10.1002/chem.201705202
Chemistry - A European Journal
COMMUNICATION
[3]
E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57,
10257.
On the basis of the results of the above-described
experiments and in consideration of previously proposed
[4]
[5]
B. Zhang, A. Studer, Chem. Soc. Rev. 2015, 44, 3505.
J. C. Callaway, D. J. McKenna, C. S. Grob, G. S. Brito, L. P. Raymon,
R. E. Poland, E. N. Andrade, E. O. Andrade, D. C. Mash, J.
Ethnopharmacol. 1999, 65, 243.
32]
•−
mechanisms,[31,
we suggest that O2
generation and
subsequent desulfonation and dehydrogenation of the N-
heterocycle substrates proceed via the mechanism outlined in
Scheme 7, with substrate 1a as an example. Specifically,
reductive cleavage of the N-tosyl group with Na/naphthalene via
single-electron transfer affords amine radical A, which can
abstract a hydrogen atom from the solvent to form 3a. In
addition to cleaving the S–N bond, naphthalene acts as an
electron shuttle, delivering a single electron to O2 to generate
O2•−, which reacts with 3a to generate HO2− and aminylradical A
via hydrogen atom transfer. Aminyl radical (A) gets immediately
reduced with Na-napthalenide that is present in large excess.
The Na-amide B formed has a highly activated alpha C-H bond.
Hence, the superoxide radical anion generated upon SET
reduction of O2 with Na-napthalenide or the hydroxyl radical
formed by reduction of in situ generated hydroperoxide abstracts
that activated H-atom to get a radical anion C that is readily
oxidized by air to give D. Rearomatization is then easily
achieved via H-abstraction either by air or the superoxide radical
anion or the hydroxyl radical.
[6]
J. Reniers, S. Robert, R. Frederick, B. Masereel, S. Vincent, J. Wouters,
J. G. Tang, Y. H. Wang, R. R. Wang, Z. J. Dong, L. M. Yang, Y. T.
Zheng, J. K. Liu, Chem. Biodiver. 2008, 5, 447.
[8]
[9]
J. M. Humphrey, Y. Liao, A. Ali, T. Rein, Y. L. Wong, H. J. Chen, A. K.
Courtney, S. F. Martin, J. Am. Chem. Soc. 2002, 124, 8584.
K. C. Nicolaou, C. J. N. Manthison, T. Montagnon, J. Am. Chem. Soc.
2004, 126, 5192.
[10] M. Zhao, L. Bi, W. Wang, C. Wang, M. Baudy-Floc’h, J. Ju, S. Peng,
Bioorg. Med. Chem. 2006, 14, 6998.
[11] M. Cain, O. Campos, F. Guzman, J. M. Cook, J. Am. Chem. Soc. 1983,
105, 907.
[12] D. Damodara, R. Arundhathi, P. R. Likhar, Adv. Synth. Catal. 2014, 356,
189.
[13] M. H. So, Y. Liu, C. M. Ho, C. M. Che, Chem. Asian J. 2009, 4, 1551.
[14] D. V. Jawale, E. Gravel, N. Shah, V. Dauvois, H. Li, I. N. Namboothiri,
E. Doris, Chem. Eur. J. 2015, 21, 7039.
[15] D. Ge, L. Hu, J. Wang, X. Li, F. Qi, J. Lu, X. Cao, H. Gu,
ChemCatChem 2013, 5, 2183.
[16] For the CAD, see: a) R. Yamaguchi, C. Ikeda, Y. Takahashi, K. Fujita, J.
Am. Chem. Soc. 2009, 131, 8410; b) K. Fujita, Y. Tanaka, M.
Kobayashi, R. Yamaguchi, J. Am. Chem. Soc. 2014, 136, 4829; c) S.
Muthaiah, S. H. Hong, Adv. Synth. Catal. 2012, 354, 3045; d) J. Wu, D.
Talwar, S. Johnston, M. Yan, J. Xiao, Angew. Chem. Int. Ed. 2013, 52,
6983; Angew. Chem. 2013, 125, 7121; e) S. Chakraborty, W. W.
