Carboxylation palladium-catalyzed

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

Sodium or potassium phenoxide can be carboxylated regioselectively in the para position in high yield by treatment with sodium or potassium carbonate and carbon monoxide. Carbon-14 labeling showed that it is the carbonate carbon that appears in the p-hydroxybenzoic acid product. The CO is converted to sodium or potassium formate. Carbon monoxide has also been used to carboxylate aromatic rings with palladium compoimds as catalysts. In addition, a palladium-catalyzed reaction has been used directly to prepare acyl fluorides ArH —> ArCOF. ... 

Scheme 8.15. Synthesis of Ketones, Esters, Carboxylic Acids, and Amides by Palladium-Catalyzed Carbonylation and Acylation... 

Wong and co-workers have prepared various quaternary cx-nitro-cx-methyl carboxylic acid esters by the palladium-catalyzed allylic alkylation of a-nitropropionate ester (Eq. 5.59). The products can be kinetically resolved by using cx-chymotrypsin and are converted into optical active a-methyl cx-amino acids. Such amino acids are important due to the unique biological activity of these nonproteinogenic a-amino acids.82... 

Bisacid 91 was used toward three different targets. For the first, a palladium-catalyzed decarboxylative Heck reaction followed by perylenequinone formation provided bis-styryl derivative 92 (Scheme 7.22) [52]. For the second, the C5,C5 -benzyl ethers were cleaved, and the more acidic carboxylic acids were then selectively benzylated using BnBr and K2CO3 (Scheme 7.22). This re-esterification... 

The palladium-catalyzed Heck carbonylation reaction is a powerful means of generating amides, esters, and carboxylic acids from aryl halides or pseudohalides [28]. The development of rapid, reliable, and convenient procedures for the introduction of carbonyl groups is important for the development of high throughput chemistry in general and high-speed microwave-mediated chemistry in particular. Unfortunately, the traditional method of introducing carbon monoxide into a reaction mixture via a balloon or gas tube is not practical because of the special requirements of microwave synthesis. 

In a process starting with the stereospecific Homer-Wadsworth-Emmons reaction of phosphonoglycinates 99 with 2-iodobenzaldehydes to afford the corresponding (Z)-didehydro-phenylalanine derivatives 100, Brown similarly utilized an intramolecular palladium-catalyzed animation of 100 (Y = 2-chloro-3-pyridyl, Ph, OBn) to form the N-substituted indole carboxylates 101 <00TL1623>. 

Scheme 8. Palladium-catalyzed carboxylations of aryl and heteroaryl bromides...

In the palladium-catalyzed coupling reactions of arenes with alkenes, the cr-arylpalladium complexes react with CO to give aromatic acids in AcOH, as shown in Scheme u 97>97a 97c This carboxylation reaction of arenes with CO proceeds catalytically with respect to Pd at room temperature under atmospheric pressure of CO, when K2S2O8 is added as an oxidant and TFA is employed as a solvent. 

The reaction of biphenyl with formic acid and K2S208 in a mixture of GF3C02H and GH2G12, using Pd(OCOCF3)2 as a catalyst, gives hydroxyl-biphenylcarboxylic acid in 45% yield (Equation (76)).101 The hydroxylation and carboxylation proceeds on one molecule. This reaction is applied to the palladium-catalyzed carboxylation of benzenes using formic acid as a carbonyl source. 

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

Palladium-catalyzed cyclic carboxylation of dienes can be utilized for the synthesis of lactones.2 Polymer-supported Pd catalyst could also be used for this reaction (Scheme 42).61 The reaction is initiated by dimerization of two molecules of diene to give a bis-7r-allylpalladium intermediate such as 123. The incorporation of C02 takes place at the internal position of an allyl unit to afford the 7r-allylpalladium carboxylate 124 which, after reductive elimination/ cyclization, yields the (5-lactone 121 (Scheme 43). 

Incorporation of the carboxylic acid group into the substrate also had an effect on the stereochemistry of the Alder-ene products. Trost and Gelling60 observed diastereoselectivity in the palladium-catalyzed cycloisomerization of 1,7-enynes when the reactions were conducted in the presence of A,A-bis(benzylidene)ethylene diamine (BBEDA, Figure 2). They were able to synthesize substituted cyclohexanes possessing vicinal (Equation (53)) and... 

