Carboxylic esters, Mizoroki-Heck

This concept was proven to be viable using the example of 4-nitrophenyl esters in the presence of a palladium(II) chloride/lithium chloride/isoquinoline catalyst system, the 4-nitrophenyl esters 3c of various aromatic, heteroaromatic and vinylic carboxylic acids were converted to the corresponding vinyl arenes 5k along with 4-nitrophenol (Figure 4.17). The latter was demonstrated to react with benzoic acid at the same temperature as required for the vinylation step (160 °C) to regenerate the corresponding ester [28], thus demonstrating that at least a two-step waste-minimized Mizoroki-Heck reaction is feasible. 

The reaction was successfully applied to both electron-rich and electron-poor 4-nitrophenyl carboxylates among them, the conversion of the electron-deficient esters was found to be faster and more efficient. Many functional groups are tolerated on both the side of the carboxylic ester (halo, keto, formyl, ester, cyano, nitro and protected amino groups, heterocyclic and a,-unsaturated carboxylic esters) and of the alkene (electron-rich alkyl-substituted alkenes, electron-poor acrylate derivatives, trimethylvinylsilane as an ethylene surrogate). The cinnamate derivatives could become particularly useful substrates, since the availability of the synthetically equivalent vinyl halides is rather limited. In analogy to conventional Mizoroki-Heck chemistry, linear (Zi)-substituted alkenes are predominantly but not exclusively obtained. Selected examples are shown in Table 4.1. 

Beside 4-nitrophenyl esters, other activated esters and amides (e.g. of pentafluorophenol, imidazole and meanwhile even 3-chlorophenol) have been shown to be viable substrates. However, substantial additional progress in catalyst development is required to extend the scope of the reaction further to carboxylic acid alkyl esters, which can be regenerated by in situ esterification. This is strictly required, as a two-step process is not likely to be able to compete with the standard Mizoroki-Heck reaction from a purely economical standpoint. 

Aiming to overcome the limitations of the previous protocols, GooKen et al. then extended their own studies using easily available carboxylic esters [29], This indeed paved the way to waste-minimized Mizoroki-Heck reactions, in which any byproduct was efficiently recyclable such that waste formation was limited to carbon monoxide and water (47->48 Scheme 7.10). Subsequently, this technique has proven to be viable for converting various 4-nitrophenyl esters 47 in the presence of a PdCfi-LiCl-isoquinoline catalyst system into styrenes 48. Under Lewis acid catalysis, 4-nitrophenol (49) cleanly reacts with benzoic acid at the same temperature required for the Mizoroki-Heck arylation (49 47), thereby regenerating 4-nitrophenyl ester 47. 

A tentative mechanism for the Mizoroki-Heck arylation of carboxylic esters is shown in Scheme 7.11 [29]. The initial step of the catalytic cycle is the oxidative addition of the C(0)—O bond of carboxylic ester 47 to palladium catalyst 1, forming acylpaUadium complex 50 (1 50). Ligand exchange of alkoxide for halide (50—>... 

Scheme 7.11 Proposed mechanism for the waste-minimized Mizoroki-Heck reaction of carboxylic esters.

Pd catalysts also promote the decarbonylative Mizoroki-Heck reactions of even poorly reactive p-nitrophenyl aryl carboxylates with olefins to give the vinyl arenes in good to excellent yields, along with CO and the corresponding phenols [40]. Mizoroki-Heck-type arylation of styrene and acrylate esters by use of aroyl chlorides can also be performed in the presence of PdCljlPhCN) / (PhCHjlBUjNCl as the catalytic system without adding base [41]. 

Allylic esters act as effective conpling partners (Scheme 22.28). Electron-rich substituents on the aromatic moiety of the carboxylic acids provide the expected Mizoroki-Heck products in high yields. On the other hand, 2,6-diflnoro-, 2,4,6-triflnoro-, and perfluorobenzoic acids afford only very low yields of the Mizoroki-Heck prodncts. Substituted allylic esters react efficiently in this ARCIS reaction [17]. 

---