Direct and site-selective palladium-catalyzed c-7 acylation of indolines with aldehydes

Article abstract of DOI:10.1002/adsc.201400942

The palladium-catalyzed oxidative acylation of indolines at the C-7 position with aldehydes or alcohols via C-H bond activation is described. This protocol represents a facile access to 7-acylated indolines, which can be readily transformed into 7-acylated indoles with diverse biological properties.

Full text of DOI:10.1002/adsc.201400942

UPDATES
DOI: 10.1002/adsc.201400942
Direct and Site-Selective Palladium-Catalyzed C-7 Acylation of
Indolines with Aldehydes
a
a
a
a
Youngmi Shin, Satyasheel Sharma, Neeraj Kumar Mishra, Sangil Han,
a
a
a
a
a
Jihye Park, Hyunji Oh, Jimin Ha, Hyunwu Yoo, Young Hoon Jung,
a,
and In Su Kim *
a
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
Fax : (+82)-31-292-8800; e-mail: insukim@skku.edu
Received: September 26, 2014; Revised: October 20, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400942.
Abstract: The palladium-catalyzed oxidative acyla-
tion of indolines at the C-7 position with aldehydes
or alcohols via CÀH bond activation is described.
general, the acylation of indoles occurs preferentially
at the more electron-rich C-3 position through elec-
trophilic substitution reactions. Friedel–Crafts acyla-
[
12]
[13]
This protocol represents a facile access to 7-acylat-
ed indolines, which can be readily transformed into
tions,
Vilsmeier–Haack reactions,
and the cou-
[
14]
pling reaction between indoles and nitrilium or N-
[
15]
7-acylated indoles with diverse biological proper-
(a-haloacyl)-pyridinium salts are common methods
for the preparation of C-3 acylated indoles. The cata-
lytic alternatives include the Ru- or Fe-catalyzed car-
bonylations of the indolic C-3 position with anilines
as carbonyl sources, the Pd-catalyzed addition of in-
doles to nitriles, and the Cu-mediated decarboxyla-
ties.
Keywords: acylation; CÀH activation; indoles; in-
[
16]
dolines; palladium
[
17]
[18]
tive C-3 acylation of indoles with a-keto acids. The
-acylated indoles can be generated from the direct
2
[19]
addition of acyl equivalents into 2-lithioindoles or
The indole and indoline scaffolds have been recog-
nized as privileged structural motifs with diverse bio-
[
1]
logical and medicinal applications. In particular,
many pharmaceutical agents include C-7 substituted
[
2]
indole and indoline frameworks. With the develop-
[
3]
ment of CÀH bond functionalization, it has become
the most straightforward protocol leading to C-7 sub-
stituted indoles and indolines. Recently, a great deal
of effort has been devoted to the formation of C-2
and C-3 functionalized indoles via the transition
[
4]
metal-catalyzed CÀH bond activation process. Nev-
ertheless, the catalytic CÀH bond functionalization of
indoles and indolines at the C-7 position remains rela-
tively unexplored. For example, Maleczka and Smith
reported the iridium-catalyzed nitrogen-directed C-7
[
5]
borylation of 2-substituted indoles. Hartwig et al.
described the iridium-catalyzed silyl-directed boryla-
[
6]
tion of indoles at the C-7 position. In addition,
recent progress has been made on the directing
[
7]
[8]
group-assisted CÀH arylation, alkenylation, alkyla-
[9]
[10]
tion, and amidation reactions of indolines at the
C-7 position.
The C-7 acylated indoles are known as heterocyclic
compounds found in a number of natural products Figure 1. Selected examples of natural and synthetic C-7
[
11]
and bioactive synthetic molecules (Figure 1).
In acylated indoles.
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UPDATES
Scheme 1. Catalytic functionalization of indolines at the C-7 position.
