The asymmetric nucleophilic catalysis by fluoride ions at a carbon-based electrophile has been demonstrated for the first time. Using a library of ad hoc designed bifunctional phase-transfer catalysts in which both the anion and the cation are directly involved in the reaction, the desymmetrisation of meso-succinic and -glutaric anhydrides is possible. 19F NMR spectroscopic studies support the intermediacy of an acyl fluoride intermediate.

A new bifunctional phase-transfer catalyst that employs hydrogen bonding as a control element was developed to promote efficient enantioselective S 2 reactions for the construction all-carbon quaternary stereocenters in high yield and excellent enantioselectivity (up to 97 % ee) utilizing the alkylation of a malleable oxindole substrate. The utility of the methodology was demonstrated through a concise and highly enantioselective synthesis of (-)-debromoflustramine B.

The first divergents ynthesis of both g-amino acid and g-lactam derivativesf rom meso-glutaric anhydrides is described. The organocatalytic desymmetrisation with TMSN 3 relies on controlled generation of an ucleophilic ammoniuma zide species mediated by ap olystyrene-bound base to promote efficients ilylazidation. After Curtiusr earrangemento ft he acyl azide intermediatet o access the corresponding isocyanate, hydrolysis/alcoholysis provided uniformlyh igh yields of g-aminoa cids and their N-protected counterparts. The same intermediates were shown to undergo an unprecedented decarboxylation-cyclisation cascade in situ to provide synthetically useful yields of g-lactamd erivatives without using anyf urther activating agents. Mechanistic insights invoke the intermediacy of an unconventional g-N-carboxyanhydride (g-NCA) in the latter process. Among the examples prepared using this transformation are 8APIs/moleculeso f considerable medicinali nterest.

The first small anion‐triggered Steglich rearrangements are reported. Tetrabutylammonium carboxylates‐, cyanide‐ and fluoride promote the O‐ to C‐acyl transfer of a range of O‐acylated oxindoles to form 3,3‐disubstituted oxindole products with new quaternary stereocentres. DFT calculations on the TBAF‐mediated reaction strongly support a nucleophilic catalysis mechanism involving initial attack of fluoride on the O‐acyl group to give an enolate and an acyl fluoride in the rate determining step.