signature=1096d16b19864a7f2d703cf98450f2f7,Ru-Catalyzed highly enantioselective hydrogenation of α-k...

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