Palladium-catalyzed sp 2 and sp 3 C-H bond activation and addition to isatin toward 3-hydroxy-2-oxindoles

Article abstract of DOI:10.1021/ol402494e

The first Pd(II)-catalyzed C-H addition to isatins by direct sp ²/sp³ C-H bond activation for the construction of 3-substituted-3-hydroxy-2-oxindoles is reported. The bidentate nitrogen ligands were found to promote this reaction. Specifically, the preliminary bioassay indicated that 3-(5-chlorobenzoxazole)-3-hydroxy-N-benzyl-2-oxindole (2w) is a new inhibitor of human kidney cancer and hepatocellular carcinoma cells. Moreover, this reaction system exhibits great functional group tolerance and requires no directing group, extra base, or additives.

Full text of DOI:10.1021/ol402494e

ORGANIC
LETTERS
Palladium-Catalyzed sp2 and sp3 CꢀH
Bond Activation and Addition to Isatin
toward 3‑Hydroxy-2-oxindoles
XXXX
Vol. XX, No. XX
000–000
Gang-Wei Wang,† An-Xi Zhou,† Jun-Jiao Wang,† Rong-Bin Hu,† and
Shang-Dong Yang*,†,‡
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou
730000, P. R. China, and State Key Laboratory for Oxo Synthesis and Selective
Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou 730000, P. R. China
yangshd@lzu.edu.cn
Received August 30, 2013
ABSTRACT
The first Pd(II)-catalyzed CꢀH addition to isatins by direct sp2/sp3 CꢀH bond activation for the construction of 3-substituted-3-hydroxy-2-
oxindoles is reported. The bidentate nitrogen ligands were found to promote this reaction. Specifically, the preliminary bioassay indicated that
3-(5-chlorobenzoxazole)-3-hydroxy-N-benzyl-2-oxindole (2w) is a new inhibitor of human kidney cancer and hepatocellular carcinoma cells.
Moreover, this reaction system exhibits great functional group tolerance and requires no directing group, extra base, or additives.
Veryrecently, nucleophilicaddition to imine or carbonyl
via transition-metal-catalyzed direct CꢀH bond activation
provides a concise and highly efficient pathway to synthe-
size amines and alcohols.1 Over the past several years,
spectacular progress has been achieved by many groups,
independently realizing direct CꢀH addition to aldehydes
and imines with different aromatic compounds by using
different transition metal catalysts such as Pd, Ir, Mn, Re,
and Rh to promote CꢀH activation at the metal center.2,3
Nevertheless, extending this protocol to nucleophilic addi-
tion to the carbonyl of ketones is still a formidable
challenge and has been rarely reported until now.4 More-
over, all these groundbreaking methods of CꢀH addition
to carbonyls generally require a directing group or need to
† Lanzhou University.
‡ Lanzhou Institute of Chemical Physics.
(1) For selected reviews on CꢀH activation, see: (a) Dyker, G.
Handbook of CꢀH Transformation: Application in Organic Synthesis;
Wiley-VCH: Weinheim, 2005. (b) Seregin, I. V.; Gevorgyan, V. Chem. Soc.
Rev. 2007, 36, 1173. (c) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc.
Chem. Res. 2009, 42, 1074. (d) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu,
J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (e) Li, C.-J. Acc. Chem. Res.
2009, 42, 335. (f) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev.
2010, 110, 624. (g) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110,
1147. (h) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res.
(3) For CꢀH addition to aldehydes, see: (a) Fukumoto, Y.; Sawada,
K.; Hagihara, M.; Chatani, N.; Murai, S. Angew. Chem., Int. Ed. 2002,
41, 2779. (b) Kuninobu, Y.; Nishina, Y.; Nakagawa, C.; Takai, K.
J. Am. Chem. Soc. 2006, 128, 12376. (c) Kuninobu, Y.; Nishina, Y.;
Takeuchi, T.; Takai, K. Angew. Chem., Int. Ed. 2007, 46, 6518. (d)
Kuninobu, Y.; Fujii, Y.; Matsuki, T.; Nishina, Y.; Takai, K. Org. Lett.
