Intramolecular Fujiwara-Moritani Reactions Stoichiometric in Palladium

1 Intramolecular Fujiwara-Moritani Reactions Stoichiometric in Palladium 

1 equiv AgBp4, room temperature, then NaBlLj) to provide 93a. TheiV-methyl derivative 92b also cyclized cleanly, ruling out a mechanism involving iV-palladation followed by rearrangement to a C(2)-palladated species. Indole 94, with one additional carbon in the linker between the indole and the bicyclooctane moiety, cyclized to form both 95 and 96. Oxindole 96 likely arose from palladation-cyclization at C(4), followed by air oxidation. Lastly, indole 97, featuring an exocyclic alkene, underwent the palladium(II)-mediated cyclization to afford compound 98 in good yield. 

2 Intramolecular Fujiwara-Moritani Reactions Catalytic in Palladium 

The choice of solvent also proved to be important in these indole annulations. In standard solvents and in the absence of catalyst, the annulated indole products were susceptible to oxidative decomposition. After a thorough analysis of solvent and catalyst effects, it was found that the products were stabilized in the presence of the Pd(OAc)2/ethyl nicotinate catalyst in a 4 1 mixture of tert-amyl alcohol/AcOH as the solvent. Since the oxidative decomposition of indoles is generally initiated by addition at C(3), it was hypothesized that the catalyst and/or AcOH can act as a competitive inhibitor. With this carefully optimized system, the oxidatively annulated indoles could be accessed in good to excellent yields. 

Building upon this promising chemistry, Stoltz and coworkers [50] extended the scope of the mild oxidation system to the formation of other cyclic compounds - specifically, benzo-furans and dihydrobenzofurans. Aryl allyl ether 142 was subjected to the Pd(OAc)2/ethyl nicotinate catalyst under a variety of oxidants to provide benzofuran 144. Presumably, this reaction proceeds by initial palladation, followed by alkene insertion and )3-hydride elimination to form vinylic intermediate 143, which then isomerizes to the more thermodynamically stable benzofuran 144. Although molecular oxygen was a suitable oxidant for this reaction (Table 9.2 entry 1), benzoquinone appeared to be the optimal reoxidant (Table 9.2 entry 2), providing the highest overall yields. 

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