Reports: G1
47137-G1 New Catalysts for Asymmetric Intermolecular C-H Amination
Our research conducted with financial assistance from the Petroleum Research Fund has resulted in the discovery of a catalyst system that allows highly enantioselective amination of benzylic and allylic CH bonds. This system utilizes a novel ruthenium(II) catalyst, distinguishing it from rhodium-based catalysts that have been explored by other researchers. The results of this research were communicated in Angewandte Chemie, Int. Ed. (Milczek, E.; Boudet, N.; Blakey, S. Angew. Chem., Int. Ed. 2008, 47, 6825).
Although we have not discovered a catalyst system for Lewis base directed intermolecular CH amination, our research in the area of metallonitrene chemistry has lead to the discovery of a powerful new metallonitrene/alkyne metathesis cascade. This reaction allows particularly simple acyclic molecules containing both an alkyne and a tethered sulfamate ester to be converted to highly functionalized, complex polycyclic alkaloid structures in a single transformation. A preliminary communication describing this work was published in the Journal of the American Chemical Society earlier this year (Thornton, A. R.; Blakey, S. B. J. Am. Chem. Soc. 2008, 130, 5020).
More recently we have begun to investigate alternative directing groups for intermolecular directed C-H amination. We are in the process of combining out Ru(II)-pybox platform with a U-turn/hydrogen-bonding molecular recognition motif based on Kemps triacid, recently disclose by the groups of Brudwig and Crabtree in the context of directed C-H oxidation. While there is close analogy in the molecular recognition motif, the significant differences between C-H oxygenation and C-H amination ensure that this remains a rich area of research. The preliminary results obtained with the financial assistance of the Petroleum Research Fund starter grant allowed us to become involved in an NSF funded Center for Chemical Innovation, with the explicit aims of developing C-H functionalization into a powerful tool for organic synthesis (Co PIs: Davies, Musaev, Yu, Du Bois, White and Blakey). Our novel catalyst development work, initiated by the PRF grant continues to develop in this context.
Continuing research in our laboratory focuses on utilizing metallonitrenes as reactive intermediates for the controlled functionalization of simple hydrocarbon substrates, with a focus on using interchangeable molecular recognition units to fine tune selectivity (both regioselectivity and stereoselectivity).
