Isoquinoline N-oxide synthesis under Pd-Catalysed C-H activation/annulation processes

Article abstract of DOI:10.1055/s-0033-1339671

An oxime directed C-H activation-annulation reaction for the selective synthesis of a range of isoquinoline N-oxides has been developed. Under palladium-catalyzed acid-assisted conditions, the reaction undergoes concerted metallation deprotonation followed by carbopalladation and transmetallation to give poly substituted isoquinoline N-oxides in moderate to good yields. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339671

LETTER
▌2431
lIestteor quinoline N-Oxide Synthesis under Pd-Catalysed C–H Activation/Annula-
tion Processes
Isoquinoline N-Oxide Synthesis
Bingyao Li,a,b Pingxuan Jiao,a Hongban Zhong,a Jianhui Huang*a,b
a
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University,
Tianjin 300072, P. R. of China
Fax +86(22)27404031; E-mail: jhuang@tju.edu.cn
b
Synergetic Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, P. R. of China
Received: 02.07.2013; Accepted after revision: 03.08.2013
Abstract: An oxime directed C–H activation–annulation reaction
for the selective synthesis of a range of isoquinoline N-oxides has
been developed. Under palladium-catalyzed acid-assisted condi-
tions, the reaction undergoes concerted metallation deprotonation
followed by carbopalladation and transmetallation to give poly-
substituted isoquinoline N-oxides in moderate to good yields.
Key words: oxime C–H activation–annulation, isoquinoline N-oxide,
palladium catalysis
(From left to right) Binyao Li did her undergraduate studies at Tianjin
Medical University from 2007–2011. She then moved to Tianjin Uni-
versity for her master degree under the supervision of Dr. Jianhui
Huang, jointly supervised by Professor Kang Zhao at the School of
Pharmaceutical Science and Technology. Her research project
involves the development of new synthetic methodologies.
Pingxuan Jiao started his undergraduate studies in 2010, in the
Ligand-associated transition-metal-catalysed C–H activa-
tion–annulation (CHAA) reaction has become one of the
most efficient approaches for the construction of carbocy-
cles and heterocycles.1 In the last five years, a consider-
School of Pharmaceutical Science and Technology at Tianjin Univer-
able number of well-established C–H activation–
annulation approaches has been developed for the modu-
lar syntheses of useful ring systems. For instance, the syn-
theses of isoindolone,2 indole,3 isoquinolone,4 isobenzo-
furanone,5 benzofuran,6 and isochromenone7 can be
achieved via bimolecular multihydrogen bonds (C–H,
N–H, or O–H bond) activation (Scheme 1).
sity. He is currently in his final year under the direction of Dr. Jianhui
Huang working with the synthesis of useful heterocycles.
Hongban Zhong joined the School of Phamaceutical Science and
Technology at Tianjin University in 2005. He then stayed in the same
school for his postgraduate study where he obtained his master degree
in 2012. After leaving the group he joined a pharmaceutical research
centre in Zhejiang.
Jianhui Huang obtained a BSc Degree in 2000 at Hu’nan University,
China, and his PhD with Professor Peter O’Brien at the University of
York in 2006. He then spent three years as a postdoctoral research fel-
low with Professor Joseph Harrity at the University of Sheffield as
well as with Dr. Simon Macdonald at GlaxoSmithKline, Stevenage
before taking an associate professorship at Tianjin University in July,
2010. His research interests are broadly in the development and appli-
cation of synthetic methods, particularly transition-metal-mediated
direct C–H functionalization and the applications on active pharma-
ceutical ingredient synthesis.
C–H activation/annulation
M (cat.)
DG
DG
H
O
O
O
H
N
NH
NH
modular syntheses of isoquinoline developed by Cheng
and Li utilising rhodium as the catalyst validated the con-
struction of isoquinoline skeleton by the reaction of aryl
oximes and alkyens (Scheme 2, eq. 1).9 Jeganmoban and
Ackermann recently developed the similar transformation
using a relatively less expensive ruthenium catalyst
(Scheme 2, eq. 2).10 With our ongoing research interests
on the heterocycle ring construction under palladium-cat-
alysed CHAA reaction, an oxime-directed isoquinoline
N-oxide synthesis is developed. Different from rhodium
and ruthenium catalyses, the palladium-catalysed reaction
has shown excellent selectivity towards the isoquinoline
N-oxide formation prior to the corresponding isoquinoline
(Scheme 2, eq. 3).
