A novel and metal-free approach towards α-ketoamides using a TBHP/I2-promoted tandem reaction of amines with β-diketones via C-C bond cleavage

Article abstract of DOI:10.1039/c2ra22116k

A novel approach towards the synthesis of α-ketoamides using a TBHP/I₂-promoted tandem reaction of amines with β-diketones via C-C bond cleavage has been developed. This one-pot reaction proceeded well under metal-free conditions and generated

Full text of DOI:10.1039/c2ra22116k

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A novel and metalꢀfree approach towards αꢀketoamides
using TBHP/I2ꢀpromoted tandem reaction of amines with
βꢀdiketones via C–C bond cleavage
Xiaobin Zhang,a Min Wang,a Yicheng Zhang,a and Lei Wang*a,b
Abstract ： A metalꢀfree TBHP/I2ꢀpromoted synthesis of αꢀketoamides
through tandem reaction of amines with βꢀdiketones via C–C cleavage has
been developed.
a
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui
235000, P R China; Eꢀmail: leiwang@chnu.edu.cn
Tel.: +86ꢀ561ꢀ380ꢀ2069; fax: +86ꢀ561ꢀ309ꢀ0518
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032,
P R China
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Cite this: DOI: 10.1039/c0xx00000x
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ARTICLE
A novel and metalꢀfree approach towards αꢀketoamides using TBHP/I2ꢀ
promoted tandem reaction of amines with βꢀdiketones via C–C bond
cleavage†
Xiaobin Zhang,a Min Wang,a Yicheng Zhang,a and Lei Wang*a,b
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
A novel approach towards the synthesis of αꢀketoamides using TBHP/I2ꢀpromoted tandem reaction of amines with βꢀ
diketones via C–C bond cleavage has been developed. This oneꢀpot reactions proceeded well under metalꢀfree
conditions and generated the corresponding products in good yields.
10 C−C bond activation, similar to the recent emergence of C–H 50 reagents.13 However, it is either short of effective procedure to
bond activation in synthetic chemistry, has attracted much
attention, not only because of its scientific interest, but also its
potential utility in organic synthesis. It can change the
conventional chemical transformations so that chemists approach
prepare starting materials, or impractical because of the required
toxic or expensive reagents. The recently developed oxidative
coupling reactions offer particularly appealing approaches to αꢀ
ketoamides, such as Pdꢀ and Cuꢀcatalyzed aerobic oxidative
15 the desired molecules by allowing nontraditional retrosynthetic 55 cleavage
of
preformed
αꢀarylamino
amides,14
and
disconnections and reorganizing the existing molecular
skeletons.1 However, it is a challenging field owing to relatively
high bond strengths and directional σ orbitals of the carbonꢀ
carbon linkages.2 To overcome these drawbacks, various
amidation/diketonization of terminal alkynes,15 Cuꢀcatalyzed
oxidative coupling of aryl acetaldehydes with anilines16 and aryl
methyl ketones with amines.17 Obviously, these processes need
transition metals to catalyze the reactions. Metalꢀfree organic
20 processes involving different modes to activate the relatively inert 60 reactions can overcome the drawbacks of the expensive,
bonds have been developed, such as employing the strained ring
systems,3 forming a stable complex by chelation,4 or other
means.5 In general, these processes were mainly mediated by
transition metals, for example, Pd,3d,3f,5b,5d Rh,3a,4c,5g Ru,3e,4d Cu5a
poisonous, and airꢀsensitive properties of metals or
organometallics,18 and metalꢀfree oxidation is one of the best
