Heck coupling mechanism

It has been observed that reductive elimination can also occur for aryl-Pd-carbene complexes. Such complexes were investigated in mechanistic studies on Heck coupling and catalyst decomposition routes. Reductive elimination products with direct imidazolium-aryl coupling were observed and in one case fully characterized. Such products provide direct evidence of the Heck coupling mechanism and of intermediates in the catalytic cycle. Important mechanistic studies on the oxidative addition of aryl chlorides to a 14-electron Pd(0)(carbene)2 complex have demonstrated that oxidative addition occurs via a dissociative process and this step is probably the rate-determining step in the amination of aryl chlorides. Aryl-carbene reductive coupling was observed in this study of the amination reaction, and directly coupled aryl-imidazolium compounds were isolated. A further study on an (aryl)Pd(carbene) complex has also demonstrated that such complexes undergo facile reductive elimination to form aryl-imidazolium salt. ... 

Fig. 13.26. Mechanism of a Heck coupling with acrylic acid methyl ester. The elementary steps 1-3 correspond to those in Figures 13.7 and 13.14, and the further course of the reaction is described in the text.

As an alternative to the classical reaction mechanism, they investigated the possibility of a direct deprotonation of the y5-agostic insertion product by the amine base, which is usually required for successful Heck coupling reactions. The new proposal actually replaces the last two steps of the classical catalytic cycle, P-Vi elimination and base-assisted reductive elimination of HX (Scheme 2). 

The first proposal has never been supported by experimental results [203). In contrast, the second mechanism has been extensively investigated and supported first by Augustine and O Leary for reactions of aroyl chlorides [204, 205). In a modified form, this defective site model has been transferred to typical Heck couplings by a variety of researchers investigating Heck catalysis by Pd colloids [6, 7,... 

IV.2.1.1 SCOPE, MECHANISM, AND OTHER ASPECTS OF THE HECK REACTION 1163 TABLE 2. Intermolecular Heck Coupling Reactions... 

Having seen steps such as oxidative addition, insertion, and reductive elimination in the context of transition metal-catalyzed hydrogenation using Wilkinsons catalyst, we can now see how these same types of mechanistic steps are involved in a mechanism proposed for the Heck-Mizoroki reaction. Aspects of the Heck-Mizoroki mechanism are similar to steps proposed for other cross-coupling reactions as well, although there are variations and certain steps that are specific to each, and not all of the steps below are involved or serve the same purpose in other cross-coupling reactions. 

A tridentate ligand based on 1,8-naphthyridine (NP), which bears a ferroceneyl amide pendant arm, was synthesized and used to support dipalladium(I) and diruthenium(I) compounds [69]. The synthesis of the dipalladium(I) compound 104 started with a Pd(II) precursor, but the detail of the redox reaction was not discussed in the original article (Scheme 10.54). Complex 104 is diamagnetic and the Pd(I)-Pd(I) bond is short at 2.3952(8) A (Entry 14, Table 10.7). Compound 104 was proven to be an active catalyst for Suzuki and Heck coupling, and a bimetallic-synergy mechanism was proposed for the pivotal oxidative addition/reductive elimination steps. 

SCHEME 13.3. A general mechanism for the Heck coupling reaction. 

Heck C-C coupling reactions were also facilitated by the presence of a palladium catalyst when Pd was deposited on a tubular membrane of porous glass. Thus, the coupling of iodobenzene with allyl alcohol affording 3-phenylpropionaldehyde in the presence of this Pd catalyst had several advantages - the ease of catalyst manufacture, mechanical strength, thermal stability, and resistance to organic solvents [46],... 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

The Heck reaction, first disclosed by the Mori and Heck groups in the early 1970s [65, 66], is the Pd-catalyzed coupling reaction of organohalides (or triflates) with olefins. Nowadays, it has become an indispensable tool for organic chemists. Inevitably, many applications to heterocyclic chemistry have been pursued and successfully executed. In one case, Ohta et al. reacted 2-chloro-3,6-dimethylpyrazine (49) with styrene to furnish ( )-2,5-dimethyl-3-styrylpyrazine (50) [67]. Here, only the E isomer was observed. The outcome will become apparent during the ensuing discussions on the mechanism. 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

---