O
O
O
O
Scheme 1 CHAA reaction for the construction of useful heterocycle
ring systems
Among the numerous metal-mediated CHAA reactions,
oxime-directed8 C–H activation–annulation reactions for
the syntheses of isoquinolines have been established
under rhodium- and ruthenium-catalysed conditions. The
SYNLETT 2013, 24, 2431–2436
Advanced online publication: 28.08.2013
DOI: 10.1055/s-0033-1339671; Art ID: ST-2013-W0609-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
To evaluate the reactivity and selectivity of the formation
of isoquinoline N-oxide, oxime 1a and commercially

2432
B. Li et al.
LETTER
valent palladium source is also a potentially useful cata-
lyst for this transformation albeit with low yield (Table 1,
entry 16). The role of ZnBr2 as the additive is likely to be
the halogen source for the soft ligand exchange for the
generation of the more reactive palladium intermediate
for both C–H activation and carbopalladation process-
es.4c,11
Rh catalysis: Cheng (2009), Li (2011)
R1
R1
OH
Rh (cat.)
N
N
(1)
R3
R2
R2
R3
Table 1 Screening of Reaction Conditionsa
Ru catalysis: Jeganmohan (2012), Ackermann (2012)
R1
R1
Ph
Ph (2a)
O
Pd (cat.), acid, additive
N
OH
NOH
Ru (cat.)
N
N
(2)
PhCl–dioxane (2:1)
air, 120 °C
Ph
H
R3
Ph
R2
R2
R3
1a
3a
Pd catalysis: isoquinoline N-oxide synthesis
Entry
Pd cat.
Acid
Additive Yield (%)
R1
R1
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
–
–
0
0
O
OH
Pd (cat.)
N
N
(3)
TFA
–
R3
R2
3
PTSA
ZnCl2
ZnBr2
Zn(OAc)2
Zn(OTf)2
CuCl2
CuBr2
AgOTf
ZnBr2
ZnBr2
ZnBr2
–
38
59
74
22
41
0
R2
R3
4
–
Scheme 2 Oxime-directed CHAA reaction under rhodium-, rutheni-
um-, and palladium-catalysed conditions
5
–
6
–
available diphenylacetylene (2a) were employed for our
initial studies. Mixed solvent PhCl–dioxane (2:1) demon-
strated to be the optimal solvent system during our prelim-
inary studies. When Pd(OAc)2 was used without any
additives, no product was detected, only trace amount of
aryl ketone was isolated due to the hydrolysis of oxime
1a. The introduction of 0.2 equivalents of trifluoroacetic
acid (TFA) accelerated the hydrolysis processes and no
oxime was detected after the reaction mixture was heated
at 130 °C for four hours. Pleasingly, however, when 0.2
equivalents of strong Brønsted acid (PTSA) was used, our
desired isoquinoline N-oxide 3a was isolated in a useful
38% yield, interestingly, however, no corresponding iso-
7
–
8
–
9
–
0
10
11
12
13
14
–
0
AcOH
TFA
TFA
TFA
TFA
TFA
78
89
44
0
Pd(PPh3)2Cl2
Pd(TFA)2
ZnBr2
ZnBr2
ZnBr2
quinoline was detected in the 1H NMR spectrum from the 15
57
31
crude reaction mixture. The acid screening was fruitful,
when zinc halide salts (Lewis acid) were introduced in-
16
Pd2(dba)3
stead of a strong Brønsted acid, the reaction yields were a Reaction conditions: oxime 1a (0.3 mmol), alkyne 2a (0.45 mmol),
Pd(OAc)2 (10 mol%), ZnBr2 (1.0 equiv), and TFA (0.2 equiv) at 120
improved to 58% (ZnCl2) and 74% (ZnBr2), respectively.
