第十七届全国金属有机化学学术讨论会 2012.10 北京
Ru-Catalyzed highly enantioselective hydrogenation
of α-keto Weinreb amides
Mengmeng Zhao 1, Wanfang Li 1, Zhaoguo Zhang 1, 2
1 School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
2 State Key Lab. of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, 345 Lingling Road, Shanghai 200032, China
Enantiomerically pure α-hydroxy Weinreb amides are key intermediates for many pharmaceuticals,1
agrochemicals, and biologically relevant compounds because they provide useful precursors for α-hydroxy
ketones or aldehydes. Chiral α-hydroxy Weinreb amides were routinely obtained from α-hydroxy acids, esters or
acyl chlorides with commercially available N,O-dimethylhydroxylamine hydrochloride.2, 3 However, these
synthetic routes suffer from poor efficiency and enantioselectivity and need over stoichiometric amount of
activating agents. Obviously, the enantioselective hydrogenation of α-keto Weinreb amides is the most
straightforward method to provide these important chiral blocks. However, only a few examples were reported on
the enantioselective hydrogenation of α-keto amides and the efficiency and substrate scope were rather limited.4, 5
We have developed an efficient catalytic system for the asymmetric hydrogenation of α-keto Weinreb amides
and a series of enantiopure α-hydroxy Weinreb amides (up to 97% ee