Stereocontrolled synthesis of polyketide libraries: Boron-mediated aldol reactions with aldehydes on solid support

Article abstract of DOI:10.1016/S0040-4020(98)00940-5

Two complementary classes of chiral boron enolates for adaptation to aldol additions to resin-bound aldehydes were studied: (i) the thioester- derived enolate 1 bearing chiral ligands on boron, and (ii) the chiral ketone-derived enolate 2. The viability of performing highly enantioselective, boron-mediated, aldol reactions was demonstrated by the preparation of resin-bound adducts 15 (91% ee) and 21 (88% ee). The solid phase aldol reactions of enolate 2 can be combined with an in situ reduction of the intermediate aldolate using LiBH₄, leading to the controlled introduction of four contiguous stereocentres, as in 33 → 40 (>96% diastereoselectivity). The choice of linker is crucial and the available experimental evidence suggests that trityl and silyl linkers are optimal. This methodology should be amenable to the stereocontrolled synthesis of polyketide libraries.