Facile regioselective synthesis of functionalized heterocycle-tethered spiro compounds via an intramolecular electrophilic Ipso - Iodocyclization process

Article abstract of DOI:10.1055/s-0031-1289526

A general, regioselective, and efficient intramolecular electrophilic ipso-iodocyclization of a series of N-alkyl-N-aryl phenylpropiolamides in the presence of I₂ (molecular iodine) and NaHCO₃ via 5-endo-dig mode of cyclization has been developed for the synthesis of hitherto unreported coumarin, quinolone, and pyrimidine-annelated heterocyclic compounds in excellent yields (84-92%). The development of this methodology provides efficient and mild reaction conditions that allow for easy isolation of products. The synthesized spiro derivatives offer an attractive and useful scope for further functionalization and to synthesize new bioactive heterocycles. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289526

LETTER
2657
Facile Regioselective Synthesis of Functionalized Heterocycle-Tethered Spiro
Compounds via an Intramolecular Electrophilic Ipso-Iodocyclization Process
S
ynthesis of Funct
.
ionalized He
C
terocycle-Tether
.
e
d
Spiro Com
M
pounds ajumdar,* Tapas Ghosh, Pranab K. Shyam
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
E-mail: kcm_ku@yahoo.co.in
Received 19 July 2011
Intramolecular electrophilic iodocyclization of the aryl
Abstract: A general, regioselective, and efficient intramolecular
electrophilic ipso-iodocyclization of a series of N-alkyl-N-aryl phe-
nylpropiolamides in the presence of I2 (molecular iodine) and
NaHCO3 via 5-endo-dig mode of cyclization has been developed
alkynes has recently emerged as an important area of in-
terest in synthetic organic chemistry due to its widespread
utility in the synthesis of carbocycles as well as heterocy-
for the synthesis of hitherto unreported coumarin, quinolone, and cles, natural and biologically active compounds.5,6 Iodoni-
pyrimidine-annelated heterocyclic compounds in excellent yields
um-promoted heteroannulations have drawn much
(84–92%). The development of this methodology provides efficient
attention because they offer an alternative protocol for the
and mild reaction conditions that allow for easy isolation of prod-
synthesis of complex molecules that are not easily acces-
ucts. The synthesized spiro derivatives offer an attractive and useful
sible by the usual organometallic reagents. Currently,
scope for further functionalization and to synthesize new bioactive
many such electrophilic cyclization strategies are carried
out between alkyne and o-arene substitutions to construct
several highly functionalized heterocycles as well as car-
bocycles.5 Recently, another pathway involving an alkyne
and an ipso-arene substitution to construct spirocycles7
has been reported. However, the latter pathway has not yet
been extensively investigated, only few reports appeared
in the literature.7 Literature search revealed that only few
attempts have been made to synthesize spirocycles fused
with potentially biologically active coumarin, quinolone,
and pyrimidine systems. Applications of these substituted
heterocycles are profound and spread in a wide range
from pharmaceuticals and agrochemicals to electronics.
Consequently, synthetic organic chemists are engaged in
developing new strategies to meet the requirements of
variously substituted heterocycles. Spirocyclic com-
pounds are of considerable importance due to their ubi-
quitous presence in many natural products and
pharmacologically active compounds.8,9 Recent literature
reveals renewed interest in terms of the synthesis of dif-
ferently functionalized spirocyclic molecules implement-
ing diverse approaches.10 However, there are only few
methods known to date that describe the synthesis of
spiro-fused quinoline core.11 Pyrimidine-annelated het-
erocycles have received much attention due to their wide
spectrum of biological activities.12,13 A number of pyri-
midine- and uracil-based molecules,14 such as 3¢-azido-3¢-
deoxythiamidine (AZT), 2,3-dideoxycytidine (DDC), and
(E)-5-[2-(bromovinyl)-2¢-deoxyuridine (BVDU), are ac-
tive against cancer and AIDS viruses15 and have already
been synthesized. The introduction of functionality at the
C-5 and C-6 positions of uracil leads to biologically inter-
esting molecules. Earlier we have reported the synthesis
of pyrimidine-annelated spiro heterocycles using tinhy-
dride-mediated radical cyclization,16 however, there are
many drawbacks associated with such tin-based radical
chemistry.17 Naturally, there is always a demand for new
synthetic methodology that provides easy access to the
target molecules. In continuation of our interest in the de-
heterocycles.
