Palladium(II)-Catalyzed Efficient C-3 Functionalization of Indoles with Benzylic and Allylic Alcohols
trophilic mechanism involving the intermedicacy of X-Ray Crystallography
a carbenium ion may be operating in the present
CCDC 918766 (3q) contains the supplementary crystallo-
Pd(II)-catalyzed alkylation of indole.[5f,14,15] In the case
of N-unprotected indoles, one cannot completely rule
out the possibility of a pathway involving Brønsted
acid-type catalysis.[16,17] Such a pathway may operate
in tandem with the proposed Friedel–Crafts alkyla-
tion.
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data
In summary, PdCl2ACTHNUTRGNE(NUG MeCN)2 has been found to be
an effective catalyst for regioselective functionaliza-
tion of indoles with benzylic and allylic alcohols. Co-
Acknowledgements
S.R. and D.D. thank DST and CSIR for funds and fellow-
catalysts, acid/base, additive, external ligand are not ships.
required in this alkylation, which is thus of great
promise. The easy handling of the catalyst makes the
reaction more attractive, simple and practical.
References
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Experimental Section
Syntheses and Characterization of [(C8H7N)PdCl2]2
(Complex 1)
Solid PdCl2ACHTUNGTRENNUNG(MeCN)2 (130 mg, 0.5 mmol) was added in one
portion to a stirred solution of indole (59 mg, 0.5 mmol) in
CH2Cl2 (5 mL) resulting in a sharp color change. After
15 min, petroleum ether (30 mL) was added while stirring
was continued for a further period of 5 min. The dark red
solid was separated by filtration, washed with petroleum
1
ether and dried in vacuum; yield: 55%. H NMR (200 MHz,
CDCl3): d=6.34 (s, 1H), 7.31–7.52 (m, 3H), 8.02. (d, 1H,
J=7.6 Hz), 8.22 (br s, 1H), 10.59 (br s, 1H); 13C NMR
(100 MHz, CDCl3): d=77.4, 114.3, 125.10, 125.14, 128.2,
130.6, 134.4, 142.8; anal. calcd. for C16H14Cl4N2Pd2: C 32.63,
H 2.40, N 4.76; found: C 32.29, H 2.21, N 4.93.
Procedures for the Catalytic C3-Functionalization of
Indole
a) Representative Procedure for the Benzylation of Indoles
with Benzylic Alcohols: A mixture of phenylpropan-2-ol 1a
(82 mg, 0.60 mmol), 1-benzyl-1H-indole 2a (103.4 mg,
[5] The importance of alcohol as an alkylating agent is of
recent interest and conventional acids, bases and Lewis
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0.5 mmol), PdCl2ACHTUNGTRENNUNG(MeCN)2 (6.5 mg, 0.025 mmol) in 2 mL of
DCE was stirred at 908C for the appropriate time. Then, the
solvent was removed under reduced pressure, and the mix-
ture was subjected to column chromatography over silica gel
(100–200 mesh, eluent: petroleum ether 60–808C/ethyl ace-
tate, 50:1 v/v) to afford the desired alkylated product 3a as
a colorless oil; yield: 146 mg (90%).
b) Representative Procedure for the Alkylation of Indoles
with Allylic Alcohols: A mixture of (E)-1,3-diphenylprop-2-
en-1-ol 4a (126 mg, 0.60 mmol), 1H-indole (58.5 mg,
0.5 mmol), PdCl
(MeCN)2 (3.9 mg, 0.015 mmol) in 2 mL of
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G. V. M. Sharma, C. Bruneau, Angew. Chem. 2010, 122,
2842; Angew. Chem. Int. Ed. 2010, 49, 2782; d) B. Sun-
DCE was stirred at room temperature (308C) for the appro-
priate time. Then, the solvent was removed under reduced
pressure, and the mixture was subjected to column chroma-
tography over silica gel (100–200 mesh, eluent: petroleum
ether 60–808C/ethyl acetate, 9:1 v/v) to afford the alkylated
product 5a as a yellow solid; yield: 124 mg (80%).
Adv. Synth. Catal. 2013, 355, 1308 – 1314
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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