Palladium decarboxylative coupling

Palladium-catalyzed coupling of allylic acetate 113 (Scheme 23) with diethyl malonate, or with acetylated diethyl tartronate, yielded the Boc-protected allylic amines 114 in 99 1 E stereoselectivity.1 "1 Saponification of 114 (R1 = H) and decarboxylation gave the Tyr- Ala alkene isostere 116 in quantitative yield, whereas 114 (R = OAc) was converted into the Tyr-Gly alkene isostere 115 in a two-step procedure in 62% overall yield. Considering the number of steps and the overall yield, this procedure is among the most efficient to prepare Xaatp, CH=CH]Gly dipeptide isosteres. 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

Pyridine N-oxides will decarboxylatively couple with a-oxocarboxylic acids in the presence of a number of catalysts recently, a silver catalyst, which is cheaper and more readily available than the typical palladium catalysts, was shown to initiate this transformation under mild conditions (Scheme 38). The yields were moderate (43-81%) for a number of... 

Voutchkova, A., Coplin, A., Leadbeater, N. E., Crabtree, R. H. (2008). Palladium-catalyzed decarboxylative coupling of aromatic acids with aryl halides or unactivated arenes using microwave heating. Chemical... 

Very recently, Tan and coworkers [20] reported the synthesis of unsymmetrical biaryls via palladium-catalyzed decarboxylative coupling between aryl carboxylic acids and phenylboronic acids. Under the optimized conditions, where the choice of solvent was found to be crucial for achieving a straightforward and simple coupling reaction, a variety of substituted benzoic acids were found to undergo decarboxylative coupling with several phenylboronic acids (Scheme 3.8). Despite poor substrate scope, this method could be useful and complementary to the Pd-catalyzed... 

There has been a DFT study of the decarboxylative coupling of cyanoacetate salts with aryl halides. Decarboxylation is likely to be rate determining in the palladium-catalysed formation of a-arylnitriles. The ortho-cyanatioa of arenes carrying a DG by A -cyano-iV-phenyl-p-toluenesulfonamide is catalysed by rhodium. As shown in Scheme 21, the mechanism is likely to involve rate-determining formation of a five-membered rhoda-cycle intermediate, (160), followed by insertion of the cyanide and elimination of a tosylaniline coordinated rhodium complex. ... 

The palladium-catalyzed decarboxylative coupling of potassium pentafluoroben-zoate with aryl chlorides, bromides and triflates was shown to be a useful method for the synthesis of polyfluorobiaryls from readily accessible polyfluorobenzoate salts. For instance, 2- and 3-chlorothiophens 218, 219 reacted with potassium pentafluorobenzoate to produce pentafluorophenyl derivatives 210 and 220. The reaction proceeded in refluxed diglyme in the presence palladium acetate(ll) [111],... 

The ability of palladium to mediate decarboxylations of certain heteroaromatic carboxylates was demonstrated by Steglich et al. for intramolecular couplings, as well as by Forgione and Bilodeau for intermolecular couplings (Scheme 16) [56-58]. However, the scope of this reaction indeed seems to be more limited than its bimetallic counterpart. It so far includes mainly five-ring heteroarenes with carboxylate groups in the 2-position. AUcynylcarboxylic acids have also been decarboxylatively coupled with palladium alone [59]. 

The oxidative coupling of a benzoic acid with phenylboronic acid is achievable (Scheme 4.9) [13]. Thus, in the presence of a palladium catalyst together with a silver salt oxidant, decarboxylative coupling takes place selectively to produce 2,4,6-trimethoxybiphenyl. In contrast, under conditions using a copper catalyst in place of Pd, a Chan-Evans-Lam type reaction proceeds to afford phenyl 2,4,6-trimethoxybenzoate. 

A conjugated oligomer is synthesized through the palladium-catalyzed decarboxylative coupling of pyrrole-2,5-dicarboxylic acid derivatives with dibromoarenes (Scheme 4.45) [50]. 

Electron-deficient and electron-neutral cinnamic acids undergo decarboxylative coupling with iodobenzenes under palladium catalysis to produce stilbenes... 

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]. 

