NHC-catalyzed Generation of Homoenolates

Shortly thereafter, the Bode group reported the remarkable finding that a similar cyclopentene formation catalyzed by a chiral triazolium salt led to the formation of cis-disubstituted cyclopentenes in good yield and with 

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Scheme 7 New concept NHC-catalyzed generation of homoenolate equivalents...

From the first reports by Glorias and Bode on the NHC-catalyzed generation of homoenolate equivalents, it was recognized that conjugate additions of these species to unsaturated carbonyls could lead to cyclopentanones (Scheme 14.16). This was first achieved by Nair, who made the surprising finding that imi-dazolium-catalyzed additions of a,p-unsaturated aldehydes to chalcones led to... 

For NHC-catalyzed generation (For NHC-catalyzed generation of homoenolates) of enolates and acyl anions)... 

MCRs through Homoenolates Since the pioneering works by Bode [43] and Glorius and Burstein [44] describing the first NHC-catalyzed generation of reactive... 

Since these initial reports, the NHC-catalyzed generation of activated carboxylates from a-functionalized aldehydes has been extended to a remarkably wide range of substrate classes. Bode first reported the generation of activated carboxylates from a,p-unsaturated aldehydes as part of his work on the catalytic generation of homoenolates vide infra) These studies were further explored to develop improved catalysts and render this a general process. This work, which identified the uniquely high reactivity of A-mesityl substituted triazolium pre-catalysts as superior to all other catalyst classes for NHC-catalyzed redox reactions of a,p-unsaturated aldehydes, was crucial to the development of the remarkable annulation reactions described below. Zeitler reported analogous... 

The Scheidt group reported a highly diastereo- and enantioselective NHC-catalyzed reaction of a,p-unsaturated aldehydes with nitrones to afford y-amino esters. It is postulated that a rare six-membered heterocycle is generated as the initial product of the reaction, which gives the final y-amino ester product upon the addition of an alcohol. The mechanism for this reaction involves the addition of the homoenolate equivalent to the nitrone as the stereochemical-determining step, and catalyst turnover is promoted by an intramolecular acylation after the tautomerization of enol to acyl azolium (Scheme 7.60). 

In 2013, the Chi group disclosed a substrate-independent selective generation of enolates over homoenolate equivalents in NHC-catalyzed reactions of enals and chalcones. Acid co-catalysts play vital roles in control of the reaction pathways, as the acid might promote the enal p-protonation by increasing the proton concentration. Also, the competing enolate/homoeno-late pathways were found to be sensitive to the steric bulkiness of the enal and enone substrates (Scheme 7.74). 

In 2008, Zhang, Ying, and co-workers reported an organocatalytic p-amination reaction of a,p-unsaturated aldehydes with nitrosobenzene catalyzed by an NHC. Specifically, the addition of NHC to a,p-unsaturated aldehyde generates a homoenolate intermediate that reacts with nitrosobenzene to afford Af-phenylisoxazolidin-5-ones, followed by an acid-catalyzed esterification and Bamberger-type rearrangement to produce Af-PMP-protected p-amino esters. A preliminary study on the enantioselective reaction of... 

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). 

On the other hand, an example of direct amination of homoenolates catalyzed by 20mol% of chiral A-heterocyclic carbene has been achieved recently (Scheme 11.49). The reaction of hydrocinnamaldehyde with the acylaryldiazene catalyzed by in s/tM-generated NHC catalyst, from the reaction of precatalyst 62 with DBU, afforded chiral pyrazolidinones in moderate yield and excellent enantiomeric excess under mild reaction conditions [130]. In this process, the a, 3-unsaturated aldehyde after reaction with the carbene is converted, after rearrangement, into the... 

To date, there have been no reports of C-alkylations of the homoenolates or enolates catalytically generated with NHCs. Fischer and Fu, however, reported an interesting example of an NHC-catalyzed cyclization that proceeds via the... 

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