 3 80 62:38 (i) b 6ce7c NO 2 H 48 8 2 40 50:50 (s) 6de7d OCH 3 H 20 10 3 65 57:43 (i) b 6ee7e CF 3 H 96 8 3 84 53:47 (s) 6fe7f Br Cl 44 8 3 95 58:42 (i) b 6ge7g NO 2 Cl 64 9 3 64 36:64 (s) 6he7h CH 3 CN 96 8 3 84 56:44 (i) b a Total yields of diastereomeric cycloadducts. b Assigned isomeric ratio using 1 H NMR. i¼inseparable mixture s¼separated. * Corresponding author. Tel.: þ90 374 2541243; fax: þ90 374 2534642; e-mail address: yasardurust@ibu.edu.tr (Y. D€ ur€ ust). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2011.03.017 Tetrahedron 67 (2011) 3209e3215