Arene Olefination Oxidative Heck Reaction

An interesting application of the Fujiwara-Moritani/oxidative Heck reaction for the synthesis of benzo furans was recently reported by the Stoltz lab [31]. A variety of allyl phenyl ethers (all containing electron-rich aryl components) react with 10 mol% palladium acetate, 20 mol% ethyl nicotinate, 20 mol% sodium acetate, and one equivalent of benzoquinone at 100°C to provide benzofurans in 52-79% yield (e.g. 16—>17). The mechanism of this transformation begins with arene palladation of Pd(II) followed by olefin insertion, p-hydrogen elimination, and olefin isomerization to the thermodynamically favored benzofuran product. The resulting Pd(0) species is then oxidized to Pd(ll) thus regenerating the active catalyst. 

The Fujiwara-Moritani reaction enables the coupling of alkenes with arenes under oxidative conditions—also named oxidative Heck reaction (for the mechanism, see Ref [ 29]) Garcia-Rubia et al. used this Pd"-catalyzed oxidative direct C-H alkenylation to produce /rans-stilbene derivatives.As exemplified by their synthesis of pterostilene (Scheme 5-45), a partially methylated resveratrol derivative, a 2-pyridyl sulfinyl group efficiently promotes the Pd"-catalyzed ortho C-H olefination of arenes and can be readily removed or transformed into a thiol group. 

More recently, cationic intermediates have been observed in the Heck reactions of arene diazonium salts catalyzed by triolefinic macrocycle Pd(0) complexes [17,59], o-iodophenols and enoates to form new lactones [60], and o-iodophenols with olefins (the oxa-Heck reaction) [61 ]. In the first case ions were formed by oxidation of the analyte at the capillary, or by association of [NH4] or Na". In the two other cases ionization occurred through the more typical loss of a halide ligand. The oxa-Heck reaction provides a good example of how these experiments are typically performed and the type of information that can be obtained. The oxyarylations of olefins were performed in acetone, catalyzed by palladium, and required the presence of sodium carbonate as base. Samples from the reaction mixtures were diluted with acetonitrile and analyzed by ESI(+)-MS. Loss of iodide after oxidative addition of o-iodophenol to palladium afforded positively-charged intermediates. Species consistent with oxidative addition, such as [Pd(PPh3)2(C6H50)], and the formation of palladacycles of the type seen in Scheme 8 were observed. Based on this, a mechanism for the reaction was proposed (Scheme 8). 

The intermolecular oxidative arylation of olefins has been reported in most cases with acrylic acid derivatives. This process could be developed as an alternative to the Heck reaction, which occurs with aryl halides. Several groups have reported versions of this oxidative C-C bond formation. Fujiwara reported intermolecular examples of this reaction catalyzed by palladium and copper (Equation 18.64). Intermolecular versions of this reaction have also been reported with ruthenium catalysts and as the oxidant. Other oxidative reactions in which electron-rich arenes add to olefins (Equation 18.66) have been reported as stoidiiometric steps of natural products syntheses, and later as a catalytic process. ... 

Similar palladium-catalyzed cascade arylations also occur with acyclic alkenes, including a,p-unsaturated sulfones (Equation 19.153), sulfonamides, phosphine oxides, and phosphonate esters. In contrast, typical conjugated olefins, such as a, 3-unsaturated esters and enones almost exclusively react to form products from Heck reactions. Direct arylations have also been conducted with disubstituted alkynes containing a terminal arene and a large group, such as an aryl or ferf-butyl group (Equation 19.154). ... 

For the first time, therefore, several cationic intermediates of the oxidative addition step of the Heck reaction involving arene diazonium salts were detected and characterized by ESI-MS(/MS). A dynamic, time-dependent process with ligand equilibria between several ionic intermediates was observed for the oxidative addition step. The most reactive intermediate for olefin addition (the ion of m/z 488 in Figure 3.5) was also detected and characterized, and this species predominates after mixing the arene diazonium salt and [Pd2(dba)3] dba after about 90 min. Therefore, a novel protocol for the Heck reaction with a delay of 90 min for olefin addition was established for maximum yield. A detailed catalytic cycle for the Heck... 

One remarkable reaction catalyzed by Rn complexes is the Murai conpling, in which alkyl arenes 44 are formed by hydroarylations of olefins. Interestingly, P-hydride elimination is not a problem in these reactions, as would be expected with other transition metal catalysts." " Murai-type protocols are especially nseful as they can employ electron-rich olefins, which are typically low-yielding snbstrates in Pd-catalyzed, oxidative Heck (Fujiwara-Moritani) reactions." " ... 

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