Boron-mediated aldol reaction of carboxylic esters

Boron-mediated aldol reaction of carboxylic esters is described in detail. Contrary to the general belief that carboxylic esters are inert toward the conventional enolization conditions, propionate esters are shown to have adequate reactivity on the boron-mediated aldol reaction. More importantly, the stereochemical course of the aldol reaction can be controlled by the judicious choice of the enolization reagents. Complementary anti- and syn-selective asymmetric aldol reaction of structurally related chiral esters are developed. Also, novel double aldol reaction is discovered with acetate esters, which provides a precursor to the synthesis of chiral triols of C-3-symmetry. Extensive NMR experiments lead to characterize the first carbon-bound boron enolates and the novel doubly borylate enolates as intermediates of the double aldol reaction. A plausible mechanism of the double aldol reaction is proposed.