Zn(OAc)2 and Zn(OTf)2 are less efficient Lewis acids
°C in PhCl–dioxane (2:1; 1.5 mL, 0.2 M), 6–12 h.
which provided the desired isoquinoline N-oxide in 22%
and 41% yields. Copper and silver salts, however, failed
to give any of our desired product instead only hydrolysis
product was observed after the reaction mixture was heat-
ed at 120 °C for five hours (Table 1, entries 8–10). Pleas-
ingly, when acetic acid (AcOH) or TFA were added as the
additive, the yields have been improved to 78% and 89%,
respectively. In addition other palladium sources are also
proved to be active catalysts for this reaction, where PdCl2
gave the corresponding product in 44% yield.
Pd(PPh3)2Cl2, however, due to the two phosphine ligands,
failed to give any of our desired products while Pd(TFA)2
provided isoquinoline N-oxide 3a in a moderate 57%
yield. We are pleased to find that Pd2(dba)3 as the low-
With the optimal conditions in hand, we evaluated the
scope and limitations of the reaction. When aryl oximes
were utilised, a number of electron-rich and electron-defi-
cient aryl oximes were evaluated, and the corresponding
isoquinoline N-oxides were successfully prepared in mod-
erate to good yields (Scheme 3). No isoquinolines were
observed in most of the cases. Hydrolysis products and
Beckmann rearrangement products were the major side
products generated during the reaction as these reactions
were carried out under Lewis acidic conditions. The reac-
tion of p-methylbenzyl oxime underwent the CHAA reac-
tion fluently to give our desired product in 77% yield.
Aryl oximes bearing an electron-withdrawing group at the
Synlett 2013, 24, 2431–2436
© Georg Thieme Verlag Stuttgart · New York

LETTER
Isoquinoline N-Oxide Synthesis
2433
para position provided the corresponding products in 3l and 3l′ as a 2:1 mixture of regioisomers, which have
moderate yields. As the side-reaction hydrolysis occurred been assigned via NOE studies. Similar to other CHAA
during the reaction in the presence of acids resulting in the reactions, the regioselectivity favours the carbopallada-
corresponding ketones. On the contrary, aryl oxime with tion onto the less hindered position of the alkynes.2,3
electron-donating substituents at the para position gave
The isoquinoline N-oxides could be readily reduced onto
similar moderate to good yields due to the Beckmann re-
the isoquinolines under Cheng’s conditions.12 The se-
arrangement reactions. meta-Substituted aryl oximes also
quential synthesis of isoquinoline N-oxides followed by
provided our desired isoquinoline N-oxides 3g and 3h in
zinc reduction provided the corresponding isoquinolines
4a–e in good overall yields (52–82%) from starting ben-
zamides (Scheme 4). It is worth noting that no column
chromatographic workup was needed between the two se-
useful 49% and 53% yields. Biaryl oximes are also toler-
ated in this transformation, multiaryl-substituted isoquin-
oline N-oxide 3i was isolated in 77% yield. Reactions of
aryl oxime with alkynes other than diphenyl acetylene
quential steps.
were also successful, symmetrical dialkyl alkyne facilitat-
ed the corresponding product 3j in 59% yield.
R0
R0
OH
1. standard conditions
2. Zn, MeCN, reflux
R0
R0
N
N
R1
R2 (2)
O
R2
Pd(OAc)2, ZnBr2
NOH
N
Ar
Ar
R1
TFA, PhCl–dioxane (2:1)
air, 120 oC.
H
R2
3
4
R1
3
1
N
N
Ph
Ph
O
O
N
O
Ph
Ph
N
N
4a (82%)
4b (67%)
F
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a (89%)
3b (77%)
3c (50%)
N
N
Et
Ph
Pr
O
O
N
O
Ph
Pr
N
N
4c (70%)
4d (52%)
Ph
MeO
Ph
Cl
Cl
Ph
Ph
3f (72%)
Ph
Ph
Ph
Scheme 4 Synthesis of isoquinoline from isoquinoline N-oxide. Re-
agents and conditions: 1) oxime 1 (0.3 mmol), alkyne 2 (0.45 mmol),
Pd(OAc)2 (10 mol%), ZnBr2 (1.0 equiv), and TFA (0.2 equiv) at 120
°C in PhCl–dioxane (2:1; 1.5 mL, 0.2 M), 6–12 h; 2) Zn powder (5
equiv) in MeCN (1.5 mL), reflux, 5–10 h.
