Base catalysis enolate formation

Lewis-Base Catalysis via Intermediate Formation of a Chiral Zwitterionic Enolate... 

These results establish that the base-catalyzed dehydration is slow relative to the reverse of the addition phase for the branched-chain isomer. The reason for selective formation of the straight-chain product under conditions of base catalysis is then apparent. In base, the straight-chain ketol is the only intermediate which is dehydrated. The branched-chain ketol reverts to starting material. Under acid conditions, both intermediates are dehydrated however, the branched-chain ketol is formed most rapidly, because of the preference for acid-catalyzed enolization to give the more substituted enol (see Section 7.3 of Part A). 

Catalysis of the enolization of indan-2-one (96 pKa = 12.2) by a-, j8-, y-, and modified cyclodextrins (of similar pKa) indicate that the latter act as general bases.139 There is also an inclusion component to the catalysis saturation kinetics consistent with 1 1 binding are observed for enolate formation. 

W-Alkylidene derivatives of glycine esters are the preferred starting compounds for the synthesis of unnatural amino acids via the deprotonation/alkylation procedure. Enolate formation is achieved with a strong base (LDA, BuLi, or phosphazene bases such as 2- tert-butylimino)-2-(ethylamino)-l,3-dimethyl-l,3,2-diazaphosphinane) or by phase-transfer catalysis (tetraalkylammonium salts with NaOH or the latter method allows... 

France S, Shah MH, Weatherwax A, Wack H, Roth JP, Lectka T (2(X)5) Bifunctioneil Lewis acid-nucleophile-based asymmetric catalysis mechanistic evidence for imine activation working in tandem with chiral enolate formation in the synthesis of p-lacttuns. J Am Chem Soc 127 1206-1215... 

These experiments employing acidic media were at best only semi-quantitative, and none comprised a systematic investigation of the catalysis. Nevertheless, they placed the transformation in a new light and broadened the opportunities for investigating its mechanism. From the dependence of the reactions on the concentrations of formate, acetate, or succinate ions, Ashmarin argued for a general add and base catalysis. The results of Petuely s experiments implied the same kind of catalytic effect, and Petuely wrote the reaction as an enolization catalyzed by acids and bases. 

Cyclodextrins with two imidazole groups on the primary hydroxyl side can enhance the enolate formation [86] of a simple bound ketone by bifunctional acid-base catalysis and accelerating the intramolecular aldol condensation of bound ketoaldehyde and dialdehyde. The aldolase mimics which catalyzed crossed aldol condensations were obtained by the assembly of (i-CD and various amino moieties as Schiff base [87]. 

The required aldol condensation, whether base- or acid-catalysed, exerts regioselectivity in the case of unsymmetrical ketones. For instance, the quinoline formation from methyl ethyl ketone and 2-benzoylaniline 66 occurs by base catalysis via the enolate giving the 2-ethyl-4-phenylquinoline 67. However, under acid catalysis via the enol, it affords 2,3-dimethyl-4-phenylquinoline 68 ... 

Acid catalysis of enol formation and base catalysis of enolate formation are also key steps in the aldol reaction. " The base-catalyzed reaction is shown in Figure 7.11, and the acid-catalyzed reaction is illustrated in Figure 7.12. The analogous reaction involving ketones is usually not synthetically useful because addition of an enolate ion to a ketone is less favorable than is addition to an aldehyde. ... 

Metal-free bisoxazolines catalyzed Diels-Alder reaction of A-substituted maleim-ides 137 with anthrone 136 derivatives was achieved by Gbbel, et al. Scheme 3.45 [61]. With the photoelectron spectra and other studies, the Br0nsted-base catalysis is assumed to be involved with formation of an ion pair between the protonated catalyst 138 and the anthrone enolate, acting as diene. 

The direct asymmetric aldol reaction is a powerful tool for C-C bond formation. Enamine-iminium catalysis is the most developed, and it is nicely complimented by other modes of activation that rely on hydrogen bond formation. Mechanistically, all proline-based catalysts activate donors through the formation of an enamine intermediate. Other activation modes rely on enolate formation, ionic interactions, or hydrogen bond formation, though the mechanism is not always known. 

Now, formation of an enolate anion (base catalysis) or the enol itself (acid catalysis) is generally fast and reversible so that the rate determining step is that one in which a a bond is made between the two carbon atoms. 

Mechanism of enol formation under both acid-catalyzed and base-catalyzed conditions, (a) Acid catalysis involves (D) initial protonation of the carbonyl oxygen followed by ( ) removal of H from the a position, (b) Base catalysis involves (Q) initial deprotonation of the a position to give an enolate ion, followed by (0) reprotonation on oxygen. 

---