Preliminary results have outlined the finding of a unique """"""""mono-Claisen"""""""" rearrangement. Model studies have indicated that this represents the discovery of a general substituent accelerating effect on the Claisen rearrangement. It also represents the first violation of the Carpenter qualitative resonance rules for prediction of substituent effects. Combination of this novel reaction with Pi-allyl palladium mediated alkylation has permitted a short selective synthesis of the pseudomonic acids. In order to gain a better understanding of this new discovery for predictable synthetic applications, we have proposed 1) a detailed rate study to comfirm the observed substituent effect and delineate its scope and nature, 2) extension of these results to a more generalized study of the effect of electron donating substituents on the rate of the Claisen rearrangement. We have also proposed 3) a stereoelectronic origin for the observed rate acceleration term the """"""""vinylogous anomeric effect"""""""". By analogy with the anomeric effect, this may have broad conformational and chemical ramifications. Several methods to evaluate the magnitude and possible importance of the proposed vinylogous anomeric effect are outlined. Finally, 4) synthetic endeavors employing the new selectivity observed in combination with other reactions, are presented. Topical targets include pseudomonic acids, nanaomycins, and various chiral lactones and acyclic building blocks.
| Curran, D P; Suh, Y G (1987) Selective mono-Claisen rearrangement of carbohydrate glycals. A chemical consequence of the vinylogous anomeric effect. Carbohydr Res 171:161-91 |
