Highly chemo- and regioselective rearrangement of α,β-epoxy ketones to 1,3-dicarbonyl compounds in 5 mol dm-3 lithium perchlorate-diethyl ether medium

Article abstract of DOI:10.1039/a905619j

Epoxides from α,β-unsaturated ketones undergo highly chemo- and regioselective rearrangement to 1,3-dicarbonyl compounds in 5 mol dm^-3 lithium perchlorate-diethyl ether medium by a 1,2-migration of the carbonyl group at ambient conditions. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a905619j

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Highly chemo- and regioselective rearrangement of ꢀ,ꢁ-epoxy
ketones to 1,3-dicarbonyl compounds in 5 mol dm؊3 lithium
perchlorate–diethyl ether medium
S. Sankararaman* and J. E. Nesakumar
Department of Chemistry, Indian Institute of Technology, Madras-600 036, India
Received (in Cambridge, UK) 12th July 1999, Accepted 13th September 1999
Epoxides from α,β-unsaturated ketones undergo highly chemo- and regioselective rearrangement to 1,3-dicarbonyl
compounds in 5 mol dmϪ3 lithium perchlorate–diethyl ether medium by a 1,2-migration of the carbonyl group at
ambient conditions.
However, the corresponding β-methyl derivatives 12 and 17
Introduction
reacted in LPDE at room temperature. In the case of epoxide
12, rearrangement accompanied by ring contraction resulted
in the formation of the keto aldehyde 13 whereas epoxide 17
yielded the α-hydroxy ketone 18 as the sole product. Similarly,
isophorone oxide 14 underwent ring contraction to give 15 as
the only product. In the case of 16, an α-methyl-substituted
derivative, no reaction occurred under various conditions
employed. In the case of epoxide 19 rearrangement resulted in
ring enlargement to yield the diketone 20. The bicyclic epoxide
21 yielded the α-hydroxy enone 22. Both the epoxides 19 and 21
rearranged only in the presence of Yb(OTf)3 in LPDE.
Conversion of an epoxide to a carbonyl compound is a syn-
thetically useful and important transformation.1 However, the
lack of chemo-, regio- and stereoselectivities in the ring-
opening/rearrangement steps can limit the use of this reaction
in synthetic sequences. Although the most commonly used
reagent for this reaction is BF3, it does not offer any chemo-
selectivity.1 Recently we have reported highly chemo-, regio-
and stereoselective conversion of epoxides of simple olefins to
carbonyl compounds in 5 mol dmϪ3 lithium perchlorate–diethyl
ether (LPDE) medium.2 Rearrangement of epoxides from
α,β-unsaturated carbonyl compounds offers a convenient
method for the synthesis of 1,2- and 1,3-dicarbonyl compounds
and spirodiketones.3 Herein, we report highly selective trans-
formation of epoxides from α,β-unsaturated ketones to 1,3-
dicarbonyl compounds in 5 mol dmϪ3 lithium perchlorate–
diethyl ether medium under mild reaction conditions.
