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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM034862-01
Application #
3286608
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1985-09-12
Project End
1987-08-31
Budget Start
1985-09-12
Budget End
1987-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213