Asymmetric Diels−Alder Reactions of Unsaturated β-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes

摘要

The enantioselective formation of all-carbon quaternary centersnis an area of intense research in which Diels Alder reactions playna major role.n1nAs a possible alternative to ,u0001-unsaturated alde-nhydes, doubly activated -methylene u0001-ketoesters have beennemployed as dienophiles.n2nHowever, more bulky unsaturatednu0001-ketoesters, such as cyclic carboxypentenones, are much lessnreactive dienophiles and challenge the known protocols due to theirntendency to polymerization and keto enol tautomerization.n3nAd-nditionally, the corresponding tetrahydro-1-indanones are formed innlow yield under harsh conditions,n4nand to the best of our knowledge,nno enantioselective synthesis has been reported yet. We report herenthat our dicationic ruthenium PNNP complexes,n5nwhich efficientlyncatalyze the asymmetric Michael addition,n6nhydroxylation,n7nandnfluorination8nof saturated u0001-ketoesters, also promote the enantiose-nlective Diels Alder reaction of -methylene u0001-keto esters to giventetrahydro-1-indanones. In particular, we show that the methodologyngives access to enantiomerically pure ent- (or nat-) estronenderivatives, which is interesting in view of the application potentialnof these compounds, including the treatment of breast cancer.nnnC H activation.