Palladium- and Ruthenium-Catalyzed Decarboxylative Allylations and Michael Addition-Allylation Reactions. Applications in Nitrogen Heterocycle Synthesis

Abstract

Our group has a long-standing interest in Pd or Ru-catalyzed decarboxylative coupling reactions. It has been shown that allyl ?-ketoesters, upon treatment with palladium or ruthenium, generate freely diffusing enolates and ?-allyl electrophiles. Consequently, we were curious about whether appropriate reactants (such as Michael acceptors) could be used to intercept these intermediates during the reaction. It has been since shown that a [Cp*RuCl]4/bipyridyl catalyst effectively induces a regioselective tandem Michael addition-allylation reaction. This protocol works well with a variety of allyl ?-ketoesters and Michael acceptors. Interestingly, ruthenium complexes behave as bifunctional catalysts, which activate the electrophilic allyl fragment and catalyze the decarboxylative formation of enolate nucleophiles. In addition, we have shown that cyclic carbamates diastereoselectively produce vinyl azetidines in good yields via a decarboxylative ring contraction. The diastereoselectivity is facilitated by rapid epimerization of the C5 stereocenter through ?-?-? allyl interconversion. This allows the synthesis of highly diastereoenriched azetidines from diastereomeric mixtures of cyclic allylic carbamates. Furthermore, in the presence of Michael acceptors, the cyclic carbamates undergo tandem Michael addition-allylation to produce highly substituted piperidines with good diastereoselectivity. Moreover, we have demonstrated that vinyl benzoxazinones undergo decarboxylative allylation to generate a series of dihydroquinoline derivatives. Once again, reaction in the presence of Michael acceptors led to a formal decarboxylative [4+2] cycloaddition. The analogous reaction in the presence of nonracemic palladium catalysts led to a highly enantioselective reaction. Lastly, a selenium-catalyzed oxidative halogenation of carbonyl compounds was developed. Interestingly, phenylselenides were found to be efficient and selective catalysts that enhance the electrophilicity of oxidized halogen sources such as NCS toward ?-halogenation of carbonyl containing compounds such as ketones, ?-ketoesters, and even ?,?-unsaturated ketones. In most cases, monohalogenated products were generated exclusively.