synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 32
1.3 Heck Coupling Reaction
The Heck reaction has become one of the most fundamental metal-catalyzed C-C
bond forming process for the synthesis of complex molecules. [95] The
carbopalladation of an alkene by an organopalladium halide is an essential step in
organic synthesis. Richard Heck and his group transferred this reaction into a
catalytically reaction and started to demonstrate its usefulness as well as its rather
broad scope. Therefore the applications range from the preparation of
hydrocarbons, novel polymers and dyes to new advanced enantioselective
synthesis of natural products and biologically active non-natural compounds. The
Heck reaction is one true “power tool” in contemporary organic synthesis and a
continuous annual growth in publications of 15% per year, competing favorably
with the Diels-Alder reactions (25000 references), olefin metathesis (1500
references), Wittig reaction (15000 references) or Claisen rearrangement (15000
references). [7]
The first step of the mechanism starts with the oxidative addition of a haloalkene
or haloarene to the unsaturated palladium(0)complex, generating a �-alkenyl- or
�-aryl-palladium(II)complex. [96] The complex accepts an alkene molecule in its
coordination sphere. If the alkenyl residue and alkene ligand on palladium are in
cis-orientation, rotation of the alkene can lead to its in plane coordination, and
subsequent syn-insertion of the �-alkenyl- or �-aryl-palladium bond into the C=C
double bond occurs to yield a �-(�-alkenyl) or �-(�-aryl)alkylpalladium complex. In
the next step �-hydride elimination takes place. The subsequent syn-elimination
yielding an alkene and a hydridopalladium halide is reversible. Therefore more
stable (E)-alkene is generally obtained when the coupling reaction is performed
with a terminal alkene. Reductive elimination of HX from the hydridopalladium
halide aided by the added base regenerates the active catalyst and completes the
catalytic cycle.
This review discusses only the palladium-catalyzed Heck reaction and the
intramolecular Heck reaction of indoles. [97]
An application of the intramolecular Heck reaction via palladium coupling is the
access to paullone analogues. Paullones [98] are a series of structures from 7,12-