Hypervalent iodine(III)-induced methylene acetoxylation of 3-oxo-n-substituted butanamides

Article abstract of DOI:10.3762/bjoc.7.167

1-Carbamoyl-2-oxopropyl acetate derivatives were synthesized through an acetoxylation process to methylene with the aid of (diacetoxyiodo)benzene (DIB) as the oxidant. Not only mild reaction conditions, but also excellent yields and good substrate scope m

Full text of DOI:10.3762/bjoc.7.167

Hypervalent iodine(III)-induced methylene
acetoxylation of 3-oxo-N-substituted butanamides
Wei-Bing Liu1, Cui Chen1, Qing Zhang1 and Zhi-Bo Zhu*2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 1436–1440.
1School of Chemistry and Life Science, Guangdong University of
Petrochemical Technology, Maoming 525000, China and 2College of
Pharmaceutical Sciences, Southern Medical University, Guangzhou
510515, China
doi:10.3762/bjoc.7.167
Received: 02 September 2011
Accepted: 23 September 2011
Published: 19 October 2011
Email:
Zhi-Bo Zhu* - zzb24@yahoo.com.cn
Associate Editor: B. Stoltz
* Corresponding author
© 2011 Liu et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
1-carbamoyl-2-oxopropyl acetate derivatives; C-hetero bond;
(diacetoxyiodo)benzene; methylene acetoxylation
Abstract
1-Carbamoyl-2-oxopropyl acetate derivatives were synthesized through an acetoxylation process to methylene with the aid of
(diacetoxyiodo)benzene (DIB) as the oxidant. Not only mild reaction conditions, but also excellent yields and good substrate scope
make the present protocol potentially useful in organic synthesis.
Introduction
Carbon–carbon, carbon–heteroatom bond formation leading The availability of iodine(III) and iodine(V) compounds and the
to useful molecular structures is one of the most interesting development of new reagents, along with their low toxicity,
and challenging research topics in organic chemistry [1-14]. ready availability, easy handling, clean transformation and
Indeed, direct oxidative C–H bond functionalization provides reactivity, their selectivity under a variety of conditions,
an atom-economical and efficient pathway to achieve these and their tolerance to different functional groups make
goals. Representative examples have been elegantly utilized these compounds valuable tools in organic synthesis [31-36].
not only in academic research, but also in the production Our interest in the chemistry of polyvalent iodine(III)
of a variety of fine chemicals, such as pharmaceuticals, reagents [37-39] prompted us to exploit the reactivity
agrochemicals, and intermediates [15-18]. The field of chem- of (diacetoxyiodo)benzene (DIB). We report herein the
istry concerning organic polyvalent iodine compounds has use of DIB, as a nucleophile and oxidant, to perform an
witnessed a great expansion during the last few decades, acetoxylation reaction with 3-oxo-N-substituted butanamides
an expansion which continues at an increasing pace [19-30]. (Scheme 1).
1436

Beilstein J. Org. Chem. 2011, 7, 1436–1440.
To explore the substrate scope and limitations of this reaction, a
range of 3-oxo-N-phenylbutanamides were then examined
under the optimized reaction conditions. The results are shown
in Scheme 2.
We found that the reaction led to the corresponding products
2a–2l in excellent isolated yields with all substrates. The reac-
tion appears to be quite tolerant to differences in the position,
number and electronic contribution of the substituent on the
Scheme 1: Synthesis of 1-carbamoyl-2-oxopropyl acetates.
Results and Discussion
Initially, we employed 3-oxo-N-phenylbutanamide (1a) as the benzene ring. For example, the reactions of 3-oxo-N-phenylbu-
model substrate and tried to establish an effective reaction tanamide, N-(4-methoxyphenyl)-3-oxobutanamide, N-(2-
system for the synthesis. The results are shown in Table 1. It methoxyphenyl)-3-oxobutanamide, N-(2,5-dichlorophenyl)-3-
was found that the reaction afforded the desired product oxobutanamide, N-(2,4-dimethoxyphenyl)-3-oxobutanamide as
1-(phenylcarbamoyl)-2-oxopropyl acetate (2a) by using DIB as well as N-(4-chloro-2,5-dimethoxyphenyl)-3-oxobutanamide all
the additive, and the optimum reaction time was 2 hours lead to the corresponding products (2a, 2e, 2f, 2g, 2j, and 2k,
(Table 1, entries 1–3), whereas almost no desired product was respectively) in excellent isolated yield. Similarly, the reactions
obtained when Lewis acids were added (Table 1, entries 4–6). of other N-(alkylsubstituted)-3-oxobutanamides were investi-
Among the various solvents examined, dioxane, DCE and DMF gated, such as that of N-methyl-3-oxobutanamide (1l), which
were practical solvents (Table 1, entries 2, 7–9). It is note- led to 1-(methylcarbamoyl)-2-oxopropyl acetate in 89% yield.
worthy that the reaction led to an obvious decrease of the yield Furthermore, we applied this method to non-carbamoyl 1,3-
of 2a when either 0.5 or 2 equiv of DIB were used (Table 1, dicarbonyl compounds. These substrates, namely 1-phenylbu-
entries 11 and 13) compared to 1.3 equiv (Table 1, entry 12), tane-1,3-dione, 1,3-diphenylpropane-1,3-dione and ethyl 3-oxo-
which was found to be the optimum amount of DIB (Table 1, 3-phenylpropanoate, all produced products in moderate isolated
entries 11–13).
yields (2m, 2n, 2o).
Table 1: Optimization of reaction conditions.a
entry
solvent
additive (1.0 equiv)
time (h)
yield (%)b
1
2
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
cyclohexane
DCE
—
—
1
2
3
2
2
2
2
2
2
2
2
2
2
66
80
3
—
81
4
FeCl3
ZnCl2
CuCl2
—
trace
trace
trace
36
5
6
7
8
—
82
9
DMF
—
71
10
11c
12d
13e
DMSO
DCE
—
47
—
35
DCE
—
89
DCE
—
75
a1a (0.25 mmol), solvent (2 mL), DIB (1.0 equiv); bGC yield; cDIB (0.5 equiv); dDIB (1.3 equiv); eDIB (2.0 equiv).
1437