choices in the pharmaceutical industry due to the avoidance of
metal contamination.19 The metalꢀfree aerobic oxidative reactions,
25 and Ni5c etc. Compared with the selective C−C cleavage of 65 such as formal oxidative coupling of aliphatic aldehydes with
tertiary,6 and secondary alcohols,7 epoxides8 and others,9 the
selective C−C cleavage of βꢀdiketones was less reported,
although they have been used as the important substrates
involved in organic reactions.10 Most recently, an elegant method
isocyanides,20 and oxidative amidation of 2,2ꢀdibromoꢀ1ꢀaryl
with heteroaryl ethanones21 have proved to be the particularly
appealing approaches to αꢀketoamides. Most recently, a TBHP
(tertꢀbutyl hydroperoxide)/I2ꢀpromoted tandem oxidative
30 on the CuIꢀcatalyzed arylation/C−C bond activation of βꢀ 70 coupling of acetophenones with amines for the synthesis of αꢀ
diketones with aryl halides for the preparation of αꢀarylketones
ketoamides was developed by us.22
To the best of our knowledge, there is no report on the metalꢀ
free synthesis of αꢀketoamides from βꢀdiketones via C−C bond
cleavage so far. In our ongoing interest in the construction of Nꢀ
was developed by Lei et al.11
αꢀKetoamides are prevalent structural motifs that are
frequently found in natural products, pharmaceuticals and
35 synthetic intermediates.12 Accordingly, the synthesis of αꢀ 75 containing compounds and metalꢀfree organic reactions,23 we
ketoamides is a great valuable project and a number of
methodologies have been developed. The classical method for the
synthesis of αꢀketoamides is based on amidation of αꢀketo acids
in the presence of dicyclohexylcarbodiimide or other activating
report herein a novel TBHP/I2ꢀpromoted tandem reaction of
amines with βꢀdiketones via C−C bond cleavage, which
illustrated a practical straightforward route to a variety of αꢀ
ketoamides under metalꢀfree conditions from simple and readily
80 available starting materials (Scheme 1).
40
a Department of Chemistry, Huaibei Normal University, Huaibei, Anhui
235000, P R China; Eꢀmail: leiwang@chnu.edu.cn
Tel.: +86ꢀ561ꢀ380ꢀ2069; fax: +86ꢀ561ꢀ309ꢀ0518
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of
45 Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P
R China
†
Electronic Supplementary Information (ESI) available: Detailed
1
procedures, analytical data, H and 13C NMR spectra of all products see
DOI: 10.1039/b000000x/
Scheme 1 The tandem oxidative coupling of βꢀdiketones with
amines.
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Initially, 1,3ꢀdiphenylpropaneꢀ1,3ꢀdione (1a) and morpholine
Having the optimized reaction conditions in our hand, the
substrate generality was examined and the results were presented
in Table 2. A wide range of 1,3ꢀdiarylꢀpropanꢀ1,3ꢀdiones reacted
with morpholine (2a), and moderate to good yields of αꢀ
(2a) were chosen as model substrates to examine a variety of
reaction condition parameters and the results were summarized in
Table 1. When the model reaction was performed in the presence
5
of TBHP/I2, 51% yield of the desired product 3a was isolated 35 ketoamides 3a−i were obtained (Table 2, entries 1−9). The results
under solventꢀfree conditions at 80 oC (Table 1, entry 1). A
number of oxidants were examined under solventꢀless conditions
and TBHP was found to be the most effective. The use of diꢀtertꢀ
butyl peroxide (DTBP), cumyl hydroperoxide, tertꢀbutyl
indicated that the reaction is relatively sensitive to the electronic
characteristics of substituent groups on the aromatic rings.
