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The Heck reaction, generally defined as the substitution of a vinylic hydrogen with an aryl, vinyl, or benzyl group, is widely regarded as one of the premier synthetic tools for the construction of new C–C bonds. The oxidative Heck reaction, which commences with the generation of the key arylpalladium species under palladium(II) catalysis, has emerged as a powerful alternative to the palladium(0)-catalyzed Mizoroki−Heck reaction over the past decade. This chapter gives an overview of the various olefin and aryl/vinyl substrate classes that have been utilized in this reaction. The material is organized according to the reaction type (inter- or intramolecular), the electronic nature of the olefin (electron-poor, electron-rich, or neutral), and the olefin coupling partner. Special emphasis is given to some of the more recent advances in this area and, where applicable, a critical review of the most synthetically useful methods is presented.

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Internal ligand-controlled Heck vinylations of enamides were performed with high regioselectivity and delivered moderate to good yields of dienamides. Controlled heating by microwave irradiation accelerated the palladium-catalyzed reactions, and full conversions were achieved after reaction times of only 15-30 min. New bidentate fluorous-tagged 1,3-bis(diphenylphosphino)propane ligands (F-dppp's) were synthesized and examined. The cationic vinylations of the enamides with F-dppp ligands rendered essentially the same α-selectivity and catalytic activity as in those vinylations where nonfluorous ligands were employed. After reaction, the fluorous-tagged ligand material was easily removed by convenient solid fluorous phase separation. The high selectivity, simplicity, and generality of the experimental procedure should make this approach to 2-acylamino-1,3-butadienes attractive.

Internal ligand-controlled Heck vinylations of enamides were performed with high regioselectivity and delivered moderate to good yields of dienamides. Controlled heating by microwave irradiation accelerated the palladium-catalyzed reactions, and full conversions were achieved after reaction times of only 15-30 min. New bidentate fluorous-tagged 1,3-bis(diphenylphosphino)propane ligands (F-dppp's) were synthesized and examined. The cationic vinylations of the enamides with F-dppp ligands rendered essentially the same alpha-selectivity and catalytic activity as in those vinylations where nonfluorous ligands were employed. After reaction, the fluorous-tagged ligand material was easily removed by convenient solid fluorous phase separation. The high selectivity, simplicity, and generality of the experimental procedure should make this approach to 2-acylamino-1,3-butadienes attractive.

[GRAPHICS] By combining the advantages of metal activation, in situ carbon monoxide delivery, and microwave heating, benzophenones were efficiently synthesized in 6-10 s. These ultrafast carbonylation reactions occur under air by flash heating of aryl iodides in the presence of dicobalt octacarbonyl.

The efficiency of microwave flash heating in accelerating organic transformations (reaction times reduced from days and hours to minutes and seconds) has recently-been proven in several different fields of organic chemistry. This specific account mainly summarizes our own experiences in developing rapid, robust, and selective microwave-assisted transition metal-catalyzed homogeneous reactions. Applications include selective Heck couplings, cross-couplings, and asymmetric substitutions. The science of green chemistry was developed to meet the increasing demand for environmentally benign chemical processes. We believe the combination of metal catalysis and microwave heating will be of importance in the search for green laboratory-scale synthesis., QC 20100525

Palladium-catalyzed Heck arylations in the polar and robust ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF(6)), have for the first time been accomplished under microwave irradiation. The couplings were efficiently performed in sealed tubes within 5-45 min of heating. Without significant reductions in yield, a phosphine-free ionic catalyst phase could be recycled in five successive 20 min reactions at 180 degreesC. The product was easily removed from the reaction medium by distillation.

Dimethylformamide (DMF) acts as an efficient source of carbon monoxide and dimethylamine in the palladium-catalyzed aminocarbonylation (Heck carbonylation) of p-tolyl bromide to provide the dimethylamide. Addition of amines to the reaction mixture in excess delivers the corresponding aryl amides in good yields. The amines employed, benzylamine, morpholine, and aniline, all constitute good reaction partners. The reaction proceeds smoothly with bromobenzene and more electron-rich aryl bromides, but electron-deficient aryl bromides fail to undergo aminocarbonylation. The reactions are conducted at 180-190 degreesC for 15-20 min with microwave heating in a reaction mixture containing imidazole and potassium tert-butoxide: the latter is required to promote decomposition of the DMF solvent at a suitable rate. The beneficial effects of controlled microwave irradiation as an energy source for the rapid heating of the carbonylation reaction mixture are demonstrated. The carbonylation procedure reported herein, which relies on the in situ generation of carbon monoxide, serves as a convenient alternative to other carbonylation methods and is particularly applicable to small-scale reactions where short reaction times are desired and the direct use of carbon monoxide gas is impractical.

This article describes the development of new auxiliary-accelerated Heck multiarylations by intramolecular presentation of the oxidative addition complex. The introduction of a specific, palladium-coordinating dimethylamino group allows for the desired chelation-accelerated and chelation-controlled triand diarylation reactions. We report (a) the first example of a Heck triarylation process, (b) highly selective palladium-catalyzed diarylations of alkyl vinyl ethers, and (c) a very rapid two-phase protocol for the microwave-assisted hydrolysis of amino-substituted, arylated vinyl ethers constituting an entry to diarylated ethanals and substituted desoxybenzoins. X-ray structures and product patterns support the suggested substrate-controlled Heck reaction pathway. The catalyst-directing alkyl dimethylamino functionality was rapidly (1-2 min) and efficiently released by microwave hydrolysis after Heck multiarylation reactions. The liberated aromatic carbonyl compounds were thereafter isolated and fully characterized.

Highly selective palladium-catalyzed internal alpha -arylations of alkyl vinyl ethers with aryl and heteroaryl bromides were conveniently conducted in aqueous DMF with potassium carbonate as base and with DPPP as bidentate ligand. The corresponding acetyl arene products were, after hydrolysis, isolated in good to excellent yields. This Heck reaction procedure does not require toxic thallium or expensive silver salt additives, is promoted by water, and is suggested to proceed via charged organopalladium intermediates. Single-mode microwave irradiation was utilized in one example to shorten the reaction time.

In both lead identification and lead optimization processes there is an acute need for new organic small molecules. Traditional methods of organic synthesis are orders of magnitude too slow to satisfy the demand for these compounds. The fields of combinatorial and automated medicinal chemistry have been developed to meet the increasing requirement of new compounds for drug discovery; within these fields, speed is of the essence. The efficiency of microwave flash-heating chemistry in dramatically reducing reaction times (reduced from days and hours to minutes and seconds) has recently been proven in several different fields of organic chemistry. We believe that the time saved by using focused microwaves is potentially important in traditional organic synthesis but could be of even greater importance in high-speed combinatorial and medicinal chemistry.