Regio- and stereo-selective aza-Diels–Alder reaction of ethyl glyoxylate 4-methoxyphenylimine with 1,3-dienes in the presence of BF 3 $Et 2 O. Evidence for a non-concerted mechanism M. Jos e Alves, * Nuno G. Azoia and A. Gil Fortes Departamento de Qu ımica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal Received 4 October 2006; revised 26 October 2006; accepted 29 October 2006 Available online 15 November 2006 Abstract—Cycloadditions of the glyoxylate imine 1 with 1-substituted and 1,4-disubstituted 1,3-dienes furnished tetrahydroquinoline com- pounds 4 and 5/15 with total regio- and stereo-control, except for one case where a mixture of isomers was formed. A stepwise mechanism is proposed in view of the stereochemistry of the products. Ó 2006 Elsevier Ltd. All rights reserved. 1. Introduction Various tetrahydroquinolines are biologically active com- pounds, several of them with pharmaceutical applications. 1 As an example they have been investigated for the treatment of severe pain as an alternative to opiates. 2 There are several methods for the synthesis of tetrahydroqui- nolines, but the aza-Diels–Alder reaction of arylimines with dienophiles, usually in the presence of a Lewis acid catalyst, is one of the most powerful tools for obtaining 1,2,3,4- tetrahydro derivatives. 3 Cycloadditions of arylimines to dienophiles including enolates, 4–12 thioenolates, 4,11 enami- nes, 4,7,13,14 and cyclic dienes such as cyclopentadiene and cyclohexadiene 4,9,11,15,16 are well documented in the litera- ture. However, cycloadditions of arylimines to open chain dienes acting as dienophiles are less abundant. 17 Scheme 1 gives a summary of the literature. Tetrahydroquinolines are formed by an ‘inverse electron demand’ reaction. A competition with ‘normal electron de- mand’ reaction occurs in the case where the diene possesses Scheme 1. Keywords: 2-Azadienes; Glyoxylate arylimines; Diels–Alder cycloaddition. * Corresponding author. E-mail: mja@quimica.uminho.pt 0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2006.10.085 Tetrahedron 63 (2007) 727–734