COMPUTER-ASSISTED DESIGN AND SYNTHETIC APPLICATIONS OF CHIRAL ENOL BORINATES - NOVEL, HIGHLY ENANTIOSELECTIVE ALDOL REAGENTS

We have recently described the development of a quantitative transitio n state model for the prediction of stereoselectivity in the boron-med iated aldol reaction. This model provides qualitative insights into th e factors contributing to the stereochemical outcome of a variety of r eactions of synthetic importance. The force field model was used to as sist the design and preparation of new chiral boron ligands derived fr om menthone. The chiral boron enolates were employed in various stereo selective processes, including the addition to chiral aldehydes and th e reagent-controlled total synthesis of (3S,4S)-statine. The chiral en olates derived from alpha-halo and alpha-oxysubstituted thioacetates w ere added to aldehydes and imines. Addition to imines leads to the ena ntioselective synthesis of chiral aziridines, a formal total synthesis of (+/-)-thiamphenicol, and a new highly efficient synthesis of the p aclitaxel (taxol(R)) C-13 side-chain and taxol semisynthesis from bacc atin III. The stereochemical outcome of the addition to imines was rat ionalised with the aid of computational studies. Enantioselective addi tion reactions of the chiral boron enolate derived from thioacetate ha ve successfully been applied to solid phase bound aldehydes to give al dol products in comparable yields and enantioselectivities to the usua l solution conditions.