Phosphine-catalyzed [4þ2] cycloaddition of sulfamate-derived cyclic imines with allenoates: synthesis of sulfamate-fused tetrahydropyridines Hao Yu, Lei Zhang, Zhen Li, Honglei Liu, Bo Wang, Yumei Xiao, Hongchao Guo * Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, PR China article info Article history: Received 18 July 2013 Received in revised form 11 November 2013 Accepted 18 November 2013 Available online 23 November 2013 Keywords: Phosphine Cycloaddition Allenoate Cyclic imines Sulfamate abstract Using n-PrPPh 2 as the nucleophilic catalyst, the [4þ2] cycloaddition reaction of the sulfamate-derived cyclic imines with allenoates works efficiently to yield various sulfamate-fused tetrahydropyridines in high yields with excellent diastereoselectivities. Using amino acid-based bifunctional phosphine as chiral catalyst, an asymmetric [4þ2] cycloaddition reaction was achieved, giving chiral sulfamate-fused tet- rahydropyridines in high yields with good enantiomeric excesses. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction The tetrahydropyridines are key units in or building blocks of many pharmaceuticals, agrochemicals, biologically active com- pounds, and natural products. 1 Therefore, the development of generally applicable synthetic tools toward tetrahydropyridine- fused compounds is highly desirable and has attracted much at- tention. Various efficient reactions have been reported for the preparation of the functionalized tetrahydropyridine. 2 Among these reactions, phosphine-catalyzed [4þ2] cycloaddition of N- tosylaldimines with allenoates provided an expedient and efficient route. 3 In 2003, Kwon first reported this seminal work and dem- onstrated under phosphine catalysis conditions, a variety of alle- noates carry out [4þ2] cycloaddition with N-tosylaldimines to give the tetrahydropyridine derivatives in high yield. 4 In 2005, Fu de- veloped asymmetric variant of this reaction by using binaphthyl- based C 2 -symmetric monophosphine as chiral catalyst and ach- ieved excellent enantioselectivity in the synthesis of functionalized tetrahydropyridines. 5 In 2011, Zhao described another impressive asymmetric version by employing a kind of simple and accessible bifunctional N-acyl-aminophosphine, providing facile accesses to optically active tetrahydropyridines. 6 In 2012, Ye extended the substrate scope of the reaction from aldimines to cyclic ketimines, and achieved phosphane-catalyzed [4þ2] annulation of allenoates with cyclic ketimines to give sultam-fused tetrahydropyridines. 7 Although the N-tosylaldimines and cyclic ketimines in phosphine-catalyzed [4þ2] cycloaddition with allenoates have been explored, the application of the sulfamate-derived cyclic aldimines in this reaction has never been reported. Since various sulfamate-containing compounds display the remarkable bio- activity, 8 the synthesis of sulfamate-fused tetrahydropyridines with two kinds of pharmacophores by phosphine-catalyzed [4þ2] cy- cloaddition of the sulfamate-derived cyclic aldimines with alle- noates will be very significant. As part of our research on the development of annulation reactions 9 for the synthesis of hetero- cycles, we herein describe phosphine-catalyzed [4þ2] annulation of sulfamate-derived cyclic aldimines with a-substituted allenoates to afford the sulfamate-fused tetrahydropyridines. 2. Results and discussion In initial attempt, we conducted a reaction of the benzol[e] [1,2,3]oxathiazine 2,2-dioxide (1a) with ethyl 2-benzylbuta-2,3- dienoate (2a) in dichloromethane at room temperature for 24 h in the presence of 20 mol % PPh 3 . To our delight, the target [4þ2] cycloaddition product 3aa was obtained in 83% yield with excellent diastereoselectivity (Table 1 , entry 1). However, using more nu- cleophilic phosphines, such as PBu 3 , PMe 3 , and Me 2 PPh as the catalyst, only trace of [4þ2] cycloaddition product was obtained, * Corresponding author. E-mail address: hchguo@cau.edu.cn (H. Guo). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tet.2013.11.063 Tetrahedron 70 (2014) 340e348