Mechanism
Spectroscopic evidences strongly suggest that lithium ion in
LPDE medium is a weak Lewis acid, its Lewis acidity being
moderated by the coordination of the ether oxygen to the
lithium ion.6 The high selectivities observed in organic trans-
formations carried out in LPDE medium is attributed to
the mild Lewis acidity of the lithium ion.7 Earlier we had
reported chemo-, regio- and stereoselective conversion of
simple epoxides to carbonyl compounds and we attributed the
observed selectivitites to the mild Lewis acidity of the lithium
ion in LPDE medium.2 The epoxide ring-opening/rearrange-
ment reaction in LPDE medium could proceed by the tentative
mechanism shown in Scheme 1. The lithium ion coordinates
to the epoxide oxygen and the carbonyl oxygen, resulting
in weakening of the epoxide C–O bond followed by regio-
selective cleavage of the C–O bond to give the most stable
carbenium ion (Scheme 1). This explains why only β-substi-
tuted epoxides undergo rearrangement because only then can a
stable tertiary carbenium ion be formed. The migration of the
acyl group to the carbenium ion center leads to the formation
of the 1,3-dicarbonyl compound as the product of rearrange-
ment. Attempts to trap any carbenium ion intermediates that
could be formed during the ring-opening step using a silyl enol
ether as a nucleophile failed. For example, the rearrangement of
epoxide 5 in the presence of 1-(trimethylsilyloxy)cyclohexene
yielded only the rearranged product although retardation of
the rate of the reaction was observed in the presence of the silyl
enol ether. Whereas in the absence of the silyl enol ether the
rearrangement of 5 was complete within 30 min, in the presence
of the same the reaction was complete only after 36 h, under
otherwise identical conditions. Similarly the rearrangement of
epoxide 14 in LPDE in the presence of 1-(trimethylsilyloxy)-
cyclohexene also yielded only the keto aldehyde 15 and there is
no evidence for the formation of any trapping product from the
silyl enol ether. However, in the presence of the enol ether the
Results and discussion
The epoxide 1 of benzalacetone reacted in 5 mol dmϪ3 LPDE
medium at room temperature to give 3-oxo-2-phenylbutanal 2
as the only product in 78% yield after chromatographic purifi-
cation. However, the epoxide of benzalacetophenone, 3, failed
to undergo any reaction under a variety of conditions listed in
Table 1 and the starting material was recovered in all cases. The
use of a stronger Lewis acid such as ytterbium triflate in
catalytic amount in LPDE resulted in the conversion of epoxide
3 into 2,3-diphenyl-3-oxopropanal 4 as the sole product in 73%
yield. Control experiments clearly showed that yttribium triflate
alone in diethyl ether did not cause any reaction in the absence
of lithium perchlorate. In sharp contrast, epoxide 5 bearing an
electron donating methoxy group in the para position under-
went rearrangement smoothly to yield the keto aldehyde 6 in
good yield within 30 min. Although it is well known in the
literature that electron-donating substituents on the phenyl ring
accelerate the rearrangement of epoxides from α,β-unsaturated
ketones,4 the chemoselectivity observed between epoxides 1 and
3 is surprising and such selectivity is not observed when a
stronger Lewis acid such as BF3 is used. The epoxide 7 of
mesityl oxide (4-methylpent-3-en-2-one), rearranged to give
the keto aldehyde 8 whereas epoxide 9 did not undergo any
reaction in this medium. In all these cases the formation of the
1,3-dicarbonyl compounds can be explained by a selective C–O
bond cleavage followed by a 1,2-acyl migration mechanism.5
The epoxides from cyclohex-2-enone, 10, and cyclopent-2-
enone, 11, were both inert and did not undergo any reaction in
LPDE medium under a variety of conditions given in Table 1.
J. Chem. Soc., Perkin Trans. 1, 1999, 3173–3175
This journal is © The Royal Society of Chemistry 1999
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Table 1 Rearrangement of α,β-epoxy ketones in LPDE
Epoxide Product
Ref.
9
Conditionsa
A, 30 min
Yield (%)
78
A–D, 2 days
10
E, 20 h
73
10, 11
12
A, 30 min
75
53
A, 21 h
A, C, 2 days
A–E, 2 days
A–E, 2 days
9, 13
A, 21 h
A, 21 h
68
69
14
A–E, 2 days
13, 15
A, 6 h
74
13
16
E, 20 h
E, 21 h
70
65
a Reaction conditions: A: 5 mol dmϪ3 LPDE, rt; B: 5 mol dmϪ3 LPDE, 60 ЊC; C: 5 mol dmϪ3 LPNM, rt; D: 5 mol dmϪ3, LPNM, 60 ЊC; E: 5 mol dmϪ3
LPDE, 10% Yb(OTf)3, rt.
