Base-catalyzed, acylation compounds

Acylation of 3,4,7,8-tetramethylglycoluril by the method of Sun and Harrison [34] leads to the monoacyl derivatives, which can be further selectively acylated with lithium diisopropylamide (LDA) and acyl chlorides. The resulting symmetrical or asymmetrical diacyl compounds undergo a base-catalyzed acyl transfer reaction. Consequently, the glycoluril acts as a temporary template that facilitates a condensation between acyl units. The absence of O-acylation products is explained by chelation of the lithium by the intermediate enolate. 

The pharmacologically active and commercially important 5//-dibenz[/>,/]azepines 40 are available by base-catalyzed dehydrobromination of their 5-acyl- 10-bromo-l 0.11-dihydro derivatives 38,118 followed by hydrolysis of the isolable tV-acyl compounds 39 29.119-121... 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

Acyl-phosphates also display an unusual U -shaped pH profile for the rate of hydrolysis (see Fig. 1). This reflects the fact that acyl-phosphate compounds are susceptible to both acid- and base-catalyzed hydrolysis, and the shoulder at less acidic pH values reflects the slightly faster hydrolysis of the monoanion, compared to the dianion. Observation of a U -shape pH-rate profile for a previously uncharacterized phosphoryl-enzyme intermediate supports the inference that an acyl-phosphate has formed. 

The intermediacy of an anhydro base (57) was referred to in Scheme 46. Analogous anhydro bases (pyridone methides) can be formed by deprotonation of quaternary salts of 2- and 4-benzylpyridines and the like. The pyridone methides are usually highly reactive and not readily isolable some stable examples are shown in Scheme 49. Pyridine methides are intermediates in the base-catalyzed alkylation and acylation reactions of pyridinium salts at the exocyclic carbon. Compounds of type (60) have been estimated to have 25-30% dipolar character. Protonation of (60) occurs at the 2 - and 3 -positions in the ratio 4 1 respectively (70JCS(C)800). 

Cobalt complexes derived from Schiff bases 388 catalyzed the hydroxyacylation of electron-deficient alkenes (Fig. 90) [431, 432]. Thus, methyl acrylate 387 reacted with aliphatic aldehydes 386 in the presence of 5 mol% of the in situ generated catalyst, molecular oxygen, and acetic anhydride to 2-acyloxy-4-oxoesters 389 in 56-77% yield. When acetic anhydride was omitted, the yields of products were lower and mixtures of the free hydroxy compounds and acylated compounds resulting from Tishchenko reactions were obtained. Electron-rich alkenes did not undergo the transformation, since the addition of the acyl radical is much slower. The acylcobalt species inserts oxygen instead and acts as an epoxidation catalyst. 

Assuming that the above enzymatic reaction was run in an ether-rich medium, the products can be isolated by thin-layer chromatography. Thus, the fatty acids released from the sn-2 position can be easily recovered as well as the lysophosphatidylethanolamine. The latter derivative will contain the fatty acyl groups associated with the sn-1 ester position. Base-catalyzed metha-nolysis of the lyso compound will produce the methyl esters. In the usual instance, these will contain mainly saturated chains. In any event the attack by phospholipase A2 can proceed smoothly to completion. These results would strongly support an sn-3 stereochemical configuration for the parent diacylphosphatidy lethanolamine. 

The phenyl derivative (173 R1 =Ph, R2 = H) has been obtained (66%) by N-amination of 1-phenacylpyrazole followed by base-catalyzed cyclodehydration. Using a different approach the l-acyl-2-methyl compound (173 R1 = Me, Rz = COMe) is formed (58%) by condensation of 1-aminopyrazole with 3-chloropentane-2,4-dione [CHCl(COMe)2]. Treatment of the derivative (173 R1 = Me, R2 = COMe) with hot concentrated hydrochloric acid gives the 2-methyl derivative (173 R1 = Me, R2 = H) (78TL1291). 

The importance of a-diazo ketones as synthetic intermediates has led to the development of a number of general methods for their preparation.5 Particularly popular approaches include the acylation of diazo alkanes and the base-catalyzed "diazo group transfer" reaction of sulfonyl azides with 8-dicarbonyl compounds.6-7 While direct diazo transfer to ketone enolates is usually not a feasible process,8-9 diazo transfer to simple ketones can be achieved in two steps by employing an indirect deformylative diazo transfer strategy in which the ketone is first formylated under Claisen condensation conditions, and then treated with a sulfonyl azide reagent such as p-toluenesulfonyl azide.6a,6c,9,i0,11... 

Complex multi-ring heterocyclic molecules like 136 have been prepared in one pot and under mild conditions by combining a base-catalyzed intermolecular Michael addition reaction of an a,p-unsaturated carbonyl compound and a suitable p-ketoamide pronucleophile with an acid-catalyzed intramolecular N-acyl iminium ion cyclization of the resulting adduct (Scheme 3.40). 

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