Generally, 1,3ꢀdiarylꢀpropaneꢀ1,3ꢀdiones bearing electronꢀ
withdrawing groups (CN, Cl, Br and I) on the benzene rings
10 perbenzoate (TBPB), K2S2O8, Ag2O, and O2 showed relatively 40 enhanced the reactions and resulted in the higher yields of the
lower efficiency, and only 13–42% yields of 3a were obtained
(Table 1, entries 2–7). PhI(OAc)2 and PhIO were inactive in the
reaction (Table 1, entries 8 and 9). When TBN (tertꢀbutyl nitrite)
was used instead of TBHP, however, no 3a was observed (Table
products than that of the ones bearing electronꢀdonating groups
(CH3O, CH3) (Table 2, entries 5−9 vs 2−4). In addition, the orthoꢀ
position effect was obvious in the reaction (Table 2, entry 3). It
should be noted that halides, such as Cl, Br and I attached to the
15 1, entry 10). Subsequently, the effect of solvent on the model 45 benzene rings were compatible with the reaction conditions and
reaction was investigated and the screening of a range of solvents
showed that CH3CO2C2H5 was the most suitable media for this
transformation, giving 3a in 75% yield (Table 1, entry 11). The
reactions carried out in CH3CN, dioxane, 1,2ꢀdichloroethane
afforded halogenated αꢀketoamides, which were useful synthetic
intermediates for the further transformation via transitionꢀmetalꢀ
catalyzed crossꢀcoupling reactions. When we subjected 1,3ꢀ
di(aliphatic)ꢀ1,3ꢀdiketones, such as pentaneꢀ2,4ꢀdione to the
20 (DCE), DMF, toluene, and THF, provided 3a in lower yields 50 reaction with 2a, unfortunately, no desired αꢀketoamide product
(Table 1, entries 12−17). It should be noted that no 3a was
detected when the model reaction was performed in the absence
of TBHP or I2 (Table 1, entries 18 and 19). When nꢀBu4NI was
used instead of I2, 46% yield of 3a was obtained (Table 1, entry
was obtained. For the unsymmetrical 1,3ꢀdiarylꢀ1,3ꢀdiketone, 1ꢀ
(4ꢀchlorophenyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)propaneꢀ1,3ꢀdione reacted
with morpholine, affording a mixture of 3d and 3e in 31 and 49%
yields (Table 2, entry 10). While 1,3ꢀaromatic/aliphatic 1,3ꢀ
25 20). The optimal amount of I2 and TBHP used in the model 55 diketone, such as 1ꢀphenylbutaneꢀ1,3ꢀdione was engaged in the
reaction was found to be 0.4 equiv and 3 equiv, respectively
when the model reaction was carried out in CH3CO2C2H5 at 80
°C for 8 h.
reaction, which exhibited excellent selectivity, only providing 3a
in 54% isolated yield (Table 2, entry 11). Notably, various 1,3ꢀ
diarylꢀ1,3ꢀdiketones containing heteroaromatic rings at Cꢀ1 and
Cꢀ3 positions were also transformed efficiently with morpholine
60 into the valuable corresponding products αꢀketoamides 3j and 3k
(Table 2, entries 12 and 13). It was also found that 1,3ꢀ
di(thiophenꢀ2ꢀyl)propaneꢀ1,3ꢀdione showed a better reactivity
than 1,3ꢀdi(furanꢀ2ꢀyl)propaneꢀ1,3ꢀdione, which may be
correlated with their aromaticity. Similarly, unsymmetric 1,3ꢀ
30 Table 1 Optimization of the model reaction conditionsa
65 aromatic/aliphaticꢀ1,3ꢀdiketones,
4,4,4ꢀtrifluoroꢀ1ꢀ(furanꢀ2ꢀ
Entry
1
2
3
4
5
6
7
8
Oxidant
TBHP
DTBP
Solvent
neat
neat
neat
neat
neat
neat
neat
neat
Yield (%)b
yl)butaneꢀ1,3ꢀdione participated in the reaction to give the
selective product 3j in moderate yield (Table 2, entry 14). This
reaction condition was also suitable for the reaction of various
symmetrical 1,3ꢀdiarylꢀ1,3ꢀdiketones with other secondary
70 amines, such as piperidine, 1ꢀmethylpiperazine, and diethylamine,
and the corresponding products (3l−q) were isolated in moderate
to good yields (Table 2, entries 15–20). It is noteworthy to
mention that 1ꢀmethylpiperazine demonstrated a higher reactivity
than other secondary amines (Table 2, entries 18 and 19). When
75 ethyl 3ꢀoxoꢀ3ꢀphenylpropanoate was used to react with
morpholine (2a) under the present reaction conditions, the
corresponding product 3a was obtained in 47% yield (Table 2,
entry 21).