2009, 11, 2711. (e) Li, B.-J.; Shi, Z.-J. Chem. Sci. 2011, 2, 488. (f) Yang,
L.; Correia, C. A.; Li, C.-J. Adv. Synth. Catal. 2011, 353, 1269. (g) Li, Y.;
Zhang, X.-S.; Chen, K.; He, K.-H.; Pan, F.; Li, B.-J.; Shi, Z.-J. Org. Lett.
2012, 14, 636. (h) Li, Y.; Zhang, X.-S.; Zhu, Q.-L.; Shi, Z.-J. Org. Lett.
2012, 14, 4498. (i) Lian, Y.-J.; Bergman, R. G.; Ellman, J. A. Chem. Sci.
2012, 3, 3088. (j) Satyasheel, S.; Eonjeomg, P.; Jihye, P.; Kim, I. S. Org.
Lett. 2012, 14, 906. (k) Zhou, B.; Yang, Y.; Li, Y. Chem. Commun. 2012,
48, 5163. (l) Tauchert, M. E.; Incarvito, C. D.; Rheingold, A. L.;
Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2012, 134, 1482. (m)
Lian, Y.-J.; Huber, T.; Hesp, K. D.; Bergman, R. G.; Ellman, J. A.
Angew. Chem., Int. Ed. 2013, 52, 629.
€
2011, 45, 788. (i) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F.
Chem. Soc. Rev. 2011, 40, 4740. (j) Yeung, C. S.; Dong, V. M. Chem. Rev.
2011, 111, 1215. (k) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem.
Soc. Rev. 2011, 40, 5068.
(2) For CꢀH addition to imines, see: (a) Wei, C. M.; Li, C.-J. J. Am.
Chem. Soc. 2002, 124, 5638. (b) Qian, B.; Guo, S.; Shao, J.; Zhu, Q.;
Yang, L.; Xia, C.; Huang, H. M. J. Am. Chem. Soc. 2010, 132, 3650. (c)
Tsai, A. S.; Tauchert, M. E.; Bergman, R. G.; Ellman, J. A. J. Am. Chem.
Soc. 2011, 133, 1248. (d) Li, Y.; Li, B.-J.; Wang, W.-H.; Huang, W.-P.;
Zhang, X.-S.; Chen, K.; Shi, Z.-J. Angew. Chem., Int. Ed. 2011, 50, 2115.
(e) Hesp, K. D.; Bergman, R. G.; Ellman, J. A. Org. Lett. 2012, 14, 2304.
(f) Li, Y.; Zhang, X.-S.; Li, H.; Wang, W.-H.; Chen, K.; Li, B.-J.; Shi,
Z.-J. Chem. Sci. 2012, 3, 1634.
(4) Tsuchikama, K.; Hashimoto, Y.; Endo, K.; Shibata, T. Adv.
Synth. Catal. 2009, 351, 2850.
r
10.1021/ol402494e
XXXX American Chemical Society

activate the aldehydes beforehand through the addition of
nucleophilic reagents, and special additives are often re-
quired. Therefore, further development for a simple and
convenient catalytic system is highly desired. Herein we
demonstrate the first example of Pd-catalyzed intermole-
cular CꢀH addition to isatins by direct sp2/sp3 CꢀH
activation for the construction of 3-substituted-3-hydro-
xy-2-oxindoles (Scheme 1). Thereinto, 3-azole-3-hydroxy-
2-oxindoles are a kind of new structural heterocycle, which
have the potential to act as maxi-K channel openers or in
the modulation of human neuronal sodium channel iso-
form (hNav) 1.2 currents and hippocampal neuron action
potential firing.5 Additionally, in contrast to other CꢀH
additions to carbonyls that have been reported, our pro-
tocol requires no directing group, extra base, or additives.
The bidentate nitrogen ligands were found to significantly
promote this reaction.
