NHC-catalyzed ring expansions and cascade reactions

Abstract

In recent years, N-hetereocyclic carbenes (NHCs) have received considerable attention as organocatalysts due to their unusual ability to induce a reversal of reactivity (Umpolung) in aldehydes. Indeed, NHCs’ unique properties have been applied to the efficient and metal-free synthesis of organic compounds that have proven elusive using traditional approaches.

My Master’s research program has been focused on the use of NHCs as organocatalysts in ring expansion reactions and their applications to cascade reactions.

During my Masters studies, an NHC-catalyzed efficient ring expansion of 4-, 5-, and 6-membered oxacycloalkane-2-carboxaldehydes to generate the corresponding lactone derivatives was developed. This reaction provides access to a variety of lactones using readily available NHCs under mild conditions.

Then, the ring-expansion lactonization has been successfully extended to an efficient lactamization using azacycloalkane-carboxaldehydes, which could provide functionalized lactams in moderate yields under mild conditions.

In addition, intrigued by the possibility of effecting the Umpolung of electron-poor dienes using NHC catalysts, the ring-expansion lactonization was applied to an attempted Diels-Alder-ring expansion cascade reaction. Though no cascade reactions were observed, some very interesting results were obtained, and those results will guide future investigations in this area.