LETTER
Oxidative Rearrangement of Tertiary Allylic Alcohols
2145
Table 2 Copper(II) Chloride Catalyzed Oxidative Rearrangement
of Tertiary Allylic Alcohols Mediated by TEMPO (continued)
(7) (a) Semmelhack, M. F.; Schmid, C. R.; Cortés, D. A.; Chou,
C. S. J. Am. Chem. Soc. 1984, 106, 3374. (b) Miyazawa, T.;
Endo, T. J. Mol. Catal. 1985, 32, 357. (c) Tsubokawa, N.;
Kimoto, T.; Endo, T. J. Mol. Catal. A: Chem. 1995, 101, 45.
(d) Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507.
(e) Ragagnin, G.; Betzemeier, B.; Qiuci, S.; Knochel, P.
Tetrahedron 2002, 58, 3985. (f) Gamez, P.; Arends, I. W. C.
E.; Sheldon, R. A.; Reedijk, J. Adv. Synth. Catal. 2004, 346,
805. (g) Velusamy, S.; Srinivasan, A.; Punniyamurthy, T.
Tetrahedron Lett. 2006, 47, 923. (h) Striegler, S.
Entry Substrate
12
Methoda Time (h) Product (%)b,c
n-Bu
CHO
B
B
48
30
n-Bu
OH
O
(65)e
(45)f
Tetrahedron 2006, 62, 9109. (i) Jiang, N.; Ragauskas, A. J.
J. Org. Chem. 2006, 71, 7087. (j) Figiel, P. J.; Leskala, M.;
Repo, T. Adv. Synth. Catal. 2007, 349, 1173. (k) Mannam,
S.; Alamsetti, S. K.; Sekar, J. Adv. Synth. Catal. 2007, 349,
2253. (l) Lin, L.; Liuyan, J.; Yunyang, W. Catal. Commun.
2008, 9, 1379.
OH
13
a Method A: TEMPO (0.1 equiv), CuCl2·2H2O (0.5 equiv), O2 (bal-
loon), 4 Å MS, r.t.; Method B: TEMPO (0.1 equiv), CuCl2·2H2O (2
(8) Gamez, P.; Simons, C.; Steensma, R.; Driessen, W. L.;
Challa, G.; Reedijk, J. Eur. Polym. J. 2001, 37, 1293.
(9) For examples of the use of molecular sieves as acid
scavenger, see: (a) Vatèle, J.-M. Tetrahedron 2002, 58,
5689. (b) Urata, H.; Hu, N.-X.; Maekawa, H.; Fuchikami, T.
Tetrahedron Lett. 1991, 32, 4733. (c) Banks, A. R.; Fibiger,
R. F.; Jones, T. J. Org. Chem. 1977, 42, 3965.
equiv), 4 Å MS, r.t.
b Isolated yield.
c All synthesized compounds were characterized by 1H and 13C NMR
spectroscopy.
d Ratio E/Z = 1.8:1.
e Ratio E/Z = 2.5:1.
f Ratio E/Z = 1.8:1.
(10) Typical Procedure for Copper-Catalyzed Oxidative
Rearrangement of Tertiary Allylic Alcohols Mediated by
TEMPO. Method A: 3-Butylcyclohex-2-en-1-one (entry 1):
To a stirred solution of 1-butylcyclohex-2-en-1-ol (0.1 g,
0.65 mmol) in acetonitrile (2.5 mL) were successively added
TEMPO (0.01 g, 0.1 equiv), 4 Å molecular sieves (0.1 g) and
CuCl2·2H2O (0.056 g, 0.5 equiv). The brown suspension was
stirred under oxygen (balloon) for 7 h, then the suspension
was diluted with Et2O, washed twice with water, dried
(Na2SO4) and evaporated. The residue was purified by
chromatography on silica gel (PE–EtOAc, 5:1) to give the
enone as a liquid. 1H NMR (CDCl3, 200 MHz): d = 0.88 (t,
J = 7.1 Hz, 1 H, Me), 1.2–1.53 (m, 4 H, 2 × CH2), 1.95 (sept,
J = 6.2 Hz, 2 H), 2.18 (t, J = 7.7 Hz, 2 H, CH2), 2.29 (t, 4 H,
2 × CH2), 5.84 (s, 1 H). 13C NMR (50 MHz): d = 13.8, 22.3,
22.8, 29.1, 29.7, 37.4, 37.8, 125.6, 166.8, 199.9. HRMS:
m/z calcd for C10H16O: 152.1201; found: 152.1190. Method
B: 2-(tert-Butyldiphenylsilyloxymethyl)-3-methylcyclohex-
2-en-1-one (entry 7): To a stirred solution of 2-(tert-butyl-
diphenylsilyloxymethyl)-1-methylcyclohex-2-en-1-ol (0.1
g, 0.26 mmol) in acetonitrile (2 mL) were successively
added TEMPO (0.004 g, 0.1 equiv), molecular sieves (0.05
g) and CuCl2·2H2O (0.089 g, 2 equiv). After stirring the
reaction mixture for 10 h, work-up as described in method A
gave an oil, which was purified by flash chromatography
(PE–Et2O, 6:1) to afford an oil that crystallized on standing.