Key words: azaspiro heterocycle, electrophilic ipso-iodocycliza-
tion, coumarin, quinolone, uracil
Many natural and biologically active compounds contain
ring systems connected with each other by a spiro carbon
atom. Spirocyclic systems are of immense importance
owing to their ubiquitous presence in several natural prod-
ucts. For example, all the alkaloids depicted in Figure 1
share an azaspirocyclic framework. Pinnaic acid, isolated
from the Okinawan bivalic Pinna muricata, exhibits in-
hibitory activity against phospholipase A2.1 Halichlorine,
produced by the marine sponge Halichondria okadai, was
found to inhibit the vascular cell adhesion molecule-1
(VCAM-1).1,2 Cephalotaxine, the major alkaloid of Ceph-
alotaxus harringtonia var. drupacea, and its esters (har-
ringtonines) show high antileukaemic activity.3The
selective construction of the spiro fragment presents a
challenge for these unique alkaloids and various related
products.4
H
Me
H
HO
O
N
O
NH
O
H
Cl
H
Cl
O
O
N
HO
OH
pinnaic acid
OH
halichlorine
H
RO
OMe
(–)-cephalotaxine R = H
Figure 1
SYNLETT 2011, No. 18, pp 2657–2662
Advanced online publication: 19.10.2011
DOI: 10.1055/s-0031-1289526; Art ID: B13711ST
x
x
.x
x
.2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

2658
K. C. Majumdar et al.
LETTER
velopment of general methods for the synthesis of phar-
macologically important and potentially bioactive
heterocyclic systems,18 we have explored the feasibility of
synthesizing the spiro-fused coumarins, quinolones, and
pyrimidines via 5-endo-dig mode of electrophilic iodocy-
clization. Herein we report our results.
Table 1 Screening of Optimal Reaction Conditions
Ph
O
MeO
N
Ph
I
H
I2
Me
O
N
base
Me
O
N
O
N
For the construction of practical building blocks for the
synthesis of spiro compounds and for further development
of our iodocyclization project, we have carried out the
ipso-iodocyclization of aryl propiolamides 2.19 The pre-
cursors 2a–j for the iodocyclization reaction were access-
ed from the corresponding amines 1a–j by amidification
reaction with phenylpropiolyl chloride (which was in turn
prepared by refluxing phenylpropiolic acid with thionyl
chloride) in the presence of a phase-transfer catalyst
(TBAHS) and aqueous K2CO3 (Scheme 1).
Me
Me
3c
2c
Entry Solventa Base
(equiv)
Iodinating
Temp Time Yield
(h) (%)b
agent (equiv) (°C)
1
2
3
MeCN
MeCN
MeCN
NaHCO3 (3) I2 (1)
NaHCO3 (3) I2 (1.5)
NaHCO3 (3) I2 (3)
NaHCO3 (3) I2 (3)
NaHCO3 (3) I2 (5)
NaHCO3 (3) I2 (3)
NaHCO3 (3) NIS (3)
r.t.
r.t.
r.t.
r.t.
r.t.
60
r.t.
r.t.
r.t.
r.t.
r.t.
4
4
8
4
4
3
6
4
4
4
4
42
46
88
92
86
80
76
n.r.d
34
39
42
4c MeCN
Ph
5
6
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
MeOH
O
NR
(i)
NHR
7
O
X
O
X
8
–
I2 (3)
I2 (3)
1a, X = O, R = Me
1b, X = O, R = Et
1c, X = NMe, R = Me
1d, X = NMe, R = Et
1e, X = NEt, R = Me
1f, X = NEt, R = Et
2a, X = O, R = Me
2b, X = O, R = Et
2c, X = NMe, R = Me
2d, X = NMe, R = Et
2e, X = NEt, R = Me
2f, X = NEt, R = Et
9
K2CO3 (3)
10
11
NaHCO3 (3) I2 (3)
NaHCO3 (3) I2 (3)
O
R2
N
O
a 1.5 equiv of MeOH was used in each case (entries 1–10).
b Isolated yield.
R1
O
O
R1
O
NHR2
(i)
N
N
c Optimized reaction conditions.
d n.r. = no reaction.
