Esters palladium-catalyzed

The alkaloid dubamine contains a single bond between the two heteroarene units. This lond was formed in 79% yield by the generally valuable palladium-catalyzed eoupling of an ryltrimethylstannane with an aryl triflate (see section 1.6). The requisite stannane was pre-ared from l,3-benzodioxol-5-yl triflate and hexamethyldistannane with the same palladium atalyst, the triflate ester was obtained from 2(1 f/)-quinolinone and trifluoromethanesulfonic jihydride (A.M. Echavarren, 1987). An earlier attempt to perform this aryl coupling by dassical means gave a yield of only 1 %. 

Oxidative Carbonylation of Ethylene—Elimination of Alcohol from p-Alkoxypropionates. Spectacular progress in the 1970s led to the rapid development of organotransition-metal chemistry, particularly to catalyze olefin reactions (93,94). A number of patents have been issued (28,95—97) for the oxidative carbonylation of ethylene to provide acryUc acid and esters. The procedure is based on the palladium catalyzed carbonylation of ethylene in the Hquid phase at temperatures of 50—200°C. Esters are formed when alcohols are included. Anhydrous conditions are desirable to minimize the formation of by-products including acetaldehyde and carbon dioxide (see Acetaldehyde). 

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. 

SYNTHESIS OF N-( -BUTOXYCARBONYL)-P-IODOALANINE METHYL ESTER A USEFUL BUILDING BLOCK IN THE SYNTHESIS OF NONNATURAL a-AMINO ACIDS VIA PALLADIUM CATALYZED CROSS COUPLING REACTIONS... 

The N-substituted aminoacids required could be prepared by microwave-assisted reductive amination of aminoacid methyl esters with aldehydes, and although in the Westman report soluble NaBH(OAc)3 was used to perform this step, other reports have shown how this transformation can be performed in using polymer-supported borohydrides (such as polymer-supported cyanoborohydride) under microwave irradiation [90]. An additional point of diversity could be inserted by use of a palladium-catalyzed reaction if suitably substituted aldehydes had been used. Again, these transformations might eventually be accomplished using supported palladium catalysts under microwave irradiation, as reported by several groups [91-93]. 

Independently, Antane reported that arylisonipecotic acids were obtained from aryl bromides in a two-step process involving microwave-assisted palladium-catalyzed amination with ethyl isonipecotate followed by ester hydrolysis with KOH (Scheme 91) [96]. Interestingly, toluene, which is the standard solvent for Buchwald-Hartwig aminations under conventional heating, was used as the sole reaction medium, although it is a very weak... 

The synthesis of 1-alkenylboronic acids from l-alkenylmagnesiums or -lithiums suffers from difficulty in retaining the stereochemistry of 1-aikenyl halides, but the palladium-catalyzed coupling reaction of diboron 82 with 1-aikenyl halides or tri-flates directly provides 1-alkenylboronic esters (Scheme 1-43) [157, 158]. Although the reaction conditions applied to the aryl coupling resulted in the formation of an... 

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

The palladium-catalyzed carbonylation of aryl halides in the presence of various nucleophiles is a convenient method for synthesizing various aromatic carbonyl compounds (e.g., acids, esters, amides, thioesters, aldehydes, and ketones). Aromatic acids bearing different aromatic fragments and having various substituents on the benzene ring have been prepared from aryl iodides at room temperature under 1 atm... 

In recentyears, metal NPs synthesized in ILs were recognized as suitable materials to promote the formation of chemical bonds in reactions other than palladium-catalyzed carbon-carbon cross-coupling reactions. For example, aldehydes and esters... 

Allylic carbonates are better electrophiles than allylic acetates for the palladium-catalyzed allylic alkylation.77 Reaction of Eq. 5.54 shows the selective allylic alkylation of a-nitro ester with allylic carbonates without affecting allylic acetates.78... 

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... 

The next task was removal of the C3,C3 -esters. Although the palladium-catalyzed decarboxylation protocol performed well in previous systems, a competing C-H insertion reaction was discovered with the methylidene bridge needed for cercosporin (see below). Since reexamination of alternate decarboxylation methods [48] led to no success, a decarbonylation strategy was explored [49]. Formation of the requisite dialdehyde was best accomplished by overreduction using DIB AL and... 