51
42
38
32
23
19
13
0
Cumyl hydroperoxide
TBPB
K2S2O8
Ag2O
O2
PhI(OAc)2
PhIO
TBN
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
9
neat
neat
0
0
10
11
12
13
14
15
16
17
18
19
20
CH3CO2C2H5
CH3CN
DCE
Toluene
Dioxane
DMF
75
58
46
43
21
19
12
0 c
0
During the model reaction was performed under the
80 present reaction conditions,
a solid Nꢀiodomorpholineꢀ
hydrogen iodide (A) was isolated from the reaction of I2 with
morpholine (Scheme 2, Eq. 1).24 The obtained A was further
converted into intermediate (B) with 1,3ꢀdiphenylpropaneꢀ1,3ꢀ
dione (1a) in the presence of 2a (2.0 equiv), providing 52%
85 yield (Scheme 2, Eq. 2). Meanwhile, the reaction of A with 1a
did not occur in the absence of 2a, and the starting material
was recovered (Scheme 2, Eq. 3). On the other hand, when the
prepared 1,3ꢀdiphenylpropaneꢀ2ꢀiodoꢀ1,3ꢀdione reacted with
2a, no product was detected, suggesting that the reaction is
THF
TBHP
CH3CO2C2H5
CH3CO2C2H5
CH3CO2C2H5
−
TBHP
46 d
a
Reaction conditions: 1a (0.50 mmol), 2a (1.5 mmol), I2 (0.20
mmol), oxidant (3 equiv., 1.5 mmol), solvent (2.0 mL) if needed
90 not
through
1,3ꢀdiphenylpropaneꢀ2ꢀiodoꢀ1,3ꢀdione
at 80 C for 8 h. Isolated yields. c In the absence of I2. d nꢀ
o
b
intermediate (Scheme 2, Eq. 4). Further investigation revealed
Bu4NI (0.20 mmol) was added instead of I2.
2
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that the reaction of B with TBHP underwent smoothly to
generate the final product αꢀketoamide 3a in 64% yield
(Scheme 2, Eq. 5), indicating that B is a key intermediate in
the tandem reaction.
5
Table 2 The tandem oxidative coupling of amines with βꢀdiketones via C−C bond cleavage to αꢀketoamidesa
Entry
1
βꢀDiketone (1)
Amine (2)
Product
3 + 3’ Yield (%)b
3a
3b
3c
3d
75
62
47
53
O
O
N
2
3
4
O
5
6
3e
3f
84
80
7
3g
77
8
9
3h
3i
81
86
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3d
31
10
3e
3a
3j
3k
3j
3l
49
54
53
69
42
70
11
12
13
14
15
O
N
16
17
3m
3n
76
50
O
Cl
18
19
20
21
3o
3p
3q
3a
86
89
55
47
O
O
Cl
Cl
a
Reaction conditions: 1 (0.5 mmol), 2 (1.5 mmol), I2 (0.20 mmol), TBHP (1.50 mmol), CH3CO2C2H5 (2.0
mL) at 80 oC for 8 h.
4
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b Isolated yields.
25
Scheme 3 Possible reaction mechanism
Conclusion
In conclusion, we have developed a metalꢀfree, mild, and
environmentalꢀfriendly method for the construction of useful
compounds αꢀketoamides through C−C bond cleavage. βꢀ
30 Diketones and secondary amines could undergo tandem
reactions smoothly in the presence of I2 and tertꢀbutyl
hydroperoxide (TBHP) in ethyl acetate at 80 oC for 8 h, in
which included C−C bond cleavage, amidation, and oxidation
in oneꢀpot. Various αꢀketoamides could be efficiently
35 synthesized from this novel method in moderate to good
yields. Further studies of the reaction mechanism and
application of this kind of oxidative system under metalꢀfree
conditions are currently underway in our laboratory.
