Chiral β-amino nitriles are versatile synthetic intermediates, which can be readily transformed into optically active compounds such as β-amino acids and 1,3-diamines. The asymmetric addition of silyl ketene imines (SKIs)[1] to imines provides a straightforward procedure for such compounds. Moreover, the unique structure of SKIs, known as cumulenes and readily racemization, offers a significant advantage in the construction of quaternary stereogenic carbon centers, which remains refractory in synthetic organic chemistry. In our study, catalytic asymmetric Mannich reactions of SKIs with aldimines[2a] or ketimines[2b] have been realized by chiral N,N'-dioxide complexes[3] under convenient and mild reaction conditions. A variety of β-amino nitriles containing quaternary stereogenic carbon centers were obtained in excellent outcomes (up to 98% yield, &gt;19:1 d.r., 99% ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of asymmetric inductivity. References: [1] S. E. Denmark, T. W. Wilson, Angew. Chem. Int. Ed. 2012, 51, 9980-9992. [2] a) J. N. Zhao, X. H. Liu, W. W. Luo, M. S. Xie, L. L. Lin, X. M. Feng, Angew. Chem. Int. Ed. 2013, 52, 3473-3477; b) submitted to Angew. Chem. Int. Ed.. [3] X. H. Liu, L. L. Lin, X. M. Feng, Acc. Chem. Res. 2011, 44, 574-587.

Asymmetric synthesis of β-amino nitriles via Mannich reactions of silyl ketene imines

249th National Meeting (2015)

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