Highly stereoselective and scalable anti-aldol reactions using N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide: scope and origins of stereoselectivities

A highly enantio- and diastereoselective anti-aldol process catalyzed by a proline mimetic, N-(dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide, is developed. The studies have shown that the origins of enhanced diastereoselectivity are because of the presence of nonclassical hydrogen bonds between the sulfonamide, the electrophile, and the catalyst enamine that favor the major anti-Re aldol TS in the Houk-List model.