COMMUNICATION
DOI: 10.1002/chem.201002547
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Pd-Catalyzed Direct and Selective
ACHUTGTNRENNUGC H Functionalization: ACHTUNGTRENCNNGU 3-Acetoxylation
of Indoles
Qiang Liu,[a] Gang Li,[a] Hong Yi,[a] Pan Wu,[a] Jie Liu,[a] and Aiwen Lei*[a, b]
À
Direct functionalization of C H bonds has been a hot
topic in organic chemistry during recent years.[1–11] Arenes—
one of the most abundant chemical motifs—usually have
by, for example, pyridine, imine, or amides groups were re-
ported recently.[17,22–26] Yu et al. also described a nice Cu-cat-
alyzed acetoxylation of arenes directed by pyridine.[27] Even
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multiple C H bonds. Although, some examples of direct
for traditional C O cross-coupling reactions that employ
functionalizations of arenes have been reported recently,[1,3]
ArX as the electrophile, efficient examples are rare.[18–21]
On the other hand, the electrophilic palladation of indole
derivatives first takes place in a selective manner (in C3-po-
sition) and then the C2-isomer is formed from the 1,2-migra-
tion of the C3-isomer.[30] Due to our interest in PdIV chemis-
try,[31,32] we envisioned that, in the presence of appropriate
oxidant, the C3–PdII species could be easily oxidized, owing
to the existence of a carbon anion as a d-donor and the pro-
posed direct and selective acetoxylation of indole deriva-
tives could be accomplished (Scheme 1C).
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the selectivity of C H bond activation remains a challenge
(Scheme 1A).[5] Several strategies have been applied to ach-
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ieve selective C H activation; these mainly included ortho-
directing groups[12–14] or selective deprotonation–metalla-
tion.[15–17]
Indole derivatives are of great scientific interest on ac-
count of their biological activities.[33–36] 3-Acetoxyindole is a
useful compound for the detection of acetylcholinesterase in
tissue slices and this technique can also be applied in
serum.[37] Many C C bond formation reactions involving
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indole derivatives as nucleophiles have been studied.[30,38]
However, to the best of our knowledge, no examples for
direct and selective C3-acetoxylation of indole derivatives
have been disclosed. In addition, a published method for
C3-acetoxylation of indoles suffered from multiple steps, the
expensive AgACTHNUTRGNEUNG
(OAc) reagent, and low yield (28%).[37]
Herein, we report an efficient Pd-catalyzed oxidative ace-
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Scheme 1. Selectivities of direct C H functionalizations of arenes:
A) without and B) with a directing group as well as C) the approach used
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toxylation of indole derivatives through C H activation in a
herein. FG=functional group; DG=directing group; the wavy lines
highlight the chemical bonds involved in C H activation process and rep-
resent the neglected structures in the molecules.
highly regioselective fashion without the assistance of a di-
recting group. Only a few examples of selective oxidative
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acetoxylation of C H bonds without chelation assistance
By employing the directing-group strategy (Scheme 1B),
have been reported so far.[28,29]
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direct acetoxylation of arene C H bonds has received con-
The reaction of N-benzylindole (1a) and (diacetoxy-
siderable attention during the past few years.[5] Pioneered by
Sanford et al., Pd-catalyzed acetoxylation of arenes directed
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
alyst precursor, KOH as the base, and MeCN as the solvent
at 708C (Table 1, entry 10). Both phosphine ligands and ni-
trogen ligands inhibited this transformation (Table 1, en-
tries 1–6). The presence of CO did not affect the reaction
significantly (Table 1, entry 7). Pd precursors were critical
[a] Q. Liu, G. Li, H. Yi, P. Wu, J. Liu, Prof. A. Lei
The College of Chemistry and Molecular Sciences
Wuhan University, Wuhan, Hubei (P.R. China)
Fax : (+86)27-68754067
[b] Prof. A. Lei
for the reactions. When [PdCl2ACTHNUTRGNEU(NG MeCN)2] and PdCl2 were
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics
Chinese Academy of Sciences
employed as catalyst precursors, the reactions gave poor
yields (Table 1, entries 8 and 9). When dimethylacetamide
(DMA), toluene, or dioxane was used as solvents, the yields
were also reduced (Table 1, entries 11–13). Without a Pd
catalysts, only 7% acetoxylation product was obtained
730000, Lanzhou (P.R. China)
Supporting information for this article is available on the WWW
Chem. Eur. J. 2011, 17, 2353 – 2357
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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