Large-scale Synthesis of Enantioselective Epoxidation Catalysts


The Shi method is used for entioselective epoxidation of alkenes, which is converting alkenes into a specific enantiomer of an epoxide. 

Problem Addressed

The absence of ent-Shi ketone has been a drawback to the utility of the Shi method for approximately 10 years. The Shi method is the assymetric epoxidation of alkenes with oxone and a fructose-derived catalyst. 


As shown in the attached scheme, enti-Shi Ketone (the described catalyst) synthesis starts with L-absorbic acid (vitamin C), a very inexpensive material. It is converted to aldehyde 1 in three known steps. Aldehyde 1 is also commercially available, and thus the synthesis can alternatively begin here. There are 3 key steps in the synthesis. The first is a published reaction, a catalytic enatioselective aldol reaction. The second step (“Step 5” in the Scheme) is the key aspect of this invention. In a one-flask procedure, the product of the aldol reaction (compound 2) is transformed into the direct precursor (3) of the enti-Shi catalyst in very good yield and on 200-gram scale. This step has never been published or otherwise documented and, because of so many desired chemical transformations, it is non-obvious to those skilled in the art. The final step (“Step 6”) is a procedure published for the enantiomer of the compound. 


  • Ability to synthesize large volumes of enti-Shi catalyst
  • Increases rate of enantiomer epoxide syntheses