Table 1. Nucleopilic Addition Different Isatins and Heteroarenesa
Scheme 1. Transition-Metal-Catalyzed CꢀH Addition to
Unsaturated Compounds
We began our exploration with N-methylisatin 1a and
benzoxazole as model substrates to identify suitable reac-
tion conditions because isatins are activated electrophilic
species and its two carbonyls are easier to coordinate with
transition metals leading to nucleophilic addition.6 Nota-
bly various 3-substituted-3-hydroxy-2-oxindole scaffolds
are well-known for their significant biological applications
and wide-ranging utility as drug candidates and pharma-
ceuticals.7 Furthermore, transition-metal-catalyzed direct
(5) (a) Hewawasam, P.; Meanwell, N. A.; Gribkoff, V. K.; Dworetzky,
S. I.; Boissard, C. G. Bioorg. Med. Chem. Lett. 1997, 7, 1255. (b) Chowdhury,
S.; Chafeev, M.; Liu, S.; Sun, J.; Raina, V.; Chui, R.; Young, W.; Kwan, R.;
Fu, J.; Cadieux, J. A. Bioorg. Med. Chem. Lett. 2011, 21, 3676.
(6) (a) Nair, V.; Vellalath, S.; Poonoth, M.; Mohan, R.; Suresh, E.
Org. Lett. 2006, 8, 507. (b) Zhou, F.; Liu, Y.-L.; Zhou, J. Adv. Synth.
Catal. 2010, 352, 1381. (c) Zheng, K.; Yin, C. K; Liu, X. H.; Lin, L. L.;
Feng, X. M. Angew. Chem., Int. Ed. 2011, 50, 2573. (d) Liu, L.; Zhang,
S. L.; Xue, F.; Lou, G. S.; Zhang, H. Y.; Ma, S. C.; Duan, W. H.; Wang,
W. Chem.;Eur. J. 2011, 17, 7791. (e) Sun, L.-H.; Shen, L.-T.; Ye, S.
Chem. Commun. 2011, 47, 10136. (f) Zhong, F. R.; Chen, G. Y.; Lu,
Y. X. Org. Lett. 2011, 13, 82. (g) Gutierrez, E. G.; Wong, C. J.; Sahin,
A. H.; Franz, A. K. Org. Lett. 2011, 13, 5754. (h) Niu, R.; Xiao, J.; Liang,
T.; Li, X. W. Org. Lett. 2012, 14, 676. (i) Dugal-Tessier, J.; Bryan, E. A .
O.; Schroeder, T. B. H.; Cohen, D. T.; Scheidt, K. A. Angew. Chem., Int.
Ed. 2012, 51, 4963. (j) Yao, C. S.; Xiao, Z. X.; Liu, R.; Li, T. J.; Jiao,
W. H.; Yu, C. X. Chem.;Eur. J. 2013, 19, 456.
a The reaction was carried out with Pd(OAc)2 (10 mol %), Bipy
(15 mol %), and 1aꢀ1o (0.30 mmol) in dioxane (1.0 mL) at 120 °C for
24 h under argon. b Isolated yield. c Solvent is DMF, 140 °C. d Hetero-
arenes in 10 equiv.
(7) For selected reviews, see: (a) Marti, C.; Carreira, E. M. Eur. J.
Org. Chem. 2003, 2209. (b) Lin, H.; Danishefsky, S. J. Angew. Chem., Int.
Ed. 2003, 42, 36. (c) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003,
103, 2945. (d) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed.
2007, 46, 8748. (e) Peddibhotla, S. Curr. Bioact. Compd. 2009, 5, 20.
(8) For selected reviews on CꢀH activation of azoles, see: (a) Alberico,
D.;Scott, M. E.;Lautens, M. Chem. Rev. 2007, 107, 174. (b) Ackermann, L.;
Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792. (c)
Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074.
(d) Dudnik, A. S.; Gevorgyan, V. Angew. Chem., Int. Ed. 2010, 49, 2096.
