Decarboxylation alkenylation

The decarboxylative alkenylation of electron-deficient benzoic acids was found to occur by using a cheaper oxidant, benzoquinone, in place of the silver salt (Scheme 4.22) [27]. A CuF2/benzoquinone oxidant system can mediate the reaction of electron-rich benzoic acids [28]. The decarboxylative alkenylation of both electron-rich and electron-deficient benzoic acids using dioxygen as the terminal oxidant can be performed (Scheme 4.23) [29]. 

Rhodium catalysts can be used for the decarboxylative alkenylation. For example, or//io-fluorrnated benzoic acids react with acrylate esters to give the corresponding cinnamates, together with minor amounts of 3-arylpropanoates (Scheme 4.27) [33]. 

Imidazole, 4-acetyl-5-methyl-2-phenyl-synthesis, 5, 475 Imidazole, 1-acyl-reactions, 5, 452 rearrangement, 5, 379 Imidazole, 2-acyl-synthesis, 5, 392, 402, 408 Imidazole, 4-acyl-synthesis, 5, 468 Imidazole, C-acyl-UV spectra, 5, 356 Imidazole, N-acyl-hydrolysis rate constant, 5, 350 reactions, 5, 451-453 synthesis, 5, 54, 390-393 Imidazole, alkenyl-oxidation, 5, 437 polymerization, 5, 437 Imidazole, 1-alkoxycarbonyl-decarboxylation, 5, 453 Imidazole, 2-alkoxy-l-methyl-reactions, 5, 102 thermal rearrangement, 5, 443 Imidazole, 4-alkoxymethyl-synthesis, 5, 480 Imidazole, alkyl-oxidation, 5, 430 synthesis, 5, 484 UV spectra, 5, 355 Imidazole, 1-alkyl-alkylation, 5, 73 bromination, 5, 398, 399 HNMR, 5, 353 synthesis, 5, 383 thermal rearrangement, 5, 363 Imidazole, 2-alkyl-reactions, 5, 88 synthesis, 5, 469... 

The mechanisms proposed for these reactions are all quite analogous, and only the intramolecular cases will be considered in detail (Scheme 5). Oxidative addition by Pd° into the allylic C—O bond of the allyl 0-ketocaiboxylate produces an allylpalladium caxboxylate. This species then undergoes decarboxylation to yield an allylpalladium enolate (oxa-ir-allyl), which subsequently eliminates a 0-H to form the enone and provide an allyl-Pd-H. Reductive elimination from the allyl-Pd-H yields propene and returns Pd to its zero oxidation state. A similar mechanism can be imagined for the alkenyl allylcarbonate. Oxidative addition by the Pd° forms an allylpalladium carbonate, which decarboxylates again to give an allylpalladium enolate (oxa-ir-allyl). 0-Hydride elimination and reductive elimination complete the process. The intermolecular cases derive the same allylpalladium enolate intermediates, only now as the result of bimolecular processes. 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

Elaboration of isoxazolines has been used in the synthesis of other heterocycles. Electrophilic cyclization reactions of 5-alkenyl-substituted isoxazolines (150) have been used in the synthesis of cyclic ethers (Scheme 68) (87JA7577 90JOC283). Hydrogenolysis and decarboxylation of the... 

ALIPHATIC, ALKENYL, AND ALKYNYL SUBSTITUTION, ELECTROPHILIC TABLE 12.2. Some Acids that Undergo Decarboxylation Fairly Readily"... 

Selective V-alkylation or -alkenylation of pyrimidinethiones is difficult to achieve because of preferential reactivity of the sulfur with the electrophile. 5,V-Disubstitution proceeds readily, however, as in the formation of the 2,3-dihydrothiazolo[3,2-c]pyrimidinium-8-olates (477). The protons of the dihydrothiazolo ring are acidic, especially in the 3-position. Strong base abstraction of an //3-proton leads to ring-opening to the V-vinylpyrimidinone (479). The latter is also formed from the 3-carboxy derivative (478) by ready pyrolytic decarboxylation promoted by the adjacent pyrimidinium nitrogen atom <84JHC1149>. 

Many carboxy derivatives are available by primary syntheses. Otherwise the best route to simple pyrimidinecarboxylic acid derivatives is oxidative. This statement is even more applicable to our present situation with readily available acyl-, alkenyl-, or alkynylpyrimidine substrates from the coupling procedures, which serve as excellent substrates for oxidative reactions. The normal carboxylic acid reactions are observed ester formation, ester hydrolysis, aminolysis, acid chloride formation and reactions. A carboxy group in an electrophilic position may readily be lost when the pyrimidine ring is further depleted of 7t-electrons by its substitution pattern selective decarboxylation can be effected in pyrimidinedicarboxylic acids. 

Transition metal-catalyzed cross-coupling reactions of halogenopyrazines is an efficient synthetic method for alkyl-, alkenyl-, and alkynylpyrazines (Section 6.03.5.4.2). Palladium and nickel complexes are particularly effective as catalysts in this reaction. The Wittig reaction of halogenomethyl-pyrazines likewise leads to the formation of alkenylpyrazines (Section 6.03.8.1). Dehalogenation of halogeno pyrazines is a very practical synthetic method for alkyl- or aryl-substituted pyrazines. For example, phenylpyrazine has been prepared by catalytic hydrogenolysis of the 2-chloro-3-phenyl compound in the presence of triethylamine. This product is also obtained by decarboxylation of... 