[
20]
[a]
the Pd-catalyzed tandem cyclization reactions. Re- Table 1. Selected optimization of the reaction conditions.
cently, the directing group-assisted C-2 acylations of
[
21]
[22]
indoles using aldehydes or a-oxocarboxylic acids
were described. Very recently, our group has reported
the Pd-catalyzed decarboxylative acylation of indo-
[
23]
lines with a-keto acids. However, to the best of our
knowledge, there has been only a single example of
catalytic CÀH acylation at the C-7 position of indoline
[b]
[
24]
Entry Catalyst (mol%) Oxidant (equiv.) Solvent Yield
using arylaldehyde, reported by Yu et al.
Transition metal-catalyzed CÀH acylation of indo-
lines using acyl surrogates is a promising synthetic
strategy for C-7 acylated indolines, which can be read-
ily converted to C-7 acylated indoles under oxidative
conditions. Inspired by recent studies on the catalytic
[c]
1
2
3
4
5
6
7
8
9
1
1
1
1
Pd(OAc) (5)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (3)
TBHP (2)
DTBP (2)
TBPB (2)
BPO (2)
DCE
DCE
DCE
DCE
THF
20%
29%
78%
35%
32%
2
[c]
PdCl (5)
2
[
[
[
c]
c]
c]
Pd(TFA) (5)
2
Pd(OTf) (5)
2
Pd(TFA) (5)
2
2
[25]
[c]
acylation of sp CÀH bonds with aldehydes,
alco-
Pd(TFA) (5)
2
CH Cl 59%
2
2
[
[
[
d]
d]
d]
[
26]
[27]
Pd(TFA) (5)
DCE
80%
14%
79%
81%
trace
12%
trace
16%
46%
trace
hols, and a-keto acids, we herein disclose the pal-
ladium-catalyzed oxidative C-7 acylation of indolines
with aldehydes or alcohols via CÀH bond activation
2
Pd(TFA) (5)
H O
2
2
Pd(TFA) (5)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
2
[
d]
0
1
2
3
Pd(TFA) (5)
2
(
Scheme 1).
[e]
[f]
[g]
Pd(TFA) (5)
2
Our examination was initiated by the coupling of
N-pivaloylindoline 1a with benzaldehyde (2a), and
the selected results are summarized in Table 1.
Pd(TFA) (5)
2
Pd(TFA) (5)
2
[
h]
14[
Pd(TFA) (5)
DCP (2)
2
d]
To our delight, the combination of 5 mol% of 15
Pd(TFA) (2.5) TBHP (2)
2
[
d,i]
Pd(OAc) and 4 equiv. of TBHP in DCE solvent at 16
Pd(TFA)
(5)
TBHP (2)
2
2
8
08C can promote the coupling of 1a and 2a to pro-
[a]
Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), Pd
catalyst (quantity noted), oxidant (quantity noted), sol-
vent (1 mL) at 808C for 16 h in pressure tubes.
Yield isolated by flash column chromatography.
TBHP (5.0–6.0M in decane).
vide acylated indoline 3a in 20% yield (Table 1,
entry 1). Exclusion of either Pd(OAc) or TBHP re-
sulted in no observation of the desired product 3a.
After screening of a range of palladium catalysts,
2
[
[
[
[
[
[
[
[
b]
c]
d]
e]
f]
Pd(TFA) was found to exhibit the highest reactivity
TBHP (70% in H O).
2
2
(
Table 1, entries 2–4). Further screening of solvents
DTBP=di-tert-butyl peroxide.
TBPB=tert-butyl peroxybenzoate.
BPO=benzoyl peroxide.
DCP=dicumyl peroxide.
At room temperature for 40 h.
under otherwise identical conditions revealed that
DCE was the most effective solvent in this coupling
reaction, whereas other solvents such as THF and
CH Cl were less effective (Table 1, entries 5 and 6).
g]
h]
i]
2
2
Interestingly, this process provided the coupling prod-
uct 3a by the use of aqueous TBHP oxidant in 80% (Table 1, entry 8). Further optimization revealed that
yield (Table 1, entry 7). However, when indoline 1a 2 equiv. of TBHP facilitated high levels of conversion
was coupled with 2a under aqueous solvent conditions to provide 3a in high yield (81%) (Table 1, entry 10).
it afforded our desired product 3a in low yield Moreover, other oxidants such as DTBP, TBPB, BPO,
2
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Direct and Site-Selective Palladium-Catalyzed C-7 Acylation of Indolines
[a]
Table 2. Scope of the indolines.