CꢀH functionalization of azoles also provided a rapid,
straightforward access to different aryl-heteroaryl motifs.8,9
Here, we wished to extend this protocol to the nucleophilic
addition to the carbonyl of N-methylisatin 1a and access
3-azole-3-hydroxy-2-oxindoles. From our endeavors,
B
Org. Lett., Vol. XX, No. XX, XXXX

the new protocol of palladium-catalyzed intermolecular
CꢀH addition to isatins by direct sp2 CꢀH activation was
built and the optimal reaction conditions were obtained by
using Pd(OAc)2 (10 mol %) as the catalyst, 2,20-bipyridine
(15mol %) astheligand in1mLofdioxanefor0.3 mmol of
1a, and 4 equiv of benzoxazole at 120 °C under an argon
atmosphere (for details, see Table S1 in Supporting In-
formation (SI)).
carcinoma cell line SMMC-7721 (Figure S1 in SI).10 The
results showed that the N-protection groups of benzyl and
the substituent group on the benzoxazole were the key to
the improvement of antitumor activity, and 2w yielded the
lowest IC50 value of 42 and 45 μM. Thus, from a diverse
array of structural modification and deprotection assays,
we were convinced that the activity of 2w would improve
and that we would locate the antihuman kidney cancer and
hepatocellular carcinoma target.
Having established optimal reaction conditions (Table S1,
entry 18), we further investigated the scope of isatins and
heteroarenes. As shown in Table 1, an investigation into
different N-protection groups revealed that methyl and
benzyl were appropriate for the reaction (2aꢀ2b), but tosyl
failed (2c). When the solvent was changed to DMF, the
N-free isatin has been converted into the desired prod-
uct 2d in 41% yield. Various substituted N-methylisatins
worked very well, and the corresponding products were
obtained in good to excellent yields regardless of the steric
hindrance and electronic properties of the substituents
(2eꢀ2o). Toourdelight, different substituted benzoxazoles
alsounderwent nucleophilicaddition smoothlyand readily
converted to the products in 76ꢀ97% yields (2pꢀ2v).
Moreover, the N-benzyl protected isatin reacted with
5-Cl-benzoxazole to afford the product 2w in 76% yield.
The reaction conditions displayed noteworthy tolerance to
the nitro group such that the desired products 2k and 2t
were afforded in 79% and 77% yields. Yet, other azoles
such as imidazole, benzothiazole, 2-phenyl-1,3,4-oxadiazole,
and their derivatives were also compatible with this trans-
formation, and the corresponding products were ob-
tained in moderate to excellent yields (2xꢀ2ad). It should
be noted that the product 2z was only afforded in a 45%
yield, presumably because the methyl group played a
negative role in CꢀH bond activation.
During the screening of solvents, we found that acetoni-
trile was activated instead of benzoxazole under initial
reaction conditions. Moreover, acetonitrile provided nu-
cleophilic addition to isatin toward the product of 3a in
67% yield. Further optimization indicated that the best
reaction condition is 10 mol % Pd(OAc)2 and 15 mol %
1,10-phenanthroline in the mixture of DMF and CH3CN
(1:1) at 100 °C. Use of these conditions improved the yield
of 3a to 87%. A survey of recent literature indicates that
activation of the sp3 CꢀH bond of acetonitrile has at-
tracted much attention, among some examples also in-
volved in nucleophilic addition to carbonyl by using Ru
and Cu complex catalysts in the presence of base or/and
special additives.11 Our protocol involves very different
activationpatterns, and itssuccess requiresneitheranextra
base nor an additive. Therefore, we decided to investigate
the scope of different substituted N-methylisatins within
our catalytic system. Indeed, our system displayed excel-
lent functional group tolerance, and the corresponding
products were obtainedingood to excellent yields (Table2,
entries 1ꢀ12). Furthermore, using our product of 3a as
starting material, we can easily synthesize (()-CPC-1 in
85% yield by reductive cyclization and methylation with
As new structural heterocycles, these acquired 3-azole-3-
hydroxy-2-oxindoles may possess antitumor potential on
the cellular level. The results of the preliminary biological
activity assay indicate that some of products do in fact
possess antitumor activity. Encouraged by this result,
we further evaluated the antitumor activity by using the
kidney cancer cell of A498 and human hepatocellular
Table 2. Nucleopilic Addition Different Isatins with CH3CNa,b
(9) For selected examples on CꢀH activation of azoles, see: (a) Do,
H. Q.; Khan, R. M. K.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 15185.
(b) Cho, S. H.; Kim, J. Y.; Lee, S. Y.; Chang, S. Angew. Chem., Int. Ed.
