Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous ...

Heterogeneous Pd Catalyzed C−C Coupling Reactions Chemical Reviews, 2007, Vol. 107, No. 1 167
allyl acetates. Unlike in a genuine Heck reaction where
hydride is eliminated after the oxidative addition, acetate
serves as leaving group in this case (Table 80). 270 Substrates
bearing electron-donating groups required longer reaction
times (entry 5). However, substrates with strongly electronwithdrawing
substituents led to rapid isomerization of the
alkenes to the thermodynamically more stable styryl system
(entries 6 and 8). Both chloro and bromo substituents (entries
2 and 3) were tolerated under the reaction conditions. 270
Table 80. Heck-Type Coupling of Allyl Acetate with Various
Aryl Iodides
a Isolated yields. b 5% Pd/C was used; 18% of internal olefin was
observed.
A possible mechanism (Scheme 59) for this reaction
involves initial oxidative addition to Pd(0) followed by
carbopalladation of the olefin. Subsequent �-acetoxy elimination
gives the final allyl product. Reduction of the resulting
Pd(II) to Pd(0) is most likely achieved by coordination of
an amine base followed by �-hydride transfer and reductive
elimination of hydrogen iodide.
9. Pd on Solid Support in Tandem Reactions
Solid-supported Pd-catalyzed coupling reactions by C-Cbond
formation, such as Sonogashira or Heck reaction, can
Scheme 59. Proposed Mechanism for the Heck-Type
Coupling
be followed by further addition reactions. In this way,
heterocycles can be formed under cyclization.
9.1. Sonogashira Coupling in Tandem Reactions
When o-aminoaryl iodides are submitted to Sonogashira
reactions, intramolecular addition of the amino group to the
C-C triple bond can lead to the formation of indoles. As
one possibility, Pd/C-CuI could be used as catalyst (Scheme
60). 271 The intermediate compound 225 resulting from the
Sonogashira C-C coupling reaction between 2-iodoaniline
and phenylacetylene was never observed in these experiments.
This indicates that the heteroannulation is rapid under
the reaction conditions.
Scheme 60. Pd/C-Catalyzed Synthesis of 2-Phenylindole a
a Reaction conditions: 5 mmol of 2-iodoaniline, 5 mmol of phenylacetylene,
15 mmol of Et3N, 1 mol % Pd/C, 1 mol % CuI, 15 mL of DMF/H2O
(1:1), 120 °C,6h.
Pal and co-workers reported a general one-pot synthesis
of 2-alkyl/aryl-substituted indoles 228 via Pd/C-mediated
coupling/5-endo-dig cyclization of terminal alkynes with
o-iodo-N-mesylanilines 227 in water. 272 The reaction was
carried out using PPh3 and CuI as cocatalyst and 2-aminoethanol
as a base (3 equiv). The reaction appeared to tolerate
a variety of functional groups present in the alkynes and did
not require the use of any organic cosolvent (Table 81).
A greater variety of N-substituents at the 2-iodoanilines
was possible when Pd-NaY was used as catalyst (Table
82). 273 Cu catalysis was not necessary. It was found that the
product formation largely depended on the solvent, base, and
reaction temperature. The recycled catalyst showed good
reusability in this heteroannulation reaction.
[Pd(NH3)4] 2+ /(NH4)Y as catalysts allowed implementation
of the synthesis of 2-phenylindole starting from o-iodoaniline
and phenylacetylene under Cu-free conditions in 72% yield
(Table 83). 191 Similarly, microporous [Pd(NH3)4] 2+ /NaY or
mesoporous [Pd]/SBA-15 silica could be used for the
syntheses of a series of 2-substituted indoles. 29
When o-iodophenols were submitted to Sonogashira
coupling with alkynes the subsequent intramolecular cyclization
led to benzo[b]furans. Because of its relevance to
natural products and to pharmacy many 2-substituted benzo-
[b]furan derivatives were prepared in this way during the
last years using a homogeneous palladium catalyst and
copper iodide as cocatalyst under mild conditions. 274-277 As
a heterogeneous alternative, Pd/C was applied in the presence