Abstract
Nucleophilic substitution on an sp³ carbon center is one of the most fundamental and widely used transformations in organic chemistry. While the stereochemical outcome of a SN2 reaction is well known - it takes place with configuration inversion - its unimolecular analog, the SN1 reaction, more often than not leads to racemic mixtures. It is also frequently accompanied by undesirable competing reactions, such as proton elimination, as well as rearrangements by hydride or alkyl migration. As a result, controlling stereochemistry in SN1-type reactions remains a major challenge.
In this talk, we present a novel, robust and fully predictable strategy for controlling the stereochemistry of SN1-type processes. This approach opens up new perspectives for the stereoselective synthesis of acyclic systems, based on the use of non-classical carbocations.
In specific SN1 reactions, our method enables the transformation to be directed selectively towards complete inversion or total configuration retention. It thus gives access to acyclic products obtained in the form of a single regioisomer, diastereoisomer and enantiomer, with several adjacent stereogenic centers. We will also show how to take advantage of well-documented carbocation rearrangements involving the breaking of C-C bonds, in order to form new stereo-defined C-C bonds at positions remote from the initial carbocation, with full stereochemical control, including in the presence of sensitive functional groups.
