Heck reaction electron-deficient alkene arylation

Arylation of alkenes catalyzed by palladium compounds is known as the Heck reaction [65]. While these reactions are very sensitive to steric effects, subtle electronic contributions to the regiochemical outcome may be assessed by comparing reactions of alkenes with similar substitution patterns. The arylating agents, being the nucleophilic arylpalladium species, tend to dictate the facility of their reaction with unsym-metrical, electron-deficient alkenes. 

An aryl group can be introduced to a substituted P-posittion of an a,p-unsaturated ketone or other electron-deficient alkenes by the Heck reaction in the presence of a... 

Aerobic oxidative Heck reactions also proceed between olefins and other aryl nucleophiles such as aryl tin and aryl boron reagents (Eq. (8.22)). This field started by utilizing aryl tin reagents and electron-deficient alkenes with stoichiometric base additives such as NaOAc [100], but has been significantly improved by... 

Recently, a fluorescence-based assay for high-throughput screening of a Heck reaction was described (Scheme 48). ° The assay involves coupling of an electron-deficient alkene, containing a tethered fluorophore, with an aryl halide attached to a Wang resin. A... 

Vinyl halides and triflates serve as good Mizoroki-Heck vinylating agents, yielding synthetically important diene products [12, 13]. Vinylation occurs in the terminal j8-position of electron-deficient alkenes, as in the case of the arylation reactions, and the same... 

In general, the Mizoroki-Heck coupling of aryl halides with both electron-rich and electron-poor terminal alkenes affords monoarylated products. With electron-deficient alkenes under selected reaction conditions, such as with excess of the aryl halide, with special catalysts at high temperatures or under high pressure, a twofold terminal arylation to give 1,1-diarylalkene derivatives may occur (Figure 3.41) [103]. Triple arylations... 

When the initial aryl-palladium species has more than one possible proton in the vicinity, the C—H activation can take place several times. Carretero and coworkers [77] observed three C—H activations after the initial Mizoroki-Heck reaction nsing o, /i-nnsatnrated snlfones 134 and iodobenzene. Under normal conditions, the expected Mizoroki-Heck product 135 is formed however, using an excess of iodobenzene, 136 is obtained in high yield. In this transformation, three molecules of iodobenzene are incorporated into the final product. On the other hand, a later study showed that, under the same conditions, similar electron-deficient alkenes as enones do not nndergo this domino reaction instead, only the Mizoroki-Heck product is obtained [78]. A computational analysis of the transformation explained this finding with the difference in the energy of the transition states that ultimately lead to the five-membered ring palladacycle PdCl (Scheme 8.35). 

Dhudshia and Thadani [28] used (ADC)Pd complexes with A1 (Scheme 11.3) in an intermolecular Heck reaction of aryl bromides with an electron-deficient alkene. The target species were isolated in 78-85% yields under optimized catalytic... 

An important virtue of the Heck reaction is that it can be applied with much success to essentially every type of olefin, although electron-deficient olefins are particularly well-suited. Moreover, the Heck reaction tolerates a variety of functional groups, and often does not require rigorous exclusion of oxygen and water.llb In fact, many alkene arylations proceed very efficiently in water.14... 

Representative examples of Heck reactions are depicted in Scheme 8.8. Terminal alkenes react faster than internal alkenes, and the formation of mixtures of products resulting from further arylation or vinylation of the initial product is therefore only observed when a large excess of halide and long reaction times are employed. Electron-poor alkenes usually react more rapidly than electron-rich alkenes, and the new C-C bond is usually formed at the most electron-deficient carbon atom. 

Heck reaction. Solvent-free conditions with microwave irradiation have been developed for the Heck reaction. Phosphites are excellent ligands such that even electron-deficient aryl chlorides can be used to couple with different alkenes. Isoquinolines are formed by using the more conventional procedure note the same 3-(o-iodobenzylamino)acrylic esters give dihydroisoindole derivatives when they are exposed to Bu,SnH-AIBN. A combination of BUjP and dppp together with /-Pr NEt constitutes support for Pd(OAc)2 in an intramolecular coupling which leads to benzophenanthridines. ... 

The Heck reaction (Mizoroki-Heck reaction) is the reaction of an unsaturated halide (or triflate) with an alkene and a strong base and palladium catalyst to form a substituted alkene [41, 42]. The reaction is performed in the presence of an organo-palladium catalyst. The halide or triflate is an aryl, benzyl, or vinyl compound, and the alkene contains at least one proton and is often electron deficient, such as acrylate ester or an acrylonitrile. The catalyst can be tetrakis(triphenylphosphine)palladium... 

The Mizoroki-Heck reaction is a subtle and complex reaction which involves a great variety of intermediate palladium complexes. The four main steps proposed by Heck (oxidative addition, alkene insertion, )3-hydride elimination and reductive elimination) have been confirmed. However, they involved a considerable number of different Pd(0) and Pd(Il) intermediates whose structure and reactivity depend on the experimental conditions, namely the catalytic precursor (Pd(0) complexes, Pd(OAc)2, palladacycles), the Ugand (mono- or bis-phosphines, carbenes, bulky monophosphines), the additives (hahdes, acetates), the aryl derivatives (ArX, ArOTf), the alkenes (electron-rich versus electron-deficient ones), which may also be ligands for Pd(0) complexes, and at least the base, which can play a... 

Oxidations. Cu(OAc)2 has been used as a reoxidant in Pd catalyzed reactions of aryl and alkenyl boronic acids with alkenes and alkynes, and aryltins, and aryl or alkenyl silanols with electron deficient olefins (eq 26). This Mizoroki-Heck type reaction supposedly proceeds through a Pd(II)-boron transmetallation step, followed by addition across the double (triple) bond and final... 

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