Cerium(IV) ammonium nitrate-catalyzed synthesis of β-keto enol ethers from cyclic β-diketones and their deprotection

Article abstract of DOI:10.1246/cl.2006.16

A mild and efficient method for etherification of cyclic β-diketones with alcohols has been developed using a catalytic amount of cerium(IV) ammonium nitrate at room temperature to afford the corresponding β-keto enol ethers in good to excellent yields. The deprotections of enol ethers in water-acetonitrile (1:1) using a catalytic amount (10 mol %) of cerium(IV) ammonium nitrate have also been achieved. Copyright

Full text of DOI:10.1246/cl.2006.16

16
Chemistry Letters Vol.35, No.1 (2006)
Cerium(IV) Ammonium Nitrate-catalyzed Synthesis of ꢀ-Keto Enol Ethers
from Cyclic ꢀ-Diketones and Their Deprotection
Biplab Banerjee, Samir Kumar Mandal, and Subhas Chandra Royꢀ
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
(Received September 26, 2005; CL-051219)
A mild and efficient method for etherification of cyclic ꢀ-di-
Table 1. CAN-catalyzed etherification of cyclic ꢀ-diketones
and their deprotection
ketones with alcohols has been developed using a catalytic
amount of cerium(IV) ammonium nitrate at room temperature
to afford the corresponding ꢀ-keto enol ethers in good to excel-
lent yields. The deprotections of enol ethers in water–acetonitrile
(1:1) using a catalytic amount (10 mol %) of cerium(IV) ammo-
nium nitrate have also been achieved.
Yield (%) of
enol ether
(reaction time) (reaction time)
Yield (%) of
deprotection
a
Entry
Substrate
O
Alcohol
MeOH
EtOH
Product
O
O
O
O
O
O
1
2
93 (8 min)
91 (7 min)
91 (0.5 h)
92 (0.5 h)
O
OMe
1
O
ꢀ-Keto enol ethers are versatile intermediates in synthetic
organic chemistry.1 For example, they have been widely used
as precursors for the synthesis of different optically active com-
pounds.2 Usually, ethers are prepared by coupling reactions of
alkoxide or alcohols with different alkyl halides in basic condi-
tions.3 Although several methods have been demonstrated for
the synthesis of ꢀ-keto enol ethers from cyclic ꢀ-diketones such
as p-toluene sulfonic acid catalyzed etherification,4 methyl ether
from 3-chlorocycloalk-2-enones,5 methylation using diazo-
methane,1 and catalytic etherification by TiCl4,6 iodine,7 and
B(C6F5)3,8 the use of lanthanides as reagents in this field is
not much explored. In recent years, several lanthanide com-
plexes have proven to be extraordinarily effective catalysts for
various organic transformations.9 We wish to report here a mild
and efficient synthesis of ꢀ-keto enol ethers from cyclic ꢀ-dike-
tones in good to excellent yields using a catalytic amount of
CAN (10 mol %) at room temperature.
Cerium(IV) ammonium nitrate (CAN) has been widely used
in carbon–carbon9 as well as carbon–heteroatom10 bond forming
reactions and also as a powerful one electron oxidant11 in organ-
ic synthesis for several years. In continuation to our efforts12 to
develop novel methodologies in organic synthesis using com-
mercially available CAN as a catalyst, we treated cyclic ꢀ-dike-
tones with an excess of alcohols (also act as solvents) at room
temperature to afford the corresponding ꢀ-keto enol ethers in
good to excellent yields (Scheme 1).
O
OEt
2
3
O
O
3
4
CH3(CH2)2CH2OH
CH3(CH2)4CH2OH
88 (12 min)
86 (22 min)
90 (0.75 h)
84 (1 h)
O
O
OCH2(CH2)2CH3
OCH2(CH2)4CH3
OCH2Ph
4
5
O
O
O
5
PhCH2OH
PhCH2CH2OH
OH
90 (15 min)
88 (0.75 h)
O
O
O
6
7
89 (14 min)
89 (18 min)
83 (1 h)
84 (2 h)
OCH2CH2Ph
6
7
O
O
O
O
O
O
O
O
8
9
MeOH
EtOH
92 (9 min)
90 (0.5 h)
89 (0.5 h)
O
O
O
OMe
OEt
O
8
9
90 (10 min)
10
90 (16 min)
87 (1.5 h)
OH
10
O
O
O
(CH3)2CHOH
11
12
70 (25 min)
62 (35 min)
80 (2.5 h)
75 (3 h)
OCH(CH3)2
O
O
11
12
O
Thus, cyclohexan-1,3-dione and 5,5-dimethylcyclohexan-
1,3-dione (dimedone) were subjected to the etherification reac-
tion13 at room temperature with various alcohols in the presence
of a catalytic amount of CAN (10 mol %) to furnish ꢀ-keto enol
ethers 1–12 and the results are summarized in Table 1.