2009, 48, 9127. (c) Canivet, J.; Yamaguchi, J.; Ban, I.; Itami, K. Org.
Lett. 2009, 11, 1733. (d) Ackermann, L.; Althammer, A.; Fenner, S.
Angew. Chem., Int. Ed. 2009, 48, 201. (e) Xi, P. H.; Yang, F.; Qin, S.;
Zhao, D. B.; Lan, J. B.; Gao, G.; Hu, C. W.; You, J. S. J. Am. Chem. Soc.
2010, 132, 1822. (f) Zhang, L.; Cheng, J. H.; Ohishi, T.; Hou, Z. M.
Angew. Chem., Int. Ed. 2010, 49, 8670. (g) Wu, X. F.; Anbarasan, P.;
Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2010, 49, 7316. (h)
Kawano, T.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2010,
132, 6900. (i) Vechorkin, O.; Proust, V.; Hu, X. L. Angew. Chem., Int. Ed.
2010, 49, 3061. (j) Huang, J.; Chan, J.; Chen, Y.; Broths, C.; Baucom,
J. K. D.; Larsen, R. D.; Faul, M. M. J. Am. Chem. Soc. 2010, 132, 3674.
(k) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2010, 49, 2202. (l) Han, W.; Mayer, P.; Ofial, A. R. Angew. Chem.,
Int. Ed. 2011, 50, 2178. (m) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh,
T.; Miura, M. J. Am. Chem. Soc. 2011, 133, 2160. (n) Zhao, X.; Wu, G.;
Zhang, Y.; Wang, J. B. J. Am. Chem. Soc. 2011, 133, 3296. (o) Wu, G.;
Zhou, J.; Zhang, M.; Hu, P.; Su, W.-P. Chem. Commun. 2012, 48, 8964.
(p) Nishino, M.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2012, 51, 6993. (q) Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem.
Soc. 2012, 134, 169.
a The reaction was carried out with Pd(OAc)2 (10 mol %), Phen
(15 mol %), 1a (0.30 mmol), and acetonitrile (1.5 mL) with DMF
(1.5 mL) at 100 °C for 24 h under argon. b Yield of isolated product.
(10) (a) Ning, S.; Trisler, K.; Wessels, B. W.; Knox, S. J. Cancer 1997,
80, 2519. (b) Li, L.; Qi, Z.; Qian, J.; Bi, F.; Lv, J.; Xu, L.; Zhang, L.;
Chen, H.; Jia, R. Mol. Cell Biochem. 2010, 342, 125.
(11) (a) Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124,
9330. (b) You, J.; Verkade, J. G. Angew. Chem., Int. Ed. 2003, 42, 5051.
(c) Suto, Y.; Kumagai, N.; Matsunaga, S.; Kanai, M.; Shibasaki, M.
Org. Lett. 2003, 5, 3147. (d) Kumagai, N.; Matsunaga, S.; Shibasaki, M.
J. Am. Chem. Soc. 2004, 126, 13632. (e) Suto, Y.; Tsuji, R.; Kanai, M.;
Shibasaki, M. Org. Lett. 2005, 7, 3757. (f) Kumagai, N.; Matsunaga, S.;
Shibasaki, M. Tetrahedron. 2007, 63, 8598. (g) Wu, T.; Mu, X.; Liu, G. S.
Angew. Chem., Int. Ed. 2011, 50, 12578.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 2. Deuterium-Labeled Nucleophilic Addition to Isatin
Scheme 3. Proposed Mechanisms of Pd(OAc)2-Catalyzed
Nucleophilic Addition to Isatin by sp2 and sp3 CꢀH Activation
NaCNBH3 and CH3I under the basic conditions respec-
tively (Scheme S1 in SI).