N
N
R1
R1
Ph
1g, R1 = Me, R2 = Me
1h, R1 = Me, R2 = Et
1i, R1 = Et, R2 = Me
1j, R1 = Et, R2 = Et
2g, R1 = Me, R2 = Me
2h, R1 = Me, R2 = Et
2i, R1 = Et, R2 = Me
2j, R1 = Et, R2 = Et
creasing the amount of iodine from three equivalents to
five equivalents did not improve the yield of the product.
Increasing the reaction time from four hours to eight hours
also did not improve the yield of the cyclized product.
Subsequently, the temperature effect was investigated,
and it turned out that the reactions at room temperature
gave better results. Although the reaction rate was en-
hanced at 60 °C, the yield of the product decreased. We
also used N-iodosuccinimide (NIS) as an iodinating agent
in place of molecular iodine (Table 1, entry 7). However,
the reaction required a longer reaction time (6 h), and also
the yield of the reaction was relatively lower, 76% of the
cyclized product 3c was obtained from 2c. The presence
of a base proved to be important for the reaction, because
the reaction does not occur without a base. The effect of
K2CO3 as a base was also investigated. However, K2CO3
provided a much lower yield of the cyclized product 3c
than that when NaHCO3 was used as base. Methanol plays
a key role in the reaction. When the reaction was carried
out under dry conditions, that is, using dry MeCN, without
MeOH, we did not get the desired product. In the presence
of a few drops of MeOH, the reaction occurs to afford the
spiro product. Thus the optimized conditions for the reac-
tion are three equivalents of I2, three equivalents of
NaHCO3, MeCN–MeOH at room temperature. These
conditions worked well for the synthesis of different spiro
Scheme 1 Reagents and conditions: (i) phenylpropiolyl chloride
(1.0 equiv), TBAHS, K2CO3, CHCl3–H2O, r.t., 12 h.
To standardize the reaction conditions for the synthesis of
spiro heterocycles a series of experiments were performed
with or without a base (NaHCO3, K2CO3) and by varying
the amounts of molecular iodine in different solvents such
as MeCN, MeOH, and CH2Cl2. N-Methyl-N-(1-methyl-2-
oxo-1,2-dihydroquinolin-6-yl)-3-phenylpropiolamide
(2c) was used as a model substrate for this purpose, and
the results are summarized in Table 1.
To our delight, the reaction of the amide 2c with I2 (3
equiv) and NaHCO3 (3 equiv) in MeCN–MeOH at room
temperature for four hours proceeded selectively to afford
the corresponding 4-iodo-5¢-methoxy-1,1¢-dimethyl-3-
phenyl-1¢H-spiro[pyrrole-2,6¢-quinoline]-2¢,5(1H,5¢H)-
dione (3c) in 92% yield (Table 1, entry 4). Solvents like
CH2Cl2 and MeOH resulted in lower yield of the product.
Reducing the amount of I2 from three to 1.5 equivalents
and one equivalent afforded the compound 3c in 46% and
42% yields (Table 1, entries 1 and 2), respectively. In-
Synlett 2011, No. 18, 2657–2662 © Thieme Stuttgart · New York

LETTER
Synthesis of Functionalized Heterocycle-Tethered Spiro Compounds
2659
Ph
initial interaction of electrophilic iodine with the alkyne
residue 2 to give the iodonium intermediate A. This may
undergo a nucleophilic attack of the aromatic p-electrons
on the activated triple bond by a 5-endo-dig mode of cy-
clization triggering an intramolecular electrophilic ipso-
cyclization of intermediate A to form the spirocyclic inter-
mediate B. Finally, reaction of nucleophilic MeOH with
the intermediate B may lead to the desired spiro com-
pound 3.
