5882
T. Nishii et al. / Tetrahedron Letters 53 (2012) 5880–5882
Table 3
Optimization of the reaction conditions for 1
CuCla) / dpPhen (10 mol %)
DBAD (10 mol %)
Cs2CO3 (200 mol %)
2 + 4
1
Air or O2, Tol, r.t., 3 h
1 mmol
Entry
Conditions
Yield of 2 + 4 (%)
Ratio (2/4)
Tol (mL)
Concn (M)
Oxidizing agent
1
2
3
4
5
1
1.0
0.1
0.05
0.02
0.02
Air
Air
Air
Air
O2
57
89
84
54
98
3/1
7/1
>10/1
>20/1
>20/1
10
20
50
50
a
CuCl (99.995+% purity, Aldrich).
References and notes
Table 4
Aerobic oxidation of primary alcohols
1. Modern Oxidation Methods; Bäckvall, J.-E., Ed.; Wiley-VCH: Weinheim,
Germany, 2004.
CuCla) / dpPhen (10 mol %)
2. For the most promising protocol in this field, see: Shibuya, M.; Osada, Y.;
Sasano, Y.; Tomizawa, M.; Iwabuchi, Y. J. Am. Chem. Soc. 2011, 133, 6497–6500.
3. For metal-free systems, see: Ref. 2 and references cited therein.
4. As metal-catalyzed systems, a wide variety of transition metals such as Pd, Ru,
Cu, and Co have been investigated. We have listed here only copper-catalyzed
processes see: (a) Markó, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C.
J. Science 1996, 274, 2044–2046; (b) Markó, I. E.; Tsukazai, M.; Giles, P. R.;
Brown, S. M.; Urch, C. J. Angew. Chem., Int. Ed. 1997, 36, 2208–2210; c) Markó, I.
E.; Gautier, A.; Chellé-Regnaut, I.; Giles, P. R.; Tsukazaki, M.; Urch, C. J.; Brown,
S. M. J. Org. Chem. 1998, 63, 7576–7577; (d) Markó, I. E.; Giles, P. R.; Tsukazaki,
M.; Chellé-Regnaut, I.; Gautier, A.; Brown, S. M.; Urch, C. J. J. Org. Chem. 1999,
64, 2433–2439; (e) Markó, I. E.; Gautier, A.; Mutonkole, J.-L.; Dumeunier, R.;
Ates, A.; Urch, C. J.; Brown, S. M. J. Organomet. Chem. 2001, 624, 344–347; (f)
Markó, I. E.; Gautier, A.; Dumeunier, R.; Doda, K.; Philippart, F.; Brown, S. M.;
Urch, C. J. Angew. Chem., Int. Ed. 2004, 43, 1588–1591; (g) Kitajima, N.; Whang,
K.; Moro-oka, Y.; Uchida, A.; Sasada, Y. J. Chem. Soc. 1986, 1504–1505; (h)
Wang, Y.; Stack, T. D. P. J. Am. Chem. Soc. 1996, 118, 13097–13098; (i) Wang, Y.;
Du Bois, J. L.; Hedman, B.; Hodgson, K.; Stack, T. D. P. Science 1998, 279, 537–
540; (j) Chaudhuri, P.; Hess, M.; Flörke, U.; Wieghardt, K. Angew. Chem., Int. Ed.
1998, 37, 2217–2220; (k) Mahadevan, V.; Du Bois, J. L.; Hedman, B.; Hodgson,
K.; Stack, T. D. P. J. Am. Chem. Soc. 1999, 121, 5583–5584; (l) Semmelhack, M. F.;
Schmid, C. R.; Cortes, D. A.; Chou, S. J. Am. Chem. Soc. 1984, 106, 3374–3376; (m)
Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Org. Biomol. Chem. 2003, 1,
3232–3237; (n) Shen, S.-S.; Kartika, V.; Tan, Y. S.; Webster, R. D.; Narasaka, K.