3d (45%)
3e (41%)
O
MeO
O
O
N
N
N
The kinetic isotope effect (KIE) studies have revealed that
the C–H activation process is the turnover limiting step as
we have observed 2:1 and 3:1 as the KIE values for both
internal and external competition reactions. When aryl ox-
ime 1iD was treated with alkyne 2a under our standard re-
action conditions, a mixture of 3i and 3iD was isolated in
a 2:1 ratio (Scheme 5; for experimental details see Sup-
porting Information).
Ph
Ph
Ph
Ph
Ph
Ph
3g (49%)
3h (53%)
3i (77%)
Ph
Et
Ph
N
O
O
N
O
N
Ph
Pr
Ph
Pr
In addition, bimolecular competition between oxime 1a
and 1aD provided a similar KIE value as shown in
Scheme 6 (for experimental details see Supporting Infor-
mation).
OMe
3j (59%)
3k (71%)
3l (56%, 2:1)
Scheme 3 Reaction scope. Reagents and conditions: oxime 1 (0.3
mmol), alkyne 2 (0.45 mmol), Pd(OAc)2 (10 mol%), ZnBr2 (1.0
equiv), and TFA (0.2 equiv) at 120 °C in PhCl–dioxane (2:1; 1.5 mL,
0.2 M), 6–12 h.
Similar to the reactions of isoquinoline and isoquinolone
syntheses, the reaction is supposed to undergo oxime di-
rected C–H activation via a CMD or/and Friedel–Crafts-
type of processes to give palladacycle 6. Active palladium
intermediate 7 is formed after carbopalladation of the pal-
ladium species 6 with the addition onto the less hindered
carbon of the unsymmetrical alkyne. Further transmetalla-
tion of nitrogen onto the palladium centre, the seven-
Reactions with unsymmetric alkynes were also feasible,
however, the regioselectivity varies when different al-
kynes were utilised. When phenyl propyne was used, 3k
was isolated exclusively in a good 71% yield while the re-
action of unsymmetric diaryl alkyne provide the product
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2431–2436

2434
B. Li et al.
LETTER
D
D
D
D
D
D
D
D
2a, Pd (cat.)
D
O
D
D
D
D
O
standard
conditions
NOH
N
N
D
Ph
Ph
Ph
3iD
Ph
1iD
3i
3i/3iD = 2:1
Scheme 5 Intramolecular KIE studies
O
NOH
N
N
Ph
1a
3a
Ph
Ph
2a, Pd (cat.)
3a/3aD = 3:1
D
D
D
D
standard
conditions
D
D
D
O
NOH
D
D
Ph
1aD
3aD
Scheme 6 Intermolecular KIE studies
membered palladacycle 8 was then formed. The final re- In summary, we have demonstrated the selective forma-
ductive elimination could facilitate our desired isoquino- tion of isoquinoline N-oxide under palladium-catalysed
line N-oxide 3 after the releasing Pd(0) which can be oxime-directed CHAA reaction. This methodology gives
reoxidised back to palladium(II) 5 to start the next catalyt- an insight of mild C–H activation under palladium cataly-
ic cycle (Scheme 7).
sis which could be a potential direction for the sensitive
functional group within C–H activation reactions.
Pd(OAc)2
R
NOH
R
Pd(II)
air [O]
O
1
N
CMD
5
or/and
Friedel–Crafts
C–H activation
R
RL
Pd(0)
OH
RS
N
3
Pd
6
X
R
O
N
Pd
RL
R
RS
N
OH
Pd
X
8
RL
6
R
RS
OH
2
N
Pd
RL
X
RS
7
Scheme 7 Plausible catalytic cycle
Synlett 2013, 24, 2431–2436
© Georg Thieme Verlag Stuttgart · New York

LETTER
Isoquinoline N-Oxide Synthesis
2435
References
(1) For selected examples, see: (a) Wang, L.; Huang, J.; Peng,
S.; Liu, H.; Jiang, X.; Wang, J. Angew. Chem. Int. Ed. 2013,
52, 1768. (b) Gandeepan, P.; Cheng, C.-H. Org. Lett. 2013,
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Lett. 2011, 13, 1214. (b) McAtee, D. M. S.; Dasgupta, S.;
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T. T.; Wang, G. W. Chem. Commun. 2011, 47, 12789.
(d) Wang, F.; Song, G. Y.; Li, X. W. Org. Lett. 2010, 12,
5430.