Experimental Section
Scheme 2 Controlled experimental results
40 All the direct oxidative coupling reactions of βꢀdiketones with
amines were carried out under an air atmosphere. 1H and 13C
NMR spectra were measured on a Bruker Avance 400 MHz NMR
spectrometer with CDCl3 as solvent and recorded in ppm relative
to internal tetramethylsilane standard. High resolution mass
45 spectroscopy data of the product were collected on a Waters
Micromass GCT or a Bruker Apex IV FTMS instrument. General
chemicals were purchased from commercial suppliers and used
without further purification.
5
Although the exact mechanism of this reaction is not clear till
now, a possible tandem reaction pathway was proposed on the
basis of our above experimental data and previous publications,
as shown in Scheme 3. Initially, 1,3ꢀdiphenylpropaneꢀ1,3ꢀdione
(1a) reacted with morpholine (2a, a secondary amine) to afford
10 enamine C,25 which further reacted with A, generated from the
reaction of I2 with 2a24 in situ to produce intermediate D. Then
obtained
D was followed by hydrolysis to give 2a and
Typical procedure for TBHP/I2ꢀpromoted tandem reaction of
50 amines with βꢀdiketones
intermediate B. The generated B next underwent a free radical
substitution of its methylene with tertꢀbutylperoxy, a radical
15 generated from the homolytic cleavage of tertꢀbutyl
hydroperoxide26 to generate intermediate E, which underwent
further oxidation with TBHP to afford the final product αꢀ
ketoamide 3a.27 When the reaction was carried out in the
presence of a radical scavenger, such as TEMPO (2,2,6,6ꢀ
20 tetramethylꢀpiperidylꢀ1ꢀoxyl) and ascorbic acid up to 2.0 equiv,
the oxidative coupling reaction did not occur and the starting
material was recovered.18c,28
A sealable reaction tube equipped with a magnetic stirrer bar
was charged with βꢀdiketone (0.5 mmol), amine (1.5 mmol),
I2 (0.20 mmol), tertꢀbutyl hydroperoxide (TBHP, 1.5 mmol).
The reaction vessel was carried out at 80 °C. After stirring the
55 mixture for 8 h, it was diluted with ethyl acetate, washed with
water and brine, dried with Mg2SO4. After the solvent was
removed under reduced pressure, the residue was purified by
column chromatography on silica gel (eluant: hexane/ethyl
acetate 5:1) to afford the corresponding product.
60
Acknowledgements
This work was financially supported by the National Science
Foundation of China (Nos. 21172092, 20972057).
65 Notes and reference
1
2
3
M. Murakami and Y. Ito, In Activation of Unreactive Bonds and
Organic Synthesis; S. Murai, Ed.; Springer: Berlin, 1999; p 97.
(a) B. Rybtchinski and D. Milstein, Angew. Chem. Int. Ed., 1999, 38,
870; (b) R. H. Crabtree, Chem. Rev., 1985, 85, 245.
(a) T. Seiser and N. Cramer, J. Am. Chem. Soc., 2010, 132, 5340; (b)
C. Winter and N. Krause, Angew. Chem., Int. Ed., 2009, 48, 2460; (c)
S. Matsumura, Y. Maeda, T. Nishimura and S. Uemura, J. Am. Chem.
Soc., 2003, 125, 8862; (d) S. C. Bart and P. J. Chirik, J. Am. Chem.
Soc., 2003, 125, 886; (e) T. Kondo, Y. Kaneko, Y. Taguchi, A.