[
[
a]
b]
Reaction conditions: 1a–1l (0.2 mmol), 2a (0.6 mmol), Pd(TFA) (5 mol%), TBHP (2 equiv.), DCE (1 mL) at 808C for
2
1
6 h in pressure tubes.
Yield isolated by flash column chromatography.
and DCP were found to be less effective (Table 1, en- acylation reaction to provide 4i and 4j, relatively in
tries 11–14). A decreased loading of palladium cata- low yields, under the current reaction conditions. To
lyst, under otherwise identical conditions, led to rela- our pleasure, this reaction is not limited to aryl alde-
tively decreased formation of 3a (Table 1, entry 15). hydes. Aliphatic aldehydes such as cyclohexanecarbal-
Finally, we observed that this coupling reaction did dehyde (2k), isobutyraldehyde (21), and 1-hexanal
not proceed at room temperature, even for longer re- (2m) were also found to be favored in the oxidative
action times (Table 1, entry 16).
coupling to furnish 7-acylated indolines 4k–4m in
To evaluate the substrate scope of this process, 40%, 52% and 60% yields, respectively.
a range of indolines was tested under the optimal re-
In previous reports, alcohols have been used as effi-
action conditions (Table 2). The coupling reactions of cient acylating agents under various oxidative condi-
[
26]
C-2 or C-3 unsubstituted indolines 1b and 1c with 2a tions. Thus we sought to expand the substrate scope
were found to be favored in the acylation reaction to from aldehydes to alcohols (Table 4). Subsequently,
afford the corresponding products 3b and 3c in mod- we found that indoline 1a was coupled with benzylic
erate yields. This reaction was also compatible with alcohols 5a–5c containing electron neutral, electron-
C-2 methyl-substituted indolines 1d–1g furnishing the donating and electron-withdrawing substituents under
corresponding products 3d–3g in moderate to good slightly modified reaction conditions to afford the cor-
yields. In addition, mono- or disubstituted indolines responding products 3a, 4b and 4c in high yields.
1
h–1k at the C-3 position underwent the oxidative Moreover, aliphatic alcohol 5d also participated in
acylation reaction to provide 3h–3k with slightly de- this catalytic acylation to furnish 4m in 25% yield.
creased reactivity under the present reaction condi- To demonstrate the practicable preparation of 7-
tions. We were pleased to observe C-8 acylation of acylated indolines, we successfully scaled the reactions
tetrahydroquinoline providing the corresponding to 2.5 mmol using benzaldehyde (2a) or benzyl alco-
product 3l in 50% yield.
hol (5a), and obtained 0.75 g (80% isolated yield from
To further explore the substrate scope and limita- 2a) and 0.73 g (76% isolated yield from 5a) of 3a, re-
tions, a range of aldehydes was examined under the spectively, after 28 h (Scheme 2).
optimal reaction conditions (Table 3). Electron-rich
To highlight the transformation of C-7 acylated in-
and electron-deficient benzaldehydes 2b–2h were dolines, the removal of the N-pivaloyl group of 3b
found to be favored in the acylation reaction, regard- under basic hydrolysis conditions was first performed
less of the position of the substituent on the aromatic to provide the free (NH)-indoline 6a in 87% yield
ring, affording the corresponding products 4b–4h in (Scheme 3). In addition, we performed the oxidation
good to high yields. Additionally, heteroaromatic al- of 3b using DDQ to furnish 7-acylated indole 6b in
dehyde 2i and enal 2j participated in the oxidative 57% yield.
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[a]
Table 3. Scope of the aldehydes.
[
[
a]
b]
Reaction conditions: 1a (0.2 mmol), 2b–2m (0.6 mmol), Pd(TFA) (5 mol%), TBHP (2 equiv.), DCE (1 mL) at 808C for
2
1
6 h in pressure tubes.
Yield isolated by flash column chromatography.
