Stoichiometric Fujiwara-Moritani Reactions

The first example of a direct oxidative coupling of arenes with aUcenes was described by Fujiwara and Moritani, wherein the double bond of alkenes undergoes substitution reactions with aromatic compounds in the presence of paUadiumfll) salts [3]. Although stoichiometric and with very low yields, this novel reaction opened a new area of palladium(II)-catalysed reactions between aromatic compounds and alkenes. 

Fujiwara and Moritani discovered in 1%7 that when styrene-palladium chloride complex 1 was heated in benzene (2a), toluene (2b) or p-xylene (2c), in the presence of acetic acid, tra 5-stilbene (3a), rram -methylstilbene (3b) or tra -2,5-dimethylstilbene (3c) were produced respectively, albeit in low yields (Equation (9.1)) [3], No stilbene derivative was obtained, however, in the case of mesitylene, which may be attributed to the steric hindrance of three methyl groups on the benzene ring [3]. Shortly thereafter, Fujiwara and coworkers [4] found that arylation of styrene (4a) occurred much more efficiently in the presence of stoichiometric palladium acetate instead of the styrene-palladium chloride complex (1). Thus, equimolar amounts of styrene (4a) and palladium acetate were refluxed in benzene (2a) in the presence of acetic acid, affording a 90% yield of rran -stilbene (3a). In the case of toluene (2b) and p-xylene (2c), fran5-4-methylstilbene (3b, 58%) and rran5-2,5-dimethylstilbene (3c, 47%) were obtained (Equation (9.2)). 

The direct alkenylation of aromatics tolerates a variety of alkenes. Besides the alkenes mentioned above, lower alkenes (e.g. 1-butene, propene) [6], alkenes containing polar groups (e.g. acrylonitrile) [4b] and cychc alkenes such as cyclooctene [7] all participate in the palladium(II)-promoted substitution of arenes. In most cases, however, the yields of these reactions were prohibitively low (less than 20%). 

The arene substrates are not limited to simple benzene derivatives. A variety of het-eroarenes can also participate in alkene arylations to generate the desired coupling products. Stoichiometric oxidative coupling of aromatic heterocycles such as furan, thiophene, selenophene, A-methylpyrrole, benzofiiran and benzothiophene with a variety of alkenes, including acrylonitrile, styrene and methyl acrylate, have been extensively studied by Fu-jiwara and coworkers [8]. Furan, thiophene, selenophene and A-methylpyrrole are easily alkenylated with alkenes to give 2-alkenylated and 2,5-dialkenylated heterocycles in relatively low yields (3 6%) [8a], while the reactions of benzofuran and benzothiophene with alkenes produced a mixture of 2- and 3-alkenylated products [8b]. 

Importantly, one can effect a chemoselective direct alkenylation of aromatic halides without reacting with the carbon-halogen bond [11]. Murakami and coworkers [12] reported a chemoselective C-3 alkenylation of 4-bromo-l-tosylindole (17) with methyl 2-ferf-butoxycarbamoylacrylate (18) in the presence of stoichiometric Pd(OAc)2 and 1 equiv chloranil. The reaction smoothly generated 4-bromodehydrotryptophan derivative 

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In addition to the several reports of intermolecular Fujiwara-Moritani reactions, there have been a nnmber of examples of intramolecular reactions, both stoichiometric and catalytic in palladinm. In considering an intramolecular oxidative Heck reaction, one can again draw a direct analogy to the classical Heck reaction (Figure 9.3). In the standard Heck reaction, a halogenated arene nndergoes an oxidative addition by palladium(0), followed by alkene insertion and jS-hydride elimination. In an oxidative version, a C—H bond of... 

Intramolecular Fujiwara-Moritani Reactions Stoichiometric in Palladium... 

In feet, Norman et ol disclosed the first example of an intramolecular Fujiwara-Moritani reaction back in 1970 [124] it was. however, understood as a Friedel-Crafts-type process involving alkene activation by palladium(II). Aside from this seminal report, a few oxidative cydizations of 1.4-quinones using stoichiometric amounts of... 

Meanwhile, direct C-H bond alkenylation reactions have been developed to provide more simple synthetic routes for alkenylarene derivatives. As the first example, in 1967, Moritani and Fujiwara [1] reported dehydrogenative alkenylation of benzene with styrene in the presence of a stoichiometric amount of a palladium complex to produce stilbene (Scheme 18.1). Later, these authors succeeded in conducting the reaction in a catalytic manner by using an appropriate oxidant (the Fujiwara-Moritani reaction. Section 18.2.1) [2]. Unfortunately, the reaction of substituted benzenes such as toluene usually gave a mixture of regioisomers of alkenylated products. 

The first waste-free vinylation of arenes under C—H activation is as old as the Mizoroki-Heck reaction itself already in 1967, Moritani and Fujiwara [6] revealed a stoichiometric reaction of styrene-palladium(II) chloride dimers with benzene in the presence of acetic acid to give stilbenes in a modest 24% yield. During this process, the palladium(II) precursor is reduced to palladium(O), so that the key to closing the catalytic cycle was to add an efficient reoxidation step to regenerate an active palladium(II) species. One year later, the same group presented a first approach, substoichiometric in palladium. 

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