Beilstein J. Org. Chem. 2011, 7, 1436–1440.
Scheme 2: The synthesis of 1-carbamoyl-2-oxopropyl acetates. Conditions: 1 (1.0 mmol), DCE (2 mL), DIB (1.3 equiv); %: Isolated yield.
A plausible mechanism for the described transformation can be attacks the C–C double bond of the enol derived from 1a and
rationalized as shown in Scheme 3. The reaction initiates with forms intermediate 6 [46,47]. The subsequent N–I, O–I and C–I
the attack of the lone-pair electrons of the carbamoyl nitrogen bond cleavage along with the nucleophilic attack of the acetate
[39-41] or carbonyl oxygen [42-45] on the iodine(III) of DIB, ion on the C–N or C–C double bond of the intermediate 4, 5 or
forming intermediates 3 and 5, respectively. Alternatively, DIB 6 affords the final product 2a.
1438

Beilstein J. Org. Chem. 2011, 7, 1436–1440.
6. Fagnoni, M.; Dondi, D.; Ravelli, D.; Albini, A. Chem. Rev. 2007, 107,
2725–2756. doi:10.1021/cr068352x
7. Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev.
2007, 107, 5318–5365. doi:10.1021/cr068006f
8. Tong, X.; Beller, M.; Tse, M. K. J. Am. Chem. Soc. 2007, 129,
4906–4907. doi:10.1021/ja070919j
9. Niu, J.; Zhou, H.; Li, Z.; Xu, J.; Hu, S. J. Org. Chem. 2008, 73,
7814–7817. doi:10.1021/jo801002c
10.Lee, J. M.; Park, E. J.; Cho, S. H.; Chang, S. J. Am. Chem. Soc. 2008,
130, 7824–7825. doi:10.1021/ja8031218
11.Ueda, S.; Nagasawa, H. J. Org. Chem. 2009, 74, 4272–4277.
doi:10.1021/jo900513z
12.Liang, Z.; Hou, W.; Du, Y.; Zhang, Y.; Pan, Y.; Mao, D.; Zhao, K.
Org. Lett. 2009, 11, 4978–4981. doi:10.1021/ol902157c
13.Peng, Y.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2009, 131,
5062–5063. doi:10.1021/ja901048w
14.Mizuhara, T.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2010, 75,
265–268. doi:10.1021/jo902327n
15.Markó, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C. J.
Science 1996, 274, 2044–2046. doi:10.1126/science.274.5295.2044
16.ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. Science 2000, 287,
1636–1639. doi:10.1126/science.287.5458.1636
17.Enache, D. I.; Edwards, J. K.; Landon, P.; Solsona-Espriu, B.;
Carley, A. F.; Herzing, A. A.; Watanabe, M.; Kiely, C. J.; Knight, D. W.;
Hutchings, G. J. Science 2006, 311, 362–365.
Scheme 3: Possible reaction mechanism.
Conclusion
In conclusion, we have shown an efficient and operationally
simple method to synthesize 1-carbamoyl-2-oxopropyl acetate
derivatives. The readily accessible starting materials, cheap
oxidant DIB, as well as the mild reaction conditions and excel-
lent yields make the present protocol potentially useful in
organic synthesis. Further studies on the application to more
valuable compounds and detailed investigations of the reaction
mechanism are in progress.
doi:10.1126/science.1120560
18.Piera, J.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2008, 47, 3506–3523.
doi:10.1002/anie.200700604
19.Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine; VCH:
New York, 1992.
20.Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic
Press: London, 1997.
21.Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523–2584.
doi:10.1021/cr010003+
22.Wirth, T., Ed. Hypervalent Iodine Chemistry; Springer-Verlag: Berlin,
2003.
Supporting Information
23.Richardson, R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006, 45,
4402–4404. doi:10.1002/anie.200601817
Supporting Information File 1
24.Ciufolini, M. A.; Braun, N. A.; Canesi, S.; Ousmer, M.; Chang, J.;
Chai, D. Synthesis 2007, 3759–3772. doi:10.1055/s-2007-990906
25.Quideau, S.; Pouységu, L.; Deffieux, D. Synlett 2008, 467–495.
doi:10.1055/s-2008-1032094
Experimental details and copies of NMR spectra.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-167-S1.pdf]
26.Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299–5358.
doi:10.1021/cr800332c
Acknowledgements
The authors thank the College of Pharmaceutical Sciences of
the Southern Medical University of China for financial support
of this work.
27.Koller, R.; Stanek, K.; Stolz, D.; Aardoom, R.; Niedermann, K.;
Togni, A. Angew. Chem., Int. Ed. 2009, 48, 4332–4336.
doi:10.1002/anie.200900974
28.Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed. 2010, 49,
2175–2177. doi:10.1002/anie.200907352
29.Niedermann, K.; Früh, N.; Vinogradova, E.; Wiehn, M. S.; Moreno, A.;
Togni, A. Angew. Chem., Int. Ed. 2011, 50, 1059–1063.
doi:10.1002/anie.201006021
References
1. Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731–1770.
doi:10.1021/cr0104330
30.Brand, J. P.; González, D. F.; Nicolai, S.; Waser, J. Chem. Commun.
2011, 47, 102–115. doi:10.1039/c0cc02265a
2. Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077–1101.
doi:10.1002/adsc.200303094
31.Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem. 2008, 4229–4239.
doi:10.1002/ejoc.200800416
3. Dilman, A. D.; Ioffe, S. L. Chem. Rev. 2003, 103, 733–772.
doi:10.1021/cr020003p
32.Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073–2085.
doi:10.1039/b821747e
4. Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169–196.
doi:10.1021/cr020007u
33.Jen, T.; Mendelsohn, B. A.; Ciufolini, M. A. J. Org. Chem. 2011, 76,
728–731. doi:10.1021/jo102241s
5. Li, C.-J. Chem. Rev. 2005, 105, 3095–3166. doi:10.1021/cr030009u
1439

