Cationic C-C fragment coupling – CatCoupling

According to organic chemistry textbooks, the bimolecular nucleophilic substitution reaction (SN2) is limited to primary and secondary electrophiles. For tertiary electrophiles, based on steric arguments, only the SN1 mechanism is applicable, resulting in a general loss of stereochemical information at the affected carbon center. However, an inspection of the literature reveals that there are several exceptions to this rule with regards to heteroatom nucleophiles. Here we propose that under well-defined conditions it should be possible to perform substitution reactions of tertiary electrophiles and organometallic reagents with inversion of configuration. These transformations are not currently part of the repertoire of organic synthesis, yet holding exciting potential to solve important challenges in constructing complex organic molecules. The CatCoupling project focuses on various fundamental investigations concerning the interplay between Lewis acid, leaving group and organometallic reagent, the stereochemistry involved in such processes and rational approaches towards the identification of new reactions. The realization of this proposal will push the use of organometallic reagents into widely unexplored areas of chemical reactivity. In consequence, new synthetic strategies will be made available in particular in the challenging field of molecules incorporating a quaternary carbon stereocenter.