C O M M U N I C A T I O N S
Table 3. Comparison of Catalytic Efficiencies of TEMPO and
In summary, we have disclosed the excellent catalytic oxidizing
abilities of AZADO and 1-Me-AZADO for the oxidation of
alcohols, which offer complementary use with TEMPO-type
nitroxyl radicals. Information on the structure-activity correlation
of these compounds should inspire new designs of organocatalysts
with increased catalytic efficiencies.
1-Me-AZADO toward Various Secondary Alcoholsa
Acknowledgment. We thank Prof. Emeritus Kunio Ogasawara
of Tohoku University for his encouragement and helpful discussion.
This work was supported by JST, JSPS, and MEXT, Japan.
Supporting Information Available: Experimental procedures,
spectral data for all new compounds. This material is available free of
References
(1) (a) Schlecht, M. F. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Ley, S. V., Eds.; Pergamon: Oxford, 1991; Vol 7, pp 251-
327. (b) Modern Oxidation Methods; Ba¨ckvall, J.-E., Ed.; Willey-VCH:
Weinheim, Germany, 2004.
(2) (a) Noyori, R.; Aoki, M.; Sato, K. Chem. Commun. 2003, 1977-1980.
(b) Mallat, T.; Baiker, A. Chem. ReV. 2004, 104, 3037-3058. (c) Uozumi,
Y.; Nakao, R. Angew. Chem., Int. Ed. 2003, 42, 194-197. (d) Nishide,
K.; Patra, P. K.; Matoba, M.; Shanmugasundaram, K.; Node, M. Green
Chem. 2004, 6, 142-146. (e) Drugger, R. W.; Ragan, J. A.; Brown Ripin,
D. H. Org. Proc. Res. DeV. 2005, 9, 253-258.
(3) (a) de Nooy, A. E.; Besemer, A. C.; van Bekkum, H. Synthesis 1996,
1153-1174. (b) Sheldon, R. A.; Arends, I. W. C. E. AdV. Synth. Catal.
2004, 346, 1051-1071.
(4) (a) Cella, J. A.; Kelly, J. A.; Kenehan, E. F. J. Org. Chem. 1975, 40,
1860-1862. (b) Semmelhack, M. F.; Schmid, C. R.; Corte´s, D. A.; Chou,
C. S. J. Am. Chem. Soc. 1984, 106, 3374-3376. (c) Anelli, P. L.; Banfi,
C.; Montanari, F.; Quici, S. J. Org. Chem. 1987, 52, 2559-2562. (d)
Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. J. Org. Chem. 1989, 54,
2970-2972. (e) De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974-6977. (f) Biom, C.; Magus,
A. S.; Hildebrand, J. P. Org. Lett. 2000, 2, 1173-1175. (g) Bjørsvik, H.;
Liguori, L.; Costantino, F.; Minisci, F. Org. Proc. Res. DeV. 2002, 6,
197-200. (h) Miller, R. A.; Hoerrner, R. S. Org. Lett. 2003, 5, 285-
287. (i) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004,
126, 4112-4113.
(5) (a) Siedlecka, R.; Skarzewski, J.; Michowski, J. Tetrahedron Lett. 1990,
31, 2177-2180. (b) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H.
Tetrahedron 1995, 51, 8023-8032.
(6) Dupeyre, R. M.; Rassat, A. Tetrahedron 1978, 34, 1901-1907.
a Method A: reactions were catalyzed by TEMPO or 1-Me-AZADO (1
mol %) with NaOCl (150 mol %), KBr (10 mol %), Bu4NBr (5 mol %),
aq. NaHCO3 in CH2Cl2 at 0 °C for 20 min. Method B: reactions were
catalyzed by TEMPO or 1-Me-AZADO (1 mol%) with 1.1. equiv of
PhI(OAc)2 in CH2Cl2 for 9 h at room temperature. b Isolated yield.
c Reaction was run using 20 g of substrate. d Not determined. e Reaction
was run using 3.3 equiv of PhI(OAc)2 for 14 h at room temperature.
f Reaction was run using 5.1 equiv of PhI(OAc)2 for 30 h at room
temperature.
(7) (a) Stetter, H.; Tacke, P.; Garner, J. J. Chem. Ber. 1964, 97, 3480-3487.
(b) Henkel, J. G.; Faith, W. C. J. Org. Chem. 1981, 46, 4953-4959.
