synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 63
In the presence of Pd2(dba)3 and ligand J, together with the weak organic base
DBU, N-methyl-5-nonaflate-indole 194 was converted with aniline to the aminated
product 195 in excellent yield (99%). In only 30 min at 150 °C the indole derivative
was fully converted and isolated. Several substrates (amines and aryl nonaflates)
with a broad scope of functional groups were utilized in the microwave supported
C-N bond forming process and led to new interesting compounds in very good to
excellent yields.
1.6 Diaryl Ether Coupling Reaction
An important class in organic chemistry are diaryl ethers throughout in life science
and polymer industry. [143] A number of diaryl ethers have been reported to possess
significant biological activity, like natural products of the isodityrosine family, the
antibiotic vancomycin, [144] angiotensin-converting enzyme inhibitor K-13, [145]
(+)-piperazinomycin, [146] the antitumor compounds bouvardin and bastadin, [147]
[148]
some new neuropeptide Y5 antagonists, and numerous weed-killing
chemicals. [149] Fritz Ullmann and Irma Goldberg started their pioneering work on
copper-mediated and copper-catalyzed coupling reactions a hundred years ago.
For the first time they coupled inactivated aryl halides with various nucleophiles
like amines, phenols and carboxyamides. The classic arylation of phenols with aryl
halides under standard Ullmann reaction conditions usually requires harsh
reaction conditions and needs stoichiometric amounts of copper, large excess of
phenols and high temperatures. [150] Buchwald and Hartwig introduced palladiumcatalyzed
approaches to overcome these synthetic problems. Even 100 years
after the discovery of Ullmann diaryl ether synthesis, copper-mediated arylcouplings
still remain the reaction of choice for large- and industrial-scale
formation of the diaryl ether bond in pharmaceutical, agrochemical, fine and
polymer chemistries. [151]
Nevertheless and with the best of our knowledge we just found one publication
that investigated the palladium-catalyzed diaryl ether coupling reaction of indoles.
Beller and co-workers described C-O coupling reactions of electron-rich indole
derivatives pictures in Scheme 52. [152] They presented a general palladiumcatalyzed
diaryl ether formation of electron-rich indoles to 3,5-dioxyindole