Beilstein J. Org. Chem. 2011, 7, 1436–1440.
34.Sun, Y.; Fan, R. H. Chem. Commun. 2010, 46, 6834–6836.
doi:10.1039/c0cc01911a
35.Chen, L.; Shi, E.; Liu, Z.; Chen, S.; Wei, W.; Li, H.; Xu, K.; Wan, X.
Chem.–Eur. J. 2011, 17, 4085–4089. doi:10.1002/chem.201100192
36.Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed. 2010, 49,
2175–2177. doi:10.1002/anie.200907352
37.Liu, W.; Jiang, H.; Huang, L. Org. Lett. 2010, 12, 312–315.
doi:10.1021/ol9026478
38.Liu, W.; Chen, C.; Zhang, Q. Org. Biomol. Chem. 2011, 9, 6484–6486.
doi:10.1039/c1ob05958k
39.Li, X.; Du, Y.; Liang, Z.; Li, X.; Pan, Y.; Zhao, K. Org. Lett. 2009, 11,
2643–2646. doi:10.1021/ol9006663
40.Malamidou-Xenikaki, E.; Spyroudis, S.; Tsanakopoulou, M.;
Hadjipavlou-Litina, D. J. Org. Chem. 2009, 74, 7315–7321.
doi:10.1021/jo9013063
41.Serna, S.; Tellitu, I.; Domínguez, E.; Moreno, I.; SanMartín, R.
Org. Lett. 2005, 7, 3073–3076. doi:10.1021/ol0510623
42.Harayama, Y.; Yoshida, M.; Kamimura, D.; Kita, Y. Chem. Commun.
2005, 1764–1766. doi:10.1039/b418212j
43.Singh, C. B.; Ghosh, H.; Murru, S.; Patel, B. K. J. Org. Chem. 2008, 73,
2924–2927. doi:10.1021/jo702628g
44.Mizukami, F.; Ando, M.; Tanaka, T.; Imamura, J. Bull. Chem. Soc. Jpn.
1978, 51, 335–336. doi:10.1246/bcsj.51.335
45.Kawano, Y.; Togo, H. Synlett 2008, 217–220.
doi:10.1055/s-2007-1000871
46.Yu, J.; Tian, J.; Zhang, C. Adv. Synth. Catal. 2010, 352, 531–546.
doi:10.1002/adsc.200900737
47.Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K.
J. Am. Chem. Soc. 2005, 127, 12244–12245. doi:10.1021/ja0542800
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.7.167
1440