Synthesis of polyfluoroalkyl cyclobutenes from 3-aza-1,5-enynes via an aza-Claisen rearrangement/cyclization cascade

Article abstract of DOI:10.1021/ol4020738

A facile synthetic route to access polyfluoroalkyl functionalized cyclobutenes bearing an exo cyclic double bond from 3-aza-1,5-enynes is reported. The reaction proceeds via a thermal aza-Claisen rearrangement to give an allene-imine intermediate; subsequent cyclization affords the cyclobutene core. The kinetics of the transformation of starting material and the intermediate was studied by ¹H NMR spectroscopy, where a consecutive reaction was revealed.

Full text of DOI:10.1021/ol4020738

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Synthesis of Polyfluoroalkyl
Cyclobutenes from 3‑Aza-1,5-enynes
via an Aza-Claisen Rearrangement/
Cyclization Cascade
Xiaoyi Xin, Dongping Wang, Fan Wu, Chunxiang Wang, Haolong Wang, Xincheng Li,
and Boshun Wan*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences,
457 Zhongshan Road, Dalian 116023, China
bswan@dicp.ac.cn
Received July 23, 2013
ABSTRACT
A facile synthetic route to access polyfluoroalkyl functionalized cyclobutenes bearing an exo cyclic double bond from 3-aza-1,5-enynes is
reported. The reaction proceeds via a thermal aza-Claisen rearrangement to give an allene-imine intermediate; subsequent cyclization affords the
cyclobutene core. The kinetics of the transformation of starting material and the intermediate was studied by 1H NMR spectroscopy, where a
consecutive reaction was revealed.
Cyclobutenes are fascinating small-ring compounds
found in many natural products and biologically active
compounds,1 and they are also versatile building blocks for
the synthesis of a wide range of organic compounds due to
the inherent ring strain.2Accessing cyclobutenes that are not
easily synthesized by conventional methods remains a topic
of considerable interest. The synthetic procedures for the
construction of a cyclobutene ring are divided into four
major categories: (1) [2 þ 2] cycloaddition of alkynes with
alkenes or allenes (Scheme 1a),3 which represents the most
straightforward method to access cyclobutene structures; (2)
ring expansions of cyclopropane derivatives (Scheme 1b);4
(3) cycloisomerization reactions of enynes (Scheme 1c);5 and
(4) electrocyclization of vinylallenes (Scheme 1d).6 Besides
these major methodologies, other sporadic diverse strategies
have also been developed.7 Here we report an approach for
the synthesis of polyfluoroalkyl substituted cyclobutenes
from 3-aza-1,5-enynes via an aza-Claisen rearrangement/
cyclization process (Scheme 1e, left). This transformation
(3) Selected examples on synthesis of cyclobutenes via [2 þ 2] cycloaddi-
tion: (a) Sakai, K.; Kochi, T.; Kakiuchi, F. Org. Lett. 2013, 15, 1024. (b)
Nishimura, A.; Ohashi, M.; Ogoshi, S. J. Am. Chem. Soc. 2012, 134, 15692.
(c) Smith, D. L.; Chidipudi, S. R.; Goundry, W. R.; Lam, H. W. Org. Lett.
2012, 14, 4934. (d)Lu, B. L.;Shi, M. Angew. Chem., Int. Ed. 2011, 50, 12027.
(e) Schotes, C.; Mezzetti, A. Angew. Chem., Int. Ed. 2011, 50, 3072. (f)
ꢀ
Lopez-Carrillo, V.; Echavarren, A. M. J. Am. Chem. Soc. 2010, 132, 9292.
(g)Li, H.;Hsung, R. P.;DeKorver, K. A.;Wei, Y.Org. Lett. 2010, 12, 3780.
(h) Hilt, G.; Paul, A.; Treutwein, J. Org. Lett. 2010, 12, 1536. (i) Fan, B.-M.;
Li, X.-J.; Peng, F.-Z.; Zhang, H.-B.; Chan, A. S. C.; Shao, Z.-H. Org. Lett.
