synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 44
The group around Nakamura described heterocycles containing propargylic
diisopropylamines. [115] These propargyl-diisopropylamines were easily prepared
from heterocyclic bromides by Sonogashira coupling reaction. Followed by allene
transformation reaction the corresponding heterocyclic allenes were produced in
good to high yields. Allenes are very important building blocks for organic
synthesis. [116] The heterocyclic allenes precursors were synthesized using
Sonogashira coupling reaction of N,N-diisopropylprop-2-ynylamine 139 with
different heterocyclic bromides. Scheme 35 shows the coupling reaction of the
indole example 138. The reaction was carried out in the presence of Pd(PPh3)4,
CuI and Et3N in CH3CN at 60 °C.
Br
N(iPr) 2
Pd(PPh 3) 4 (5 mol%)
CuI (10 mol%)
(iPr) 2N
N
Et3N, CH3CN N
138 Boc 139 140(26%) Boc
H
141 (88%)
N
Boc
Scheme 35. Sonogashira coupling reaction of Boc-protected 5-bromoindole with N,Ndiisopropylprop-2-ynylamine.
The authors reported that the reaction with N-unprotected 5-bromoindole did not
undergo the Sonogashira coupling however, the reaction with N-Boc-5bromoindole
138 gave desired product 140 in a yield of 26%. For the palladiumcatalyzed
allene transformation, compound 140 was converted in the presence of
Pd2(dba)3·CHCl3 (2.5 mol%) as catalyst, and 1,2-bis[bis(pentafluorophenyl)phosphino]ethan
(10 mol%) at 100 °C in CHCl3. The indole allene 141 resulted in
a yield of 88%.
Santelli and colleagues described the Sonogahira reaction of heteroaryl halides
with alkynes catalyzed by a palladium-tetraphosphine-complex. [117] They used the
same catalytic system described already in the Suzuki part in Scheme 17. The
Tedicyp/PdCl(C3H5)]2 catalytic system catalyzed the Sonogashira reaction of