STEREOCONTROLLED SYNTHESIS OF POLYKETIDE LIBRARIES - BORON-MEDIATED ALDOL REACTIONS WITH ALDEHYDES ON SOLID SUPPORT

Two complementary classes of chiral boron enolates for adaptation to a ldol additions to resin-bound aldehydes were studied : (i) the thioest er-derived enolate 1 bearing chiral ligands on boron, and (ii) the chi ral ketone-derived enolate 2. The viability of performing highly enant ioselective, boron-mediated, aldol reactions was demonstrated by the p reparation of resin-bound adducts 15 (91% ee) and 21 (88% ee). Thc sol id phase aldol reactions of enolate 2 can be combined with an bl situ reduction of the intermediate aldolate using LiBH4, leading to the con trolled 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 he amenable to the stereocontrol led synthesis of polyketide libraries. (C) 1998 Elsevier Science Ltd. All rights reserved.