2010, 12, 304. (j) Ishihara, K.; Fushimi, M. J. Am. Chem. Soc. 2008, 130,
7532. (k) Treutwein, J.; Hilt, G. Angew. Chem., Int. Ed. 2008, 47, 6811. (l)
Inanaga, K.; Takasu, K.; Ihara, M. J. Am. Chem. Soc. 2005, 127, 3668. (m)
Liu, Y.; Liu, M.; Song, Z. J. Am. Chem. Soc. 2005, 127, 3662. (n) Shibata,
T.; Takami, K.; Kawachi, A. Org. Lett. 2006, 8, 1343. (o) Sweis, R. F.;
Schramm, M. P.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 7442. (p)
Shen, Q.; Hammond, G. B. J. Am. Chem. Soc. 2002, 124, 6534. (q) Huang,
D.-J.; Rayabarapu, D. K.; Li, L.-P.; Sambaiah, T.; Cheng, C.-H. Chem.;
Eur. J. 2000, 6, 3706. (r) Yi, C. S.; Lee, D. W.; Chen, Y. Organometallics
1999, 18, 2043. (s) Narasaka, K.; Hayashi, Y.; Shimadzu, H.; Niihata, S.
J. Am. Chem. Soc. 1992, 114, 8869. (t) Faron, K. L.; Wulff, W. D. J. Am.
Chem. Soc. 1988, 110, 8727. (u) Snider, B. B.; Rodini, D. J.; Cionn, R. S. E.;
Sealfon, S. J. Am. Chem. Soc. 1979, 101, 5283.
(1) For a review on four-membered ring containing natural products,
see: Dembitsky, V. M. J. Nat. Med. 2008, 62, 1.
(2) (a) Namyslo, J. C.; Kaufmann, D. E. Chem. Rev. 2003, 103, 1485.
(b) Lee-Ruff, E.; Mladenova, G. Chem. Rev. 2003, 103, 1449. (c) Gauvry,
N.; Lescop, C.; Huet, F. Eur. J. Org. Chem. 2006, 5207.
r
10.1021/ol4020738
XXXX American Chemical Society

allows the preparation of fully substituted cyclobutene deri-
vatives bearing a new pattern of substituents.
(see infra). As a result, an enlightening reaction pathway was
revealed and amazing carbocycles were obtained. Experi-
mentally, 3-aza-1,5-enyne 1a (R1 = R2 = Ph, RF = CF3)
was used as a starting substrate (Table 1). When 1a was
heated in toluene in the absence of any transition metal or
additive, cyclobutene 2a was obtained in 36% isolated yield.
The structures of 2a and its p-Cl-substituted derivative 2r
were unambiguously confirmed by X-ray crystallography
(see the Supporting Information). This highly substituted
cyclobutene product with a quaternary carbon center10 is
functionalized with a polyfluoroalkyl group, a sulfamide
group,11 and an exo cyclic double bond.
The 3-aza-1,5-enyne framwork is versatile for their
selectivities and could be switched by simple changes in
the reaction conditions or structure of starting materials.8
It is known that introduction of the trifluoromethyl (CF3)
group (or other perfluoroalkyl/polyfluoroalkyl groups)
into organic molecules can significantly change their phy-
sical, chemical, and biological properties.9 In our previous
work, diester-substituted 3-aza-1,5-enynes were success-
fully transformed into functionalized pyrroles via sulfonyl
group migration (Scheme 1e, right).8b We envisioned that
replacing one of the two ester groups of this framework with
polyfluoroalkyl groups may switch the reaction selectivity
Scheme 1. Summary for Approaches
(4) Selected example on ring expansions of cyclopropane derivatives
to cyclobutenes and cyclobutanes: (a) Li, C.-W.; Pati, K.; Lin, G.-Y.;
Abu Sohel, S. M.; Hung, H.-H.; Liu, R.-S. Angew. Chem., Int. Ed. 2010,
49, 9891. (b) Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2009, 131,
ꢀ
ꢀ
9178. (c) Barluenga, J.; Riesgo, L.; Lopez, L. A.; Rubio, E.; Tomas, M.
Angew. Chem., Int. Ed. 2009, 48, 7569. (d) Liu, L.; Zhang, J. L. Angew.
