| An enantioselective approach to bicyclo[2.2.2]octenone structures utilizing a copper-mediated asymmetric oxidative dearomatization/[4+2] dimerization cascade has been developed. This approach takes advantage of the diastereoselective dimerization of chiral ortho-quinols, which arc prepared from oxidation of disubstituted phenols with a [(--)-sparteine]2Cu202(PF6)2 complex. Utilizing this methodology, the total synthesis and absolute stereochemistry assignment of the novel bis-sesquiterpene (+)-aquaticol has been achieved.;We have also investigated a retro-Diels-Alder/Diels-Alder cascade of enantiomerically pure ortho-quinol dimers. By utilizing a microwave-assisted parallel screen of dienophiles and dienes, the reactivity of ortho-quinols in [4+2] reactions has been evaluated. Computational studies have also been conducted in order to rationalize the observed diastereoselectivity. Furthermore, biological evaluation of prepared bicyclo[2.2.2]octenones and cis-decalins has identified an inhibitor of the transcription factor activator proteine-1 (AP-1).;Utilizing the tandem retro-Diels-Alder/Diels-Alder reaction, the total synthesis of the microtubule inhibitor (+)-chamaecypanone C has been achieved. Moreover, rhodium- catalyzed dehydrogenation of diarylcyclopentenones has been developed to in situ generate the corresponding diarylcyclopentadienones, which were further elaborated into derivatives of chamaecypanone C. Initial biological studies demonstrate that (+)- chamaecypanone C is an inhibitor of tubulin assembly and binds at the colchicine site.;A hypervalent iodine(III) reagent-mediated dearomatization/acyl migration cascade has been developed. Preliminary studies toward the synthesis of the antileukemic agent sorbicillactone A using this methodology, including the construction of the desired bicyclic core structure, will be described. |
