Acyl compounds, active Carboxylic acid esters

Primary, secondary, and tertiary carboxylic amides, carboxylic esters, and carboxylic acids are protonated by mineral acids or sulfonic acids at the carboxyl oxygen to a small extent (Figure 6.9). This corresponds to the activation discussed in Section 6.2.3. This activation is used in acid hydrolyses of amides and esters, in esterifications of carboxylic acids and in Friedel-Crafts acylations of aromatic compounds with carboxylic acids. 

Keto esters and amides are versatile intermediates in organic synthesis and often are prepared from acyl Meldrum s acid adducts. This method involves formation of acyl Meldrum s adducts by reaction of Meldrum s acid with activated carboxylic acids followed by decarboxylation in the presence of nucleophiles such as alcohols or amines (Scheme 21.2). The ability of readily available acyl Meldrum s acids to react with various nucleophiles allows quick access to a variety of functionalized compounds. Apphcation of this methodology in synthetic chemistry has been widely exploited. For example, acyl Meldrum s adducts can react with imines to prepare pyridinones or... 

DEPC in combination with NEtj has proved to be a new efficient reagent for the direct C-formylation of active methylene compounds with carboxylic acids and also for the iV-acylation (peptide bond formation), 5-acylation (thioester formation) and O-acylation (esterification).4,5 Reaction of DEPC with carboxylic acids 11 in the presence of triethylamine produces transient acyl cyanides, which in the presence of alcohols or thiols results in the formation of the corresponding esters (12) or thioesters (13). 

N-Acylcarboxylic acid amides s. a. Diacylamines, mixed Acyl compounds, active s. Carboxylic acid esters, active Acylcyanides... 

N-Formylsaccharin 102, an easily accessible crystalline compound, has been employed as an efficient CO source in Pd-catalyzed fluorocarbonyl-ation of aryl halides 103 to afford the corresponding acyl fluorides 104 (13OL5370). Reagent KF is expected to serve as a dual role not only as a nucleophile for Pd-catalyzed carbonylation but also as an activator for CO generation from 102. The reactions use a near-stoichiometric amount of the CO source (1.2 eq) and tolerate diverse functional groups. The acyl fluorides 104 can be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure. 

In the previous review (91YGK205, 99H1157), we reported that l-hydroxy-4-nitroindole forms active ester derivatives by reaction with carboxylic acids, which can be applied to acylation of various nucleophiles. To expand the scope of the reaction and obtain novel fungicidal compounds, an attempt has been made to prepare derivatives of wasabi phytoalexin 109 (98P1959). 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

From a biosynthetic perspective, naturally occurring tetramic acids can be regarded to arise from the assembly of an amino acid and an activated acyl entity derived from an acetyl group or a more complex activated ester, Fig. (1). Alternatively, the simple tetramic acid formed can undergo substitution at C-3 with a second acyl group. On this basis, compounds such as lactacystin (5) have not been considered [11]. The carboxylic acid... 

Diphenylthieno[3,4-d][l,3]dioxol-2-one 5,5-dioxide (304) can serve as an activating agent for peptide synthesis (76AG(E)444). The esters (305) are formed readily on admixture of a carboxylic acid with (304) in an aprotic solvent in the presence of pyridine. The activated esters (305) are stable, crystallizable compounds which react with amines readily to furnish the corresponding amides (Scheme 65). Competition experiments reveal that the esters (305) are more effective acyl transfer agents than the p- and o-nitrophenyl esters often used in peptide synthesis. 

The Gabriel-Cromwell reaction of amines with chiral c/., 3-unsaturated a-bromo carbonyl compounds was exploited for the synthesis of aziridine-2-carboxylic acid derivatives. 79 This procedure was optimized for a solid support synthesis in which the peptide resin was acylated with 2,3-dibromopropanoic acid active ester in the presence of 3 equivalents of NMM to produce directly on resin the a-bromoacrylamide for the addition of amines to produce the aziridine ring. 80 ... 

Except for lactam n-acyl derivatives, compounds such as esters, anhydrides and halogen anhydrides of carboxylic acids, which can activate lactam polymerization, can also be used as activators (promoters). 

Preparation of cyclic compounds via 5-exo-trig or 6-exo-trig manner with O-acyl esters (2) proceeds effectively [36-40]. Eq. 8.13 shows the preparation of biologically active perhydroindole-2-carboxylic acids (22a) and (22b) from an aspartic acid derivative via 5-exo-trig manner. 

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