Herein is proposed an investigation of enantioselective C,C-bond formation via the Claisen rearrangement. Both the broad synthetic applicability and the intrinsic stereo-selectivity of this reorganization recommend its development for use in enantioselective synthesis. Realization of this goal will provide synthetic access to optically pure Alpha- and/or Beta-substituted Gamma,Delta-unsaturated acids which will prove useful as synthetic intermediates in the synthesis of chiral chemotherapeutics. Developments of N-allylketene N,X-acetal Claisen substrates and Beta-alkoxy allylic ester enolates which will undergo diastereoselective Claisen rearrangement are proposed. These asymmetric procedures will be applied in the enantioselective syntheses of the antibiotic agents (+)- ikarugamycin (1) and (-)-botryodiplodin (2). Realization of these goals will provide access to these natural compounds, interesting analogs, and generate new chemistry of sufficient generality for future application in the synthesis of other bioactive molecules.
Specific aims of this proposed research are: i) to develop auxiliary reagent mediated diastereoselective aza-Claisen rearrangement substrates applicable to enantioselective synthesis. ii) to develop diastereoselective Beta-alkoxy ester enolate Claisen rearrangement substrates applicable to enantioselective synthesis. iii) to demonstrate the synthetic potential of these Claisen rearrangements in a total synthesis of the antibiotic (-)-botryodiplodin (2). iv) to achieve a total synthesis of the naturally occurring antibiotic (+)-ikarugamycin (1).
