To diazo ketones

A high-yielding intramolecular cyclopropanation using /J-dicarbonyl iodo-nium ylides (86) was reported by Moriarty and co-workers [68] [Eq. (19)]. This methodology is a viable alternative to diazo ketone route for intramolecular cyclopropanation. 

Cyclic ketones are converted smoothly to diazo ketones in the presence of HMPA. 4-Nitrophenyl azide (128) exhibits a diazo transfer reaction with malonates and cyclic 1,3-cyclohexanedione (128) in some cases diazo compound 129 further leads to fused triazole derivative (130) formation.52... 

Decomposition of diazo compounds. It is well known that diethyl fumarate is formed when ethyl diazoacetate is decomposed catalytically by copper powder.985 Grundmann applied this reaction to diazo ketones,986 obtaining a moderate yield of 3-hexene-2,5-dione from diazoacetone, and analogous products from co-diazoacetophenone and l-diazo-2-nonadecanone. 

Reaction of the acid chloride with a cold solution of excess of diazomethane to yield a diazo ketone ... 

In order to prepare an acid, a dioxan solution of the diazo ketone is added slowly to a suspension of silver oxide in a dilute solution of sodium thiosulphate Iftheco)iversion to the acid yields unsatisfactory results, it is usually advisable to prepare the ester or amide, which are generally obtained in good yields hydrolysis of the derivative gives the free acid. 

Esters of the homologous acids are prepared by adding silver oxide in portions rather than in one lot to a hot solution or suspension of the diazo ketone in an anhydrous alcohol (methyl, ethyl or n-propyl alcohol) methanol is generally used and the silver oxide is reduced to metallic silver, which usually deposits as a mirror on the sides of the flask. The production of the ester may frequently be carried out in a homogeneous medium by treating a solution of the diazo ketone in the alcohol with a solution of silver benzoate in triethylamlne. 

The conversion of a diazo ketone to an acid amide may be accomplished by treating a warm solution in dioxan with 10-28 per cent, aqueous ammonia solution containing a small amount of silver nitrate solution, after which the mixture is heated at 60°-70° for some time. Precautions should be taken (by use of a. safety glass shield) when heating mixtures containing ammoniacal silver nitrate. 

Introduce a solution of 15 g. of the diazo ketone in 100 ml. of dioxan dropwise and with stirring into a mixture of 2 g. of silver oxide (1), 3 g. of sodium thiosulphate and 5 g. of anhydrous sodium carbonate in 200 ml. of water at 50-60°. When the addition is complete, continue the stirring for 1 hour and raise the temperature of the mixture gradually to 90-100°. Cool the reaction mixture, dilute with water and acidify with dilute nitric acid. Filter off the a-naphthylacetic acid which separates and recrys-talhse it from water. The yield is 12 g., m.p. 130°. 

Ethyl a-naphthylacetate is prepared as follows. To a solution of 10 g. of the diazo ketone in 150 ml. of ethanol at 55-60°, add a small amount of aslurry of silver oxide, prepared from 10 ml. of 10 per cent, aqueous silver nitrate and stirred with 25 ml. of ethanol. As soon as the evolution of nitrogen subsides, introduce more of the silver oxide and continue the process until all the slurry has been added. Reflux the mixture for 15 minutes, add 2-3 g. of decolourising carbon, filter and evaporate the alcohol on a water bath. Distil the residue and collect the ethyl a-naph-thylacetate at 176-178°/ 1 mm. the yield is 9 g. 

Add, with stirring, a solution of 6 8 g. of the fiis-diazo ketone in 100 ml. of warm dioxan to a suspension of 7 0 g. of freshly precipitated silver oxide in 250 ml. of water containing 11 g. of sodium thiosulphate at 75°. A brisk evolution of nitrogen occurs after 1 5 hours at 75°, filter the liquid from the black silver residue. Acidify the almost colourless filtrate with nitric acid and extract the gelatinous precipitate with ether. Evaporate the dried ethereal extract the residue of crude decane-1 10-dicarboxylic acid weighs 4 -5 g. and melts at 116-117°. RecrystaUisation from 20 per cent, aqueous acetic acid raises the m.p. to 127-128°. 