€
Chem., Int. Ed. 2009, 48, 6093. (e) Masarwa, A.; Furstner, A.; Marek, I.
Chem. Commun. 2009, 5760. (f) Trost, B. M.; Xie, J.; Maulide, N. J. Am.
Chem. Soc. 2008, 130, 17258. (g) Xu, H. D.; Zhang, W.; Shu, D. X.;
Werness, J. B.; Tang, W. P. Angew. Chem., Int. Ed. 2008, 47, 8933. (h)
Tian, G.-Q.; Yuan, Z.-L.; Zhu, Z.-B.; Shi, M. Chem. Commun. 2008,
2668. (i) Shi, M.; Liu, L.-P.; Tang, J. J. Am. Chem. Soc. 2006, 128, 7430.
€
€
(j) Furstner, A.; Aussa, C. J. Am. Chem. Soc. 2006, 128, 6306. (k)
Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
9708. (l) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J.
J. Am. Chem. Soc. 1977, 99, 3088.
(5) Cycloisomerization reactions of enynes to cyclobutenes and
^
cyclobutanes: for a review, see: (a) Michelet, V.; Toullec, P. Y.; Genet,
J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268. Selected reports: (b)
ꢀ
ꢀ
ꢀ
Escribano-Cuesta, A.; Perez-Galan, P.; Herrero-Gomez, E.; Sekine,
M.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. Org. Biomol.
Chem. 2012, 10, 6105. (c) Takachi, M.; Kita, Y.; Tobisu, M.; Fukumoto,
Y.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 8717. (d) Xia, J.-B.; Liu,
W.-B.; Wang, T.-M.; You, S.-L. Chem.;Eur. J. 2010, 16, 6442. (e) Lee,
Y. T.; Kang, Y. K.; Chung, Y. K. J. Org. Chem. 2009, 74, 7922. (f)
Couty, S.; Meyer, C.; Cossy, J. Angew. Chem., Int. Ed. 2006, 45, 6726. (g)
Matsuda, T.; Kadowaki, S.; Goya, T.; Murakami, M. Synlett 2006, 575.
€
(h) Furstner, A.; Davies, P. W.; Gress, T. J. Am. Chem. Soc. 2005, 127,
ꢀ
8244. (i) Nieto-Oberhuber, C.; Lopez, S.; Echavarren, A. M. J. Am.
Chem. Soc. 2005, 127, 6178. (j) Marion, F.; Coulomb, J.; Courillon, C.;
Fensterbank, L.; Malacria, M. Org. Lett. 2004, 6, 1509.
The solvent effect was next investigated. The reaction
carried out in toluene at 100 °C provided a 53% NMR
yield of 2a (Table 1, entry 1). The use of DMF, CH2Cl2,
MeCN, or acetone as a solvent did not improve the
product yield (Table 1, entries 2ꢀ5). Utilization of benzene
or MeOH slightly improved the yield (Table 1, entries 6
and 7). When 1,2-dichloroethane or THF was employed,
the yield of 2a was further improved (Table 1, entries 8 and 9).
The highest yield of 2a (95% NMR yield) was achieved using
1,4-dioxane as a solvent (Table 1, entry 10). Reactions
performed at a lower temperature gave a diminished yield
(Table 1, entry 11). Therefore, 1,4-dioxane and 100 °C were
chosen as the optimal reaction conditions.
(6) Selected reports on electrocyclization of vinylallenes: (a) Reisinger,
C. M.; Rivera-Fuentes, P.; Lampart, S.; Schweizer, W. B.; Diederich, F.
Chem.;Eur. J. 2011, 17, 12906. (b) Delas, C.; Urabe, H.; Sato, F. J. Am.
