Iodobenzene, Heck reaction

Palladium metal catalysts supported on organic resins containing tertiary amino, cyano, carboxyl, and pyridyl groups have been recently investigated in some Heck reactions, such as the coupling of iodobenzene with methyl acrylate and methyl vinyl ether (Scheme 11) [31]. 

To assess the utility of this resin, we chose to employ it in the evaluation of the heterogeneity of a commercial polymer-entrapped Pd(OAc)2 precatalyst, Pd-EnCat, also sold by Reaxa. This precatalyst was designed with the goal of providing a heterogeneous catalyst that would allow simple removal of palladium from reactions (24-26). PVPy and QTU were first used as poisons in the Heck reaction of iodobenzene and n-butyl acrylate in DMF using PdfC as the palladium... 

General procedure for the Heck reaction. A mixture of iodobenzene (5 mol equ.), diisopropylethylamine (3 mol equ.), 2,3-dihydrofuran (1 mol eq.), and the complexes 9-12 (3 mol %) in degassed benzene was stirred at 70 °C. The progress of the reaction was monitored by GC. Upon completion, the mixture was filtered through basic alumina (58 mesh, Aldrich) to remove Pd and the products were identified using GCMS. 

Carretero and coworkers [58] encountered three C-H-activations after a first Heck reaction using a,(5-unsaturated sulfones 6/1-102 and iodobenzene. Under normal conditions, the expected Heck product 6/1-103 is formed however, if an excess of phenyliodide is used, then 6/1-104 is obtained in high yield. In this transformation three molecules of phenyliodide are incorporated into the final product (Scheme 6/1.27). 

In a later publication,[51] Heck reactions (between iodobenzene and styrene) were performed in the same way. In contrast to the PTC, the catalyst for the Heck reaction... 

Ohta s group investigated the heteroaryl Heck reaction of thiophenes and benzothiophenes with aryl halides [127] and chloropyrazines [128]. Addition of the electrophiles invariably took place at C(2) as exemplified by the formation of arylbenzothiophene 156 from the reaction of benzothiophene and p-bromobenzaldehyde [127]. As expected, the heteroaryl Heck reaction of 2-thienylnitrile, an activated thiophene, with iodobenzene afforded the arylation product 157 [129],... 

Similar results were obtained for the heteroaryl Heck reaction of iodobenzene or bromobenzene with oxazole and benzoxazole [23]. 

Haloarene chromium tricarbonyl complexes are activated to nucleophilic attack by thiolate anions [58, 59]. High yields of the thioethers are obtained under liquiddiquid two-phase conditions, but optimum yields are achieved under soliddiquid conditions. In many cases the thioether is produced directly but, where the reaction mixture contains thioether and its chromium complex, the thioether can be isolated by degradation of the complex with iodine or an excess of the thiol. Both 1,2- and 1,4-dichlorobenzenes yield only monothioethers, even when an excess of thiolate anion is used. In contrast, 1,3-dichlorobenzenes produce a mixture of the mono- and dithioethers [59]. Aryl allyl thioethers have been produced under catalysed Heck reaction conditions from S-allyl thiocarbamates and iodobenzene [60]. 

We continued our work with the reductive Heck and Domino-Heck reactions [1, 7J of new bicyclic compound (3) by treating it with different aryl- and hetaryl-iodides, as a result a series of new epibatidine analogues were synthesized, continuously separated and purificated by column chromatography on silica gel. Treatment of 3 with iodobenzene, 2-iodothiophene, 1-iodonapthalene and 2-chloro-5-iodopy-ridine under reductive Heck conditions gave new compounds 4a-d and 5b, 5d as exo-regioisomers after chromatographic separations. The reactions with iodobenzene and 1-iodonapthalene gave only 5-exo- products. The use of trimethylsily-lacetylene under Domino-Heck conditions provided alkynic bicyclic systems 6e andf. 

In the second series of experiments, O. Nuyken et al. investigated the Heck reaction of iodobenzene with styrene as a model for the numerous palladium-catalyzed coupling reactions (Scheme 6.6) [54]. In the literature only a few Heck coupling reactions of hydrophobic substrates in aqueous solution are known. The most detailed study has been performed by Jeffery et al. on the model reaction of iodobenzene with methylacrylate in the presence of tetrabutylammonia salts. Product yield was at least 95% after 2 h reaction time at 50 °C in pure aqueous solution [55], however more... 