[a]
Table 4. Scope of the alcohols.
Scheme 2. Scale-up experiments using aldehyde or alcohol.
[
[
a]
b]
Reaction conditions: 1a (0.2 mmol), 5a–5d (0.6 mmol),
Pd(TFA) (5 mol%), TBHP (3 equiv.), DCE (1 mL) at
2
808C for 16 h in pressure tubes.
Yield isolated by flash column chromatography.
Scheme 3. Transformations of 7-acylated indoline.
4
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UPDATES
Direct and Site-Selective Palladium-Catalyzed C-7 Acylation of Indolines
Scheme 4. Site-selective olefinations of C-7 acylated indolines.
2
scope to the acylation of sp CÀH bonds without di-
3
recting groups and unactivated sp CÀH bonds.
Experimental Section
Typical Procedure for C-7 Acylation of N-Pivaloyl-
indolines with Aldehydes
To an oven-dried sealed tube charged with N-pivaloylindo-
line (1a) (54.3 mg, 0.2 mmol, 100 mol%), Pd(TFA) (3.3 mg,
0.01 mmol, 5 mol%) and TBHP (0.06 mL, 0.4 mmol,
2
Scheme 5. Kinetic isotope experiments.
2
00 mol%, 70% in H O) in DCE (1 mL) was added benzal-
2
dehyde (2a) (63.7 mg, 0.6 mmol, 300 mol%). The reaction
mixture was allowed to stir at 808C for 16 h, and was then
Next, the sequential CÀH functionalization was per- cooled to room temperature. The reaction mixture was di-
luted with EtOAc (3 mL) and saturated NaHCO solution
formed by using a newly installed ketone functionality
as a directing group. We were delighted to find that
the olefination site can be controlled by using differ-
ent acyl groups such as hexanoyl and benzoyl. As
shown in Scheme 4, the olefination of 4m using n-
3
(
(
3 mL). The resulting mixture was extracted with EtOAc
5 mL). The organic layer was dried over MgSO and con-
4
centrated under vacuum. The residue was purified by flash
column chromatography (n-hexanes/EtOAc=6:1) to afford
3
a; yield: 60.8 mg (81%).
[
28]
butyl acrylate under ruthenium catalysis
afforded
C-6 olefinated indoline 7a [Eq. (1)]. Furthermore, in
the case of 3b, the olefination preferentially occurs on
the phenyl moiety, concomitant with unexpected
cleavage of the pivaloyl group, to provide the free
Acknowledgements
(
NH)-indoline 7b in 46% yield [Eq. (2)].
This research was supported by Basic Science Research Pro-
To gain a mechanistic insight, two parallel reactions gram through the National Research Foundation of Korea
of 1a and deuterio-1a with benzaldehyde (2a) under (NRF) funded by the Ministry of Education, Science and
standard reaction conditions were performed, which
Technology (No. 2013R1A2A2A01005249).
resulted in the kinetic isotope effect (k /k ) of 2.79
H
D
(
see the Supporting Information for details), thus in-
dicating that CÀH cleavage might be involved in the References
rate-limiting step (Scheme 5).
[
29]
[
1] a) J. A. Joule, K. Mills, in: Heterocyclic Chemistry,
Blackwell Science Ltd, Oxford, 2000; b) D. L. Boger,
C. W. Boyce, R. M. Garbaccio, J. A. Goldberg, Chem.
Rev. 1997, 97, 787; c) D. A. Horton, G. T. Bourne, M. L.
Smythe, Chem. Rev. 2003, 103, 893; d) F.-E. Chen, J.
Huang, Chem. Rev. 2005, 105, 4671; e) B. M. Trost,
M. K. Brennan, Synthesis 2009, 3003.
In conclusion, we have described an efficient
method for the palladium-catalyzed oxidative C-7
acylation of highly substituted indolines with alde-
hydes or alcohols as acyl equivalents via CÀH bond
activation. These transformations allow the genera-
tion of an array of C-7 acylated indoles, which are
known to be crucial scaffolds of biologically active
compounds. Our ongoing studies seek to expand the
[2] a) Y. Ozawa, K. Kusano, T. Owa, A. Yokoi, M. Asada,
K. Yoshimatsu, Cancer Chemother. Pharmacol. 2012,
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

Youngmi Shin et al.