O
I
Ph
H
MeO
NR
(i)
O
N
R
O
X
O
X
3a, X = O, R = Me
3b, X = O, R = Et
2a, X = O, R = Me
2b, X = O, R = Et
2c, X = NMe, R = Me
2d, X = NMe, R = Et
2e, X = NEt, R = Me
2f, X = NEt, R = Et
3c, X = NMe, R = Me
3d, X = NMe, R = Et
3e, X = NEt, R = Me
3f, X = NEt, R = Et
R2
N
R2
N
Me
N
Me
N
O
O
O
R1
O
O
O
I+
(i)
N
R1
O
I
N
O
N
O
N
+ I
O
N
R1
Ph
H
N
R1
Me
Me
OMe
Ph
Ph
Ph
Ph
2c
Ph
A
2g, R1 = Me, R2 = Me
2h, R1 = Me, R2 = Et
2i, R1 = Et, R2 = Me
2j, R1 = Et, R2 = Et
3g, R1 = Me, R2 = Me
3h, R1 = Me, R2 = Et
3i, R1 = Et, R2 = Me
3j, R1 = Et, R2 = Et
I
I
MeO
H
+
O
MeOH
– H+
O
N
N
Scheme 2 Reagents and conditions: (i) I2 (3.0 equiv), NaHCO3 (3.0
Me
O
N
O
N
Me
equiv), MeCN, MeOH (1.5 equiv).
Me
Me
3c
B
heterocycles from the other substrates 2a,b,d–j also
(Scheme 2).
Scheme 3 A plausible reaction mechanism
A variety of substrates were allowed to react with molec-
ular iodine and sodium bicarbonate under the optimized
reaction conditions to examine the scope of this intramo-
lecular electrophilic ipso-iodocyclization process. The re-
sults are summarized in Table 2. Substrates having a
quinolone moiety provided the best yields of the products
in a reasonable reaction time than that of the correspond-
ing coumarin-/uracil-containing substrates.
The spectral and analytical data of the compound showed
the formation of the product 3c. We were able to obtain
good-quality crystals by concentration of a dichlo-
romethane–hexane solution with compound 3c, and its
structure has been assigned unambiguously by analysis of
its single-crystal XRD data21 (Figure 2). The X-ray crystal
structure analysis of product 3c shows clearly that the
OMe group of the aromatic ring attached to the heterocy-
cle and the amide nitrogen (–N–) are cis in nature with re-
spect to each other.
Table 2 Ipso-Iodocyclization of Amides 2a–ja
Entry
Amide
2a
Time (h)
Product
3a
Yield (%)b
1
2
4.8
5
86
84
92
90
90
87
85
84
88
84
2b
2c
3b
3c
3
4
4
2d
2e
4.6
4.2
4.4
4.8
5
3d
3e
5
6
2f
3f
7
2g
3g
Figure 2 ORTEP diagram of compound 3c
8
2h
2i
3h
3i
9
5
In the recent past Li et al.22a,b have published some results
on the electrophilic ipso-iodocyclization of aryl alkynes.
They have reported that the intramolecular ipso-iodocy-
clization of 4-(4-alkylaryl)alk-1-ynes with iodine
monochloride or iodine proceeded smoothly, providing
the corresponding 8-methylene-1-azaspiro[4.5]trienes.
They applied22c the same electrophilic cyclization strategy
for the synthesis of spiro[4.5]trienyl acetates from para-
unactivated arylalkynes, including N-arylpropiolamides
10
2j
5.1
3j
a Reaction conditions: I2 (3 equiv), NaHCO3 (3 equiv), MeCN, MeOH
(1.5 equiv).
b Isolated yield.
On the basis of previous reports5,6 a probable mechanism
is outlined in Scheme 3. The formation of the spiro het-
erocycles 320 from the substrates 2 may be explained by an
Synlett 2011, No. 18, 2657–2662 © Thieme Stuttgart · New York

2660
K. C. Majumdar et al.
LETTER
(New Delhi) for providing NMR, CHN-analyzer and IR spectrome-
ters under the DST-FIST program.
and phenyl 3-phenylpropiolate in the presence of NIS and
AcOH. An electrophilic ipso-cyclization involving an
electrophile exchange process has also been developed22d
in which a variety of N-(p-methoxyaryl)propiolamides
and 4-methoxyphenyl 3-phenylpropiolate were cyclized
in the presence of CuX (X = I, Br, SCN) and electrophilic
fluoride reagents to selectively afford the corresponding
spiro[4.5]decenones. In all of their reports they have only
been able to isolate the product in moderate to good
yields. Wada et al. reported23 an efficient approach to the
synthesis of azaspiro compounds having dissymmetric di-
enone cores by ipso-iodocyclization of ethoxyethyl ether
to alkynes. They have constructed 1-aza-3-io-
dospiro[4.5]deca-3,7,9-trien-6-ones through the ipso-io-
docyclization of ethoxyethyl ether to alkynes. Batra et al.
