Diversification of heterocyclic drug scaffolds through the late stage installation of alkyl groups has become an important process in drug discovery. Radical-based methodologies, such as the Minisci reaction, have emerged as effective means to accomplish the alkylation of advanced intermediates in the drug discovery process; however, these methods often require strong oxidants and elevated temperatures. This talk will cover our recent efforts to develop an efficient method for the alkylation of heterocycles through the reductive decarboxylation of in situ generated N-acyloxy pyridinium salts. This method features the use of inexpensive heterocyclic N-oxides as both transient redox activators and coupling partners, as well as a diverse array of commercially available carboxylic acids as alkylating agents. Finally, the potential application to the alkylation of late-stage intermediates is explored.

Alkylation of heterocycles through the reductive decarboxylation of in situ generated N-acyloxy pyridinium salts

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.