The cyclopropenyl cation (CPC) is the smallest member of the Hückel aromatic systems. This type of aromatic cations with two π-electrons delocalized over three 2p orbitals are known to have considerable thermodynamic stability, despite of their molecular strain. Current synthetic strategies, developed between 1950s and 1980s, rely on multistep sequences to generate a cyclopropene precursor that leads to the CPC upon (pseudo)halide, nitrile or hydride abstraction with strong Lewis acid or Brønsted acid. Those methods show severe limitations in the scope with regards to efficiency and structural diversity. To date, synthetic methods based on a catalytic platform that reaches CPCs in one step are unknown.
The evaluation of the CPCs reactivity as electrophiles has been demonstrated principally with hard nucleophiles (RM, M = Li, MgBr, SnBu3, phosphide) and recently, the more stable trisaminocyclopropenyl cations found applications as photoelectrocatalysts, gene delivery promoters or catholytes for nonaqueous redox batteries. However, the full synthetic potential of cyclopropenyl cations has been underdeveloped and underappreciated by the synthetic community, perhaps due to the lack of general one-step processes for their synthesis. CPCs have the potential to be exploited as electrophilic reagents in the regio and stereoselective C–H bond functionalization of aromatic rings and to reach cyclopropenes which are direct precursors of one of the most important saturated carbocycles in drug discovery, the cyclopropane.
Novel and stable CPCs as well as C–H bond cyclopropenation are highly innovative and could have direct impact in human health, paving the way for the development of new bioactive compounds containing cyclopropenyl/cyclopropanyl moieties in a straightforward manner from APIs and drug intermediates.
Late CPC wants to develop the first general catalytic synthesis of cyclopropenyl cations from readily or commercially available alkynes and exploit them as electrophilic reagents for the first time in late-stage functionlization to impact medicinal chemistry.
The specific objectives of this programme include:
(1) The development of the first catalytic methodology for the synthesis of a previously elusive family of CPCs.
(2) The use of the new CPCs as electrophilic reagents in the regio- and chemoselective couplings with aromatic nucleophiles for the synthesis of valuable cyclopropenes.
(3) The development of the first late-stage electrophilic C–H bond cyclopropenation in complex natural products and drug molecules.
