| Our initial goal was to develop an efficient and novel method to prepare chiral allylic amines via palladium-catalyzed asymmetric allylic alkylation of amines and butadiene monoxide. The palladium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of a meso-epoxide successfully afforded chiral trans- and cis-2,5-dihydropyrroles, a process involving successive palladium catalyzed asymmetric alkylations of butadiene monoxide and nitrogen nucleophiles. These 2,5-dihydropyrroles are versatile intermediates, allowing entry into the syntheses of a whole host of natural products. The trans-2,5-dihydropyrrole's versatility was demonstrated by the successful synthesis of the glycosidase inhibitors (+)-broussonetine G, and (+)-DMDP, as well as the unnatural amino acid and beta-lactam antibiotic synergist (-)-bulgecinine.;In addition, the versatility of the ruthenium catalyzed [5+2]-cycloaddition of cyclopropyl enynes was investigated. The intermolecular [5+2] reaction of terminal alkynes and 1-vinylcyclopropylethers gives moderate yields of the desired seven-membered ring products. This reaction also proceeds intramolecularly to provide bicyclic systems containing seven-membered rings. The feasibility of applying these examples towards a total synthesis was explored by investigating synthetic approaches towards (-)-frondosin A, a potent anti-inflammatory agent and anti-HIV natural product. Although the synthesis of this natural product was not realized, a carbocyclic [5.3.0]-bicycle containing the necessary stereocenters was synthesized in an enantioselective fashion using the [5+2] cycloaddition reaction. |
