Imidazolium-derived homoenolates

The Bode group have documented an NHC-catalyzed enantioselective synthesis of ester enolate equivalents with a,p-unsaturated aldehydes as starting materials and their application in inverse electron demand Diels-Alder reactions with enones. Remarkably, the use of weak amine bases was crucial DMAP (conjugate acid = 9.2) andN-methyl morpholine (NMM, conjugate acid pAa = 7.4) gave the best results. A change in the co-catalytic amine base employed in these reactions could completely shift the reaction pathway to the hetero-Diels-Alder reaction, which proceeded via a catalytically generated enolate. An alternative pathway that occurred via a formal homoenolate equivalent was therefore excluded. It is demonstrated that electron-rich imidazolium-derived catalysts favor the homoenolate pathways, whereas tri-azolium-derived structures enhance protonation and lead to the enolate and activated carboxylates (Scheme 7.71). 

In order to separate structural effects from the electronic differences of these two catalyst classes. Bode synthesized chiral imidazolium salt 57 (Scheme 14.28). This allowed direct comparison of imidazolium versus triazolium precatalysts across a number of different reaction manifolds including those involving the catalytic generation of homoenolate equivalents, ester enolate equivalents, and acyl anions. These studies conclusively demonstrated that imidazolium-derived catalysts are superior for homoenolate reactions with less reactive electrophiles, while the triazolium-derived pre-catalysts are preferred for all other reactions. Interestingly, from the currently published body of the work, it does not appear to be any effects from the counterion of the azolium pre-catalysts in the presence of bases. 

Nair and coworkers showed in 2006 that Michael acceptors (112) can also act as electrophiles for achiral imidazolium-derived homoenolates, although the expected cyclopentanone products were not obtained [96]. Instead, dx-substituted cyclopentenes 114 resulting from a proton transfer, aldol, P-lactone formation, and decarboxylation sequence were isolated (Scheme 18.20). 

Homoenolate Protonation The p-protonation of homoenolates has been observed by Scheidt and co-workers, resulting in a redox transformation of enals to afford saturated esters 48. This process is catalysed by the NHC derived from imidazolium salt 46 and utilises phenol as a proton source [14]. A range of primary and secondary alcohols, and phenol itself, are competent nucleophiles with which to trap the acylazolium intermediate 47 generated by protonation (Scheme 12.8). 

The requisite homoenolates were prepared through treatment of cirmamaldehyde derivatives, e.g., 147, with (V-heterocyclic carbenes derived from imidazolium ion 148 and DBU. 

The choice of imidazolium vs. triazolium pre-catalyst is subtler. Triazolium-derived NHCs are nearly always preferred, with the exception of certain processes proceeding via catalytically generated homoenolate equivalents. For example, the y-lactone forming annulations of a,p-unsaturated aldehydes and aromatic aldehydes give extremely poor conversion with triazolium-derived pre-catalysts but proceed in excellent yield with IMes-HCl 19. When more reactive electrophiles, such as a-trifluoromethylketone or saccharine-derived imines, ° are employed, other catalyst classes including N-mesityl substituted triazoliums and thiazoliums again become viable pre-catalysts. This can be attributed to the increased electron donating... 

---