In a first test reaction, the polymer support was used for the hydroformylation of 1-octene in water in the presence of Rh(CO)2acac. Within a reaction time of 10 h at 120°C and a H2/CO (1 1) pressure of 5 MPa, conversion of up to 94% was obtained. The n iso ratio was 3 1, sometimes reaching 9 1. The quantities of 3-and 4-nonanal resulting from olefin isomerization, were below 5% [74]. The versa-tihty of the polymer support was further demonstrated with the Heck reaction of styrene and iodobenzene in the presence of Pd(OAc)2 as the metal catalyst The reaction was again performed in pure water at 50 °C and product yield of up to 80% was obtained after 20 h reaction time [75]. 

The decrease of polarity starts well under the critical point and the dielectric constant of water is approximately 31 at 225 °C and 100 bar such systems are referred to as high temperature water (HTW). Moreover, the polarity can be adjusted by changing the temperature and pressure in order to dissolve certain organic components of a catalytic reaction mixture. Under such conditions Heck reaction of iodobenzene and various cyclic alkenes, catalyzed by [Pd(OAc)2] afforded coupled products in 17-54% yield [52]. 

Coupling of 1 with iodobenzene under Heck reaction conditions gave the phenyl-substituted diene 242-Ph which was isolated in up to 78% yield [146-148]. When heated at 80 °C in DMF or MeCN with various dienophiles 244-R (acrylate, maleate, or fumarate), 242-Ph and its analogs 242-Ar obtained from 1 and other haloarenes cleanly gave the spiro[2.5]octene derivatives 245-Ar (Scheme 57). 

The dendritic palladium complexes efficiently catalyzed the Heck reaction of iodobenzene with -butylacrylate in toluene at 100°C, whereas the reaction hardly... 

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

Tethering an iodobenzene and a furane moiety through a y0-lactam led to the formation of a unique tetracyclic y0-lactam derivative (5.17.). Oxidative addition followed by the carbopalladation of the furane ring resulted in the closure of the seven membered core in a so called heteroaryl Heck reaction "... 

The palladium catalysed sequential alkylation-alkenylation of 5-iodoquinoline leads to the formation of the quinolooxepin ring system (5.20.), The process, closely related to the Catellani reaction,19 runs through an ort/zo-alkylation - Heck reaction sequence. The preparation of a series of benzoxepines has also been achieved in this manner, starting from such iodobenzene derivatives, where one of the or/7 o-positions was blocked by substitution.20... 

A dramatic increase of the TON is observed in the Heck reaction under high pressure. A value of 770 000 was achieved in the coupling reaction of iodobenzene with 2,3-dihydropyrrole under 8kbar at 100 °C. High pressure seems to stabilize the catalyst [12]. 

For the Heck reaction as discussed in Section III.2.1 the final position of the olefi-nic double bond of the products must not necessarily be the same as in the starting materials (for example Schemes 8, 9, and 10 of Section III.2.1) [1], The selectivity is often driven by stereochemical requirements, because the /1-hydrogen elimination step which forms the double bond proceeds exclusively in a syn manner (if a trans /3-hydrogen is eliminated, one should suspect major deviations from the general mechanism of the Heck reaction, for example electrophilic substitution instead of carbopalladation). An impressive example of a double bond migration is depicted in Scheme 1 - instead of olefins the coupling reaction of iodobenzene 1 with the olefmic alcohol 2 results in the isomeric aldehydes 3 and 4 as final products [2], Reactions of this type have emerged as valuable tools for the synthesis of carbonyl compounds and also as crucial steps in domino processes. 

At about the same time, Seddon reported the Heck reactions of bromo-and iodoarenes in a series of /V-hexylpyridinium [C6py] + and N,N dialkylimidazolium based liquids with [PF6] and [BF4] anions.20 The effects of changing the ionic liquid and reaction conditions upon the Heck reaction of iodobenzene with ethyl acrylate were reported using 2 mol% Pd(OAc)2. 

Muzart et al. used PdCl2 in [NBu4]Br for the Heck reaction of iodobenzene with various allylic alcohols.30 The Heck reaction of allylic alcohols can lead to the formation of aryl ketones (a- or (3-substituted) as well as the (a- or (S-J arylated allylic alcohols. However, these authors... 

A system for the Heck reaction between methyl acrylate and iodobenzene has been developed comprising an imidazolium-functionalized polystyrene monolith, initially for use in batch. This system could be reused six times before any reduction in yield was observed. Accordingly, a continuous-flow reactor system was developed using DMF at 200 °C with a residence time of 3-4 min to achieve full conversion. This system was characterized by very low palladium loadings (0.02 mol%), and ICP-MS of the solution aliquots showed leaching of less than 1 ppm. Attempts at using EtOH as solvent to provide a more environmentally and procedurally benign protocol resulted in maximum yields of 85% [144]. 

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