Although primary (Entries 1–10) as well as secondary alco-
hols (Entries 11 and 12) underwent smoothly at room tempera-
ture, the reaction with secondary alcohols took place with an in-
OH
O
aProducts were characterized by NMR, IR, and HRMS analysis
and also by comparing the spectral data with those of authentic
samples.
creased reaction time and with a lower yield of products com-
pared to the reaction with primary alcohols. The etherification
did not undergo at all with sterically crowded tert-butanol under
the reaction conditions. It is noteworthy that the reaction of prop-
argyl alcohol (Entry 7) and allyl alcohol (Entry 10) underwent
smoothly with dimedone giving excellent yields of the ꢀ-keto
enol ethers 7 and 10, respectively.
CAN (10 mol %)
O
O
O
1
R OH, rt, 7–35 min
R
R
R
CAN (10 mol %)
1
OR
O
OH
R
R
R
H O–CH CN (1:1)
2
3
R = H or CH3
reflux, 0.5–3 h
We have also successfully deprotected14 the ꢀ-keto enol
ethers (1–12) to the corresponding cyclic ꢀ-diketones in good
Scheme 1.
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.1 (2006)
17
to excellent yields by treatment with CAN (10 mol %) in water–
acetonitrile (1:1) under reflux condition as depicted in Table 1.
However, open chain ꢀ-diketones such as acetylacetone and
benzoylacetone when treated with MeOH in the presence of a
catalytic amount of CAN remained unchanged even after pro-
longed stirring. These open chain ꢀ-diketones preferably exist
in cis-enol form in the solution and serve as bidentate ligands
which may form a stable cerium complex.6 In contract, enoliza-
tion of cyclic ꢀ-diketones forms fixed trans-enols where no such
complex formation is sterically possible.
In summary, we have developed a mild and efficient
CAN-catalyzed method for the synthesis of ꢀ-keto enol ethers
from ꢀ-diketones at room temperature in good to excellent
yields. We have also developed a method for deprotection of
ꢀ-keto enol ethers to the corresponding cyclic ꢀ-diketones in
water–acetonitrile under reflux condition catalyzed by CAN
(10 mol %).
Augustine, Synlett 2003, 156.
11 a) V. Nair, J. Mathew, J. Prabhakaran, Chem. Soc. Rev. 1997,
127. b) G. A. Molander, Chem. Rev. 1992, 92, 29. c) W.-B.
Pan, F.-R. Chang, L.-M. Wei, M.-J. Wu, Y.-C. Wu, Tetra-
hedron Lett. 2003, 44, 331, and references cited therein.
12 a) S. C. Roy, S. Adhikari, Ind. J. Chem. 1992, 31B, 459. b) G.
Maity, S. C. Roy, Synth. Commun. 1993, 23, 1667. c) P. K.
Mandal, S. C. Roy, Tetrahedron 1995, 51, 7823. d) S. C.
Roy, P. K. Mandal, Tetrahedron 1996, 52, 2193. e) S. C.
Roy, P. K. Mandal, Tetrahedron 1996, 52, 12495. f) S. C.
Roy, C. Guin, K. K. Rana, G. Maiti, Synlett 2001, 226. g)
S. C. Roy, C. Guin, K. K. Rana, G. Maiti, Tetrahedron Lett.
2001, 42, 6941. h) S. C. Roy, C. Guin, G. Maiti, Tetrahedron
Lett. 2001, 42, 9253. i) G. Maiti, S. C. Roy, Synth. Commun.
2002, 32, 2269. j) S. C. Roy, B. Banerjee, Synlett 2002,
1677. k) S. C. Roy, K. K. Rana, C. Guin, B. Banerjee, Synlett
2003, 221. l) S. C. Roy, K. K. Rana, C. Guin, B. Banerjee,
ARKIVOC 2003, ix, 34.
B. B. and S. K. M. thank CSIR, New Delhi for awarding
fellowships.
13 Typical procedure for etherification: A solution of 5,5-di-
methylcyclohexan-1,3-dione (dimedone) (140 mg, 1 mmol)
in 3-methylcycloxehanol (3 mL) was stirred with CAN (55
mg, 0.1 mmol) at room temperature under N2 for 35 min.
