Esters acylation with acid chlorides

The first is the acylation of the magnesium derivative of diethyl malonate. The magnesium atom prevents 0-acylation with acid chlorides, and decarboxylation (p. 678) removes the redundant ester group. 

Camphor-10-sulfonic acid (1) is available in large quantities in both enantiomeric forms. In only 3 steps the cyclic sulfonamide 2 (sultam) can be synthesized, which can be acylated with acid chlorides after deprotonation with sodium hydride (Scheme 1) [1, 2]. The resulting amides 3 are considerable more reactive towards nucleophiles than the corresponding carboxylic esters and the a,/ -unsaturated derivatives undergo, with excellent selectivities, Diels-Alder reactions or Michael additions under mild conditions. Al-... 

The organocopper reagents are more selective and can be acylated with acid chlorides without concomitant attack on ketones, alkyl halides, and esters. 

These compounds are listed in Table XLVIII. iV-Acyl-3,5-pyra-zolidinediones are prepared either by acylation with acid chlorides,976 in which case acylation at C-4 occurs, or by cyclization.506,976 Cycliza-tion involves condensation of semicarbazides with malonic esters or cyclization of 3-acylsemicarbazides. 

Treatment with zinc/copper couple activated by ultrasound in dimethylacetamide gave the zinc homoenolate 57 stabilised by chelation to either the ester or the carbamate. Acylation with acid chlorides and Pd(0) catalysis gave the enantiomerically pure y-oxo-amino acids 58 in good yield. 

Reactions of Reformatsky reagents with esters or with acid chlorides generally give only low yields of P-keto esters. Hauser reported that ethyl a-bromoisobutyrate could be acylated in reasonable yields with either the acid chlorides or the phenyl esters of aromatic acids, but the reaction fails with acylating... 

Unbranched and substituted alkyl carbamates, such as 146 or 147 [62,88] do not cause any problems in the deprotonation step. Deuteration (with CH3OD or dissolved CH3CO2D), methoxycarbonylation (gaseous CO2, followed by diazomethane after work-up or methyl chloroformate), alkylation with methyl iodide, substitution with trialkylsilyl chlorides, trialkyltin chlorides and even tri-methyllead bromide, addition onto aldehydes and ketones, and acylation with acid chlorides or esters, all proceed without difficulties. Although a ketone is formed in the latter reactions, which is at least 15 orders of magnitude thermodynamically more acidic than the alkyl carbamate we never observed enolate formation, racemization or epimerization - with one exception it occurred to some extent after formylation with formate esters [79]. 

Acylation with Acid Chlorides 1.132.6 Acylation with Carboxylic Esters... 

Reactions. BSF is readily acylated with acid chlorides and chloroformate esters to provide Al-TMS-iV-formylamides and carbamates, respectively, which readily undergo protodesilylation (eq 17). BSF reacts with 2 equiv of an alkyl or aryl isocyanate to give l,3,5-triazine-2,4-diones in good to excellent yields (eq 18). In the case of orthocarboxamides, iV-formylform-amidines can be obtained (eq 19) ... 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

The acylation of Wittig reagents provides the most convenient means for the preparation of allenes substituted with various electron-withdrawing substituents. The preparation of o-allenic esters has been accomplished by the reaction of resonance-stabilized phosphoranes with isolable ketenes and ketene itself and with acid chlorides in the presence of a second equivalent of the phosphorane. The disadvantages of the first method are the necessity of preparing the ketene and the fact that the highly reactive mono-substituted ketenes evidently cannot be used. The second method fails when the a-carbon... 

In their original communication on the alkylation and acylation of enamines, Stork et al. (3) had reported that the pyrrolidine enamine of cyclohexanone underwent monoacylation with acid chlorides. For example, the acylation with benzoyl chloride led to monobenzoylcyclohexanone. However, Hunig and Lendle (33) found that treatment of the morpholine enamine of cyclopentanone with 2 moles of propionyl chloride followed by acid hydrolysis gave the enol ester (56), which was proposed to have arisen from the intermediate (55). 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thi2izole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding N-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs. The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/.uma, and Tsuchihaski. " ... 

The preparation of imidazolides by acylation of imidazole with acid chlorides is sometimes limited by the inaccessibility or instability of the required acid chlorides (e.g., formyl chloride, highly unsaturated acid chlorides, etc.) or by side-reactions in the case of multifunctional systems. For these reasons and due to the availability of an easy and convenient procedure involving very mild conditions, imidazolides today are usually prepared directly from the corresponding carboxylic acids with jV -carbonyldiimida-zole (CDI) or one of its analoga (see page 16). Use of these reagents has become more and more the preferred method for activation of carboxylic acids to azolides and their further transacylation to esters, amides, peptides, etc. (see subsequent Chapters). 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

Nowadays, the most economical way of preparing hydroxamic acid derivatives is the reaction of hydroxylamine with acid chlorides or esters . Unfortunately, the preparation of acid chlorides is often tedious. In addition, it is very difficult to avoid further acylation during the reaction with hydroxylamine. 

An early synthesis of A5-palmitoy]-.S -[2,3-bis(palmitoyloxy)propyl]cysteine employed cysteine methyl ester, however, this leads to difficulties in the saponification step of the tri-palmitoylated residue. 96 The optimized procedure, in which the cystine di-fert-butyl ester is used, 90 is outlined in Scheme 6 after N-acylation with palmitoyl chloride, the ester is reduced to the cysteine derivative for S-alkylation with l-bromopropane-2,3-diol to yield chirally defined isomers if optically pure bromo derivatives are used. Esterification of the hydroxy groups is best carried out with a 1.25-fold excess of palmitic acid, DCC, and DMAP. The use of a larger excess of palmitoyl chloride is not recommended due to purification problems. The diastereomeric mixture can be separated by silica gel chromatography using CH2Cl2/EtOAc (20 1) as eluent and the configuration was assigned by comparison with an optically pure sample obtained with 2R)- -bromopropane-2,3-diol. 

---