UPDATES
6
9, 1353; b) R. J. Keizer, M. K. Zamacona, M. Jansen,
G. W. Mellor, J. V. Morey, M. A. Morse, H. Nie, W. L.
Rumsey, J. J. Taggart, Bioorg. Med. Chem. Lett. 2011,
21, 2255.
D. Critchley, J. Wanders, J. H. Beijnen, J. H. M. Schell-
ens, A. D. R. Huitema, Invest. New Drugs 2009, 27,
1
40; c) T. Owa, A. Yokoi, K. Yamazaki, K. Yoshimatsu,
[12] a) R. J. Sundberg, in: The Chemistry of Indoles, Aca-
demic Press, New York, 1970; b) O. Ottoni, A. de V. F.
Neder, A. K. B. Dias, R. P. A. Cruz, L. B. Aquino, Org.
Lett. 2001, 3, 1005; c) S. K. Guchhait, M. Kashyap, H.
Kamble, J. Org. Chem. 2011, 76, 4753.
[13] a) R. A. Heacock, S. Kasparek, in: Advances in Hetero-
cyclic Chemistry, (Eds.: A. R. Katritzky, A. J. Boulton),
Academic Press, New York, 1969, pp 43; b) J. Bergman,
L. Venemalm, Tetrahedron Lett. 1987, 28, 3741.
T. Yamori, T. Nagasu, J. Med. Chem. 2002, 45, 4913;
d) R. Mohan, M. Banerjee, A. Ray, T. Manna, L.
Wilson, T. Owa, B. Bhattacharyya, D. Panda, Biochem-
istry 2006, 45, 5440.
[
3] For selected reviews on CÀH bond functionalization,
see: a) L. Ackermann, Chem. Rev. 2011, 111, 1315; b) J.
Wencel-Delord, T. Drçge, F. Kiu, F. Glorius, Chem.
Soc. Rev. 2011, 40, 4740; c) O. Baudoin, Chem. Soc.
Rev. 2011, 40, 4902; d) N. Kuhl, M. N. Hopkinson, J.
Wencel-Delord, F. Glorius, Angew. Chem. 2012, 124,
[
[
[
14] S. C. Eyley, R. G. Giles, H. Heaney, Tetrahedron Lett.
1
985, 26, 4649.
1
0382; Angew. Chem. Int. Ed. 2012, 51, 10236; e) J. J.
Mousseau, A. B. Charette, Acc. Chem. Res. 2013, 46,
12.
15] J. Bergman, J.-E. Bꢃckvall, J.-O. Lindstrçm, Tetrahe-
dron 1973, 29, 971.
4
16] a) W. Wu, W. Su, J. Am. Chem. Soc. 2011, 133, 11924;
b) L.-T. Li, J. Huang, H.-Y. Li, L.-J. Wen, P. Wang, B.
Wang, Chem. Commun. 2012, 48, 5187; c) J. Chen, B.
Liu, D. Liu, S. Liu, J. Cheng, Adv. Synth. Catal. 2012,
[
[
4] For selected reviews on catalytic C-2 and C-3 function-
alization of indoles, see: a) I. V. Seregin, V. Gevorgyan,
Chem. Soc. Rev. 2007, 36, 1173; b) L. Joucla, L. Djako-
vitch, Adv. Synth. Catal. 2009, 351, 673; c) E. M. Beck,
M. J. Gaunt, Top. Curr. Chem. 2010, 292, 85; d) S.
Cacchi, G. Fabrizi, Chem. Rev. 2011, 111, PR215.
3
54, 2438.
[
[
[
17] Y. Ma, J. You, F. Song, Chem. Eur. J. 2013, 19, 1189.
18] L. Yu, P. Lia, L. Wang, Chem. Commun. 2013, 49, 2368.
