Organic Letters
Letter
(5) (a) Alonso, E.; Ramon
́
, D. J.; Yus, M. Tetrahedron 1997, 53,
oxonium cations via one-electron oxidation and then hydro-
lyzed to produce amides 2 and alcohols B, respectively. In the
debenzylation of O-benzyl ethers, the formed debenzylated
alcohols B are further oxidized to carbonyl compounds 4
through the α-hydrogen atom abstraction by the bromo
radical.17 For the deprotection of alkyl ethers (13a−15a), a
bromo radical dominantly abstracts a hydrogen atom at a
tertiary α-carbon atom on the substrate to proceed with
alkylation.
In conclusion, we have developed an oxidative debenzylation
of N-benzyl amides and O-benzyl ethers under mild conditions
by an alkali metal bromide/oxidant system. The oxidized
bromo radical can be utilized in the reaction with a broad range
of substrates to obtain the corresponding debenzylated amides
and carbonyl compounds in high yields. This reaction is
transition-metal- and organic-reagent-free, and these reagents
are stable and much less toxic. Therefore, the present method is
green-sustainable as it does not yield any products that would
pollute the environment. We have high hopes that the
transformation via the oxidation of halides using alkali metal
halides would be applicable to fine organic synthesis.
14355−14368. (b) Liu, H.-J.; Yip, J.; Shia, K.-S. Tetrahedron Lett. 1997,
38, 2253−2256. (c) Angle, S. R.; Henry, R. M. J. Org. Chem. 1998, 63,
7490−7497.
(6) (a) du Vigneaud, V.; Behrens, O. K. J. Biol. Chem. 1937, 117, 27−
36. (b) Reist, E. J.; Bartuska, V. J.; Goodman, L. J. Org. Chem. 1964,
29, 3725−3726. (c) Schon, I. Chem. Rev. 1984, 84, 287−297.
̈
(7) (a) Congreve, M. S.; Davison, E. C.; Fuhry, M. A. M.; Holmes, A.
B.; Payne, A. N.; Robinson, R. A.; Ward, S. E. Synlett 1993, 663−664.
(b) Evans, D. A.; Ripin, D. H. B.; Halstead, D. P.; Campos, K. R. J. Am.
Chem. Soc. 1999, 121, 6816−6826. (c) Ward, D. E.; Gai, Y.; Kaller, B.
F. J. Org. Chem. 1995, 60, 7830−7836. (d) Paliakov, E.; Strekowski, L.
Tetrahedron Lett. 2004, 45, 4093−4095.
(8) (a) Angibeaud, P.; Utille, J.-P. Synthesis 1991, 737−738. (b) Fujii,
N.; Otaka, A.; Sugiyama, N.; Hatano, M.; Yajima, H. Chem. Pharm.
Bull. 1987, 35, 3880−3883. (c) Nakano, M.; Kikuchi, W.; Matsuo, J.;
Mukaiyama, T. Chem. Lett. 2001, 30, 424−425.
(9) (a) Kartha, K. P. R.; Dasgupta, F.; Singh, P. P.; Srivastava, H. C. J.
Carbohydr. Chem. 1986, 5, 437−444. (b) Hori, H.; Nishida, Y.; Ohrui,
H.; Meguro, H. J. Org. Chem. 1989, 54, 1346−1353. (c) Akiyama, T.;
Hirofuji, H.; Ozaki, S. Tetrahedron Lett. 1991, 32, 1321−1324.
(d) Yang, G.; Ding, X.; Kong, F. Tetrahedron Lett. 1997, 38, 6725−
6728. (e) Ishihara, K.; Hiraiwa, Y.; Yamamoto, H. Synlett 2000, 80−82.
(f) Falck, J. R.; Barma, D. K.; Baati, R.; Mioskowski, C. Angew. Chem.,
Int. Ed. 2001, 40, 1281−1283. (g) Polat, T.; Linhardt, R. J. Carbohydr.
Res. 2003, 338, 447−449.
(10) Bull, S. D.; Davies, S. G.; Fenton, G.; Mulvaney, A. W.; Prasad,
R. S.; Smith, A. D. J. Chem. Soc., Perkin Trans. 1 2000, 3765−3774.
(11) (a) Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett.
1982, 23, 885−888. (b) Tanaka, T.; Oikawa, Y.; Hamada, T.;
Yonemitsu, O. Tetrahedron Lett. 1986, 27, 3651−3654. (c) Singh, S. B.
