The formation of N-heterocycles remains a major goal for synthetic organic chemists. The most common techniques for pyrrolidine and imidazolidine generation involve the cyclization of linear precursors, a tactic that while effective fails to develop molecular complexity. A more productive strategy involves dipolar cycloaddition reactions, an intrinsically efficient approach as it links two molecules making two bonds simultaneously. However, the majority of prior examples require complex precursors, electron stabilizing groups, or both to function effectively. Our work revitalizes a long neglected tactic, [3+2] cycloaddition reactions starting from readily available N-oxides. Using a theory first approach we have expanded this chemistry into new areas, using non-polar dipolarophiles to form natural product like structures in three steps from base starting materials. We have also made use of polar dipolarophiles to construct a variety of high value products via a novel disconnection. In parallel with our experimental efforts, we continue to use computational chemistry to provide valuable insights into molecular mechanisms, and indicate likely targets for future exploration. Computational experiments are carried out using resource efficient Density Functional Theory (DFT), and cross checked with post-SCF methods. Our findings so far indicate that using N-oxides for [3+2] cycloaddition reactions is a very promising method for making a wide range of functionalized nitrogen rich heterocycles.

N-oxides as potent precursors for [3+2] cycloaddition reactions

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

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