ASYMMETRIC CONJUGATE ADDITION FOR THE SYNTHESIS OF α-CHIRAL HETEROCYCLES AND RHODIUM – CATALYZED NON –CARBONYL – STABILIZED CARBENOID CASCADE REACTIONS
A method for the synthesis of compounds which have chiral centers on the carbon alpha to heterocyclic rings will be first discussed. Heterocyclic compounds are known for a wide range of applications and are of particular interest in medicinal chemistry and natural product synthesis. The presented development used an air-stable boronic acid as a nucleophile for conjugate addition to a β-heteroaryl enone. Therefore, different heterocycles with different connectivity attached to the stereocenters could be obtained. An improved BINOL catalyst also was synthesized in order to speed up the reaction rate and, consequently, prevented the racemization that occurred when electron-deficient heterocycles were used. Furthermore, a BINOL catalyzed propargylic substitution reaction was simultaneously developed. Preliminary results will also be mentioned. The next project delivered the rhodium-catalyzed reactions of alkyne tethered alkyl tosylhydrazones. The novel cascade reaction generated bridged polycycles efficiently. This approach was also useful for acyclic hydrazones to form fused bicycles. Mechanistically, the reaction was found to go through a cyclopropene intermediate, which was isolated and characterized. Finally, the rhodium-catalyzed cascade reaction using diazoketones and its application toward the synthesis of maoecrystal V’s core structure will be discussed.