Takeo Fukuzumi

Cyclic ketimines as superior electrophiles for NHC-catalyzed homoenolate additions with broad scope and low catalyst loadings.

Cyclic sulfonyl imines derived from ketones were identified as stable and readily prepared compounds that serve as superior electrophiles for N-heterocyclic carbene (NHC)-catalyzed annulations with alpha,beta-unsaturated aldehydes to afford highly substituted gamma-lactams. Their superior reactivity and properties are highlighted by the first example of NHC-catalyzed reactions of enals with low catalyst loadings (0.5 mol %) and broad substrate scope encompassing alkyl, aryl, and heteroaromatic substituents. These findings and supporting studies suggest an alternative, ene-like mechanism rather than the catalytic generation of a catalyst-bound homoenolate equivalent.

A Reagent for the Convenient, Solid-Phase Synthesis of N-Terminal Peptide Hydroxylamines for Chemoselective Ligations

A new N-sulfonyloxaziridine reagent for the conversion of N-terminal peptide amines to the corresponding hydroxylamines without overoxidation or erosion of stereochemistry is described. The products are N-terminal hydroxylamines, which are substrates for chemoselective amide-bond forming reactions with alpha-ketoacids. The success of this reagent arises from covalent precomplexation with the substrate via imine bond formation followed by an intramolecular oxygen-atom transfer to the amine. An unexpected stereochemical mismatch between the racemic reagent and the chiral peptide substrates was addressed by the preparation of an enantipure version of this reagent and provides further support for the proposed mechanism.