Cyclic Aminal of TsDPEN: Synthesis and Use as Asymmetric Organocatalysts Rina Soni, Silvia Gosiewska, Guy Clarkson, Martin Wills * Department of Chemistry, University of Warwick, Coventry CV4 7AL, 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-membered N-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 (NaBH 3 CN, MeOH) which we had previously used for reductive alkylation with alkyl aldehydes. The stability of compound 8 in column purification and its X-ray structure (Figure 3)(Similar to MacMillan’s catalyst) 3 prompted us to use this compound as an organocatalyst for the Diels-Alder reaction. 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 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. 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 Table 2 Addition of aldehyde to DEAD References: (1)Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G. Angew. Chem. Int. Ed. 2008, 47, (2)Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, (3)Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, (4)Bøgevig, A.; Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2002, 41, (5)Gosiewska, S.; Soni, R.; Clarkson, G. J.; Wills, M. Tetrahedron Lett. 2010, Article in press with DOI: /j.tetlet Acknowledgement: We thank Warwick University and the WPRS for funding. References: (1)Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G. Angew. Chem. Int. Ed. 2008, 47, (2)Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, (3)Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, (4)Bøgevig, A.; Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2002, 41, (5)Gosiewska, S.; Soni, R.; Clarkson, G. J.; Wills, M. Tetrahedron Lett. 2010, Article in press with DOI: /j.tetlet Acknowledgement: We thank Warwick University and the WPRS for funding. ab