Diphosphine Oxide Catalyzed Direct Aldol Reactions

Significance

A highly stereoselective direct aldol reaction of ketones 2 to aromatic aldehydes 1 mediated by Lewis base catalyst 3 is reported. During this reaction, trichlorosilyl enolethers are generated in situ from ketones and tetrachlorosilane (three equivalents), and then activated by coordinating to the chiral diphosphine oxide catalysts. The coordination of aldehydes to the chiral cationic hypervalent silicon species has shown to be crucial for high diastereo- and enantioselectivities (see the proposed model). Both electron-rich and -poor aromatic aldehydes are tolerated with high level of stereoselectivity, but aliphatic aldehyde acceptors did not show any reactivity even at 0 ˚C. The cross-condensation of benzaldehydes with α-branched aldehydes also proceeds well under these reaction conditions.