General Procedure
A solution of oxime (0.3 mmol), alkyne (0.45 mmol), Pd(OAc)2 (10
mol%), ZnBr2 (0.3 mmol), TFA (0.06 mmol) in PhCl–dioxane (2:
1, 1.5 mL) was heated at 120 °C under air. The reaction was moni-
tored by TLC. After the reaction was complete, the reaction mixture
was cooled down to r.t. The mixture was washed with sat. aq
NaHCO3 (15 mL) to neutralise acid. The aqueous layers were ex-
tracted with EtOAc (3 × 15 mL). The combined organic layer was
dried over anhydrous Na2SO4. The solvent was removed under re-
duced pressure to provide the crude product. The crude product was
purified by flash column chromatography on silica gel.
Selected Examples
(3) For selected examples, see: (a) Ackermann, L.; Lygin, A. V.
Org. Lett. 2012, 14, 764. (b) Porcheddu, A.; Mura, M. G.;
Luca, L. D.; Pizzetti, M.; Taddei, M. Org. Lett. 2012, 14,
6112. (c) Huestis, M. P.; Chan, L.; Stuart, D. R.; Fagnou, K.
Angew. Chem. Int. Ed. 2011, 123, 1374. (d) Chen, J. L.;
Pang, Q. Y.; Sun, Y. B.; Li, X. W. J. Org. Chem. 2011, 76,
3523. (e) Wei, X. H.; Zhao, M.; Du, Z. Y.; Li, X. W. Org.
Lett. 2011, 13, 4636. (f) Zhou, F.; Han, X. L.; Lu, X. Y.
Tetrahedron Lett. 2011, 52, 4681. (g) Chen, J. L.; Song, G.
Y.; Pan, C. L.; Li, X. W. Org. Lett. 2010, 12, 5426.
(h) Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am.
Chem. Soc. 2010, 132, 18326. (i) Shi, Z.; Zhang, C.; Li, S.;
Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem. Int. Ed.
2009, 48, 4572.
(4) For selected examples, see: (a) Deponti, M.; Kozhushkov, S.
I.; Yufit, D. S.; Ackermann, L. Org. Biomol. Chem. 2013,
11, 142. (b) Lu, S.; Lin, Y.; Zhong, H.; Zhao, K.; Huang, J.
Tetrahedron Lett. 2013, 54, 2001. (c) Zhang, N.; Li, B.;
Zhong, H.; Huang, J. Org. Biomol. Chem. 2012, 10, 9429.
(d) Zhong, H.; Yang, D.; Wang, S.; Huang, J. Chem.
Commun. 2012, 48, 3236. (e) Shiota, H.; Ano, Y.; Aihara,
Y.; Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc. 2011, 133,
14952. (f) Ackermann, L.; Lygin, A. V.; Hofmann, N.
Angew. Chem. Int. Ed. 2011, 50, 6379. (g) Song, G. Y.;
Chen, D.; Pan, C. L.; Crabtree, R. H.; Li, X. W. J. Org.
Chem. 2010, 75, 7487. (h) Guimond, N.; Gouliaras, C.;
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S.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. Chem. Lett.
2010, 39, 744.
1,6-Dimethyl-3,4-diphenylisoquinoline 2-Oxide (3b)
Following the general procedure, oxime 1b (0.3 mmol, 45 mg), di-
phenylethyne (80 mg, 0.45 mmol), Pd(OAc)2 (6.7 mg, 10 mol%),
ZnBr2 (63 mg, 0.3 mmol), and TFA (6.8 mg, 0.06 mmol) in PhCl–
dioxane (2:1; 1.5 mL) was heated at 120 °C for 5 h to give the de-
sired isoquinoline oxide 3b (75 mg, 77%) as a pale yellow solid; mp
245–247 °C. 1H NMR (600 MHz, CDCl3): δ = 7.94 (d, J = 8.5 Hz,
1 H), 7.46 (d, J = 8.5 Hz, 1 H), 7.28–7.17 (m, 9 H), 7.12 (d, J = 6.7
Hz, 2 H), 2.98 (s, 3 H), 2.39 (s, 3 H). 13C NMR (151 MHz, CDCl3):
δ = 145.7, 145.4, 138.8, 135.4, 133.9, 133.3, 130.8, 130.7, 130.6,
129.5, 128.1, 127.9, 127.7, 127.6, 126.4, 125.8, 124.1, 21.9, 13.6.
