DMAP active esters from

Other acylating agents are similarly effective in the formation of ketones by reaction with homocuprates. Kim has demonstrated that activated esters such as the 2-pyridyl carboxylates are satisfactory cuprate traps.These esters can be prepared from carboxylic acids and 2-pyridyl chloroformate, provided a catalytic amount of DMAP is utilized (Scheme 35). 

In the particular case of the synthesis of the 14-member i polyoxomacrolide narbonolide, direct cyclization through the activation of thiol ester failed and then the mixed phosphoric anhydride derived from diphenylphosphorochloridate was developed to effect cyclization by Masamune and coworkers [39]. Fukumoto et al. [40] applied this procedure to the synthesis of the macrocyclic alkaloid vertaline 63). Thus, seco acid 62 was treated with diphenyl phosphorochloridate and triethylamine followed by refluxing in benzene in the presence of DMAP at high dilution afforded 63 in 54% yield (Scheme 20). 

The cinnamyl ester, which is somewhat more stable to nucleophiles, can be prepared from an activated carboxylic acid derivative and cinnamyl alcohol or by transesterification with cinnamyl alcohol in the presence of the H-Beta zeolite (toluene, reflux, 8h, 59-96% yield) or DMAP (CH3CN, heat). It is cleaved under nearly neutral conditions [Hg(OAc)2, MeOH, 23°C, 2-4 h KSCN, HjO, 23°C, 12-16 h, 90% yield] by treatment with sulfated Sn02, toluene, anisole, reflux or with K-10 clay and microwave heating. The latter conditions will also cleave crotyl and prenyl esters. Pd catalysis may also be used to induce cleavage either with a nucleophile or reductively with TEA/HC02H. ... 

Carboxylic, and arylsulfonic acid halides react rapidly with pyridines generating 1-acyl- and 1-arylsulfonylpyridinium salts in solution, and in suitable cases some of these can even be isolated as crystalline solids. The solutions, generally in excess pyridine, are commonly used for the preparation of esters and sulfonates from alcohols and of amides and sulfonamides from amines. 4-Dimethylaminopyridine (DMAP) is widely used (in catalytic quantities) to activate anhydrides in a similar manner. The salt derived from DMAP and t-butyl chloroformate is stable even in aqueous solution at room temperature. " ... 

Carboxyl Activation Synthesis of Esters and Amides from Carboxylic Acids. 4-(Dimethylamino)pyridinium chlorosulfite chloride is more reactive than either thionyl chloride or thionyl chloride/pyridine for carboxyl activation. Aliphatic and aromatic, as well as amino acids (in racemic form), undergo activation (via the acyl halide) and subsequent esterification by reaction with an alcohol at — 20 °C (eq 1). The esterification step requires the addition of a second equivalent of DMAP and this method has been applied to a range of functionalized carboxylic acids. 

Eligh yields of esters are obtained from both acid-sensitive (cyanoacetic acid) and base-sensitive carboxylic acids (3-phenyl-propionic acid and trichloroacetic acid) and, in these latter cases, use of 4-(dimethylamino)pyridinium chlorosulfite chloride is much more effective than use of thionyl chloride alone. The esterification process has been claimed to be independent of the steric environment of the carboxyl function, though this reagent may be of more limited value with heavily substituted benzoic acids. Carboxyl activation, in the presence of a primary amine, leads to the corresponding amide in excellent yield (eq 2). In both the esterification and amidation processes and the oxime dehydration reaction discussed below, recovery of DMAP is straightforward. 

In addition to the general usefulness of this class of compounds, the popularity of this chemistry is largely due to the facile preparation of the starting materials (Scheme 7). The most straightforward method of preparation of Barton esters of types I to IV is acylation by activation of the corresponding carboxylic acid (paths A and B). Accordingly, the hydroxamic acid sodium salt can be O-acylated with the acyl chlorides or, alternatively, the free hydroxamic acid can be condensed with primary carboxylic acids in the presence of N,W -dicyclohexylcarbodiimide and dimethylaminopyridine (DMAP). Likewise, condensation of the free thiohydroxamic acid or the corresponding sodium salt with the mixed anhydride formed from the acid and isobutyl chloroformate in the presence of N-methylmorpholine has proven to... 

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