Decarboxylations copper acetate

Interestingly, the Fischer indole synthesis does not easily proceed from acetaldehyde to afford indole. Usually, indole-2-carboxylic acid is prepared from phenylhydrazine with a pyruvate ester followed by hydrolysis. Traditional methods for decarboxylation of indole-2-carboxylic acid to form indole are not environmentally benign. They include pyrolysis or heating with copper-bronze powder, copper(I) chloride, copper chromite, copper acetate or copper(II) oxide, in for example, heat-transfer oils, glycerol, quinoline or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. 

The decarboxylation has also been carried out by substituting copper powder for copper acetate. 

The rest of the synthesis (Scheme 13) is completely stereospecific and most of the steps are known (20). The bicyclic acid was oxidatively decarboxylated with lead tetraacetate and copper acetate (21). The resulting enone was alkylated with methyllithium giving a single crystalline allylic tertiary alcohol. This compound was cleaved with osmium tetroxide and sodium periodate. Inverse addition of the Wittig reagent effected methylenation in 85% yield. Finally, the acid was reduced with lithium aluminum hydride to grandisol. 

Another widely used decarboxylation procedure involves the use of lead tetraacetate. Depending on the nature of the substrate and the reaction conditions, this reagent may transform a carboxylic acid into an alkane or alkene, or into the respective acetoxy derivative (Scheme 2.144). The most favorable conditions for alkane formation utilize a good hydrogen donor as the solvent. Usually this transformation is carried out as a photochemically induced oxidative decarboxylation in chloroform solution, as is exemplified in the conversion of cyclobutanecarboxylic acid in cyclobutane.In contrast, the predominant formation of alkenes occurs in the presence of co-oxidants such as copper acetate. ... 

The key step of another porphyrin synthesis is template assembhng of the porphyrin core at copper acetate, accompanying with decarboxylation. Starting from pyrrole 476, porphyrin 480 was prepared in few steps [155, 156]. 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

Thieno[3,2- ][l]benzofuran 61 was synthesized on a preparative scale starting with benzo[/ ]furan-2-carbaldehyde 344. Condensation of aldehyde 344 with 2-thioxothiazolidin-4-one in the presence of sodium acetate in acetic acid afforded 345, which by base-catalyzed hydrolysis gave 346 in good yield. Upon treatment with bromine, acid 346 was cyclized to give acid 347, which on standard decarboxylation by treatment with copper in quinoline afforded 61 in high yield (Scheme 35) <1997CCC1468>. 

Catalyst, alumina, 34, 79 35, 73 ammonium acetate, 31, 25, 27 boron trifluoride etherate, 38, 26 copper chromite, 31,32 36, 12 copper powder in quinoline for pyrolytic decarboxylation,... 

A vigorous Claisen condensation ensues when a homophthalic ester and methyl formate are treated with sodium ethoxide and the active methylene group is formylated. Cyclization takes place with ease in acidic media to produce a methyl isocoumarin-4-carboxylate (50JCS3375). Hydrolysis under acid conditions is sometimes accompanied by polymerization, but the use of boron trifluoride in acetic acid overcomes this problem. Decarboxylation may be effected in the conventional manner with copper bronze, though it sometimes accompanies the hydrolysis. 

Benzo[c]thiophene may be prepared by low-pressure (20 mm) vapor-phase catalytic dehydrogenation of l,3-dihydrobenzo[c]thio-phene (Section III,A) at 330° under nitrogen,5,8 by decarboxylation of benzo[c]thiophene-1 -carboxylic acid (Section III,C) with copper in quinoline16,38 or by dehydration of l,3-dihydrobenzo[c]thiophene 2-oxide (Section VI,A) in acetic anhydride or over aluminum oxide at 20 mm Hg and 100°-125° in a sublimation tube.52 A trace of water appears to be beneficial to the first reaction, and it has been suggested53... 

A synthesis of benzotriquinacene 396) has recently been described (Scheme 63).36s 366 Vinylmagnesium chloride transformed ketone 380 into vinyl alcohol 393 whose dehydration gave 2-vinyltriquinacene 394). Addition of dimethyl acet-ylenedicarboxylate to 394 followed by dehydrogenation led to adduct 395 which underwent ready saponification and copper-catalyzed decarboxylation to give 396. 

