Synthesis of cyclopropenium cations by carbyne transfer catalysis and applications in novel cyclopropene syntheses

Identifier:  TDX:4333

Handle: https://hdl.handle.net/20.500.11797/TDX4333

Authors:  Jeandin, Aliénor Celine Renee

Abstract:
The main objective of this Thesis was the discovery and the development of new chemical reactions involving catalytic carbyne transfer with alkynes, and applications of these new reactions to the synthesis of complex molecules. Key on this endeavor was the use of the carbyne transfer platform recently developed in the Suero group, allowing for the catalytic generation of Rh-carbynoids intermediates by the selective activation of carbyne sources, namely new I(III) reagents decorated with a diazo moiety. First, we discovered that Rh-carbynoids react with a broad range of readily available alkynes to generate cyclopropenium cations (CPCs), isolable as stable solids by filtration, and reported the first catalytic synthesis of a novel class of ester-substituted CPCs. We then demonstrated the synthetic utility of these new reagents by using them in a highly regioselective synthesis of cyclopropenes in simple reaction conditions. Importantly, the use of CPCs as synthons circumvents some of the drawbacks of preexisiting methods and gives access to previously unreported diverse cyclopropenes. After this, we used CPCs as three-carbon building blocks in an unprecendented late-stage aryl C-H bond cyclopropenylation. The process is a Friedel-Crafts-type transformation, and shows high site-, chemo-, and regioselectivities in simple (hetero)aromatic rings and in densely-functionalized environments such as drug molecules and natural products. The installed cyclopropene scaffold served, in addition, as stepping stone to access unprecedented sp3-rich architectures by taking advantage of the versatile nature the cyclopropene ring and the multiple derivatizations possibilities it offers. Overall, the use of CPCs as synthons for the synthesis of highly versatile cyclopropenes arises as a valuable addition to the synthetic toolbox of organic and medicinal chemists. We envisage that this novel class of CPCs will find further applications in organic synthesis and medicinal chemistry.