19] a) M. Saulnier, G. Gribble, J. Org. Chem. 1982, 47, 757;
b) A. R. Katritzky, K. Akutagawa, Tetrahedron Lett.
5] S. Paul, G. A. Chotana, D. Holmes, R. C. Reichle, R. E.
Maleczka, M. R. Smith, J. Am. Chem. Soc. 2006, 128,
1
5552.
1
985, 26, 5935.
[
6] D. W. Robbins, T. A. Boebel, J. F. Hartwig, J. Am.
Chem. Soc. 2010, 132, 4068.
7] a) D. Kalyani, N. R. Deprez, L. V. Desai, M. S. Sanford,
J. Am. Chem. Soc. 2005, 127, 7330; b) Z. Shi, B. Li, X.
Wan, J. Cheng, Z. Fang, B. Cao, C. Qin, Y. Wang,
Angew. Chem. 2007, 119, 5650; Angew. Chem. Int. Ed.
[
20] a) M. Ishikura, M. Terashima, J. Org. Chem. 1994, 59,
2
2
634; b) R. Soley, F. Albericio, M. Alvarez, Synthesis
007, 1559; c) M. Arthuis, R. Pontikis, J. C. Florent,
[
Org. Lett. 2009, 11, 4608.
[
[
[
21] B. Zhou, Y. Yang, Y. Li, Chem. Commun. 2012, 48,
5
163.
2
007, 46, 5554; c) T. Nishikata, A. R. Abela, S. Huang,
22] C. Pan, H. Jin, X. Liu, Y. Cheng, C. Zhu, Chem.
B. H. Lipshutz, J. Am. Chem. Soc. 2010, 132, 4978; d) S.
De, S. Ghosh, S. Bhunia, J. A. Sheikh, A. Bisai, Org.
Lett. 2012, 14, 4466; e) L.-Y. Jiao, M. Oestreich, Chem.
Eur. J. 2013, 19, 10845.
Commun. 2013, 49, 2933.
23] For the decarboxylative C-7 acylation of indolines
using a-oxocarboxylic acids, see: M. Kim, N. K. Mishra,
J. Park, S. Han, Y. Shin, S. Sharma, Y. Lee, E.-K. Lee,
J. H. Kwak, I. S. Kim, Chem. Commun. 2014, 50, 14249.
24] For a single example of the C-7 acylation of indoline
with an arylaldehyde, see: C.-W. Chan, Z. Zhou, W.-Y.
Yu, Adv. Synth. Catal. 2011, 353, 2999.
[
[
8] a) B. Urones, R. G. Arrayꢁs, J. C. Carretero, Org. Lett.
2
2
013, 15, 1120; b) L.-Y. Jiao, M. Oestreich, Org. Lett.
013, 15, 5374; c) Z. Song, R. Samanta, A. P. Anton-
[
[
chick, Org. Lett. 2013, 15, 5662.
9] a) S. R. Neufeldt, C. K. Seigerman, M. S. Sanford, Org.
Lett. 2013, 15, 2302; b) S. Pan, S. Ryu, T. Shibata, Adv.
Synth. Catal. 2014, 356, 929.
25] For selected examples of CÀH acylation using alde-
hydes, see: a) X. Jia, S. Zhang, W. Wang, F. Luo, J.
Cheng, Org. Lett. 2009, 11, 3120; b) C.-W. Chan, Z.
Zhou, A. S. C. Chan, W.-Y. Yu, Org. Lett. 2010, 12,
[
10] C. Pan, A. Abdukader, J. Han, Y. Cheng, C. Zhu,
Chem. Eur. J. 2014, 20, 3606.
3
926; c) J. Park, E. Park, A. Kim, Y. Lee, K.-W. Chi,
J. H. Kwak, Y. H. Jung, I. S. Kim, Org. Lett. 2011, 13,
390; d) S. Sharma, E. Park, J. Park, I. S. Kim, Org.
[
11] a) J. E. Saxton, Nat. Prod. Rep. 1992, 9, 393; b) D. R.
Beukes, M. T. Davies-Coleman, M. Kelly-Borges, M. K.
