0-Diketones 2-acyl-, cyclic

One of the most actively investigated aspects of enamine chemistry has been the acylation process (i). Initial intensive studies by Hiinig (373-375) showed the ease of preparing a variety of 9-diketones and particularly the synthetic potential of acylated cyclic ketones as intermediates in the preparation of aliphatic keto acids, keto dicarboxylic acids and diketo dicarboxylic acids (376-378). 

A range of acylic silyl diketonates and cyclic acetylacetonates have been reported, which possess enol ether structures with acyl cis or irons to the silyl group. The ratio of cis to irons in both series appears to depend on the incipient... 

Intramolecular acylation of ketones yields cyclic p diketones when the ring that is formed is five or six membered... 

There is some spectral evidence that acylation of enamines of cyclic ketones with acid chlorides having an a-hydrogen in the presence of triethylamine proceeds via the ketene and subsequent cycloaddition (84). The intermediate cyclobutanone is then opened to give the enamino ketone which is hydrolyzed to the 2-acyl cyclohexanone. In the case of enamines of larger cyclic ketones the alternate mode of the cyclobutanone opening predominates, with the formation of ring-expanded 1,3-diketones upon... 

For example, the reaction of nitronates (123) with a zinc copper pair in ethanol followed by treatment of the intermediate with aqueous ammonium chloride a to give an equilibrium mixture of ketoximes (124) and their cyclic esters 125. Heating of this mixture b affords pyocoles (126). Successive treatment of nitronates (123) with boron trifluoride etherate and water c affords 1,4-diketones (127). Catalytic hydrogenation of acyl nitronates (123) over platinum dioxide d or 5% rhodium on aluminum oxide e gives a-hydroxypyrrolidines (128) or pyrrolidines 129, respectively. Finally, smooth dehydration of a-hydroxypyrrolidines (128) into pyrrolines (130f) can be performed. 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

Iy2-Acyl rearrangement of a, -epoxy ketones. This rearrangement can be used for synthesis of cyclic spiro-1,3-ketones. Thus the 2-cycloheptylidenecyclopenta-none oxide 1 rearranges in the presence of BF3 etherate at 25° within one minute to the spiro-1,3-diketone 2 in 91% yield.1... 

The Claisen-type condensation reaction of cyclic vinylogous carboxylic acid triflates with lithium enolates and their analogues has provided acyclic alkynes bearing a 1,3-diketone-type moiety.19 The reaction mechanism has been proposed to proceed via a 1,2-addition of the enolate to the vinylogous acyl triflate, followed by fragmentation of the aldolate intermediate (Scheme 2). 

Zelenin and co-workers have shown (85KGS854, 85KGS1000 86KGS128 87KGS1210 88ZOR426) that the reaction products of 1,3-diketones with hydrazides in a molar ratio of 1 2 most frequently possess the cyclic structure of the corresponding 5-hydrazino-2-pyrazolines (such as 76B). They can also be produced in the reactions between the corresponding hydrazine derivatives and l-acyl-5-hydroxy-2-pyrazolines or 1-acyl-5-methylene-2-pyrazolines. 

Dithiolylium cations (see Chapter 4.31) unsubstituted on the 3- or 5-position react with active methylene compounds, in most cases with simultaneous oxidation, as shown in equation (15). This reaction has been performed with a large variety of ketones, acylic or cyclic, /3-diketones, /3-keto dithioesters and a-cyano ketones (71AHC(13)161,pp. 174,188, 80AHC(27)151,p. 183). 

Migration of an acyl substituent was observed during rearrangement of the a-diketone monooxime (28), with formation of the tetrasubstituted isoquinoline (29) presumably occurring via a cyclic imide intermediate (equation 17). 

D.J. Burnell et al. synthesized bicyclic diketones by Lewis acid-promoted geminal acylation involving cyclic acyloins tethered to an acetal. The required b/s-silyloxyalkenes were prepared by using the standard acyloin condensation conditions. ... 

Carbonylation of the cuprate reagent, R (CN)CuLi2, prepared from copper(I) cyanide and an alkyl-lithium, gives a product which can be used for the direct nucleophilic 1,4-acylation of a,3-unsaturated aldehydes and ketones (equation 16). The reaction works particularly well with cyclic a,p-unsaturated ketones to give high yields of the expected 1,4-diketone. 

The reaction of triphenylbismuth carbonate with cyclic 1,3-dicarbonyl compounds, such as dimedone and Meldrum s acid, gives highly stabilized triphenylbismuthonium ylides (Section 3.5.1). Moderately stabilized acyclic bismuthonium ylides can be prepared from triphenylbismuth dichloride and a 1,3-diketone or a 1,3-disulfone in the presence of a suitable base. A similar base-promoted reaction of triphenylbismuth dihalides with Al-sulfonylamines or amides has been used for the preparation of stabilized bismuthine imides bearing the Af-sulfonyl or Af-acyl moiety (Section 3.6.1). 

When the (acylamino)amine (5.3) is heated with t,2-diketones, a triazine ring is formed in high yield [2097]. Acidification of a 2-(acylhydrazino)amine with ethanolic hydrogen chloride is another efficient method [2319]. Moderate yields of a fused triazine are obtained by acylation of a 2-nitrophenylhydrazine followed by catalytic reduction and cyclization with mineral acid [3408]. The first cyclic product of the treatment of an o-acylhydrazino-amine with ethanolic hydrogen chloride is the unstable 1,2-dihydropyridotriazine which is dehydrogenated with either manganese dioxide or hexacyanoferrate(III) (ferricyanide) to the more stable triazine [3S26]. 

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. 

Reduction of the carbonyl group in cyclic and acylic 2-diazo- 1,3-diketones (129, 135-137, 143, 146, and 196) with NaBH in aqueous alcoholic solution, followed by hydrolysis of the reaction mixture over wet silica gel, affords the corresponding 3-hydroxy-2-diazoketones (190-195 and 197) in 58-87% yield.85 Steric hindrance at a to the carbonyl decreases the yield of reduced products.85... 

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