Nakamura, T. Okada, M. Shiotsuki, Y. Ura, K. Wada and T. Mitsudo,
70
75
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Page 7 of 7
RSC Advances
View Article Online
J. Am. Chem. Soc., 2002, 124, 6824; (f) S. Kim, D. Takeuchi and K.
Osakada, J. Am. Chem. Soc., 2002, 124, 762.
13 (a) I. Ojima, N. Yoda, M. Yatabe, T. Tanaka and T. Kogure,
Tetrahedron, 1984, 40, 1255; (b) A. Chiou, T. Markidis, V.
ConstantinouꢀKokotou, R. Verger and G. Kokotos, Org. Lett., 2000,
2, 347; (c) G. M. Dubowchik, J. L. Ditta, M. V. Vrudhula, B.
DasGupta, J. Ditta, T. Chen, S. Sheriff, K. Sipman, M. Witmer, J.
Tredup, D. M. Vyas, T. A. Verdoorn, S. Bollini and A. Vinitsky, Org.
Lett., 2001, 3, 3987.
14 L. El Kaїm, R. GamezꢀMontaño, L. Grimaud and T. IbarraꢀRivera,
Chem. Commun., 2008, 1350.
15 C. Zhang and N. Jiao, J. Am. Chem. Soc., 2010, 132, 28.
16 C. Zhang, Z. Xu, L. Zhang and N. Jiao, Angew. Chem., Int. Ed., 2011,
50, 11088.
4
(a) Y. J. Park, J.ꢀW. Park and C.ꢀH. Jun, Acc. Chem. Res., 2008, 41,
222; (b) Jun, C.ꢀH. Chem. Soc. Rev., 2004, 33, 610; (c) C.ꢀH. Jun, C.
W. Moon and D.ꢀY. Lee, Chem.ꢀEur. J., 2002, 8, 2422; (d) N.
Chatani, Y. Ie, F. Kakiuchi and S. Murai, J. Am. Chem. Soc., 1999,
121, 8645; (e) S.ꢀY. Liou, M. E. Boom and D. Milstein, Chem.
Commun., 1998, 687.
(a) T. Sugiishi, A. Kimura and H. Nakamura, J. Am. Chem. Soc., 2010,
132, 5332; (b) S. Chiba, Y.ꢀJ. Xu and Y.ꢀF. Wang, J. Am. Chem. Soc.,
2009, 131, 12886; (c) C. Najera and J. M. Sansano, Angew. Chem.,
Int. Ed., 2009, 48, 2452; (d) J. R. Schmink and N. E. Leadbeater,
Org. Lett., 2009, 11, 2575; (e) Q. Xu, B. Cheng, X. Ye and H. Zhai,
70
75
5
5
10
17 F.ꢀT. Du and J.ꢀX. Ji, Chem. Sci., 2012, 3, 460.
Org. Lett., 2009, 11, 4136; (f) T. Takahashi, Z. Song, Y.ꢀF.Hsieh, K. 80 18 (a) C.ꢀL. Sun, H. Li, D.ꢀG. Yu, M. Yu, X. Zhou, X.ꢀY. Lu, K. Huang,
15
Nakajima and K.ꢀi. Kanno, J. Am. Chem. Soc., 2008, 130, 15236; (g)
Y. Kuninobu, H. Takata, A. Kawata and K. Takai, Org. Lett., 2008,
10, 3133.
(a) M. Iwasaki, S. Hayashi, K. Hirano, H. Yorimitsu and K. Oshima, J.
Am. Chem. Soc., 2007, 129, 4463; (b) P. Zhao, C. D. Incarvito and J.
F. Hartwig, J. Am. Chem. Soc., 2006, 128, 3124.
S.ꢀF. Zheng, B.ꢀJ. Li and Z.ꢀJ. Shi, Nat. Chem., 2010, 2, 1044; (b) E.
Shirakawa, K. Itoh, T. Higashino and T. Hayashi, J. Am. Chem. Soc.,
2010, 132, 15537; (c) W. Liu, H. Cao, H. Zhang, H. Zhang, K.ꢀH.