Harper, D. J. Faulkner, J. Nat. Prod. 1998, 61, 699;
c) C. F. Sturino, N. Lachance, M. Boyd, C. Berthelette,
M. Labelle, L. Li, B. Roy, J. Scheigetz, N. Tsou, C.
Brideau, E. Cauchon, M.-C. Carriere, D. Denis, G.
Greig, S. Kargman, S. Lamontagne, M.-C. Mathieu, N.
Sawyer, D. Slipetz, G. OꢂNeill, Z. Wang, R. Zamboni,
K. M. Metters, R. N. Young, Bioorg. Med. Chem. Lett.
4
Lett. 2012, 14, 906; e) S. Sharma, J. Park, E. Park, A.
Kim, M. Kim, J. H. Kwak, Y. H. Jung, I. S. Kim, Adv.
Synth. Catal. 2013, 355, 332.
[
26] For selected examples of CÀH acylation using alcohols,
see: a) F. Xiao, Q. Shuai, F. Zhao, O. Baslꢄ, G. Deng,
C.-J. Li, Org. Lett. 2011, 13, 1614; b) J. Park, A. Kim, S.
Sharma, M. Kim, E. Park, Y. Jeon, Y. Lee, J. H. Kwak,
Y. H. Jung, I. S. Kim, Org. Biomol. Chem. 2013, 11,
2766; c) M. Kim, S. Sharma, J. Park, M. Kim, Y. Choi,
Y. Jeon, J. H. Kwak, I. S. Kim, Tetrahedron 2013, 69,
6552; d) S. Sharma, M. Kim, J. Park, M. Kim, J. H.
Kwak, Y. H. Jung, J. S. Oh, Y. Lee, I. S. Kim, Eur. J.
Org. Chem. 2013, 6656.
2
006, 16, 3043; d) J. G. Ondeyka, G. L. Helms, O. D.
Hensens, M. A. Goetz, D. L. Zink, A. Tsipouras, W. L.
Shoop, L. Slayton, A. W. Dombrowski, J. D. Polishook,
D. A. Ostlind, N. N. Tsou, R. G. Ball, S. B. Singh, J.
Am. Chem. Soc. 1997, 119, 8809; e) D. D. Miller, P.
Bamborough, J. A. Christopher, I. R. Baldwin, A. C.
Champigny, G. J. Cutler, J. K. Kerns, T. Longstaff,
6
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[
27] a) P. Fang, M. Li, H. Ge, J. Am. Chem. Soc. 2010, 132,
Park, J. Park, M. Kim, J. H. Kwak, S. H. Lee, Y. H.
Jung, I. S. Kim, Adv. Synth. Catal. 2013, 355, 667.
[28] For a selected example of the Ru-catalyzed C
nation of arenes containing a ketone directing group,
see: P. Kishor, M. Jeganmohan, Org. Lett. 2011, 13,
6144.
1
1898; b) M. Li, H. Ge, Org. Lett. 2010, 12, 3464; c) M.
ÀH olefi-
Kim, J. Park, S. Sharma, A. Kim, E. Park, J. H. Kwak,
Y. H. Jung, I. S. Kim, Chem. Commun. 2013, 49, 925;
d) J. Park, M. Kim, S. Sharma, E. Park, A. Kim, S. H.
Lee, J. H. Kwak, Y. H. Jung, I. S. Kim, Chem.
Commun. 2013, 49, 1654; e) S. Sharma, A. Kim, E.
[
29] E. M. Simmons, J. F. Hartwig, Angew. Chem. 2012, 124,
120; Angew. Chem. Int. Ed. 2012, 51, 3066.
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Direct and Site-Selective Palladium-Catalyzed C-7
Acylation of Indolines with Aldehydes
Adv. Synth. Catal. 2015, 357, 1 – 8
Youngmi Shin, Satyasheel Sharma, Neeraj Kumar Mishra,
Sangil Han, Jihye Park, Hyunji Oh, Jimin Ha, Hyunwu Yoo,
Young Hoon Jung, In Su Kim*
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These are not the final page numbers!