Brennessel, W. D. Jones, J. Am. Chem. Soc. 2014, 136, 8564; f) R. Xu,
S. Chakraborty, H. Yuan, W. D. Jones, ACS. Catal. 2015, 5, 6350.
[17] For the FLP, see: a) A. FMaier, S. Tussing, T. Schneider, U. Flörke, Z.
W. Qu, S. Grimme, J. Paradies, Angew. Chem. Int. Ed. 2016, 55,
12219; Angew. Chem. 2016, 128, 12407; b) M. Kojima, M. Kanai,
Angew. Chem. Int. Ed. 2016, 55, 12224; Angew. Chem. 2016, 128,
12412.
[18] S. Chen, Q. Q. Wan, A. K. Badu-Tawiah, Angew. Chem. Int. Ed. 2016,
55, 9345; Angew. Chem. 2016, 128, 9491.
Scheme 7. Plausible Reaction Mechanism.
[19] M. Hayyan, M. A. Hashim, I. M.AlNashef, Chem. Rev. 2016, 116, 3029.
[20] D. T. Sawyer, J. S. Valentine, Acc. Chem. Res. 1981, 14, 393.
[21] E. J. Nanni, D. T. Sawyer, J. Am. Chem. Soc. 1980, 102, 7591.
[22] Several review generated superoxide ion a) D. T. Sawyer, Oxygen
Chemistry; Oxford University Press: New York, 1991; b) I. B. Afanas’ev,
Superoxide Ion: Chemistry and Biological Implications; CRC Press:
Boca Raton, FL, 1989; Vol. 1; c) Y. W. Sheng, I. A. Abreu, D. E.
Cabelli, M. J. Maroney, A. F. Miller, M. Teixeira, J. S. Valentine, Chem.
Rev. 2014, 114, 3854.
In summary, we have developed a novel method for
dehydrogenation of N-heterocycles. Specifically, reductive
•−
electron transfer from Na/naphthalene to O2 generates O2
,
which oxidizes the N-heterocycles via a hydrogen atom transfer
mechanism. We anticipate that this general, green
dehydrogenation method will find further applications for the
synthesis of other N-heterocycles.
[23] a) V. Darley-Usmar, H. Wiseman, B. Halliwell, FEBS Lett. 1995, 369,
131; b) K. Tammeveski, M. Arulepp, T. Tenno, C. Ferrater, J. Claret,
Electrochim. Acta 1997, 42, 2961; c) J. B. De Haan, E. J. Wolvetang, F.
Cristiano, R. Iannello, C. Bladier, M. J. Kelner, I. Kola, Adv. Pharmacol.
1996, 38, 379; d) C. Tavagnacco, M. Moszner, S. Cozzi, S. Peressini,
G. Costa, J. Electroanal. Chem. 1998, 448, 41; e) V. S. Dilimon, N. S.
Venkata Narayanan, S. Sampath, Electrochim. Acta 2010, 55, 5930.
[24] N. L. Holy, Chem. Rev. 1974, 74, 243.
Acknowledgements
We are grateful to the National Natural Science Foundation
ofChina (21732002, 21672117, and 21602117) and the Tianjin
Natural Science Foundation (16JCZDJC32400) for generous
financial support forour programs.
[25] CCDC 1566085 (2f) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
Keywords: dehydrogenation • nitrogen heterocycles • redox
chemistry • single-electron transfer • superoxide ion
[26] S. O'Sullivan, E. Doni, T. Tuttle, J. A. Murphy, Angew. Chem. Int. Ed.
2014, 53, 474; Angew. Chem. 2014, 126, 484.
[27] MS (ESI+) calcd for C7H9NNa [M+Na]+130.1, found 130.1.
[28] M. Hayyan, F. S. Mjalli, M. A. Hashim, I. M. Alnashef, X. M. Tan, J.
Electroanal. Chem. 2012, 657, 150.
[1]
[2]
A. Deiters, S. F. Martin, Chem. Rev.2004, 104, 2199.
S. Süzen, Bioactive Heterocycles V, Springer, 2007, 145–178.
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