Catalytic Fujiwara-Moritani Reactions

Based on the proposed mechanism of the stoichiometric alkene arylation, it was anticipated that the same reactions could be achieved using substoichiomelric amounts of palladium salts. In the presence of an oxidant, palladium(O) could be reoxidized to palladium(II), which could then reenter the reaction, thus establishing a catalytic cycle for the arene vinylation reactions. 

Indeed, Fujiwara and coworkers [4b, 20] discovered that when copper(II) acetate or silver(I) acetate is employed together with oxygen (or air), the palladium-acetate-assisted alkene arylation reaction proceeds catalytically with respect to both palladium and copper (or silver). For example, styrene (4a) reacted with benzene (2a) in the presence of 10 mol% Pd(OAc)2, 10mol% Cu(OAc)2 and 50atm oxygen, producing tra -stilbene (3a) in 45% yield (Equation (9.7)) [20]. 

Oxidants other than Cu(OAc)2 and AgOAc have also been examined extensively to reoxidize palladium(O) in the arylation reaction of alkenes. Tsuji and Nagashima [21] reported that fert-butyl perbenzoate could be used as the stoichiometric oxidant to facihtate the palladium(n)-catalysed vinylation of benzene. Ishii and coworkers [22] found that the oxidative coupling reaction of substituted benzenes with acrylates could be achieved by the use of a catalytic amount of Pd(OAc)2 combined with molybdovanadophosphoric acid (HPMoV) under atmospheric oxygen as a terminal oxidant. 

Fujiwara and coworkers [23] extensively studied the phenylation of ethyl cinnamate (28) to produce ethyl 3-phenylcinnamate (29) in the presence of catalytic Pd(OAc)2 using a variety of oxidants, such as silver benzoate, manganese dioxide, 30% hydrogen peroxide, rerr-butyl hydrogen peroxide and the combination of rcrr-butyl hydrogen peroxide and 

The palladium(II)-catalysed alkenylation of heterocycles has also been studied extensively. Fujiwara and coworkers [8b, 26] reported that the reactions of furan and thiophene with alkenes such as methyl acrylate and acrylonitrile in the presence of 2 mol% Pd(OAc)2 and 2 equiv of Cu(OAc)2 under atmospheric oxygen or air produced both 2-alkenylated and 2,5-dialkenylated products. This method, however, was not particularly synthetically useful due to the low yields of the reactions (0.3-39%). Tsuji and Nagashima [21] also observed that furans 31a-c reacted with acrylates 4b and 4c to produce monoalkenylated compounds 32a-c, where the furan has been functionalized solely at the 2-position (or the 5-position if the 2-position is substituted) in moderate to good yields. Even a furan with an electron-withdrawing substituent (2-furaldehyde, 31c) participated in the oxidative coupling to yield a moderate 34% yield of the arylation 

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C-H bond activation and C-C bond formation are the key issues in organic synthesis [150-156]. The so-called Fujiwara-Moritani reaction has been regarded as one of the most versatile methods for activation of aromatic C-H bonds to provide a coupling product with an olefin using a catalytic amount of Pd(II) complex with an equimolar amount of a reoxidant [157-159]. 

By using an LX-type ligand, the catalytic asymmetric Fujiwara-Moritani reaction of benzene with cyclic olefins can afford the chiral phenyl-substituted cyclic olefins through syn p-H elimination from the opposite (y) side to the phenyl group (Scheme 32) [160]. 

Compared with the numerous developments of catalytic asynunetric reactions with chiral palladium(O) catalysts [ lc,e], catalytic asynunetric reactions by chiral palladium(ll) species have so far received only little attention, hi fact, the enantioselective Fujiwara-Moritani reaction still remains a significant challenge for organic chemists. Little success has been achieved thus far, presumably because of the inherent nature of the reaction, where styrene-type products absent of chiral centres arc typically formed from the -hydride elimination process. 

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 Catalytic in Palladium... 

For reviews on the Fujiwara-Moritani reaction, see (a) Fujiwara, Y. (2002) Palladium-promoted alkene-arene coupling via C—H activation, in Handbook of Organopalladium Chemistry in Organic Synthesis, Vol. 2 (eds E.-i. Negishi and A. de Meijere), John Wiley Sons, Inc., New York, pp. 2863-71 (b) Jia, C., Kitamura, T. and Fujiwara, Y. (2001) Catalytic functionalization of arenes and alkanes via C—H bond activation. Acc. Chem. Res., 34, 633-9 (c) Fujiwara, Y. and Jia, C. (2001) New developments in transition metal-catalyzed synthetic reactions viaC—H bond activation. PureAppl. Chem., 73,319-24 (d) Moritani, I. and Fujiwara, Y. (1973) Aromatic substitution of olefins by palladium salts. Synthesis, 524-33. 

Mikami, K., Hatano, M. and Terada, M. (1999) Catalytic C—H bond activation-asymmetric olefin coupling reaction the first example of asymmetric Fujiwara-Moritani reaction catalyzed by chiral paUadium(II) complexes. Chem. Lett., 28, 55-6. 

Scheme 7.45 Catalytic asymmetric intermolecular Fujiwara-Moritani reaction.

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. 

Since the early reports of the Fujiwara-Moritani reaction [2], catalytic alkenylation procedures for a broad range of aromatic substrates with various alkenes have been developed. A proposed mechanism for these Fujiwara-Moritani-type reactions is illustrated in Scheme 18.4 [4]. The reaction is initiated by electrophilic attack on an arene by a cationic palladium species [PdOAc]+, generated in situ from Pd(OAc)2, to form an arylpalladium intermediate. Subsequent alkene insertion and fi-hydrogen elimination may occur to produce an alkenylarene derivative and HPdOAc. The latter may be reoxidized by an oxidant to regenerate Pd(OAc)2. 

The catalytic asymmetric Fujiwara-Moritani-type allylation reaction of indoles and pyrroles was reported by Oestreich and co-workers. Moderate yields and ee were realized by using novel oxazoline ligands and a stereo-genic quaternary center was formed (Scheme 5.12b). Nevertheless, it still leaves room for improvement, probably by designing new ligands. 

C-H o-bond activation of hydrocarbons by transition metal complexes is of considerable importance in modern organometallic chemistry and catalytic chemistry by transition-metal complexes [1], because a functional group can be introduced into alkanes and aromatic compounds through C-H o-bond activation. For instance, Fujiwara and Moritani previously reported synthesis of styrene derivatives from benzene and alkene via C-H o-bond activation of benzene by palladium(ll) acetate [2]. Recently, Periana and his collaborators succeeded to activate the C-H o-bond of methane by the platinum(ll) complex in sulfuric acid to synthesize methanol [3], Both are good examples of the reaction including the C-H o-bond activation. 

The initial discovery of the oxidative Heck reaction was reported by Fujiwara and Moritani in 1967 when they disclosed the coupling of styrene with benzene in the presence of acetic acid and PdCl2 to give traws-stilbene and a-methylbenzyl acetate (Eq. (8.20)) [92]. Attempts to achieve catalytic turnover were made by adding Cu or Ag salts, but oidy 1-2 TONs were obtained [93]. 

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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