Heck arylations

During the course of an elegant synthesis of the multifunctional FR-900482 molecule [( )-43, Scheme 9], the Danishefsky group accomplished the assembly of tetracycle 42 using an intramolecular Heck arylation as a key step.24 In the crucial C-C bond forming reaction, exposure of aryl iodide 41 to a catalytic amount of tetra-kis(triphenylphosphine)palladium(o) and triethylamine in acetonitrile at 80 °C effects the desired Heck arylation, affording 42 in an excellent yield of 93 %. The impressive success of this cyclization reaction is noteworthy in view of the potentially sensitive functionality contained within 41. 

Scheme 9. Danishefsky s intramolecular Heck arylation approach to the synthesis of ( )-FR-900482 [( )-43].

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

Prashad M (2004) Palladium-Catalyzed Heck Arylations in the Synthesis of Active Pharmaceutical Ingredients. 6 181-204 Pretraszuk C, see Marciniec B (2004) 11 197-248... 

Scheme 21.1 Heck arylation of acrolein and acrolein diethylacetal. was the most important parameter among all those evaluated (i.e. KCl, solvent...) that affect the selectivity (Scheme 21.1, Route 3). However, moderate activity and selectivity were achieved when using the 9-bromoanthracene whatever the olefin (8). This was attributed to the large steric hindrance of this substrate.

The novel synthesis of chromanocoumarans illustrated in Scheme 159 constitutes a modification of the Heck arylation process (cf. Eq. 14 in Section IV,B,1) in which arylation of a 2H-chroman is followed by intramolecular nucleophilic displacement of the palladium moiety.235... 

Another example involves dioxygen-promoted regioselective oxidative Heck aryla-tions of electron-rich alkenes with arylboronic acids (Scheme 4.12c). For this, two types of microwave reactors have been used. In a single-mode instrument (1 mmol run 25 mL vessel), the Heck arylation was performed by first pre-pressurizing the... 

In a recent article by Botella and Najera, controlled mono- and double-Heck arylations in water catalyzed by an oxime-derived palladacycle were described [22], When the reaction was carried out under microwave irradiation at 120 °C in the presence of dicyclohexylmethylamine with only 0.01 mol% of palladium catalyst (palladium acetate or palladacycle), monoarylation took place in only 10 min with a very high turnover frequency (TOF) of > 40000 (Scheme 6.3). As regards diarylation, 1 mol% of the palladacycle catalyst and 2 equivalents of iodobenzene had to be utilized to obtain moderate to good yields of diarylated product. Whereas microwave heating at 120 °C provided a 31% yield after 10 min, a 66% isolated yield of product was obtained by heating the reaction mixture under reflux for 13 h at 100 °C. Here, the... 

Scheme 6.3 Mono- and double-Heck arylations in water using oxime-derived palladacycles.

Scheme 6.4 Synthesis of resveratrol trimethyl ether via Heck arylation.

Scheme 6.5 Double-Heck arylations of chelating alkenes with aryl bromides.

A heterogeneous Pd catalyst dispersed on supports such as o-A1203, C, MgO and CaC03 was found to be an recyclable and selective catalyst for heterogeneous Heck arylation (an important method of C-C bond formation - Chapt. 11) of several olefins (styrene, a-methylstyrene, 1-decene, acrylonitrile, etc.) with iodobenzene [45], Scheme 10.5. 

Regioselectivities that are usually high to excellent have been reported in novel palladium-catalyzed Heck arylation reactions with a variety of allylic substrates. The //-stabilizing effect of silicon enhanced regiocontrol in the internal arylation of allyl-trimethylsilane (Eq. 11.5) [18], and coordination between palladium and nitrogen... 

Traditional Heck arylation of the corresponding ethyl vinyl ether afforded high yields with most of the aryl bromides investigated (Eq. 11.11). Under continuous singlemode microwave treatment the transformations were complete within 10-12 min [25], Heck reactions without solvent in a domestic microwave oven have been examined by Diaz-Ortiz [26]. The reactions were conducted in closed vessels with reported temperatures of 150 °C. A study was performed in which reactions performed with microwave irradiation were compared with oil-bath-heated reactions with identical reaction times and temperatures. The isolated yields tended to substantially favor the microwave-heated reactions (Eq. 11.12). 

