synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 40
Pd(OAc)2/TBAB and K2CO3 in DMF. The 2-methyl-group (R 1 ) in compound 129
rendered the formation of seven-membered ring impossible, and aryl-aryl bondformation
occurred to form the eight-membered compound 131 in moderate yield
(53-60%). However, they synthesized tetracyclic indole derivatives via palladiumcatalyzed
intramolecular Heck reaction from indole containing Baylis-Hillman
adducts.
129
OAc
Br
R 1
EWG
N
R 2
R 3
Pd(OAc) 2 (10 mol%)
TBAB (1 equiv)
K 2CO 3 (2 equiv)
DMF, 100 °C
30 min - 5 h
R 1 = H, Me
R 2 = H, Me, CH 2COOEt
R 3 = H, OMe
EWG = COOMe, COOEt
R 1 = H
R 3
R 1 = Me
Scheme 33. Heck reaction with indole-containing Baylis-Hillman adducts.
1.4 Sonogashira Coupling Reaction
130
131
N
R 2
N
EWG
R 2
R 1
EWG
The Sonogashira reaction is the most frequently used method to affect the
alkynylation of an aryl halide. The traditionally accepted mechanistic pathway of
the Sonogashira reaction is similar to that originally proposed by Sonogashira and
Hagihara in 1975. [111] Typically palladium is used along with generally twice this
amount of CuI as co-catalyst. Alkynes undergo the cross-coupling reaction with
aryl- and heteroaryl halides in the presence of PdCl2(PPh3)2 as catalyst, CuI as cocatalyst
and amine as solvent. The reaction is normally conducted at room
temperature. It is believed that copper assists the reaction through formation of an
acetylide and then this group is transferred to palladium by a transmetalation step.
Nevertheless, modifications of the conditions have continued to be investigated
because copper acetylides can also lead to homocoupling products. Although