rearrangement of 14 was complete only after several days. The
retardation in the rate could be due to the competitive bind-
ing of lithium ion by the silyl enol ether thereby reducing the
effective concentration of the lithium ion. That the rate of the
rearrangement is highly dependent on the lithium ion concen-
tration is clearly demonstrated by carrying out the reaction
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under various lithium perchlorate concentrations. Reducing
the concentration of the lithium perchlorate from 5 mol dmϪ3
to 2.5 mol dmϪ3 caused a dramatic decrease in the rates of these
reactions. For example, the rearrangement of epoxide 5 was
complete within 30 min in 5 mol dmϪ3 LPDE whereas in 2.5
mol dmϪ3 LPDE it took 36 h for completion. Similarly the
rearrangement of epoxide 14 was complete only after 55 h in
2.5 mol dmϪ3 LPDE solution whereas the reaction was com-
plete within 21 h in 5 mol dmϪ3 LPDE. This type of concen-
tration effect on the rate has also been observed earlier in the
dithioacetalization of aldehydes and acetals, a Michael reaction
of enol ethers in LPDE medium.7
General procedure for the rearrangement of epoxides
A solution of an epoxide (2 mmol) in 5 mol dmϪ3 LPDE (2 cm3)
was stirred at room temperature under N2 atmosphere until its
complete disappearance as indicated by TLC. The reaction
mixture was diluted with CH2Cl2 (30 cm3) and washed with
water. The organic layer was dried over anhydrous Na2SO4
and the solvent was removed to obtain the crude product,
which was purified by column chromatography over silica gel.
The products are literature known compounds and they were
characterized in the present study by IR, high-resolution (400
1
MHz) H and 13C NMR, and mass spectroscopic data. The
literature references are given in Table 1.
Acknowledgements
Financial support from CSIR, New Delhi, in the form of a
Senior Research Fellowship (J. E .N) and a Sponsored Research
Project (S. S.) is gratefully acknowledged. We thank the
Regional Sophisticated Instrumentation Centre, IIT, Madras,
for the high-resolution NMR and mass spectral data.
References
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Scheme 1 Mechanism for the rearrangement of epoxides in LPDE
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6039.
Epoxides derived from cyclic and acyclic α,β-unsaturated
carbonyl compounds underwent highly chemo- and regioselec-
tive rearrangement to yield 1,3-dicarbonyl compounds in 5 mol
dmϪ3 LPDE medium. The high selectivities observed in the
rearrangement of epoxide are attributed to the mild Lewis
acidity of lithium ion in this medium. Addition of silyl enol
ether affected only the rate of the reaction and did not alter
the course of the rearrangement reactions.
Experimental
Materials
Preparation of 5 mol dmϪ3 LPDE and lithium perchlorate in
nitromethane (LPNM) and the instrumentation used have
been described earlier.7 The epoxides were prepared accord-
ing to the following general procedure.8 To a solution of the
α,β-unsaturated ketone (20 mmol) in methanol (140 cm3)
cooled to 0 ЊC was added a 30% aqueous solution of H2O2 (110
mmol). To this stirred mixture was added a 10% aqueous
solution of NaOH (5 cm3) and the mixture was stirred for an
additional 1–2 h at 0 ЊC. The reaction mixture was diluted with
CH2Cl2 (250 cm3), and the organic layer was separated, washed
with saturated brine (50 cm3), dried over anhydrous Na2SO4
and then concentrated under vacuum to afford the crude
epoxides, which were further purified by either recrystallization
or by vacuum distillation. All the epoxides are literature known
compounds and in the present study they were characterized by
15 C. M. Cimarusti and J. Wolinsky, J. Org. Chem., 1966, 31, 4118.
16 R. C. Klix and R. D. Bach, J. Org. Chem., 1987, 52, 580.
1
IR, high-resolution (400 MHz) H and 13C NMR, and mass
spectroscopic data.
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