Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines

• Published in: Nature communications Vol. 7; no. 1; p. 13780
• Main Authors: Rong, Jiawei, Collados, Juan F., Ortiz, Pablo, Jumde, Ravindra P., Otten, Edwin, Harutyunyan, Syuzanna R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.12.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/935; 639/638/549/933; 639/638/77/888; Carbon; Humanities and Social Sciences; Ligands; MTBE; multidisciplinary; Pharmaceutical sciences; Reagents; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13780

α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N -sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure. The stereoselective addition of Grignard reagents to ketimines is potentially a straightforward route to α-chiral amines. Here the authors report a catalytic, asymmetric Grignard addition to silyl ketimines, giving N -sulfonyl protected α-chiral silyl amines with tetrasubstituted stereocentres.