have disclosed24 a straightforward and general approach
for the diastereoselective synthesis of spiro-fused (C-
5)isoxazolino- or (C-3)pyrazolino-(C-3)quinolin-2-ones
from the Baylis–Hillman adducts of 2-nitobenzaldehyde
by sequential 1,3-dipolar cycloaddition and reductive cy-
clization. Larock et al. reported25 the synthesis of
spiro[4.5]trienones by intramolecular ipso-halocycliza-
tion reaction of 4-(p-methoxyaryl)-1-alkynes. We have
been successful in designing our strategy in such a way
References and Notes
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that
spiro[chromene-6,2¢-pyrrole]-2,5¢(1¢H,5H)-dione,
spiro[pyrrole-2,6¢-quinoline]-2¢,5(1H,5¢H)-dione, and tri-
azaspiro[4.5]dec-3-ene-2,6,8-trione derivatives were syn-
thesized in excellent yields and within a reasonable time.
Importantly, these spirocyclic compounds {specially
spiro[4,5]decane skeleton} are a prevalent motif in many
pharmacologically important compounds that widely oc-
cur in nature as well as they are often utilized as interme-
diates in organic synthesis.26 Our findings are significant
not only due to the novel heterocyclic derivatives ob-
tained, but more general as an example of an iodocycliza-
tion of hetero-1,5-enynes which are currently a topic of
general interest. The observed 5-endo-dig cyclization
mode is rare27 for such reactions where the 6-endo-dig
mode seems to be more common.28
In summary, we have developed a general, mild, and effi-
cient protocol for the intramolecular electrophilic ipso-io-
docyclization of different N-aryl phenylpropiolamides to
selectively synthesize spiro[chromene-6,2¢-pyrrole],
spiro[pyrrole-2,6¢-quinoline], and triazaspiro[4.5]decene
in excellent yields. As coumarin, quinolone, and uracil
moieties are known to be of biological relevance, the syn-
thesized azaspiro compounds tethered with those motifs
are expected to be of biological relevance too. Moreover,
an iodine atom present in the synthesized spiro derivatives
offers an attractive and useful scope for further function-
alization and, therefore, may be used for diversity-orient-
ed synthesis of new bioactive heterocycles.
Acknowledgment
We thank CSIR (New Delhi) for financial assistance. Two of us
(T.G. & P.K.S.) are grateful to CSIR (New Delhi) for their research
fellowships. We also thank Professor A. T. Khan, IIT, Guwahati for
the single crystal XRD data of the compound 3c. We thank DST
Synlett 2011, No. 18, 2657–2662 © Thieme Stuttgart · New York

LETTER
Synthesis of Functionalized Heterocycle-Tethered Spiro Compounds
2661
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N-(1-Ethyl-2-oxo-1,2-dihydroquinolin-6-yl)-N-methyl-3-
phenylpropiolamide (2e)
A mixture of phenylpropiolic acid (500 mg, 3.42 mmol) and
SOCl2 was stirred at 100 °C for 1.5 h. After evaporation of
the solvent, the residue was dissolved in CH2Cl2 (20 mL). A
solution of amine 1e (691 mg, 3.42 mmol) in CH2Cl2 (20
mL) and TBAHS (cat. amount) was added to the stirred
solution of acid chloride. To this reaction mixture an aq
solution of K2CO3 (930 mg, 6.84 mmol) was added slowly.
After stirring for 6 h at r.t., the solution was washed with 5%
HCl (2 × 20 mL) and then with 5% aq NaOH (2 × 20 mL).
The organic layer was dried (Na2SO4), and the solvent was
evaporated under reduced pressure. The residue was purified
by column chromatography over silica gel using EtOAc–PE
(3:7) as an eluent to afford amide 2e. Other compounds 2a–
d,f–j were also prepared accordingly.
White solid; mp 116–118 °C; yield 87%. IR (KBr): 2216,
1643, 1591 cm–1. 1H NMR (400 MHz, CDCl3): d = 1.39 (t, 3
H, J = 7.2 Hz), 3.43 (s, 3 H), 4.36–4.43 (m, 2 H), 6.77 (d, 1
H, J = 9.2 Hz), 7.09 (d, 2 H, J = 7.2 Hz), 7.21 (t, 2 H, J = 7.6
Hz), 7.32 (t, 1 H, J = 7.2 Hz), 7.45 (d, 2 H, J = 8.4 Hz), 7.59
(s, 1 H), 7.68 (d, 1 H, J = 9.2 Hz). 13C NMR (100 MHz,
CDCl3): d = 161.7, 154.3, 138.3, 138.2, 137.2, 132.3, 130.2,
Sopkova de Oliveira Santos, J.; Metzner, P.; Briere, J.-F.
