Molecular Editing Towards Non-Classical Carbocations Enables Unprecedented Stereocontrolled SN1 Reactions

SN1 reactions represent a possibility for stereocontrolled substitutions on tertiary and quaternary carbons, however the realization of this transformations remains an open issue.

To tackle the challenge of realizing general protocols including a stereochemical information in SN1 reactions, an intriguing viewpoint involve the exploitation of non-classical carbocation (NCCs).

NCCs intrinsically have a stereochemically robust nature since one face is shielded by their carbon skeleton, allowing an easier control of stereochemistry.

In the last years, Marek’s group have been interested in the chemistry of non-classical carbocations resulting from the dissociation of cyclopropyl carbinols.

The group has faced and rationalized this challenge, and stereospecific SN1 at quaternary stereocenters of cyclopropanes has emerged as a powerful tool for the construction of stereodefined acyclic structures.

A complete inversion of configuration was observed in the presence of different nucleophiles, filling a methodological gap in organic chemistry.

To overcome the current state of the art, the establishment of a general approach that would control stereochemistry for SN1-type reactions extending the generality of the already impressive results obtained by the host group is meticulously planned.

The aim of this proposal is to broaden the chemistry of stereocontrolled SN1 using 4-membered rings for the creation of acyclic stereo- and enantiodefined systems.

Furthermore, in the following sections a detailed description about the impact that this action will have on the growth of the hosting group, the synthetic chemistry community and my career is highlighted.