Copper(II) compounds also enhance the rate of decarboxylation of alkanoic acids with lead(IV) acetate by more efficient electron-transfer oxidation of the alkyl radicals produced alkylcopper species may be intermediates 179). 

The oxidative decarboxylation of aliphatic carboxylic acids is best achieved by treatment of the acid with LTA in benzene, in the presence of a catalytic amount of copper(II) acetate. The latter serves to trap the radical intermediate and so bring about elimination, possibly through a six-membered transition state. Primary carboxylic acids lead to terminal alkenes, indicating that carbocations are probably not involved. The reaction has been reviewed. The synthesis of an optically pure derivative of L-vinylglycine from L-aspartic acid (equation 14) is illustrative. The same transformation has also been effected with sodium persulfate and catalytic quantities of silver nitrate and copper(II) sulfate, and with the combination of iodosylbenzene diacetate and copper(II) acetate. ... 

Perfluoroalkylcopper reagents are the most studied perfluoroalkyl organometallic reagents due to their unique combination of thermal stability and chemical reactivity. They are readily prepared by copper metal insertion reactions with perfluoroalkyl halides in a coordinating solvent (e.g., formation of decarboxylation reactions of perfluoroalkanoic acid salts and copper(I) halide (e.g., formation of 2 ), or metathesis reactions (e.g., formation of 4 via 3 ). (Trifluoro-methyl)copper (4) has also been recently accessed by decomposition of methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (5) or methyl perfluoro [2-(fluorosulfonyl)ethoxy]acetate (6) in the presence of copper(I) iodide and by reaction of trimethyl(trifluoromethyl)silane (7) with fluoride and copper(I) iodide. ... 

Olefinic esters may be obtained directly by the Knoevenagel reaction. Alkyl hydrogen malonates are used in place of malonic acid. Decarboxylation then gives the ester directly as in the preparation of ethyl 2-heptenoate (78%) and methyl m-nitrocinnamate (87%). Alkyl hydrogen malonates are readily available by partial hydrolysis of dialkyl malonates. The use of malonic ester in the condensation leads to olefinic diesters, namely, alkylidenemalonates such as ethyl heptylidenemalonate (68%). A small amount of organic acid is added to the amine catalyst since the salts rather than the free amines have been shown to be the catalysts in condensations of this type. Various catalysts have been studied in the preparation of diethyl methylenemalonate. Increased yields are obtained in the presence of copper salts. Trimethylacetalde-hyde and malonic ester are condensed by acetic anhydride and zinc chloride. Acetic anhydride is also used for the condensation of furfural and malonic ester to furfurylidenemalonic ester (82%). ... 

The decarboxylation of amino acids is facilitated by copper Lewis acids. Treatment of tryptophan with copper(II) acetate in HMPA afforded tryptamine 117 in 45 % yield (Sch. 26) [58]. Chelation is thought to activate the carboxylate for elimination. The stable chelate can be isolated and undergoes decarboxylation when heated. An asymmetric version of a similar decarboxylation of malonate derivatives has been reported poor selectivity resulted from addition of chiral alkaloids [59]. 

Usually decarboxylation is accomplished by heating the acids above their melting points, often in the presence of a copper-chromium catalyst. Imidazole-4,5-dicarboxylic acid can be monodecarboxylated by heating its monoanilide imidazole- and benzimidazole-2-carboxylic acids decarboxylate very readily indeed, so readily that the carboxyl function makes a useful blocking group in metallation procedures (see Scheme 7.2.1) [3-5]. A potentially useful method of preparation of imidazole-4-carboxylic acid derivatives heats the 4,5-dicarboxylic acid (2) with acetic anhydride to form (1), which is essentially an azolide and very prone to nucleophilic attack which cleaves the nitrogen-carbonyl bond (Scheme 8.3.1). With methanol the methyl ester (3) is formed with hydrazines the 4-hydrazides (4) result [6]. 

The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum. A novel and highly stereoselective total synthesis of both the c/s and trans isomers of combretastatin A-4 was developed by J.A. Hadfield and co-workers.The (Z)-stereoisomer was prepared using the Perkin reaction as the key step in which 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxbenzaldehyde was heated with triethylamine and acetic anhydride at reflux for several hours. The a,p-unsaturated acid was isolated in good yield after acidification and had the expected ( ) stereochemistry. Decarboxylation of this acid was effected by heating it with copper powder in quinoline to afford the natural product (Z)-combretastatin A-4. 

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