Stabilized carbon nucleophiles hydrogen-bonding

Together with a shift of the proton from the a-carbon to the alkoxide oxygen, the tertiary amine is eliminated from the addition product to yield the unsaturated product 3. Early examples of the Baylis-Hillman reaction posed the problem of low conversions and slow reaction kinetics, which could not be improved with the use of simple tertiary amines. The search for catalytically active substances led to more properly adjusted, often highly specific compounds, with shorter reaction times." Suitable catalysts are, for example, the nucleophilic, sterically less hindered bases diazabicyclo[2.2.2]octane (DABCO) 6, quinuclidin-3-one 7 and quinuclidin-3-ol (3-QDL) 8. The latter compound can stabilize the zwitterionic intermediate through hydrogen bonding. ... 

Molecular modeling of the reaction predicts attack of the CN" ion on the re face of the iV-allyl benzaldimine carbon to provide an (5)-adduct. The aromatic ring of the imine and the quinuclidine hydrogen bond stabilizes the iminium above the pyridazine, blocking the rear face of the imine bond. Nucleophilic attack by CN is... 

Fig. 3.S Putative catalytic mechanism of the novel active site in fl7. The reaction begins when the nucleophilic oxygen of Thr-1 donates its proton to its own a-amino group and attacks the carbonyl carbon of the substrate. The negatively charged tetrahedral intermediate is stabilized by hydrogen bonding. The acylation step is complete when the a-amino group of Thr donates a proton to the nitrogen of the scissile peptide bond. A covalent bond is formed between the substrate...

Consideration of the stabilizing interaction between the low-lying CT "-orbital associated with the bond forming between the incoming hydride and the carbonyl carbon, and remote electron-donor o-orbitals led Cieplak to an explanation for many kinetic and stereochemical effects in cyclohexanones that were previously unexplained. The normal preference for axial attack in simple cyclohexanones was attributed to the improved electron-donor ability of carbon-hydrogen bonds over carbon-carbon bonds that would be antiperiplanar to the incoming nucleophile in the transition state. 

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