Mp 61–63 °C. IR (neat): 3049, 1667, 1634 cm–1. 1H NMR
(300 MHz): d = 1.04 (s, 9 H, Me), 1.91 (quint, J = 6.2 Hz,
2 H), 1.99 (s, 3 H, Me), 2.32–2.40 (m, 4 H, 2 × CH2), 4.47 (s,
2 H, CH2), 7.4 (m, 6 H), 7.7 (m, 4 H). 13C NMR (75 MHz):
d = 19.5, 21.5, 22.1, 27.0 (3 × Me), 33.1, 37.6, 56.3, 127.6 (4
× CH), 129.6 (2 × CH), 134 (2 × CH), 134.5, 135.8 (4 × CH),
160.5, 197.6. HRMS: m/z [M+H]+ calcd for C24H31O2Si:
379.2093; found: 379.2093.
In conclusion, we have developed a simple and conve-
nient method for the oxidative rearrangement of a wide
range of tertiary allylic alcohols using the TEMPO/Cu2+
couple, in the presence of 4Å molecular sieves. For most
substrates, oxidation was effected in the presence of a cat-
alytic amount of copper(II) salt using molecular oxygen as
a primary oxidant. Oxidative rearrangement of sterically
hindered substrates, as well as macrocyclic substrates and
acyclic substrates, occurred at a reasonable rate in the
presence of an excess of copper(II) chloride.
References and Notes
(1) (a) Babler, J. H.; Coghlan, M. J. Synth. Commun. 1976, 469.
(b) Dauben, W. G.; Michno, D. M. J. Org. Chem. 1977, 42,
682. (c) Sundararaman, P.; Herz, W. J. Org. Chem. 1977, 42,
813.
(2) For examples of the oxidative rearrangement with
chromium(VI) reagents on diversely functionalized tertiary
allylic alcohols, see: (a) Brown, P. S.; McElroy, A. B.;
Warren, S. Tetrahedron Lett. 1985, 26, 249. (b) Liotta, D.;
Brown, D.; Hoekstra, W.; Monahan, R. III. Tetrahedron
Lett. 1987, 28, 1069. (c) Majetich, G.; Condon, S.; Hull, K.;
Ahmad, S. Tetrahedron Lett. 1989, 30, 1033. (d) Öhler, E.;
Zbiral, E. Synthesis 1991, 357. (e) Nangia, A.; Rao, B.
Tetrahedron Lett. 1993, 34, 2681. (f) Luzzio, F. A.; Moore,
W. J. J. Org. Chem. 1993, 58, 2966. (g) Surya Prakash,
G. K.; Tongco, E. C.; Mathew, T.; Vankar, Y. D.; Olah,
G. A. J. Fluorine Chem. 2000, 101, 199.
(3) (a) Shibuya, M.; Ito, S.; Takahashi, M.; Iwabuchi, Y. Org.
Lett. 2004, 6, 4303. (b) Tello-Aburto, R.; Ochoa-Teran, A.;
Olivo, H. F. Tetrahedron Lett. 2006, 47, 5915.
(4) (a) Shibuya, M.; Tomizawa, M.; Iwabuchi, Y. J. Org. Chem.
2008, 73, 4750. (b) Shibuya, M.; Tomizawa, M.; Iwabuchi,
Y. Org. Lett. 2008, 10, 4715.
(11) For kinetic studies on TEMPO-mediated oxidation, see:
(a) de Nooy, A. E. J.; Besemer, A. C.; Van bekkum, H.
Tetrahedron 1995, 51, 8023. (b) Shibuya, M.; Tomizawa,
M.; Suzuki, I.; Iwabuchi, Y. J. Am. Chem. Soc. 2006, 128,
8412.
(12) For examples of the formation of fragmentation products,
see: Alvarez, F. M.; Van der Meer, R. K.; Lofgren, C. S.
Tetrahedron 1987, 43, 2897; see also refs. 1a, 1b and 2b.
(5) (a) Vatèle, J.-M. Tetrahedron Lett. 2006, 47, 715.
(b) Vatèle, J.-M. Synlett 2006, 2055.
(6) Vatèle, J.-M. Synlett 2008, 1785.
Synlett 2009, No. 13, 2143–2145 © Thieme Stuttgart · New York