Goossen and coworkers reported the decarboxylative coupling of a-keto carboxylic acids with aryl bromides (Scheme 4.67) [69]. Thus, treatment of potassium 2-oxo-2-phenylacetates with 4-bromotoluene in the presence of 1 mol% of palladium 1,1,1,5,5,5-hexafluoroacetylacetonate, 2mol% of P(o-tolyl)3, 15mol% of CuBr, 15mol% of 1,10-phenanthroline in NMP/quinoline at 170 C gives the corresponding benzophenones. 

Recently, it was shown that 0-methyl oximes can also be employed as coupling partners in the decarboxylative coupling of cx-keto carboxylic acids under palladium catalysis (Scheme 4.75) [77]. 

The copper-catalyzed decarboxylative coupling of a-keto carboxylic acids with indoles can proceed through C-H bond cleavage at their C3-position (Scheme 4.76) [78]. In contrast, the coupling with Ar-(pyrimidin-2-yl)indoles occurs at their C2-position under palladium catalysis [79]. 

The decarboxylative coupling of potassium 2-(2-pyridyl)acetates with aryl halides can be carried out efficiently under palladium catalysis (Scheme 4.77) [80]. Based on DFT calculations, it was proposed that coordination of the pyridyl nitrogen to Pd is crucial to reduce the energy barrier of the rate-limiting decarboxylation step. a-Cyanoacetates also undergo similar decarboxylative arylation to produce a-aryl nitriles (Scheme 4.78) [81]. From the same combination of substrates, a,a-diaryl nitriles can also be selectively prepared by double arylation (Scheme 4.79) [82]. 

Heteroarene carboxylic acids such as l-methylindole-3-carboxylic acid (10) also undergo similar decarboxylative coupling with alkynes (Scheme 25.9) [12], In these reactions, palladium catalyst systems are more effective than iridium. 

An alternative method for the classical Knoevenagel-type preparation of cinnamic acids has been reported this came to light during a study of the bromine-induced decarboxylation of substituted cinnamic acids. Cinnamic acid derivatives can also be prepared by the palladium-catalysed coupling of methyl acrylate with electron-rich aryl iodidessimilarly 5-arylpenta-2,4-dienoic acids (29) can be synthesized from penta-2,4-dienoic acid and bromo-aryls. A Stobbe-type condensation between aromatic aldehydes and methyl propylidenemalonate leads to the , -unsaturated acids (30), probably via a 5-lactone intermediate. ... 

Crabtree prepared rhodium, iridium, ruthenium, and palladium complexes e.g. 30) bearing NHCs by heating the carboxylate compound and an appropriate metal precursor in acetonitrile [eqn (2.7)]. It was also shown that the carboxylate of l,3-dimethylimidazol-2-ylidene (IMe) could be prepared from the direct reaction of 1-methylimidazole with dimethyl carbonate. Subsequently, Delaude showed that these species can be used in lieu of free NHCs for the synthesis of alkene metathesis pre-catalysts and to form palladium cross-coupling catalysts in situ while Olszewski has used these to prepare silver(i) and eopper(i) complexes. Falvey has shown that solvent choice is important, beeause the rate of decarboxylation is higher in less polar solvents. ... 

Recently, the Chou group reported on the palladium-catalyzed decarboxylative coupling of substituted 2,5-cyclohexadiene-l-carboxylic acids. The products obtained are 5-arylcyclohexa-1,3-dienes. ... 

The ligand-free palladium-catalysed coupling of aryl iodides and bromides with potassium oxalate monoester results in a decarboxylation reaction yielding aromatic esters such as (112). Carbon-hydrogen substitution is involved in the decarboxylative acylation reaction of cyclic enamides with a-oxocarboxylic acids, which may yield acylated enamides such as (114). The reaction is likely to involve a cyclic vinylpalladium intermediate (113) which, after decarboxylation and reductive elimination yields the acylated product. ... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

In the presence of palladium(II) and silver(I) salts, arene carboxylates could be converted to aryl palladium species, which were engaged in Heck coupling reactions.90 Since the more electrophilic palladium trifluoroacetate proved to be the bestcatalyst, decarboxylation probably occurred by aromatic electrophilic substitution... 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

GooBen LJ, Zimmermann B, Knauber T (2008) Palladium/copper-catalyzed decarboxylative cross-coupling of aryl chlorides with potassium carboxylates. Angew Chem Int Ed 47 7103-7106... 

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