It has also recently been shown that /3-trimethylsilylacrylic acids (produced in the work by circuitous means but accessible by ruthenium-catalyzed hydrosilylation71) serve as competent partners for palladium-catalyzed crosscoupling in the absence of fluoride. The authors invoke an intramolecular activation by the carboxylate similar to that in Scheme 15.7... 

The allenyl carboxylate 35 was obtained in an enantiomerically enriched form by the palladium-catalyzed reduction of the racemic phosphate 34 using a chiral proton source [53]. The two enantiomers of the (allenyl)samarium(III) intermediate are in rapid equilibrium and thus dynamic kinetic resolution was achieved for the asymmetric preparation of (i )-35 (Scheme 3.18). 

Finally, it should be noted that the synthesis of methyl 2,3-butadiene-l-carboxylate can be achieved by the palladium-catalyzed carbonylation of 1-bromoallene with carbon monoxide in methanol [25]. Similarly, 2,3-allenamides are accessible from bromoallenes, carbon monoxide and primary amines or ammonia [26]. 

In an analogous approach explored by Dixneuf et al., a conjugated enynyl carbonate is converted into an oxolenone or a bicyclic lactone in significant yields via double carbonylation in the presence of methanol (Scheme 22) [128]. When a neighboring carbonyl group is present in the substrate, it can also participate in palladium-catalyzed cyclization-carbonylation. Indeed, 4-yn-l-ones lead to cyclic ketals that can be easily converted into 2-cyclopentenone carboxylates in an acidic medium (Scheme 22) [129]. 

By 1984, the palladium-catalyzed aUyhc alkylation reaction had been extensively studied as a method for carbon-carbon bond formation, whereas the synthetic utility of other metal catalysts was largely unexplored [1, 2]. Hence, prior to this period rhodium s abihty to catalyze this transformation was cited in only a single reference, which described it as being poor by comparison with the analogous palladium-catalyzed version [6]. Nonetheless, Yamamoto and Tsuji independently described the first rhodium-catalyzed decarboxylation of allylic phenyl carbonates and the intramolecular decarboxylative aUylation of aUyl y9-keto carboxylates respectively [7, 8]. These findings undoubtedly laid the groundwork for Tsuji s seminal work on the regiospecific rho-... 

The synthesis of pyrimidine carboxylic esters can be achieved by palladium-catalyzed carbonylation of halopyrimi-dines with carbon monoxide and an alcohol < 1999T405, 2001S1098>, as shown by the formation of a variety of esters 271 from 2-chloro-4,6-dimethoxypyrimidine 270 <1999T405>. 

We reported the use of M-heterocyclic carbene complexes (NHC) for the catalytic activation of methane [55,56]. We found that solutions of N-heterocyclic carbene complexes of palladium(II) in carboxylic acids catalyze the conversion of methane to the corresponding methylesters. The high thermal stability of palladium(II) carbene complexes could be shown for complex 18 (Scheme 22), which we also structurally characterized [120]. An extraordinary feature is the unprecedented resistance of the palladium-NHC-complexes 18-22 under the acidic oxidizing conditions which are necessary for the CH-activation and functionalization. 

This transformation also indicates that carboxylation is a net syn process. The same was proved for the palladium-catalyzed reaction as well.129... 

The formation of branched acids from 1- and 2-alkenes in a palladium-catalyzed carboxylation was found to be completely regioselective, when the reaction was carried out in the presence of CuCl2, oxygen, and limited amounts of water and hydrochloric acid, under remarkably mild conditions 141... 

Catalytic systems to afford linear esters selectively are scant.306,309 A report in 1995 disclosed that palladium complexes based on l,l -bis(diphenylphosphine)fer-rocene showed excellent regioselectivity for the formation of linear a,p-unsaturated esters.309 The results with phenylacetylene are remarkable because this compound is known to exhibit a distinct preference for the formation of the branched products on palladium-catalyzed carboxylations. Mechanistic studies indicate that the alkoxycarbonylation of alkynes proceeds via the protonation of a Pd(0)-alkyne species to give a Pd-vinyl complex, followed by CO insertion and alcoholysis.310... 

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