Chung, C. He, H. Wang, F.ꢀY. Kwong and A.ꢀW. Lei, J. Am. Chem.
Soc., 2010, 132, 16737; (d) J. Zhao, Y. Zhao and H. Fu, Angew.
Chem., Int. Ed., 2011, 50, 3769.
6
85
20
7
H. Li, Y. Li, X.ꢀS. Zhang, K. Chen, X. Wang and Z.ꢀJ. Shi, J. Am.
Chem. Soc., 2011, 133, 15244.
Y. Zhang, M. Wang, P. Li and L. Wang, Org. Lett., 2012, 14, 2206.
19 (a) C. Gella, E. Ferrer, R. Alibés, F. Busqué, P. de March, M.
Figueredo and J. Font, J. Org. Chem., 2009, 74, 6365; (b) R. H. Fan,
D. M. Pu, F. Q. Wen and J. Wu, J. Org. Chem., 2007, 72, 8994.
8
9
(a) I. Pusterla and J. W. Bode, Angew. Chem., Int. Ed., 2012, 51, 513; 90 20 J. M. Grassot, G. Masson and J. Zhu, Angew. Chem. Int. Ed., 2007,
25
(b) M. Tobisu, H. Kinuta, Y. Kita, E. Remond and N. Chatani, J. Am.
Chem. Soc., 2012, 134, 115; (c) Y. Hirata, A. Yada, E. Morita, Y.
Nakao, T. Hiyama, M. Ohashi and S. Ogoshi, J. Am. Chem. Soc.,
2010, 132, 10070; (d) R. M. Cicchillo, H. Zhang, J. A. V. Blodgett, J.
46, 947.
21 D. Shanmugapriya, R. Shankar, G. Satyanarayana, V. H. Dahanukar,
U. K. Syam Kumar and N. Vembu, Synlett, 2008, 2945.
22 X. Zhang and L. Wang, Green Chem., 2012, 14, 2141.
T. Whitteck, G. Li, S. K. Nair, W. A. Donk and W. W. Metcalf, 95 23 (a) W. Chen, Y. Zhang, L. Zhang, M. Wang and L. Wang, Chem.
30
Nature, 2009, 459, 871; (e) L. J. Gooβen, G. Deng and L. M. Levy,
Science, 2006, 313, 662.
Commun., 2011, 47, 10476; (b) T. He, H. Li, P. Li and L. Wang,
Chem. Commun., 2011, 47, 8946; (c) T. He, L. Yu, L. Zhang, L.
Wang and M. Wang, Org. Lett., 2011, 13, 5016.
10 (a) J. Xie, H.ꢀL. Jiang, Y.ꢀX. Cheng and C.ꢀJ. Zhu, Chem. Commun.,
2012, 48, 979; (b) G.ꢀW. Wang and J. Gao, Green Chem., 2012, 14,
1125; (c) J. Zhao, Y.ꢀF. Zhao and H. Fu, Org. Lett., 2012, 14, 2710; 100
(d) W.ꢀP. Liu, J.ꢀH. Liu, D. Ogawa, Y. Nishihara, X.ꢀW. Guo and Z.ꢀ
P. Li, Org. Lett., 2011, 13, 6272; (e) A. Biswas, S. De Sarkar, R.
Fröhlich and A. Studer, Org. Lett., 2011, 13, 4966; (f) Z.ꢀQ. Rong,
M.ꢀQ. Jia and S.ꢀL. You, Org. Lett., 2011, 13, 4080; (g) W.ꢀB. Liu,
24 J. E. Hein, J. C. Tripp, L. B. Krasnova, K. B. Sharpless and V. V.
Fokin, Angew. Chem., Int. Ed., 2009, 48, 8018.
25 G. Stork, R. Terrell and J. Szmuszkovicz, J. Am. Chem. Soc., 1954,
76, 2029.