Then excess alcohol was removed under reduced pressure
and the residue obtained was extracted with ether (2 ꢁ 50
mL). The combined ether layer was washed successively
with water (20 mL) and brine (20 mL) and finally dried
(Na2SO4). The solvent was removed under reduced pressure
and the residue obtained was purified by column chromatog-
raphy over silica gel (30% ethyl acetate in petroleum ether)
to obtain the pure ꢀ-keto enol ether 12 (147 mg, 62%) as a
crystalline solid, mp 50–52 ꢂC; IR (KBr): 2933, 2866,
References and Notes
1
a) D. R. Marshall, T. R. Roberts, J. Chem. Soc. B 1971, 797.
b) H. House, G. H. Rasmusson, J. Org. Chem. 1963, 28, 27.
c) K. Takahashi, T. Tanaka, T. Suzuki, M. Hirama, Tetra-
hedron 1994, 50, 1327.
2
3
a) B.-C. Chen, M. C. Weismiller, F. A. Davis, Tetrahedron
1991, 47, 173. b) A. S. Demir, O. Sesenoglu, Org. Lett.
2002, 4, 2021.
a) A. W. J. Robert, M. E. Rose, Tetrahedron 1979, 35, 2169.
b) C. Brosa, J. C. Ferrer, C. Malet, J. M. Amezaga, J. Org.
Chem. 1989, 54, 3984.
1654, 1602, 1367, 1220 cmꢃ1
;
1H NMR (CDCl3, 300
4
5
H. E. Zimmerman, P. A. Wang, J. Am. Chem. Soc. 1993, 115,
2205.
MHz): ꢁ 0.92 (d, J ¼ 6:5 Hz, 3H), 1.05 (s, 6H), 1.12–1.46
(m, 4H), 1.61–2.06 (m, 5H), 2.19 (s, 2H), 2.22 (s, 2H),
4.03–4.13 (m, 1H), 5.36 (s, 1H); 13C NMR (CDCl3,
75 MHz): ꢁ 22.0, 23.6, 28.0, 28.1, 31.0, 31.1, 32.2, 33.8,
39.7, 43.2, 50.4, 76.8, 101.6, 175.0, 199.5; HRMS Calcd
for C15H24O2: ½M þ Hꢄþ 237.1855. Found 237.1829.
a) M. J. Mphahlele, T. A. Modro, J. Org. Chem. 1995, 60,
8236. b) P. H. Nelson, J. T. Nelson, Synthesis 1992, 1287.
A. Clerici, N. Pastori, O. Porta, Tetrahedron 2001, 57, 217.
R. S. Bhosale, S. V. Bhosale, T. Wang, P. K. Zubaidha,
Tetrahedron Lett. 2004, 45, 7187.
6
7
14 Typical procedure for deprotection of enol ethers: A mixture
of the ꢀ-keto enol ether 12 (354 mg, 1.5 mmol) and CAN
(82 mg, 0.15 mmol) in water (3 mL) in acetonitrile (3 mL)
was refluxed for 3 h under N2. Then the mixture was diluted
with saturated brine (20 mL) and extracted with ether
(2 ꢁ 50 mL). The combined ether extract was washed with
brine (20 mL) and finally dried (Na2SO4). Solvent was
removed under reduced pressure and the residue obtained
was purified by column chromatography on silica gel (40%
ethyl acetate in petroleum ether) to obtain 5,5-dimethyl-
cyclohexan-1,3-dione (dimedone) (158 mg, 75%).
8
9
S. Chandrasekhar, Y. S. Rao, N. R. Reddy, Synlett 2005,
1471.
a) T. Imamoto in Lanthanide Reagents in Organic Synthesis,
Academic Press, London, 1994, p. 119. b) F. J. Moreno-
Dorado, F. M. Guerra, F. L. Manzano, F. J. Aladro, Z. D.
Jorge, G. M. Massanet, Tetrahedron Lett. 2003, 44, 6691.
c) Z.-P. Zhan, K. Lang, Org. Biomol. Chem. 2005, 3, 727.
d) M. Adinolfi, A. Iadonisi, A. Ravida, M. Schiattarella,
J. Org. Chem. 2005, 70, 5316.
10 V. Nair, S. B. Panicker, L. G. Nair, T. G. George, A.
Published on the web (Advance View) November 29, 2005; DOI 10.1246/cl.2006.16