Chem. Soc. 2001, 123, 7937. (c) Murakami, M.; Amii, H.; Itami, K.; Ito, Y.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1476. (d) Arnold, B. R.; Brown,
C. E.; Lusztyk, J. J. Am. Chem. Soc. 1993, 115, 1576. (e) Rey, J. G.;
Rodrıguez, J.; de Lera, A. R. Tetrahedron Lett. 1993, 34, 6293. (f) Pasto,
D. J.; Kong, W. J. Org. Chem. 1989, 54, 4028. (g) Javaheripour, H.;
Neckers, D. C. J. Org. Chem. 1977, 42, 1844. (h) Pirkle, W. H.; McKendry,
L. H. J. Am. Chem. Soc. 1969, 91, 1179. (i) Corey, E. J.; Streith, J. J. Am.
Chem. Soc. 1964, 86, 950.
(7) (a) Yao, L.-F.; Shi, M. Chem.;Eur. J. 2009, 15, 3875. (b)
Debleds, O.; Campagne, J.-M. J. Am. Chem. Soc. 2008, 130, 1562. (c)
Shi, M.; Yao, L.-F. Chem.;Eur. J. 2008, 14, 8725. (d) Yao, L.-F.; Shi,
M. Org. Lett. 2007, 9, 5187. (e) Averina, E. B.; Karimov, R. R.;
Sedenkova, K. N.; Grishin, Y. K.; Kuznetzova, T. S.; Zefirov, N. S.
Tetrahedron 2006, 62, 8814. (f) Paih, J. L.; Derien, S.; Bruneau, C.;
Demerseman, B.; Toupet, L.; Dixneuf, P. H. Angew. Chem., Int. Ed.
2001, 40, 2912. (g) Yavari, I.; Asghari, S. Tetrahedron 1999, 55, 11853.
Following the optimization of the reaction conditions,
the scope and limitations of this reaction were explored.
Aryl R1 groups bearing different substituents, including an
electron-neutral (Table 2, entry 1), -donating (Table 2,
ꢀ
(h) Barbero, A.; Cuadrado, P.; Garcıa, C.; Rincon, J. A.; Pulido, F. J.
J. Org. Chem. 1998, 63, 7531.
(8) (a) Saito, A.; Konishi, T.; Hanzawa, Y. Org. Lett. 2010, 12, 372.
(b) Xin, X. Y.; Wang, D. P.; Li, X. C.; Wan, B. S. Angew. Chem., Int. Ed.
2012, 51, 1693. (c) Xin, X. Y.; Wang, D. P.; Wu, F.; Li, X. C.; Wan, B. S.
J. Org. Chem. 2013, 78, 4065.
(9) (a) Tomaschenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111,
4475. (b) Purser, S.; Moore, P. R.; Swallowb, S.; Gouverneur, V. Chem.
(10) (a) Bella, M.; Gasperi, T. Synthesis 2009, 1583. (b) Cozzi, P. G.;
ꢀ
Hilgraf, R.; Zimmermann, N. Eur. J. Org. Chem. 2007, 5969. (c) Ramon,
D. J.; Yus, M. Curr. Org. Chem. 2004, 8, 149.
€
Soc. Rev. 2008, 37, 320. (c) Muller, K.; Faeh, C.; Diederich, F. Science
(11) (a) Reitz, A. B.; Smith, G. R.; Parker, M. H. Expert Opin. Ther.
Patents 2009, 19, 1449. (b) Winum, J.-Y.; Scozzafava, A.; Montero,
J.-L.; Supuran, C. T. Med. Res. Rev. 2006, 26, 767.
2007, 317, 1881. (d) Kirsch, P. Modern Fluoroorganic Chemistry: Synth-
esis, Reactivity, Applications; Wiley-VCH: Weinhiem, Germany, 2004.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 1. Optimization of Reaction Conditionsa
Table 2. Scope of the Synthesis of Cyclobutenesa
entry
solvent
toluene
temp (°C)
yield (%)b
entry
1
R1
R2
RF
2, yieldb
1
100
100
100
100
100
100
100
100
100
100
80
53 (36)c
57
1
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF2Cl
C2F5
2a, 91%
2b, 76%
2c, 91%
2d, 62%
2e,c 54%
2f, 81%
2g, 85%
2h, 87%
2i, 62%
2j, 83%
2k, 44%
2
DMF
2
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-MeOC6H4
2-CF3C6H4
2-FC6H4
4-FC6H4
2-ClC6H4
2-BrC6H4
1-naphthyl
iPr
3
CH2Cl2
47
3
4
MeCN
50
4
5
acetone
51
5
6
benzene
MeOH
68
6
7
77
7
1g
1h
1i
8
1,2-dichloroethane
THF
85
8
9
88
9
10
11
1,4-dioxane
1,4-dioxane
95
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1j
91
1k
1l
d
ꢀ
a Conditions: 1a (0.1 mmol) in the corresponding solvent (0.5 mL)
was stirred under argon protection for 24 h. b NMR yield using CH2Br2
as an internal standard. c The number in the parentheses refers to the
isolated yield of 2a. Conditions: 1a (0.5 mmol) in toluene (2.5 mL) was
stirred at 80 °C for 10 h under an argon atmosphere.