Tetrahedron Lett. 2012, 53, 986–990; (o) Betzemeier, B.; Cavazzini, M.; Quici, S.;
Knochel, P. Tetrahedron Lett. 2000, 41, 4343–4346; (p) Ragagnin, G.;
Betzemeier, B.; Quici, S.; Knochel, P. Tetrahedron 2002, 58, 3985–3991; (q)
Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507–1509; (r) Gamez, P.; Arends, I. W.
C. E.; Reedijk, J.; Sheldon, R. A. Chem. Commun. 2003, 2414–2415; (s) Hoover, J.
M.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 16901–16910.
DBAD (10 mol %)
O
Cs2CO3 (200 mol %)
R
OH
R
H
O2, Tol (50 mL), r.t., Period
1 mmol
Alcohol
Period (h)
1
Product
Yield (%)
97
CHO
CHO
OH
OH
3
3
94
CHO
OH
100
a
CuCl (99.995+% purity, Aldrich).
our focus to the reaction of primary alcohols. Using the same con-
ditions for the oxidation of secondary alcohols, we were able to
convert undecanol to a mixture of aldehyde 2 and ester 4 in 57%
yield in a 3:1 ratio that favored the aldehyde (Table 3, entry 1).
However, the production of 4 could be limited by conducting the
reaction under dilute conditions (entries 2 and 3). Furthermore,
although higher dilution of the reagents slowed the reaction, we
obtained very little ester 4 (entry 4). Finally, the use of molecular
oxygen gave satisfactory results (entry 5). Under the same highly
diluted conditions, a few primary alcohols were oxidized success-
fully to afford the corresponding aldehydes (Table 4).
5. Ingredients label of 95% CuCl (Nacalai) shows that the reagent contains sulfate,
sodium, potassium, copper (II), calcium, lead, arsenic, and iron as impurities to
some extent.
6. We tested several commercially available 1,10-phenanthrolines such as 5-
chloro-, 5-nitro-, 5,6-dimethyl-, and 4,7-diphenyl-1,10-phenanthroline.
7. Highly pure Cs2CO3 (99.995%, Aldrich) could not improve the efficiency of
oxidation any more.
8. Typical procedure for oxidation: To a suspension of CuCl (9.9 mg, 0.10 mmol,
99.995+% purity, Aldrich) in toluene (1 mL) was added 4,7-diphenyl-1,10-
phenanthroline (4) (33.5 mg, 0.1 mmol) to form a dark blue solution. After
10 min, DBAD (23.4 mg, 0.1 mmol) and Cs2CO3 (650 mg, 2 mmol) were added
to the solution and stirred for 5 min. Alcohol (1 mmol) was added and the
resulting mixture was left to stir for 3 h at room temperature under
atmospheric pressure of air without a cover (when O2 was used, an oxygen
balloon covered the flask). The reaction progress was monitored by TLC. After
completion, the mixture was filtered through Celite and evaporated. The
residue was purified by SiO2 column chromatography (hexane/AcOEt = 10:1/
3:1) to afford the ketone or aldehyde.
In conclusion, we have modified Markó’s aerobic oxidation pro-
cedure and have successfully oxidized primary and secondary alco-
hols to the corresponding aldehydes and ketones in excellent yield
under mild conditions using highly pure (99.995+%) CuCl with 4,7-
diphenyl-1,10-phenanthroline (dpPhen), DBAD, and Cs2CO3 (98%
purity).
Acknowledgments
9. All of resulting ketones were known compounds and their spectra were
compared with authentic samples.
This work was supported partially by a Grant-in-Aid for Scien-
tific Research (C) from MEXT (the Ministry of Education, Culture,
Sports, Science and Technology of Japan). We are also thankful to
the MEXT-Supported Program for the Strategic Research Founda-
tion at Private Universities, 2008–2012.
10. The mixture of alcohols (cis/trans = 1/2.4) was prepared by the reduction of
(2R)-2-benzylcyclohexanone11 (92% ee) with LAH.
11. Tsunoda, T.; Kaku, H.; Nagaku, M.; Okuyama, E. Tetrahedron Lett. 1997, 38,
7759–7760.
12. The optical purity was determined by HPLC analysis using a chiral column
(Daicel: chiralcell OJ).