Ammonium enolates, catalytic protonation

The Baylis-Hillmann reaction is another bench-mark reaction in which ionic liquids have been successfully tested. The catalytic cycle of the Baylis-Hillmann reaction is reported in Figure 7. The catalyst is a highly nucleophilic tertiary amine, generally DABCO, or a tertiary phosphine, which adds to the oc,p-unsaturated electrophile in a 1,4 fashion to deliver an enolate which, in turn, adds to the aldehyde. The critical step is now a proton transfer from the enolisable position to the oxygen atom this process is catalysed by an alcohol which plays the role of a proton shuttle between the two foregoing positions. Once a P-ammonium enolate is formed, a rapid P-elimination takes place, delivering the Baylis-Hillmann condensation product. 

One arm of the imidazolium scaffold contains the catalytic centre, a bridgehead nitrogen atom possessing the required nucleophilicity, the second arm contains a Broensted acidic primary alcohol capable to speed up the critical proton transfer step which leads to the P-ammonium enolate intermediate, direct precursor of the final Baylis-Hillmann product. The reaction of RiCHO and CH2=CH-R2 is carried out under solvent free conditions at room temperature, catalyst 10 can be readily recovered from the reaction mixture and reused for at least 6 times without significant loss of catalytic activity. A few results are reported in Table 3. 

Tokunaga and coworkers reported the enantioselective hydrolysis of enol esters (111) in the presence of catalyst 8b under phase-transfer conditions with aqueous KOH. The proposed mechanism of this reaction has the protonation of the ammonium-enolate ionic complex as the enantioselective step. Their achievement of the first nonbiomimetic asymmetric hydrolysis of esters catalysed by organocatalysts with high catalytic efficiency in buffer-free conditions has considerable potential to replace enzymatic resolutions in industrial processes (Scheme 16.41). ... 

Based on the characteristic features of this neutral phase-transfer reaction, an assumed catalytic cycle of the conjugate addition of 3-aryloxindole was proposed as shown in Scheme 14.6. For the promotion of the reaction, the combination of the H20/toluene biphasic reaction system with a lipophilic phase-transfer catalyst such as (S)-7 was indispensable. In the formation of ammonium enolate 8, HBr is simultaneously generated, and in the case of toluene solvent alone the reaction mixture becomes homogeneous and hence the reverse reaction from 8 to 7 (i.e., protonation of 8) may be fast. However, in the H20/toluene biphasic reaction system, hydrophiUc HBr moves into the water phase smoothly, while UpophiUc ammonium enolate 8 remains in the toluene phase. Consequently, protonation by the contact of ammonium enolate 8 and HBr was suppressed, and hence the transformation from 7 to 8 was efficiently promoted. Then, ammonium enolate 8 and nitroolefin would combine in the toluene phase to promote the conjugate addition step (8 to 9 in Scheme 14.6) smoothly. 

---