1m
1n
1o
1p
1q
1r
1s
1t
Ph
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
nPr
2m, 59%
2n, 60%
2o, 76%
2p, 48%
2q, 93%
2r, 82%
2s, 92%
2t, 88%
2u, 78%
2v, 73%
2w, 82%
Ph
Ph
Ph
Ph
Ph
entries 2ꢀ5), -withdrawing (Table 2, entry 6), and halogen
group (Table 2, entries 7ꢀ10) were well tolerated, and the
desired products were isolated in moderate to high yields
(54ꢀ91%). Interestingly, a mixture of Z/E isomers was
obtained in 54% yield when 2-MeO-substituted 3-aza-1,5-
enyne 1ewas studied (Table 2, entry 5). A fused aryl R1 was
also suitable for this process, although a lower yield was
obtained (44%, Table 2, entry 11). However, an alkyl R1
substituent was not tolerated (Table 2, entry 12). Thus
when isopropyl-substituted 1l was allowed to react under
the standard conditions, the desired reaction did not take
place. Both aryl- and alkyl-substituted alkyne (R2) units in
the substrate were well tolerated (Table 2, entries 13ꢀ21).
The polyfluoroalkyl group (RF) was also investigated.
CF2Cl- and C2F5-substituted 1v and 1w were also good
substrates (Table 2, entries 22 and 23). In contrast, under
the same conditions, a diester-substituted substrate (the
CF3 group of 1a was changed to CO2Me) afforded 1,2-
dihydropyridine8c as the only product (95% NMR yield).
A deuterium-labeling experiment was performed to ex-
plore the reaction mechanism (Scheme 2). A substrate
deuterated at the C(4)-position (1a-D, 100 atom % of D)
was subjected to the standard reaction conditions, and the
deuterium was incorporated in the olefinic position of the
product 2a-D without any scrambling, indicating that
CꢀH cleavage is not likely involved at this position.
To gain further insight into the reaction mechanism, a
reaction intermediate was studied. When the reaction was
carried out at 80 °C, the allene-imine intermediate 3a was
observed in 63% NMR yield as a major product, together
Ph
Ph
nBu
1u
1v
1w
Ph
Cy
Ph
Ph
Ph
Ph
a Reaction conditions: 1 (0.2 mmol) in 1,4-dioxane (1 mL) was stirred
at 100 °C for 24 h under argon protection. b Isolated yields. c Z/E = 1:1
mixture, in 0.4 mmol scale. d No reaction.
Scheme 2. Deuterium-Labeling Experiment
with product 2a (14% NMR yield, Scheme 3). The allene-
imine intermediate 3a resulted from aza-Claisen rearrange-
ment,12 and the hydrolysis of the imine moiety during the
course of chromatographic purification hampered its isola-
tion. The crude mixture of 3a and 2a was allowed to react in
1,4-dioxane at 100 °C for an additional 24 h, and cyclobutene
2a was generated in 60% NMR yield, indicating that allene-
imine 3a is a reaction intermediate. To further confirm the
intermediacy of 3a, water was added to the system after 1a
was stirred in 1,4-dioxane at 80 °C for 3 h, and the resulting
ꢀ
(13) Reviews on Claisen rearrangement: (a) Tejedor, D.; Mendez-
(12) Reviews on aza-Claisen rearrangement: (a) Majumdar, K. C.;
Bhattacharyya, T.; Chattopadhyay, B.; Sinha, B. Synthesis 2009, 2117.