The development of decarboxylative allylations and benzylation of simple alkyl or alkenyl nucleophiles and the role of pre-association in Brpnsted acid-catalysed decarboxylation and related processes have been reviewed. " " The 70 years of... 

The alkylation reactions proceed with moderate to good yields with primary iodides (Entries 1,3,6, and 7) or bromides (Entries 2,4, and 5) in the absence of additives or polar solvents. The only byproducts detected were small amounts of ( )-a- and P-A -phthaloyl alanines and ( )-A -phthaloyl aspartic acid. In a few instances, small amounts of A Vinylphthalimide, resulting from double decarboxylation, were also detected. Shorter reaction times were required when the reaction was performed at 40 °C. Secondary iodides also gave alkylated derivatives (Entries 8 and 9). However, no alkylation was observed when more hindered substrates, such as a-cholestanyl iodide and menthyl iodide or bromide were used. These halides were recovered unchanged or suffered elimination to afford mixtures of alkenes after several days at room temperature. On the other hand, no alkylation took place with methyl p-toluenesulfonate, ethyl triflate, and propylene oxide under the same reaction conditions. Similarly, alkenyl and aiyl halides were unreactive with nickelacycles. 

Through the carboxyl-directed alkenylation/decarboxylation procedure, a series of meta-substituted stilbenes can be synthesized from ortho-substituted benzoic acids (Scheme 18.13). 

However, these directing groups limit the utility of the method because of their irremovability. The authors succeeded in selectively synthesizing C2-alkenylated indoles from indole-3-carboxylic acids through the carboxyl-directed alkenyla-tion/decarboxylation sequence (Scheme 18.50) [49]. This reaction seems to proceed via coordination of a carboxylic oxygen to a Pd(II) species, directed palladation at the C2 position, alkene insertion, and -hydrogen elimination. After the C2-alkenylation, decarboxylation may occur smoothly to produce a 3-unsubstituted 2-alkenylindole derivative. 

The regioselective C3-alkenylation of thiophene-2-carboxylic acids was achieved via rhodium/silver-catalyzed oxidative coupling, accompanied by decarboxylation (13JOC7216). The catalyst can also be used for ort/zo-alkenylation of benzoic acids. 

Synthesis of monomers 24 and 27 is based on diethyl malonate chemistry. DiaUcylation of a dibromide with diethyl alkenyl malonate yields a tetraester diene. Diacid diene is obtained after saponification and decarboxylation of the respective tetraester diene. Reduction to the diol is achieved with lithium aluminum hydride. Subsequently, dimesylation of the respective diol followed by reductive cleavage with hydride yields the desired monomer 24 and 27. ... 

Under similar conditions, ortho-unsubstituted benzoic acids undergo double alkenylation at the both ortho-positions and subsequent decarboxylation to form 1,3-distyrylbenzenes (Scheme 4.29). 

The decarboxylative coupling of benzoic acids with internal alkynes in a 1 2 manner was achieved under iridium catalysis to produce the corresponding benzannu-lated products (Scheme 4.31) [36]. The carboxylic group acts as a directing group, as in the rhodium-catalyzed ortho-alkenylation described above (Schemes 4.28 and 4.29). Thus, carboxylic group directed metalation at the ortho C-H bond and subsequent alkyne insertion may take place to form a seven-membered iridacycle intermediate. Then, decarboxylation, the second alkyne insertion, and... 

C-H alkenylation and decarboxylation (Scheme 4.48) [53], as in the reaction of benzoic acids described above (Schemes 4.28 and 4.29). Since the palladium-catalyzed Fujiwara-Moritani type direct alkenylation of indoles usually takes place at the C3-position, it enables alkenylation at a position complementary to that of the Fujiwara-Moritani reaction, being of unique synthetic utility. On the other hand, the reaction of thiophene-2-carboxylic acid leads to the formation of a mixture of C2- and C3-alkenylated products. Decarboxylation may take place too early to complete directed C-H alkenylation at the C3-position. In contrast, the exclusive C3-alkenylation on a thiophene ring is possible under rhodium catalysis (Scheme 4.49) [34b]. 

The palladium-catalyzed enyne synthesis is achievable via the decarboxylative coupling of propiolic acids with alkenyl bromides (Scheme 4.62) [63]. Propiolic acids also couple with benzyl halides through decarboxylation and subsequent sp C-sp C bond formation (Scheme 4.63) [64]. 

A methodology to C3-alkenylated thiophenes was disclosed using substituted thiophene 2-carboxylic acids. Whereas Pd catalysis produced decarboxylation and mixtures of C2 C3 products, Ru catalysis could selectively produced C3-alkenylated thiophenes without acid decarboxylation, but was limited in scope. As an alternative, [RhCp Cl2]2 was employed in combination with AgSbF6 and AgOAc that functioned as a terminal oxidant to regenerate Rh Various substituted thiophene 2-carboxylic acids could be selectively C3 alkenylated without decarboxylation in good to excellent yields (eq 33). 

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