A. J. Pearson, Y. Kwak / Tetrahedron Letters 46 (2005) 5417–5419
Table 2. The chemoselective oxidation of allylic and benzylic alcohols
5419
Acknowledgement
a
Entry
Substrates
Product(s)
Selectivity
We are gratefulto the NationalScience Foundation for
financialsupport of this research.
OH
OH
O
1
82% versus 0%
+
+
OH
References and notes
. (a) Larock, R. C. Comprehensive Organic Transformations,
1
OH
O
+
A Guide to Functional Group Preparation; VCH Publica-
tions: New York, 1989, pp 604–614; (b) Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Ley, S. V.,
Eds.; Pergamon: Oxford, 1991; Vol. 7, pp 251–325.
2
+
75% versus 0%
OH
OH
2
. (a) Parish, E. J.; Scott, A. D. J. Org. Chem. 1983, 48,
4766–4768; (b) Matsumoto, M.; Watanabe, N. J. Org.
Chem. 1984, 49, 3435–3436; (c) Kaneda, K.; Yamashita,
T.; Matsushita, T.; Ebitani, K. J. Org. Chem. 1998, 63,
a
1
Selectivity was determined by H NMR.
coordination of the hydroxy group to an iron catalyst
intermediate (conversions are lower for the same reac-
tion time compared with Table 1).
1
4
750–1751; (d) Lee, M.; Chang, S. Tetrahedron Lett. 2000,
1, 7507–7510; (e) Peterson, K. P.; Larock, R. C. J. Org.
Chem. 1998, 63, 3185–3189; (f) Moody, C. J.; Palmer, F.
N. Tetrahedron Lett. 2002, 43, 139–141; (g) Muldoon, J.;
Brown, S. N. Org. Lett. 2002, 4, 1043–1045.
Androst-4-ene-3,17-diolis a usefulsubstrate to test the
chemoselectivity, because it contains both allylic and
saturated alcohol moieties in the same molecule. This
compound was oxidized selectively under the given con-
ditions to afford testosterone in 76% yield after 10 h (Eq.
3. (a) Sondheimer, F.; Amendolla, C.; Rosenkranz, G. J.
Am. Chem. Soc. 1953, 75, 5930–5932; (b) Gritter, R. J.;
Wallace, T. J. J. Org. Chem. 1959, 24, 1051–1056; (c)
Burke, S. D.; Danheiser, R. L. Handbook of Reagents for
Organic Synthesis: Oxidizing and Reducing Agents; John
Wiley & Sons: New York, 1999, pp 231–236, and
references cited therein.
1
5
2
). Unreacted starting materialwas as lo recovered
20%), but extended reaction time did not improve the
(
conversion.
4
. Arnet, J. E.; Pettit, R. J. Am. Chem. Soc. 1961, 83, 2954–
955.
. Clifford, A. F.; Mukherjee, A. K. Inorg. Chem. 1963, 2,
51–153.
6. The oxidation using Fe(CO)
4
5
OH
OH
1
CHDFe(CO)3 (0.3 equiv.)
Me3NO (3 equiv.)
4 3 3
PPh with Me NO showed
moderate substituent effects, and p-chlorobenzyl alcohol
gave better conversion (p-Cl; 95%, p-H; 92%, p-MeO; 81%,
p-CH ; 71%).
acetone
O
HO
3
7
. The oxidation of these substrates using PCC in 5 mmol
scale gave 88% and 75% isolated yield with no unreacted
starting material.
. The oxidation of nerolusing PCC (3 equiv) at room
temperature furnished 87% yield with 27% isomerization.
. A rate difference between axial and equatorial alcohols
during the oxidation of allylic alcohols has been reported:
(a) Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Org.
Chem. 1997, 62, 5664–5665; (b) Fales, H. M.; Wildman,
W. C. J. Org. Chem. 1961, 26, 881–886.
7
6 %
ð2Þ
8
9
In conclusion, we have discovered a novel and efficient
method for the selective oxidation of allylic and benzylic
alcohols under mild conditions, which offers an alter-
native to the use of MnO . Further studies, including
2
catalyst development, optimization of the reaction
conditions, and mechanistic experiments are in progress.
1
1
0. Dasgupta, B.; Donaldson, W. A. Tetrahedron Lett. 1998,
9, 343–346.
1. Pearson, A. J.; Kwak, Y. Tetrahedron Lett. 2005, 46,
407–3410.
3
General procedure for the oxidation of allylic and benzylic
alcohols: A solution of allylic alcohol (1.0 mmol),
CHDFe(CO) (0.3 mmol), and Me NO (3.0 mmol) in
3
1
1
2. Shvo, Y.; Hazum, E. Chem. Commun. 1974, 336–337.
3. (a) Eekhof, J. H.; Hogeveen, H.; Kellogg, R. M. Chem.
Commun. 1976, 657; (b) Elzinga, J.; Hogeveen, H. Chem.
Commun. 1977, 705–706.
3
3
5
mL benzene was stirred for 10 h at room temperature.
Then, the reaction mixture was filtered through silica gel
and evaporated under reduced pressure to afford the
corresponding carbonyls. No additional purification is
necessary in most cases.
14. Franzen, V.; Otto, S. Chem. Ber. 1961, 94, 1360.
15. The same transformation using other oxidants is described
in Refs. 2a and 3a.