To gain insight into the reaction mechanism, we carried
out kinetic isotope effect (KIE) experiments with the equal
deuterium-labeled substrates acetonitrile-d3 and acetoni-
trile. The kinetic isotope effects were observed with a
kH/kD value of 2.86 (Scheme 2a). Similar results were
also observed in the reaction of equal deuterium-labeled
5-methylbenzoxazole-d and 5-methylbenzoxazole and
kH/kD = 2.48 (Scheme 2b).12 These findings indicate that
CꢀH bondcleavagemay serve asthe rate-determining step
in this transformation.
To deepen our understanding of the catalytic cycle of the
nucleophilic addition to isatin by sp2 and sp3 CꢀH activa-
tion, we performed mass spectrometry experiments on the
standard catalytic reaction. We were delighted to observe
both signals at m/z 381 and 761; these signals are related
to the masses of intermediates A (the complex of 2, 20-
bipyridine and Pd(OAc)2) and 2A (Cycle A, Scheme 3).
Unfortunately, mass spectrometry failed to reveal similar
signals in the sp3 CꢀH activation procedures. On the basis
of observed experimental results in this pioneering report,
we propose a plausible mechanistic pathway and outline
in Scheme 3. In cycle A, Pd(OAc)2 first coordinates with
2,20-bipyridine to form the activated palladium complex
A. Second, A reacts with benzoxazole by CꢀH bond
activation to produce a dimer of 2A. After this species
coordinates with the carbonyls of isatin and leads the
benzoxazole to occur, the migratory insertion to carbonyl
to form the complex 2B,13 which then undergoes proton
dissociations to afford the product 2a, and the palladium
catalyst would reinitiate the catalytic cycle synchronously.
The catalytic cycle of the sp3 CꢀH bond activation (Cycle B)
is the same as sp2 CꢀH bond activation, with the sole dif-
ference in the change of the ligand to 1,10-phenanthroline.
In conclusion, we have developed the first example of
palladium-catalyzed CꢀH activation for a series of azoles
and acetonitrile and subsequent nucleophilic addition to
substituted isatins to construct 3-substituted-3-hydroxy-2-
oxindoles. The bidentate nitrogen ligands play a crucial
role in the transformation and significantly promote this
reaction. Further bioassays and asymmetric nucleophilic
additions to isatin are presently underway and will be
reported in the future.
Acknowledgment. We are grateful for the NSFC (Nos.
21072079 and 21272100) and Program for New Century
Excellent Talents in University (NCET-11-0215) financial
support. Wethank S. F. Reichard, MA at the University of
Chicago for editing the manuscript.
(12) (a) Cho, S. H.; Kim, J. Y.; Lee, S. Y.; Chang, S. Angew. Chem.,
Int. Ed. 2009, 48, 9127. (b) Guo, S. M.; Qian, B.; Xie, Y. J.; Xia, C. G.;
Huang, H. M. Org. Lett. 2011, 13, 522. (c) Kim, S. H.; Yooh, J.; Chang,
S. Org. Lett. 2011, 13, 1474. (d) Tang, D.-T. D.; Collins, K. D.; Glorius,
F. J. Am. Chem. Soc. 2013, 135, 7450.
(13) (a) Chua, P. S.; Roberts, N. K.; Bosnich, B.; Okrasinski, S. J.;
Halpern, J. Chem. Commun. 1981, 17, 1278. (b) Halpern, J. Science 1982,
217, 401. (c) Landis, C. R.; Halpern, J. J. Am. Chem. Soc. 1987, 109,
1746. (d) Toullec, P. Y.; Jagt, R. B. C.; Vries, J. G. D.; Feringa, B. L.;
Minnaard, A. J. Org. Lett. 2006, 8, 2715. (e) Chen, G.; Wang, Y.; Gao,
S.; He, H.-P.; Li, S.-L.; Zhang, J.-X.; Ding, J.; Hao, X.-J. J. Heterocycl.
Chem. 2009, 46, 217.
Supporting Information Available. Experimental pro-
cedures and full spectroscopic data for all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX