Catalytic Asymmetric Addition of Alkyl Enol Ethers to 1,2-Dicarbonyls

Significance

In this paper, the first example of catalytic enantioselective hetero-ene reaction of alkyl enol ethers with 1,2-dicarbonyl compounds is reported. With the use of the chiral N,N′-dioxide complex of Mg(OTf)₂ or Co(OTf)₂ isatins, α-keto esters, and glyoxal derivatives were converted into the desired products with good to excellent yields (up to 98%) and excellent enantioselecti­vities (up to >99% ee). The protocol is notable for the broad substrate tolerance, experimental simplicity, and mild conditions. 3-Substituted 3-hydroxyindoles obtained from isatins are particularly important in light of their biological significance. The synthetic potential of the developed methodology was exemplified by preparation of (R)-convolutamydine with 97% ee. A plausible transition state was modeled based on the product stereochemistry, HRMS, and X-ray studies.