Tetrahedron Lett. 1995, 36, 2009−2012.
(12) (a) Madsen, J.; Bols, M. Angew. Chem., Int. Ed. 1998, 37, 3177−
3178. (b) Madsen, J.; Viuf, C.; Bols, M. Chem.Eur. J. 2000, 6, 1140−
1146. (c) Grayson, E. J.; Davis, B. G. Org. Lett. 2005, 7, 2361−2364.
(13) (a) Moriyama, K.; Izumisawa, Y.; Togo, H. J. Org. Chem. 2011,
76, 7249−7255. (b) Moriyama, K.; Takemura, M.; Togo, H. Org. Lett.
2012, 14, 2414−2417. (c) Moriyama, K.; Ishida, K.; Togo, H. Chem.
Commun. 2012, 48, 8574−85576.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, spectral data, and copies of NMR
spectra. This material is available free of charge via the Internet
AUTHOR INFORMATION
Corresponding Authors
■
Notes
The authors declare no competing financial interest.
(14) (a) Kamijo, S.; Amaoka, Y.; Inoue, M. Chem.Asian J. 2010, 5,
486−489. (b) Kamijo, S.; Amaoka, Y.; Inoue, M. Synthesis 2010, 42,
2475−2489.
ACKNOWLEDGMENTS
■
Financial support in the form of a Grant-in-Aid for Scientific
Research (No. 20550033) from the Ministry of Education,
Culture, Sports, Science and Technology in Japan (K.M.) and
the Futaba Electronics Memorial Foundation in Japan (K.M.) is
gratefully acknowledged. NMR and HRMS measurements were
performed at Center for Analytical Instrumentation at Chiba
University.
(15) (a) Heerden, F. R.; Dixon, J. T.; Holzapfel, C. W. Tetrahedron
Lett. 1992, 33, 7399−7402. (b) Arnone, A.; Bernardi, R.; Cavicchioli,
M.; Resnati, G. J. Org. Chem. 1995, 60, 2314−2315. (c) Kamijo, S.;
Matsumura, S.; Inoue, M. Org. Lett. 2010, 12, 4195−4197.
(16) Bull, S. D.; Davies, S. G.; Fenton, G.; Mulvaney, A. W.; Prasad,
R. S.; Smith, A. D. Chem. Commun. 2000, 337−338.
(17) Amati, A.; Dosualdo, G.; Zhao, L.; Bravo, A.; Fontana, F.;
Minisci, F.; Bjørsvik, H.-R. Org. Process. Res. Dev. 1998, 2, 261−26.
REFERENCES
■
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 4th ed.; Wiley-Interscience: New York, 2007.
́
(2) (a) Berillon, L.; Wagner, R.; Knochel, P. J. Org. Chem. 1998, 63,
9117−9121. (b) Johnson, D. C., II; Widlanski, T. S. Tetrahedron Lett.
2004, 45, 8483−8487. (c) Rombouts, F.; Franken, D.; Martínez-
Lamenca, C.; Braeken, M.; Zavattaro, C.; Chen, J.; Trabanco, A. A.
Tetrahedron Lett. 2010, 51, 4815−4818.
(3) (a) Hartung, W. H.; Simonoff, R. Org. React. 1953, 7, 263−326.
(b) Heathcock, C. H.; Ratcliffe, R. J. Am. Chem. Soc. 1971, 93, 1746−
1757. (c) Pallenberg, A. J. Tetrahedron Lett. 1992, 33, 7693−7696.
(d) Kanai, M.; Yasumoto, M.; Kuriyama, Y.; Inomiya, K.; Katsuhara,
Y.; Higashiyama, K.; Ishii, A. Chem. Lett. 2004, 33, 1424−1425.
(4) (a) Oikawa, Y.; Tanaka, T.; Horita, K.; Yonemitsu, O.
Tetrahedron Lett. 1984, 25, 5397−5400. (b) Horita, K.; Yoshioka,
T.; Tanaka, T.; Oikawa, Y.; Yonemitsu, O. Tetrahedron 1986, 42,
3021−3028. (c) Paterson, I.; Lombart, H.-G.; Allerton, C. Org. Lett.
1999, 1, 19−22. (d) Evans, D. A.; Trenkle, W. C.; Zhang, J.; Burch, J.
D. Org. Lett. 2005, 7, 3335−3338.
D
dx.doi.org/10.1021/ol501703y | Org. Lett. XXXX, XXX, XXX−XXX