The palladium-catalyzed cross-coupling reaction featured in this procedure occurs under neutral conditions in the presence of many synthetically useful functional groups (e.g. alcohol, ester, nitro, acetal, ketone, and aldehyde). The reaction works best in N,N-dimethylformamide with bis(triphenylphosphine)palladium(ll) chloride, PdCI2(PPh3)2, as the catalyst. Lithium chloride is added to prevent decomposition of the catalyst.143 13 It is presumed that conversion of the intermediate aryl palladium triflate to an aryl palladium chloride is required for the transmetallation step to proceed.9... 

The vinylcyclopropane 144, bearing two electron-withdrawing groups, undergoes the intermolecular palladium-catalyzed [3 + 2]cycloaddition reaction of the Jt-allylpalladium intermediate 145 with a,/ -unsaturated esters or ketones to provide a useful method for forming the cyclopentane ring of 146 [74], (Scheme 51)... 

A mild and efficient a-heteroarylation of simple esters and amides via nucleophilic aromatic substitution has been described <06OL1447>. Treatment of 2-chloro-benzo[//Jthiazole 99 with tert-butyl propionate in the presence of NaHMDS under nitrogen furnishes tert-butyl 2-(benzo[c(jthiazol-2-yl)propanoate 100. When the same reaction is preformed initially under nitrogen and then exposed to air, the hydroxylation product 101 is obtained. This method offers two desirable features that are either complementary or improvements to the palladium-catalyzed a-arylation reactions. First, heteroaryl chlorides... 

Scheme 6.43 Palladium-catalyzed a-arylation of esters and amides with organozinc reagents.

Scheme 6.47 Palladium-catalyzed carbonylation reactions yielding acids, esters, and lactones using molybdenum hexacarbonyl as a solid source of carbon monoxide.

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. 

Oxazolines can be obtained by the Lewis acid catalyzed epoxide ring opening of glycidic esters or amides (e.g., 118) with acetonitrile . Oxazolidines are available from the palladium-catalyzed cycloaddition of vinyl epoxides with imines <00H885> or the samarium-promoted reaction of ketimines (e.g., 120) with unfunctionalized... 

Knochel demonstrated the effectiveness of soluble potassium or cesium alkoxides such as KO Bu or CsO Bu as well as KH in iV-methylpyrrolidinone (NMP) for promoting the 5-endo-dig cyclizations of 2-alkynylanilines to 2-substituted indoles in solution or the solid-phase <00AG(E)2488>. Alternatively, Cacchi coupled a palladium-catalyzed cyclization of o-alkynyltrifluoroacetanilides with the addition of benzyl bromide or ethyl iodoacetate to afford 2-substituted-3-benzyl or 3-indolylcarboxylate esters, respectively <00SL394>. Yamamoto reported a new palladium catalyzed indole synthesis in which 2-(l-alkynyl)-Ar-alkylideneanilines 117 give 2-substituted-3-(l-alkenyl)indoles 118 directly from the imine by the in situ coupling of an aldehyde with the alkynylaniline <00JA5662>. 

Yoon and co-workers reported a methodology that yielded pyridopyrimidones 97 and 98 through the palladium-catalyzed coupling of iodouracil 94 with alkenes 95 and 96, respectively <00SC81>. It was noted that when the alkenes of type 95 (X = acetyl, ester, or nitrile) were employed, demethylated products 97 resulted, otherwise, the deaminated products 98 were favored. No mechanistic explanation of these results was supplied by the authors. 

Palladium-catalyzed cyclization of alkenes and alkynes were reported by Balme and co-workers.143 144 Intramolecular carbopalladation occurs to give polycyclic compounds. It has been shown that the nucleophile type has a large influence on the cyclization process. Both 5-exo- and 6-endo-cyclization are observed for substrates with nitrile (116 and 118) and ester (120, 122, and 124) substituents, respectively (Scheme 36). When a mixed nucleophile (CN and C02Me) is used, a mixture of 5-exo and 6-endo products is obtained. The chemoselectivity is controlled by the size of the nucleophile used. The stereochemistry of the initial double bond plays an important role on the stereoselectivity of the cyclization. (Z)-olefins (118 and 120) and (/. )-olefins (116 and 124) afford as- (119 and 121) and trans-cyclization products (117 and 123), respectively. 

Palladium-catalyzed bis-silylation of a,/ -unsaturated ketones using bis(disilanyl)dithiane affords seven-membered ring silyl enol ethers in high yields via 1,4-addition (Equation (48)).8,97 Application of this reaction to a,/ -unsaturated esters and nitriles gives five-membered ring 1,2-addition products in good yields (Equation (49)). 

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