Alternatively, treat a solution of 3 9 g. of the 6is-diazo ketone in 50 ml. of warm dioxan with 15 ml. of 20 per cent, aqueous ammonia and 3 ml. of 10 per cent, aqueous silver nitrate under reflux in a 250 or 500 ml. flask on a water bath. Nitrogen is gently evolved for a few minutes, followed by a violent reaction and the production of a dark brown and opaque mixture. Continue the heating for 30 minutes on the water bath and filter hot the diamide of decane-1 lO dicarboxyhc acid is deposited on cooling. Filter this off and dry the yield is 3 -1 g., m.p. 182-184°, raised to 184-185° after recrystallisation from 25 per cent, aqueous acetic add. Hydrolyse the diamide (1 mol) by refluxing for 2-5 hours with 3N potassium hydroxide (4 mols) acidify and recrystaUise the acid from 20 per cent, acetic acid. The yield of decane-1 10-dicarboxyhc acid, m.p. 127-128°, is almost quantitative. 

Phenyldiazonium salts react with malonaldioxime to produce a 2-isoxazoline (7 IGEPl 920245), and the diazo ketone (484) when photolyzed gave a mixture of 2-isoxazoline and an isoxazole by a 1,5 carbon-hydrogen insertion. A phenyl migration was apparently not involved (Scheme 124) (66CC689). 

Any heterocycle containing the OCH=CH moiety can in principle extrude the superfluous fragment and form oxirene, as illustrated for a five-membered ring in Scheme 105. Probably the most propitious AB fragment would be nitrogen, but the required 1,2,3-oxadiazole (123) is unknown (see Chapter 4.21), probably because of ready valence tautomerization to diazoethanal (Scheme 106) (this approach has been spectacularly successful with the sulfur analogue of (2) (8UA486)). The use of (123) as an oxirene precursor is thus closely linked to the important diazo ketone decompositions discussed in Section 5.05.6.3.4(f). 

An extensive series of low-temperature matrix isolation experiments has failed to provide any evidence of oxirene formation, either by diazo ketone photolysis (82CB2192) or by attempted photo-retro-cycloaddition (82CB2202). 

The first /3 -lactam was produced by addition of a ketene to an imine and there are now many examples of this type of approach. The ketenes are most frequently generated in situ from acid chlorides by dehydrohalogenation, but have also been produced from diazo ketones, by heating of alkoxyacetylenes and in the case of certain cyanoketenes by thermolysis of the cyclic precursors (162) and (163). 

In a first step, the carboxylic acid 1 is converted into the corresponding acyl chloride 2 by treatment with thionyl chloride or phosphorous trichloride. The acyl chloride is then treated with diazomethane to give the diazo ketone 3, which is stabilized by resonance, and hydrogen chloride ... 

The diazo ketone 3, when treated with silver oxide as catalyst, decomposes into ketocarbene 5 and dinitrogen Na. This decomposition reaction can also be achieved by heating or by irradiation with uv-light. The ketocarbene undergoes a Wolff rearrangement to give a ketene 6 ... 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Photo-de-diazoniation has found relatively little application in organic synthesis, as is clearly evident from the annual Specialist Periodical Reports on Photochemistry published by the Royal Society of Chemistry. Since the beginning of these reports (1970) they have contained a section on the elimination of nitrogen from diazo compounds, written since 1973 by Reid (1990). In the 1980s (including 1990), at least 90% of each report is concerned with dediazoniations of diazoalkanes and non-quinon-oid diazo ketones, the rest being mainly related to quinone diazides and only occasionally to arenediazonium salts. 

Diazo ketones are relatively easy to prepare (see 10-122). When treated with acid, they add a proton to give a-keto diazonium salts, which are hydrolyzed to the... 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

When diazo ketones are treated with HBr or HCl, they give the respective a-halo ketones, but HI does not give the reaction, since it reduces the product to a methyl ketone (10-87). a-Fluoro ketones can be prepared by addition of the diazo ketone to polyhydrogen fluoride-pyridine. This method is also successful for diazoalkanes. 

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