CATALYTIC ASYMMETRIC EPOXIDATION OF ALDEHYDES - OPTIMIZATION, MECHANISM, AND DISCOVERY OF STEREOELECTRONIC CONTROL INVOLVING A COMBINATION OF ANOMERIC AND CIEPLAK EFFECTS IN SULFUR YLIDE EPOXIDATIONS WITH CHIRAL 1,3-OXATHIANES

A range of 1,3-oxathianes based on camphorsulfonic acid have been prep ared and tested in the catalytic asymmetric epoxidation of carbonyl co mpounds. It was found that the 1,3-oxathiane derived from acetaldehyde 5b gave the highest yield and enantioselectivity in the epoxidation p rocess. The enantioselectivity was independent of the solvent and meta l catalyst used (although yields were dependent on both). The optimum conditions were applied to a range of aldehydes, and good enantioselec tivities and diastereoselectivities were observed. The origin of the e nantioselectivity was probed, and in particular the role of the oxygen of the 1,3-oxathiane was investigated. Thus, the sulfur and carbon an alogues of the camphorsulfonic acid based 1,3-oxathiane (derived from formaldehyde) were prepared (i.e., 1,3-dithiane and thiane analogues). With this series of analogues the steric effects are minimized so tha t the electronic effects can be investigated. The series of compounds was reacted in the catalytic cycle with benzaldehyde and gave stilbene oxides with 44% ee (sulfur analogue), 41% ee (1,3-oxathiane), and 20% ee (carbon analogue). Thus, it was concluded that the oxygen of the 1 ,3-oxathiane exerted a significant electronic effect in controlling th e face selectivity of the ylide reactions. This electronic effect was a result of combined anomeric (higher with the sulfur analogue, not pr esent with the carbon analogue) and Cieplak effects. A strong anomeric effect was observed in the X-ray structures of one of the 1,3-oxathia nes, and an even greater one was observed in the corresponding sulfoxi de (this was used as an electronic analogue of the ylide). The face se lectivity of the ylide was believed to be complete in reactions with 5 b. The minor enantiomer resulted from reaction of the miner conformer of the ylide, reacting again with high face selectivity. This was prov en by using a more substituted diazo compound, which was expected to g ive much less of the minor conformer. Indeed, reaction with mesityldia zomethane gave the corresponding epoxide in essentially enantiomerical ly pure form.