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Kostyuk, A. N.; Chernega, A. N.; Rusanov, E. B.
Synlett 2011, No. 18, 2657–2662 © Thieme Stuttgart · New York

2662
K. C. Majumdar et al.
LETTER
J.-H. Synthesis 2009, 891. (c) Tang, B.-X.; Tang, D.-J.;
Tang, S.; Yu, Q.-F.; Zhang, Y.-H.; Liang, Y.; Zhong, P.; Li,
J.-H. Org. Lett. 2008, 10, 1063. (d) Tang, B.-X.; Yin, Q.;
Tang, R.-Y.; Li, J.-H. J. Org. Chem. 2008, 73, 9008.
(23) Okitsu, T.; Nakazawa, D.; Kobayashi, A.; Mizohata, M.; In,
Y.; Ishida, T.; Wada, A. Synlett 2010, 203.
129.7, 128.6, 128.4, 127.3, 123.0, 121.2, 120.1, 114.8, 91.4,
82.5, 37.6, 36.5, 12.7. HRMS (ESI+): m/z [M + H+] calcd for
C21H18N2O2: 331.1441; found: 331.1440.
(20) General Procedure for the Synthesis of Spiro
Compounds 3a–j
Procedure for the Synthesis of 1¢-Ethyl-4-iodo-5¢-
methoxy-1-methyl-3-phenyl-1¢H-spiro[pyrrole-2,6¢-
quinoline]-2¢,5 (1H,5¢H)-dione (3e)
(24) Singh, V.; Singh, V.; Batra, S. Eur. J. Org. Chem. 2008,
5446.
Using the general procedure, compound 2e (150 mg, 0.45
mmol), NaHCO3 (115 mg, 1.36 mmol), and molecular I2
(346 mg, 1.36 mmol) were added in MeCN (5 mL)
containing MeOH (1.5 equiv) and stirred at r.t. for 4.2 h.
Then the reaction mixture was quenched similarly with 10%
Na2S2O3 solution, extracted with CH2Cl2 (3 × 15 mL),
washed with H2O (2 × 10 mL) followed by brine (10 mL),
and dried over anhyd Na2SO4. The solvent was removed to
give a crude mass which was purified by column
chromatography over silica gel (230–400 mesh) using
EtOAc–PE (1:1) as eluent to furnish the desired product 3e.
Other compounds 3a–d,f–j were also prepared accordingly.
Yellow solid; mp 184–186 °C; yield: 90%. IR (KBr): 1695,
1652, 1621 cm–1. 1H NMR (400 MHz, CDCl3): d = 1.28 (t, 3
H, J = 7.2 Hz), 2.91 (s, 3 H), 3.34 (s, 3 H), 4.13–4.19 (m, 2
H), 4.28 (s, 1 H), 6.01 (d, 1 H, J = 10.0 Hz), 6.45 (d, 1 H,
J = 9.2 Hz), 6.92 (d, 1 H, J = 10.4 Hz), 7.22 (d, 1 H, J = 9.6
Hz), 7.37–7.42 (m, 5 H). 13C NMR (100 MHz, CDCl3):
d = 167.0, 161.6, 161.4, 137.2, 136.6, 132.9, 130.4, 129.7,
128.7, 128.7, 123.5, 119.7, 114.0, 78.5, 72.4, 59.9, 38.3,
28.5, 14.5. HRMS (ESI+): m/z [M + Na+] calcd for
C22H21IN2O3: 511.0489; found: 511.0441.
(25) Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2005, 127,
12230.
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(21) CCDC-826706 contains the supplementary crystallographic
data (for compound 3c) for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
(22) (a) Yu, Q.-F.; Zhang, Y.-H.; Yin, Q.; Tang, B.-X.; Tang,
R.-Y.; Zhong, P.; Li, J.-H. J. Org. Chem. 2008, 73, 3658.
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Synlett 2011, No. 18, 2657–2662 © Thieme Stuttgart · New York

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