Rhodium-Catalyzed Enantioselective Desymmetrization

Key words

rhodium - zinc - enantioselective desymmetrization - syn-deoxypolypropionate

Significance

A rhodium-catalyzed enantioselective desymmetrization of various glutaric anhydrides with carbon nucleophiles generates syn-deoxypolypropionate synthons in good yields and high ee values. The nucleophiles are commercially available or in situ generated alkyl or benzyl zinc reagents; aryl nucleophiles, however, are not compatible. A good range of alkyl nucleophiles, including those with an ester or chloride moiety, is shown. Electron-rich benzylic nucleophiles result in lower ee values due to a background reaction. Some examples of post-modifications of the product are also provided, including a deoxygenation and a dia­stereoselective reduction producing an intermediate to the synthesis of a beetle pheromone.

Comment

The syn-deoxypolypropionate unit is a useful synthon in organic synthesis and the present paper provides a novel method to generate enantioenriched varieties of this unit. One particular example with a zinc homoenolate sheds light on the reaction mechanism. This example gives the desired product and a dimer resulting from isomerization of the nucleophile. The dimer can be reduced at higher concentrations, which suggests that the zinc nucleophile and rhodium interact before addition to the anhydride.