Aryl iodides, Heck addition

The scope of electrophile used in the vinylation reaction can be extended to aryl bromides by employing 2-(di-f-butylphosphino)-biphenyl as a ligand for palladium and raising the temperature to 50 °C (eq 3). The optimized reaction conditions employ a slightly higher loading of Da in comparison to the reaction with aryl iodides. The additional amount of Da is needed to suppress a secondary Heck reaction that provides the symmetrical stUbene as a byproduct. A broad range of styrene derivatives can be prepared by this method as shown in Table 3. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

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... 

In experiments with a supported palladium catalyst, Pd/C, satisfactory yields were obtained without the use of phosphine ligands for the Heck reactions of aryl iodide with acrylonitrile, styrene, and methyl methacrylate in the ionic liquid [BMIM]PF6 (259). The addition of triethylamine improved the yields. The Pd/C remained in the ionic liquid only. The ionic liquid containing Pd/C can be reused as... 

The first detailed study of the individual steps of the cationic pathway of the intramolecular Heck reaction was recently described by Brown (Scheme 8G.21) [46], Oxidative addition of aryl iodide 21.1 to [l,l -bis(diphenylphosphino)ferrocene](cyclooctatetraene)palladium generated 21,2. Complex 21.2 was stable at room temperature and was characterized by X-ray crystallography no interaction between the palladium center and the tethered alkene was observed in this intermediate. Treatment of 21.2 with AgOTf at -78°C removed iodide from the palladium coordination sphere, which facilitated a rapid alkene coordination and subsequent... 

The Heck addition of aryl iodides (Arl) to CH2=CHCH(0H)CF2C02Et can be catalysed by (AcO Pd in the presence of Et3N under standard conditions.84 The... 

Multiple-component difunctionalization reactions of a,/ -unsaturated carbonyl systems have been achieved by catalytic conjugate addition/aldol sequences. As Scheme 8.13 illustrates, an efficient method reported by Montgomery [46] allows regioselective addition of an aryl iodide to the /i-position of an unsaturated ester under nickel catalysis and subsequent trapping with an aldehyde to give / -hydroxyesters (e.g. 33). Significantly, premature termination of the sequence by the /Miydride elimination process that is usually observed in Pd-catalyzed Heck reactions does not occur here. 

Aryl-vinyl coupling fi-aryl-fi-amino acids.2 A novel route to P-amino acids is based on the formal conjugate addition of an aryl iodide to an enantiomerically pure dihydropyrimidinone such as 1, prepared by pivaldehyde acetalization of (R)-aspara-gine (c/., 14, 69-70). Thus 4-iodoanisole couples with 1 under Heck conditions, Pd(OAc)2, Ar3P, triethylamine, and DMF to give 2 in 78% yield. Reduction of 2... 

These fundamental steps of the catalytic cycle have been confirmed by stoichiometric reactions starting from isolated stable complexes, and by DFT calculations [11], Although many aspects of the Heck olefination can be rationalized by this textbook mechanism , it provides no explanation of the pronounced influence that counter-ions of Pd(II) pre-catalysts or added salts have on catalytic activity [12], This led Amatore and Jutand to propose a slightly different reaction mechanism [13]. They revealed that the preformation of the catalytically active species from Pd(II) salts does not lead to neutral Pd(0)L2 species a instead, three-coordinate anionic Pd(0)-complexes g are formed (Scheme 3, top). They also observed that on the addition of aryl iodides la to such an intermediate g, a new species forms quantitatively within seconds and the solution remains free of iodide and acetate anions. It may then take several minutes before the expected stable, four-... 

This methodological approach to di- and triaryl-substituted ethenylene motifs is interesting for three reasons. First, all aryl groups assembled stem from readily available aryl iodides and diiodides (Fig. 5.15). Second, by applying the Heck-Hiyama sequel they can be installed at the desired position by the addition of... 

Another example features a Heck-type 5-exo-trig cyclization of the aryl iodide 139 occurring at room temperature in dichloromethane (Scheme 22) [82]. Azomethine ylides originating from imines 133 were used to trap the Heck product 140 in a subsequent 1,3-dipolar cyclo addition. The diastereomeric products 141 and 142 both derive from an endo attack of... 

While the PNP dimer was an efficient catalyst for the ort/toalkylation/ Mizoroki-Heck reaction, the practicality of the transformation is lessened by the fact that the PNP dimer is not commercially available, and can be quite difficult to prepare. Thus, Catellani adapted the reaction conditions to include commercially available and air-stable Pd(OAc)2 as the catalyst source [46], Under these conditions, the ortho-u kylation/Mizoroki-I Ieck coupling of aryl iodides containing a pre-existing ortho substituent could be carried out. The reaction required higher temperatures, and the addition of KOAc to promote the carbopalladation of norbomene [47] and encourage the o/t/zo-alkylation pathway vs a direct Mizoroki-Heck coupling. 

The first detailed study of alkyl to aryl palladium migrations, reported in 2004, involved homobenzylic to phenyl migration (Table 5) [58], The process was demonstrated using aryl iodides tethered to an olefin. An additional hap, either intramolecular arylation or intermolecular Heck olefination, was used to hap the migrated palladium. The reaction gives high yields of the desired polycyclic products. 

Quite a few groups have performed additional research trying to answer the question as to whether the Heck reaction takes place on the surface of the clusters or if it occurs entirely or partially in solution. De Vries and coworkers applied electrospray MS (negative mode) on the Heck reaction of aryl iodides with butyl acrylate. They uncovered a number of monomeric anionic species which led them to propose the catalytic cycle depicted in Scheme 10.6 [57, 58]. 

Some of the (probably) wrong conclusions in the literature during this period are due to the fact that measurable amounts of palladium are often observed in solution only during the reaction. Due to redeposition, the palladium concentration in solution is very small or not detectable at the end of the reaction. In addition, several experimental tests on the heterogeneity of the reaction were obviously not suitable for the Heck reaction [136]. And, very importantly, most mechanistic investigations were performed with aryl iodides (or activated aryl bromides) only. It has been shown in Sections 10.3 and 10.4 that extremely low (even not detectable) amounts of palladium at the ppm or sub-ppm level are able to convert these substrates easily [58]. 

---