Diketones, acid catalyzed acylation

Such reactions are normally base catalyzed. Scheme 76 illustrates the use of this reaction to provide both fused and bridged rings. Other techniques for synthesizing the keto ester from trimethylsilyl ethers are shown in Scheme 77. The diketones shown were usually isolated as a mixture of enols or enol ethers. Acid-catalyzed acylation also provides a route to diketones not readily obtained by other routes (Scheme 78). The acid catalysts included polyphosphoric acid and naphthalene-2-sulfonic acid. In the latter example continuous removal of water facilitated the reaction. A related reaction involved treatment of an acid chloride with silver perchlorate in nitromethane (equation 41), although the yield of diketone was low. ° ... 

Complementary to the acylation of enolate anions is the acid-catalyzed acylation of the corresponding enols, where the regiochemistry of acylation can vary from that observed in base-catalyzed reactions. Although the reaction has been studied extensively in simple systems, it has not been widely used in the synthesis of complex molecules. The catalysts most frequently employed are boron trifluoride, aluminum chloride and some proton acids, and acid anhydrides are the most frequently used acylating agents. Reaction is thought to involve electrophilic attack on the enol of the ketone by a Lewis acid complex of the anhydride (Scheme 58). In the presence of a proton acid, the enol ester is probably the reactive nucleophile. In either case, the first formed 1,3-dicarbonyl compound is converted into its borofluoride complex, which may be decomposed to give the 3-diketone, sometimes isolated as its copper complex.164... 

A key step in the approach to 3(2//)-furanone ring systems via the acid-catalyzed cyclization-dehydration of appropriately substituted a -hydroxy-l,3-diketones involves the acylation of a-hydroxy-ketone dianions 11141... 

Furans can be prepared by acid catalyzed cyclization of masked 1,4-diketones. /3-Chloroallyl ketones which are obtained by alkylation of enamines or enolate ions behave as masked 1,4-diketones and afford furans on treatment with acid (67JA4557). 2,4-Dialkyl-furans (40) have been prepared by cyclization of the 3-chloroallyl ketone (39), which may be obtained by acylation of allyl chlorides (73KGS1434). 

The first synthesis of a natural diarylheptanoid, i.e. of curcumin (1) (the only compound of this type known at that time), was described by Lampe and his coworkers (4). They condensed carbomethoxyferuloyl chloride (117) with ethyl acetoacetate, decarboxylated the product (118) to the diketone 119 which was then repeatedly acylated with the acid chloride 117. Acid catalyzed deacetylation to 119 followed by removal of the blocking groups gave finally curcumin (1). 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Diketones.1 Trimethylsilyl enol ethers are C-acylated by acid chlorides in the presence of zinc chloride or antimony(III) chloride. No other Lewis acids are useful. The reaction provides a convenient route to 1,3-diketones in good to excellent yield. Addition of diethyl ether before quenching of the reaction catalyzed by ZnCl2 improves the yield but has no effect on the SbCl3-promoted reaction. 

Etiolates formed by organocopper conjugate addition may be acylated cleanly by acid chlorides to give 3-diketones. Although 0- and C-acylation are both possible, the latter is favored by the use of acid chlorides rather than anhydrides and by the use of diethyl ether as solvent, rather than DME. Good yields of 3-diketones have been obtained by acylation of the anions derived from both acyclic and cyclic unsaturated ketones with cuprates, or in copper-catalyzed Grignard reactions. Some synthetic applications are given in Scheme 54. 

Base-catalyzed cyclocondensation (a) of alkynones with malonic esters and (b) of 1,3-diketones with acetylenic acids yields esters 27 of 2H-pyran-2-one-3-carboxylic acid or 5-acyl-2H-pyran-2-ones 29, respectively. In both cases, Michael additions are the primary steps, which afford 5-oxopentenoic esters 26 or 28 providing the 2H-pyran-2-one system by enolization and enollactone formation [12] ... 

Transition metal-catalyzed silicon-based cross-coupling reaction has emerged as a versatile carbon-carbon bond-forming process with high stereocontrol and excellent functional group tolerance [35], For example, (a-benzoyloxy)alkenylsilanes 105, prepared as a pure -isomer by 0-acylation of a lithium enolate derived from the corresponding acylsilane, reacts with carboxylic acid anhydrides in the presence of [RhCl(CO)2]2, giving rise to a-acyloxy ketones 106, which are then converted into 1,2-diketones by acidic workup (Scheme 5.27) [36]. 

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