E)-stilbene was the exclusive product of the Pd colloid-catalyzed Heck arylation of styrene with chlorobenzene. Recently, a polymer-mediated self-assembly of functionalized Pd and Si02 nanoparticles have been found to be highly active catalysts for hydrogenation and Heck coupling... 

Heck arylation of ethene with, 42 494 lodomethane, catalytic decomposition, 35 144 2,3-IOI-isopropylidene-2,3-dihydroxy-l,4-bis-(dishenylphosphino) butane (DIOP) as catalyst, 25 90, 91... 

Popp BV, Stahl SS (2007) Palladium-Catalyzed Oxidation Reactions Comparison of Benzo-quinone and Molecular Oxygen as Stoichiometric Oxidants. 22 149-189 Prashad M (2004) Palladium-Catalyzed Heck Arylations in the Synthesis of Active Pharmaceutical Ingredients. 6 181-204 Prestipino C, see Zecchina A (2005) 16 1-35 Pretraszuk C, see Marciniec B (2004) 11 197-248... 

A remarkable dendritic effect in the Heck arylation of olefins by a dendrimer supported Pd-cat-alyst has recently reported by Portnoy et ah A. Dahan, M. Portnoy, Org. Lett. 2003, 5, 1197-1200. 

Brown and coworkers [22] have studied the Pd-catalyzed Heck arylation of methyl acrylate via P and NMR (see Figure 1.7). Reaction of the aryl iodide complex 23 with AgOTf (THF, 195 K) gives the THF and aquo-complexes 24 and 25, respectively, which were detected via P NMR below 203 K. Addition of HjO to the sample shifts the equilibrium towards 25, pointing to an existing fast exchange between solvates 24 and 25. Reaction of 24/25 with 3- C labeled methyl acrylate (20-fold excess, 213 K) affords the insertion product 26. Warming to 233 K leads to the formation of 27, which is in turn converted into 29, stable to... 

Using NMR the same authors have identified several intermediates in the asymmetric Heck arylation of dihydrofuran [23, 24]. Reaction of the Binap salt, 30, with 2,3-dihydrofuran below 233 K gave salt 31 as the single species (see Figure 1.8). A parallel reaction between 30 and [2- H] 2,3-dihydrofuran confirmed the structure. At 243 K, 31 slowly decomposed to form 32 and 32 with concomitant release of the coupling product 33 (91% ee). 

The twofold Heck arylation of ethylene and ethylene equivalents, initially investigated by Heck himself, provides an easy access to stilbene derivatives 39-Ar (Scheme 14)." The pressure of ethylene has to be carefully controlled, otherwise styrene derivatives, which are initially formed in this process, will be found as major products. In general, a slightly elevated pressure (1-5 bar) of ethylene is favorable for the vicinal twofold coupling leading to stilbenes in up to 69% yield." ... 

Scheme 16 Construction of a heterotetracyclic skeleton by a twofold intramolecular Heck arylation of an alkenyl group. ...

R - C02H, C02Me, , CN, N02, , CI, Figure 19 Heck arylation of ethylene in aqueous media. 

Andersson, C.-M. Karabelas, K. Hallberg, A. Andersson, C. Palla-dium/Phosphinated Polystyrene as a Catalyst in the Heck Arylation. A Comparative Study, J. Org. Chem. 1985, 50, 3891-3895. 

The Heck arylation of ethene with iodoarenes was investigated with a preformed [PdCl2(tppms)2] catalyst and gave the product styrenes in 60-100% yield (115). In contrast, when the in situ system Pd(OAc)2 -T 2tppms was used as a precursor, the conversion was less effective and yielded the hydration products. 

A very interesting and promising synthesis of pterocarpans (76CC500) involves Heck arylation of a 2-chromene (Scheme 53). The requisite chloromercuriphenol is readily available through the action of mercury(II) acetate, followed by sodium chloride, on 3,4-(methylenedioxy)phenol. 

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