Baylis-Hillmann reaction

The tertiary amine-catalyzed C-C bond forming reaction of aldehydes with a, 3 -unsaturated compounds is known as the Baylis-Hillmann reaction ". The catalytic amount of tertiary amine such as l,4-diazabicyclo(2.2.2)octane (3.28) is used. 

Research by J. Jauch showed that in the case of highiy base-sensitive substrates the Baylis-Hillmann reaction can be carried out by using lithium phenylselenide, which is a strong nucieophile but oniy weakiy basic. This variant of the reaction is highly diastereoselective and was successfully applied to the total synthesis of kuehneromycin... 

ORGANOCATALYTIC BAYLIS-HILLMANN REACTION IN IONIC LIQUIDS... 

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. 

Figure 8. DABCO-catalysed Baylis-Hillmann reaction in an ionic liquid.

Strategy C, solvent-less conditions. An example of catalyst design by tailoring a task specific ionic liquid in such a way to fulfill all the mechanistic requests of the Baylis-Hillmann reaction is offered by imidazolium derivative 10 (Figure 9). 

TABLE 3. Baylis-Hillmann reactions catalysed by 10 under solvent-free conditions. 

Figure 11. Enantioselective aza-Baylis-Hillmann reaction in the chiral ionic liquid 11.

The Baylis-Hillmann reaction, used for the preparation of functionalized a-sub-stituted acrylates, was reported to be improved by sonication (Fig. 31). ... 

In rigid and soft PUR foams, mainly tertiary amines are used as catalysts. They may in part remain in the foams after polyaddition and are capable, e.g., in contact with a PC film, of migrating into the film, thus causing a red discoloration of the PVC. The mechanism of this discoloration proceeds by what is called a Baylys-Hillmann reaction. The tertiary amine first acts as a catalyst for HCl elimination from the PVC chain and subsequently adsorbs to the polymer chain that already contains conjugated double bonds at this point [686]. 

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. 

Morita-Baylis-Hillmann carbonates were involved in an asymmetric allylic substitution reaction with diphenylphosphine oxide in the presence of chiral thiourea-phosphine organocatalysts. The enantioselectivity was > 96% (Scheme 28). ... 

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