26 E. Boess, C. Schmitz and M. Klussmann, J. Am. Chem. Soc., 2012,
134, 5317.
35
40
45
50
55
60
65
H.ꢀF. Jiang, M. Zhang and C.ꢀR. Qi, J. Org. Chem., 2010, 75, 966; (h) 105 27 J. Zhang, Z. Wang, Y. Wang, C. Wan, X. Zheng and Z. Wang, Green
P.ꢀN. Liu, L. Dang, Q.ꢀW. Wang, S.ꢀL. Zhao, F. Xia, Y.ꢀJ. Ren, X.ꢀQ.
Gong and J.ꢀQ. Chen, J. Org. Chem., 2010, 75, 5017; (i) M. Gao, Y.
Yang, Y.ꢀD. Wu, C. Deng, W.ꢀM. Shu, D.ꢀX. Zhang, L.ꢀP. Cao, N.ꢀF.
She and A.ꢀX. Wu, Org. Lett., 2010, 12, 4026.
Chem., 2009, 11, 1973.
28 (a) J. J. Warren and J. M. Mayer, J. Am. Chem. Soc., 2010, 132, 7784;
(b) C.ꢀW. Chan, Z. Zhou, A. S. C. Chan and W.ꢀY. Yu, Org. Lett.,
2010, 12, 3926.
110
11 C. He, S. Guo, L. Huang and A.ꢀW. Lei, J. Am. Chem. Soc., 2010,
132, 8273.
12 (a) Y.ꢀH. Chen, Y.ꢀH. Zhang, H.ꢀJ. Zhang, D.ꢀZ. Liu, M. Gu, J.ꢀY. Li,
F. Wu, X.ꢀZ. Zhu, J. Li and F.ꢀJ. Nan, J. Med. Chem., 2006, 49, 1613;
(b) J. Holenz, R. Mercè, J. L. Díaz, X. Guitart, X. Codony, A. Dordal,
G. Romero, A. Torrens, J. Mas, B. Andaluz, S. Hernández, X.
Monroy, E. Sánchez, E. Hernández, R. Pérez, R. Cubí, O. Sanfeliu
and H. Buschmann, J. Med. Chem., 2005, 48, 1781; (c) A. Natarajan,
K. Wang, V. Ramamurthy, J. Scheffer and B. Patrick, Org. Lett.,
2002, 4, 1443; (d) M. M. Sheha, N. M. Mahfouz, H. Y. Hassan, A. F.
Youssef, T. Mimoto and Y. Kiso, Eur. J. Med. Chem., 2000, 35, 887;
(e) S. Chatterjee, D. Dunn, M. Tao, G. Wells, Z.ꢀQ. Gu, R. Bihovsky,
M. A. Ator, R. Siman and J. P. Mallamo, Bioorg. Med. Chem. Lett.,
1999, 9, 2371; (f) Z. Li, A.ꢀC. OrtegaꢀVilain, G. S. Patil, D.ꢀL. Chu,
J. E. Foreman, D. D. Eveleth and J. C. Powers, J. Med. Chem., 1996,
39, 4089; (g) D. H. Slee, K. L. Laslo, J. H. Elder, I. R. Ollmann, A.
Gustchina, J. Kervinen, A. Zdanov, A. Wlodawer and C.ꢀH. Wong, J.
Am. Chem. Soc., 1995, 117, 11867; (h) B. E. Maryanoff, M. N.
Greco, H.ꢀC. Zhang, P. AndradeꢀGordon, J. A. Kauffman, K. C.
Nicolaou, A. Liu and P. H. Brungs, J. Am. Chem. Soc., 1995, 117,
1225; (i) M. Hagihara and S. L. Schreiber, J. Am. Chem. Soc., 1992,
114, 6570; (j) B. Munoz, C.ꢀZ. Giam and C.ꢀH. Wong, Bioorg. Med.
Chem., 1994, 2, 1085.
6
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