Intramolecular Fujiwara-Moritani

When the Heck cyclization is carried out under oxidative conditions (intramolecular Fujiwara-Moritani arylation), spirocyclic dihydrobenzofurans are formed in good yields directly from aryl ethers (Equation 139) <2004AGE6144>. 

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 5.39 The first asymmetric intramolecular Fujiwara-Moritani reaction reported by Mural.

Zhang, H., Ferreira, E.M. and Stoltz, B.M. (2004) Direct oxidative Heck cyclizations intramolecular Fujiwara-Moritani arylations for the synthesis of functionalized benzofurans and dihydrobenzofurans. Angew. Chem. Int. Ed., 43, 6144-8. 

Intramolecular Fujiwara-Moritani Reactions Stoichiometric in Palladium... 

The first example of an intramolecular Fujiwara-Moritani arylation was reported by Norman and coworkers [36] in 1970. Arenes 70a and 70b were treated with a stoichiometric amount of Pd(OAc)2 in AcOH at 80 °C to afford indenes 71a and 71b in 54% and 65% yields respectively (Scheme 9.10). The authors proposed two Friedel-Crafts-type... 

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. 

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... 

Oestreich and co-workers reported an enantioselective intramolecular Fujiwara-Moritani reaction of indole and pyrrole derivatives. Using a suitable oxidant e.g., PhCOg Bu, benzoquinone, O2), they evaluated a chiral bidentate pyridyl-oxazoline ligand (PyOx) developed by Stolz and a series of nicotine-oxazoline ligands (NicOx) with Pd(OAc)2 as a catalyst precursor (Scheme 7.25). Indoles and pyrroles underwent a 5-exo-trig cyclization, but the chemical yield and enantioselectivity were generally unsatisfactoiy. 

Arenes, especially electron-rich ones, have been found to react with alkynes in the presence of Pd(ll) or Pt(ll) species in a mixed solvent containing CF3COOH (Eq. 81) [158-160]. The intramolecular reaction is also possible (Eq. 82). The mechanism proposed for the reaction involves aromatic pallada-tion to form arylpalladium species as in Fujiwara-Moritani reaction, insertion of an alkyne, and protonolysis of the resulted vinylpalladium intermediate. 

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... 

Figure 9.3 The intramolecular Mizoroki Heck and oxidative Heck (Fujiwara Moritani)...

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