Enamine Acylation Enabled\nDesymmetrization of Malonic\nEsters

Asymmetric enamine alkylation represents a powerful tool\nfor stereoselective\nC–C bond formation; in contrast, the development of enantioselective\nenamine acylation remains elusive. Here, we report that a chiral phosphoric\nacid can render an in-situ-formed enamine to undergo a stereoselective\nintramolecular α-carbon acylation, providing an alternative\napproach for the synthesis of useful pyrrolinones and indolinones\nbearing tetrasubstituted stereocenters. Utilizing an effective integration\nof the desymmetrization strategy and bifunctional organocatalysis,\nthe first example of enantioselective enamine acylation is achieved\nby employing readily available aminomalonic esters and cyclic ketones.\nInstead of reactive and moisture-sensitive acyl chlorides, common\nesters with low electrophilicity were successfully used as efficient\nacylating reagents via hydrogen bonding interactions. The utility\nis demonstrated in the concise and enantioselective synthesis of (+)-LipidGreen\nI and II. Experimental studies and DFT calculations establish the\nreaction pathway and the origin of stereocontrol.