Fujiwara-Moritani oxidative Heck reaction

Tsuji s group coupled 2-methylfuran with ethyl acrylate to afford adduct 15 via a Pd-catalyzed Fujiwara-Moritani/oxidative Heck reaction using tert-butyl peroxybenzoate to reoxidize Pd(0) to Pd(II) [30]. The palladation of 2-methylfuran takes place at the electron-rich C(5) in a fashion akin to electrophilic aromatic substitution. The perbenzoate acts as a hydrogen acceptor. 

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 intramolecular Fujiwara-Moritani/oxidative Heck reaction was applied to the synthesis of functionalized benzo[fe]furans and dihydrobenzo[h]furans in 50-80% yields, and 15 examples are given in the article <04AG(E)6144->. Ionic liquid ([bmimJBF4) was found to be an effective solvent for the PdCl -catalyzed intramolecular Heck reaction to realize benzofurans <04TL6235>. Another palladium-catalyzed intramolecular Heck reaction between vinyl triflate and benzo[(j]furan was utilized to construct the seven-membered ring based (-)-frondosin B <04T9675>. 

Scheme 2.21 Example of Fujiwara-Moritani Oxidative Heck Reaction.

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]. 

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... 

In order to elucidate the mechanism of this reaction, a substrate probe was designed. Diastereomerically pure indole 140 was synthesized and subjected to the aerobic oxidative cyclization (Scheme 9.20). Annulated indole 141 was produced as a single diastereomer. The outcome of this reaction strongly suggested a mechanism involving initial palladation of the indole, followed by alkene insertion and )3-hydride elimination (an intramolecular Fujiwara-Moritani reaction). If the reaction proceeded by alkene activation followed by nucleophilic attack of the indole, then the opposite diastereomer would have been observed. This experiment confirmed that an oxidative Heck reaction pathway was operative in this aerobic indole annulation. 

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. 

Oxidative Heck-Type Reactions (Fujiwara-Moritani Reactions)... 

Oxidative Heck-Type Reactions (Fujiwara-Moritani Reactions) 373 Table 9.2 The palladium-catalysed oxidative cyclization of aryl allyl ethers oxidant studies. 

This transformation, often termed the oxidative Mizoroki-Heck reaction, was actually reported by Moritani and Fujiwara [5] prior to pubUcation of the initial descriptions of the Mizoroki-Heck reaction [1, 2]. During the early years, the oxidation of palladium(O) by molecular oxygen required copper(II) as a redox mediator, although in recent years modified protocols were developed (see Section 7.4.2.1) [113],... 

Ru complexes catalyze the reaction between 2-aryl pyridines and alkenyl esters (Scheme 23.16) [75]. These types of olefins are often only slowly reacting substrates in oxidative Heck (Fujiwara-Moritani) reactions [18] thus, their use in Ru-catalyzed C-H olefinations is a remarkable advance. The shown reaction is overall redox neutral and produces 1 equivalent of alcohol or acid as side product. A variety of heterocyclic directing groups can be employed, and many functional groups are tolerated. However, the olefin scope of the reaction is somewhat limited to alkyl- and aryl-substituted alkenes. 

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." " ... 

In order to find alternative routes to functimial olefins via the very useful Heck reaction [52] oxidative dehydrogenative cross-coupling of sp C-H bonds with (alkene) C-H bond was first discovered using Pd(II) catalyst and an oxidant, by Moritani and Fujiwara [25,53], This oxidative alkenylation of aromatic C-H bonds profitably performed using cheap and stable mthenium(ll) catalysts was shown for the first time in 2011 successively by the groups of Satoh and Miura [54], Ackermann [55], Bruneau and Dixneuf [56], and Jegaiunohan [57] [(Eq. 2)]. This Ru(n)-catalysed alkenylation reaction offers a potential to reach a large variety of functional alkenes at low cost and has been extended to annulation reactions with alkynes for a fast access to heterocycles. 

W. Rauf and J. M. Brown, Reactive Intermediates in Catatytic Alkenylation Pathways for Mizoroki-Heck, Oxidative Heck and Fujiwara-Moritani Reactions, Chem. Commun., 2013, 49, 8430. 

The groundbreaking work of Shue, de Vries and van Leeuwen others on oxidative olefinations and the contributions of Lu, Fagnou, DeBoef and others on direct arylations laid the foundation for the development of an impressive number of transition-metal-catalyzed selective cross-dehydrogenative sp C-H couplings. Notably, the Fujiwara-Moritani reaction is also commonly termed the oxidative Mizoroki-Heck reaction . Progress in this area has been extensively reviewed and will thus only be briefly mentioned here, notwithstanding their great importance. 

In 1999, Mikami s group reported the first example of an intermolecular asymmetric Fujiwara-Moritani reaction of benzene with cyclic alkenes using a Pd catalyst co-ordinating to a chiral sulfonylamide-oxazoline ligand (Scheme 7.24). With PhCOs Bu as the oxidant, the coupling reaction occurred with moderate enantioselectivity (up to 49% ee), although the chemical yield was low. The reaction is considered to involve the formation of a phenyl-Pd species via electrophilic C-H substitution by Pd(ii), and Heck-type cyclization followed by re-oxidation of the resultant Pd(0) species. 

Prior to the concept of cross-dehydrogenative-coupling (CDC), Moritani and Fujiwara developed the oxidative formation of Heck-type reaction products directly from arenes and alkenes, instead of aryl halides and... 

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