Synthesis and Reactivity of Umpolung Reagents Through Transition Metal Catalysis

The cyclopropanol-derived palladium-homoenolates have previously been exploited as a unique class of cross-coupling partners in our group. The major advantage of using cyclopropanols as the cross-coupling partners is the fact that the functional group content is preserved. Specifically, cyclopropanol forms the corresponding -functionalized carbonyl product which can be used for further transformations. We developed an efficient method towards the synthesis of quinoline derivatives with broad functional group tolerance using series of cyclopropanols and ortho-bromoanilines as the cross-coupling partners in the presence of a palladium-catalyst. A deuterium labeling study revealed that a second equivalent of ortho-bromoaniline is the terminal oxidant in this reaction.
Considering the importance of aza-aromatic heterocycles in biologically active drug molecules, there is a continuous demand for rapid and benign methods towards their functionalization. Hence, we wanted to exploit a transition-metal catalyzed free-radical ring opening reaction of cyclopropanols towards rapid and efficient functionalization of pyridine derivatives. We development a silver-catalyzed direct functionalization of heteroaromatic compounds with a well-defined silver catalyst. Through this study, we gained strong evidence which suggests that silver-pyridine complexes are the catalytically active species for free-radical ring-opening of the cyclopropanol. Acylsilanes are classic umpolung reagents with broad synthetic applications. Specifically, acylsilanes undergo polarity inversion at the carbonyl-carbon via the 1,2-Brook rearrangement with a concomitant reaction with an electrophile. Unfortunately, synthetic methods for acylsilanes often involve many steps and harsh conditions. We explored a mild synthetic method for the preparation of ,-unsaturated acylsilanes via perrhenate-catalyzed Meyer-Schuster rearrangement of 3-silyl propargylic alcohols.