ESI-HRMS: m/z calcd for C23H19NO [M + H]: 326.1545; found:
325.1546.
6-Chloro-1-methyl-3,4-diphenylisoquinoline 2-Oxide (3d)
Following the general procedure, oxime 1d (0.3 mmol, 51 mg), di-
phenylethyne (80 mg, 0.45 mmol), Pd(OAc)2 (6.7 mg, 10 mol%),
ZnBr2 (62.5 mg, 0.3 mmol), and TFA (6.84 mg, 0.06 mmol) in
PhCl–dioxane (2:1, 1.5 mL) was heated at 120 °C for 8 h to give the
desired isoquinoline oxide 3d (47 mg, 45%) as a pale yellow solid;
mp 206–208 °C. 1H NMR (600 MHz, CDCl3): δ = 7.96 (d, J = 9.0
Hz, 1 H), 7.56 (d, J = 9.0 Hz, 1 H), 7.42 (s, 1 H), 7.29–7.26 (m, 3
H), 7.24–7.18 (m, 5 H), 7.11 (d, J = 6.0 Hz, 2 H), 2.96 (s, 3 H). 13
C
NMR (151 MHz, CDCl3): δ = 146.9, 144.9, 134.7, 134.3, 133.6,
132.8, 130.5, 130.4, 129.7, 129.5, 128.3, 128.1, 128.0, 127.8, 126.7,
125.7, 125.6, 13.7. ESI-HRMS: m/z calcd for C22H1635ClNO [M +
H]: 346.0999; found: 346.1001.
1-Phenyl-3,4-dipropylisoquinoline 2-Oxide (3j)
Following the general procedure, oxime 1i (0.3 mmol, 59 mg), di-
propylacetylene (50 mg, 0.45 mmol), Pd(OAc)2 (6.7 mg, 10 mol%),
and ZnBr2 (63 mg, 0.3 mmol) in PhCl–dioxane (2:1, 1.5 mL) was
heated at 120 °C for 5 h to give the desired isoquinoline oxide 3j (54
(5) For selected examples, see: (a) Shi, X. Y.; Li, C. J. Adv.
Synth. Catal. 2012, 354, 2933. (b) Ackermann, L.; Pospech,
J. Org. Lett. 2011, 13, 4153. (c) Ueura, K.; Satoh, T.; Miura,
M. J. Org. Chem. 2007, 72, 5362.
1
mg, 59%) as a pale yellow solid; mp 172–174 °C. H NMR (600
MHz, CDCl3): δ = 8.15 (d, J = 8.0 Hz, 1 H), 7.97 (t, J = 8.0 Hz, 1
H), 7.79–7.72 (m, 3 H), 7.66 (t, J = 7.5 Hz, 1 H), 7.64–7.60 (m, 3
H), 3.47–3.36 (m, 2 H), 3.22–3.12 (m, 2 H), 1.89–1.888 (m, 2 H),
1.80–1.79 (m, 2 H), 1.22–1.17 (m, 3 H), 1.15–1.10 (m, 3 H). 13C
NMR (151 MHz, CDCl3): δ = 147.0, 136.2, 135.7, 134.5, 130.8,
130.5, 130.3, 129.6, 128.6, 128.2, 127.1, 124.0, 100.0, 31.0, 30.9,
24.0, 22.1, 14.7, 14.4. ESI-HRMS: m/z calcd for C21H23NO [M +
H]: 306.1858; found: 306.1861.
(6) For selected examples, see: (a) Kuram, M. R.;
Bhanuchandra, M.; Sahoo, A. K. Angew. Chem. Int. Ed.
2013, 52, 4607. (b) Lee, D. H.; Kwon, K. H.; Yi, C. S. J. Am.
Chem. Soc. 2012, 134, 7325. (c) Kundu, D.; Samim, M.;
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Acknowledgment
The financial support from the National Natural Science Foundati-
on of China (Grant No. 21342001), Tianjin Natural Science Foun-
dation (Grant No. 13JCQNJC04800), and the Innovation
Foundation of Tianjin University (2013XJ-0005) are gratefully ack-
nowledged.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
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Synlett 2013, 24, 2431–2436
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