Acid bromide, enol from carboxylic acid

Acid bromide, enol of, 849 from carboxylic acids, 800... 

This latter thought has an important consequence if compounds with C=0 double bonds are sorted in decreasing order of resonance stabilization of their C=0 group they are at the same time sorted according to their increasing propensity to enolization. So as the resonance stabilization of the C=0 double bond decreases from 22 kcal/mol to somewhere near zero in the order carboxylic acid amide > carboxylic acid ester/carboxylic acid > ketone > aldehyde > carboxylic acid chloride/-bromide, the enol content increases in this same order (Figure 12.2). These circumstances immediately explain why no enol reactions whatsoever are known of carboxylic acid amides, virtually none of normal carboxylic acid esters/carboxylic acids, but are commonly encountered with ketones, aldehydes and carboxylic acid halides. 

The procedure described here involves the metallation of dihydrofuran and subsequent alkylation with an alkyl iodide (bromides are much less reactive).5 The resulting substituted dihydrofuran, the intermediate postulated in the Larson procedure, is then treated with chromic acid to hydrolyze the enol ether and oxidize the resulting primary alcohol to the corresponding carboxylic acid as in the Larson procedure. The isolated oxidation product is of suitable purity for subsequent reactions, but if necessary, recrystallization from hexanes is readily accomplished. ... 

The TDS ester is prepared from a carboxylic acid and the silyl bromide by reaction with AgOTf in CH2CI2 (84-93% yield). It is stable to -BuLi, LiAlHt, AcOH, aqueous NaOH at 50 C, and 1 N HCl at 40°C, but is cleaved with Pyr-HF, THF, 50°C and f-BuOK/DMSO at 25°C. It is not deprotonated at the a-carbon of the ester with -BuLi and thus this group also serves to protect these hydrogens from enolization. ... 

The idea that a polymer support could help to isolate polymer-bound reactive species from one another was suggested and illustrated sh y after the flrst solid phase peptide syntheses. Cyclic tetrapeptides were obtained in higher yields from polymer-bound 2-nitrophenyl esters than from analogous micromolecular active esters (Scheme 1) (X). Polymer-bound ester enolates were formed at 0 °C and trapped with alkyl bromides and carboxylic acid chlorides with no competing selfcondensation (Scheme 2) (Z). Soluble analogs gave primarily self-condensation. 

Whereas carboxylic esters had been considered to be inert under the conditions of boron enolate formation by enolization [2c], Corey s group elaborated protocols that allowed for the generation of boron enolates from esters. Thus, trans-boron enolates 100 result from simple carboxylic esters by deprotonation, while 5-phenyl thiopropionate formed cis-enolate 101 - in accordance with Masamune s observation. In both cases, the C2-symmetric diazaborolidine 99 served as the Lewis acid for enolization (Scheme 2.28) [112]. The stereochemical divergence of ester and thioester has been rationalized by postulating an E2-type elimination mechanism starting from the complex 102 that loses bromide in a... 

The Pd-catalyzed coupling reaction of the propargyl acetate 53 and 4-pentynoic acid (54) in the presence of potassium bromide produced the unsaturated exo-enol lactone 55 [66], The reaction proceeded via oxypalladation of the triple bond of 54 with an allenylpalladium intermediate, which was formed from Pd(0) and 53 and the carboxylate as shown in Scheme 3.30. 

In a similar manner the reaction of sodium 2-bromobenzoate with the carbanion derived from pentane-2,4-dione initially yields the dioxo acid (490). In ethanol, a retro-Claisen deacylation leads to 2-acetonylbenzoic acid (491), but at higher temperatures 3-methyI-isocoumarin is formed (Scheme 177) (75JCS(P1)1267). Copper(I) bromide may be used as a catalyst, although this is only necessary for the initial step. The cyclization process is considered to involve reaction between the carboxylate group and an enolate ion arising from loss of one of the acyl groups. A similar reaction occurs with l-bromo-2-naphthoic and 3-bromo-2-naphthoic acids giving the naphtho[2,l-c]pyran-4-one (492) and naphtho[2,3-c]pyran-l-one (493), respectively. 

The Lessen rearrangement differs from the Hofmaim rearrangement only in that the leaving group is carboxylate anion rather than bromide ion. The starting material is the ester of hydroxamic add (RCONHOH), which is decomposed in presence of base. The hydroxamic acids exhibit tautomerism - the keto-form is termed hydroxamic form while the enol-form is called hydroximic add. As the reaction is normally carried out in water, the process furnishes the amine directly (Scheme 6.39). 

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