Cyclic Aminal of TsDPEN : Synthesis and Use as Asymmetric Organocatalysts

1. Cyclic Aminal of TsDPEN: Synthesis and Use as Asymmetric Organocatalysts RinaSoni, Silvia Gosiewska, Guy Clarkson, Martin Wills* Department of Chemistry, University of Warwick, Coventry CV4 7AL, E-mail: R.C.Soni@warwick.ac.uk The use of enantiomerically pure amines as catalysts for organic reactions has proved to be a productive area of research in recent years.1,2 Of the successful homochiral amines investigated, a large proportion are based on five-memberedN-containing rings, notably pyrrolidine derivatives such as 1-4 and imidazolidinone derivatives 5-6 (Figure 1). During the course of studies on the functionalisation of TsDPEN 7 through a reductive alkylation reaction, we found that the reaction with α-trialkylsilyloxy-substituted aldehyde resulted in the formation of a stable aminal 8 (Scheme 1). This was not reduced under in situ reduction conditions (NaBH3CN, MeOH) which we had previously used for reductive alkylation with alkyl aldehydes.The stability ofcompound 8 in column purification and its X-ray structure (Figure 3)(Similar to MacMillan’s catalyst)3prompted us to use this compound as an organocatalyst for the Diels-Alder reaction. a b Figure 3 X-ray structure of 8. (a) H atoms removed for clarity, (b) with H atoms shown. Compound 8 has shown good selectivity for Diels-Alder reaction giving a product in up to 72% ee (Scheme 2, Table 1). On the basis of this result, different derivatives 9-11 were synthesized and screened for selectivity, but they were inferior to 8 (Figure 2, Table 1) Table 1 Diels-Alder reaction Figure 4 (a) Variation in mol% of catalyst 8 (b) Effect of different acids (c) Variation in mol% of acid (d) Effect of different acid on %ee • Further, compounds 8-11 (Scheme 1, Figure 3) were investigated as organocatalysts for other asymmetric reactions. Of these, the addition of aldehyde to DEAD (Scheme 3) was found to be the most promising.4 The reaction conditions were optimized with compound 8, as it again demonstrated the highest reactivity and selectivity (Figure 4, Table 2). Conclusion: Compound 8 has shown very good selectivity for addition of aldehyde to DEAD.5 Further, different asymmetric reactions are under investigation by using compound 8 as organocatalyst . Table 2 Addition of aldehyde to DEAD • References: • Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G. Angew. Chem. Int. Ed. 2008, 47, 6138-6171. • Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719-724 • Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243-4244. • Bøgevig, A.; Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2002, 41, 1790-1793. • Gosiewska, S.; Soni, R.; Clarkson, G. J.; Wills, M. Tetrahedron Lett. 2010, Article in press with DOI: 10.1016/j.tetlet.2010.06.017 • Acknowledgement: We thank Warwick University and the WPRS for funding.