(b) Nubbemeyer, U. Synthesis 2003, 961. (c) Nubbemeyer, U. Top. Curr.
Chem. 2005, 244, 149.
Abt, G.; Cotos, L.; Garcıa-Tellado, F. Chem. Soc. Rev. 2013, 42, 458. (b)
Majumdar, K. C.; Alam, S.; Chattopadhyay, B. Tetrahedron 2008, 64,
597. (c) Hiersemann, M.; Abraham, L. Eur. J. Org. Chem. 2002, 1461. (d)
Ito, H.; Taguchi, T. Chem. Soc. Rev. 1999, 28, 43.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 3. Mechanistic Studies
Scheme 4. Proposed Mechanism
k1 = 0.57( 0.01hꢀ1, k2 = 0.26( 0.02hꢀ1 (based on 3a) or
0.18 ( 0.01 hꢀ1 (based on 2a). Thus the transformation of
3a to 2a was the rate-determining step.
A reaction mechanism was proposed based on the above
results (Scheme 4). Aza-Claisen rearrangement of 3-aza-
1,5-enyne 1 leads to allene-imine 3. A polyfluoroalkyl
group is more electronegative than an ester group; there-
fore, the polyfluoroalkyl substituted allene-imine inter-
mediate probably tends to isomerize to allene-enamine
instead of direct cyclization.8b Isomerization of the imine
moiety of 3 to allene-enamine 5 and subsequent 4π-
electrocyclization6 give cyclobutene 2.
In summary, we have realized an efficient route to access
polyfluoroalkyl functionalized cyclobutenes from 3-aza-
1,5-enynes. The reaction proceeded through an aza-Clai-
sen rearrangement/cyclization process. The observed aza-
Claisen rearrangement intermediate allene-imine and the
kinetics of the transformation of the consecutive reaction
support the proposed reaction mechanism. The use of
easily available 3-aza-1,5-enynes as starting materials for
generation of reactive intermediates emphasizes the versa-
tile reactivity and synthetic value of this framework. The
multifunctionalized cyclobutenes bearing an exo cyclic
double bond are advantageous for further derivatization.
Further studies on the scope, mechanism, and synthetic
applications of this reaction are underway.
Figure 1. Kinetic profile of starting material 1a, intermediate 3a,
and product 2a.
mixture was allowed to react at rt for 4 h. As expected, allene-
enol 4a, which is the hydrolyzed product of 3a, was obtained
in 44% yield (Scheme 3). Moreover, 4a is a corresponding
product of the Claisen rearrangement of propargyl vinyl
ethers.13 Therefore, this transformation provided an alter-
native approach to allene-enols.
Acknowledgment. We thank the National Natural
Science Foundation of China (21172218) for financial
support. We thank Prof. Xingwei Li (Dalian Institute of
Chemical Physics, Chinese Academy of Sciences) for help-
ful discussions on experiment details and proofreading this
manuscript. We also thank Prof. Hongjun Fan (Dalian
Institute of Chemical Physics, Chinese Academy of
Sciences) for the help in calculating rate constants.
To gain more reaction information, we monitored the
reaction of 1a using 1H NMR spectroscopy in 1,4-dioxane-
d8 at 80 °C (Figure 1). In the first 0.5 h, the amount of
reactant 1a decreased sharply, and ∼90% of 1a was
consumed in ∼4 h. The formation and consumption of
3a took place simultaneously, and after ∼2 h, the concen-
tration of 3a reached its maximum amount. In the whole
process, the amount of 2a increased steadily, and the
product formed in ∼60% yield after 8 h.
Supporting Information Available. Experimental pro-
cedures; characterization data for new compounds; co-
pies of spectra; and X-ray crystallographic data (CIF) for
1a, 2a, and 2r. This material is available free of charge via
the Internet at http://pubs.acs.org.
The kinetic profile follows a two-step irreversible con-
secutive process (Figure 1). The calculated first-order rate
constants using the data in the first 6 h were as follows:
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX