Chiral Michael additions of methyl vinyl ketone (MVK) to indanone 2-carboxylic esters are well precedented in the literature.1 However, many of these methods are not applicable to 2-alkylindanones such as 1, containing a proton less acidic than the /3-keto ester.2 Here we report j.®-a an addition of MVK to indanone 1 catalyzed by the quaternary salts of Cinchona alkaloids in 95% yield and up to 80% enantiomeric excess (ee). This chiral Michael addition,3 followed by aldol condensation to complete the Robinson annelation, was the key step in our preparation of drug candidate 3.4 Cinchona alkaloids are not basic enough to catalyze Michael additions to the 2-propylindanone 1. Wynberg reportslb that the corresponding quaternary salts are not as effective as catalysts as the free bases.5 However, excellent results have been obtained in these laboratories in phase-transfer alkylations with quaternary Cinchona alkaloid catalysts6 leading to a synthesis of 3 employing
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