(8) See Supporting Information.
(9) Representative procedure for oxidation of alcohols under Anelli’s
condition.4c To a stirring mixture of 3-phenylpropanol (200 mg, 1.47
mmol), 1-Me-AZADO (3) (0.244 mg, 1.47 µmol) in CH2Cl2 (3.9 mL)
and aqueous sat. NaHCO3 (2 mL) containing KBr (17.5 mg, 0.074 M)
and Bu4NBr (23.7 mg, 0.037 M) was added dropwise a premixed solution
of aqueous NaOCl (8% Cl) and aqueous sat. NaHCO3 (3.3 mL, 1:1.4
v/v) at 0 °C over 6 min. The mixture was vigorously stirred for 20 min
at 0 °C, then quenched with aqueous sat. Na2S2O3 (4 mL). The aqueous
layer was separated and extracted with Et2O. The combined organic layers
were washed with brine, dried over MgSO4, and concentrated. The residue
was purified by flash column chromatography (SiO2, 1:6 Et2O:hexane)
to give 3-phenylpropanal (177 mg, 1.32 mmol, 90%) as colorless oil.
(10) Representative procedure for oxidation of alcohols under Margarita’s
condition.4e PhI(OAc)2 (720 mg, 2.24 mmol) was added to a solution of
cinnamyl alcohol (200 mg, 1.49 mmol) and 1-Me-AZADO (3) (2.47 mg,
14.9 µmol) in CH2Cl2 (1.5 mL). The reaction mixture was stirred for 40
min, it was then diluted with Et2O and quenched with aqueous sat.
NaHCO3 (4 mL), followed by aqueous sat. Na2S2O3 (4 mL). The layer
was separated, and the aqueous layer was extracted with Et2O. The
combined organic layers were washed with brine, dried over MgSO4, and
concentrated. The residue was purified by flash column chromatography
(SiO2, 1:9 Et2O:hexane) to give cinnamaldehyde (183 mg, 1.39 mmol,
93%) as colorless oil.
To gain insight into the origin of the remarkable catalytic
efficiency of AZADO-type nitroxyl radicals, we synthesized 1,3-
dimethyl-AZADO (4)8 and examined its catalytic efficiency. 1,3-
Dimethyl-AZADO exhibits an activity for the oxidation of
3-phenylpropanol comparable to those exhibited by AZADO (2)
and 1-Me-AZADO (3). On the other hand, it does not efficiently
oxidize l-menthol similarly to TEMPO (1), showing a remarkable
difference from 1-Me-AZADO and AZADO. Cyclic voltammetric
measurements revealed that 2, 3, and 4 show well-defined redox
waves, of which the forms were unchanged after more than 100
cycle measurements, demonstrating their high durability as oxidation
catalysts.8 The E°′ values of the nitroxyl radicals are in the order
of 4 (136 mV) < 3 (186 mV) < 2 (236 mV) < 1 (294 mV).8
However, the total efficiencies of the nitroxyl radicals as catalyst
are in the order of 1 ∼ 4 , 3 ∼ 2.14 These observations support
the notion that the aggressive catalytic natures of 2 and 3 are due
to kinetic factors derived from decreased steric hindrance around
the reaction center.
(11) Gonsalvi, L.; Arends, I. W. C. E.; Sheldon, R. A. Org. Lett. 2002, 4,
1659-1661.
(12) (a) Tu, Y.; Frohn, M.; Wang, Z.; Shi, Y. Org. Synth. 2003, 80, 1-8. (b)
Wang, Z.; Shu, L.; Frohn, M.; Tu, Y.; Shi, Y. Org. Synth. 2003, 80, 9-17.
(13) (a) Robin, M.; Sarker, S.; Samano, V.; Wnuk, S. Tetrahedron 1997, 52,
447-456. (b) Nguyen-Trung, N. Q.; Botta, O.; Terenzi, S.; Strazewski,
P. J. Org. Chem. 2003, 68, 2038-2041.
(14) (a) Bobbitt, J. M.; Flores, M. C. Heterocycles 1988, 27, 509-533. (b)
Rychnovsky, S. D.; Vaidyanathan, R.; Beauchamp, T.; Lin, R.; Farmer,
P. J. J. Org. Chem. 1999, 64, 6745-6749.
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