Highly regio- and stereoselective rearrangement of epoxides to aldehydes catalyzed by high-valent metalloporphyrin complex, Cr(TPP)OTf

Article abstract of DOI:10.1021/ja047104k

Chromium(III) tetraphenylporphyrin triflate, Cr(TPP)OTf, works as an efficient and characteristic Lewis acid catalyst in the regio- and stereoselective rearrangement of epoxides to aldehydes. This Cr(TPP)OTf-catalyzed reaction is an operationally simple a

Full text of DOI:10.1021/ja047104k

Published on Web 07/20/2004
Highly Regio- and Stereoselective Rearrangement of Epoxides to Aldehydes
Catalyzed by High-Valent Metalloporphyrin Complex, Cr(TPP)OTf
Kohji Suda,* Taketoshi Kikkawa, Shin-ichiro Nakajima, and Toshikatsu Takanami
Meiji Pharmaceutical UniVersity, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Received May 17, 2004; E-mail: suda@my-pharm.ac.jp
Scheme 1
Lewis acid-promoted rearrangement of epoxides into carbonyl
compounds is among the most synthetically useful and important
functionalization reactions of organic compounds. The rearrange-
ment has widely been applied to the synthesis of various biologically
active natural products with unique structural properties,1,5 but it
is well-known that the yield and regio- and stereoselectivity of these
rearrangements markedly vary with the mode of substituents on
the ring and the reaction conditions.2 Hence, the control of regio-
and stereochemistry of the rearrangements still remains an important
Table 1. Screening of Metalloporphyrin Catalysts and Solvents for
and fundamental puzzle to be solved in epoxide chemistry.
As illustrated in Scheme 1, the rearrangement of substituted
epoxides 1, in principle, proceeds from a cleavage of the Câ-O
bond followed by hydrogen migration (route A) or alkyl (R1)
migration (route B), leading to the corresponding ketones 2 or
aldehydes 3, respectively. Although considerable efforts have
recently been made for the development of efficient reagents and
catalysts which allow access to ketones 2,3,7a for the rearrangement
to aldehydes 3, a bulky organoaluminum reagent, methylaluminum
bis(4-bromo-2,6-di-tert-butyl-phenoxide) (MABR), is still the sole
reagent available for this purpose.4 MABR is, unfortunately, a
reagent rather than a catalyst: more than a stoichiometric amount
of the reagent is usually necessary to promote the rearrangement.6
We report herein a highly regio- and stereoselective rearrange-
ment of epoxides 1 to aldehydes 3 with a porpyrin-based Lewis
acid catalyst, chromium(III) tetraphenylporphyrin triflate, Cr(TPP)-
OTf, in low catalyst loading (1-20 mol %) under very mild
conditions.7,8 This Cr(TPP)OTf-catalyzed reaction is especially
appropriate for the synthesis of optically active â-siloxy aldehydes,
useful intermediates in natural product synthesis, from 2,3-epoxy
silyl ethers which are readily available in enantiomerically enriched
forms by the Sharpless epoxidation of allylic alcohols9 followed
by silylation.10,11
the Rearrangement of Epoxides to Aldehydes
yield (%)a
entry
catalyst(mol %)/solvents/temp.(°C)/time (h)
2a
3a
1
2
3
4
5
6
7
8
9
Fe(TPP)ClO4 (1)/dioxane/100/0.5
Fe(TPP)ClO4 (1)/Cl(CH2)2Cl /83/0.5
Mn(TPP)ClO4 (1)/Cl(CH2)2Cl/83/1
Cr(TPP)ClO4 (1)/Cl(CH2)2Cl/83/2
Cr(TPP)OTf (1)/Cl(CH2)2Cl/83/1
B(C6F5)3 (2)/Cl(CH2)2Cl/83/40
B(C6F5)3 (2)/toluene/110/40
>99
65
53
11
0
0
32
45
87
97b
15
14
no reaction
16
33
Cr(salen)OTf (2)/Cl(CH2)2Cl/83/40c
Mn(salen)OTf (2)/Cl(CH2)2Cl/83/22d
40
34
a Isolated yield. b A trace amount (<2%) of ketone 2a could be detected
in the 1H NMR spectrum of the crude reaction mixture. c Cr(salen)OTf:
(S,S)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino chro-
mium(III) triflate. d Mn(salen)OTf: (S,S)-(+)-N,N′-bis(3,5-di-tert-butyl-
salicylidene)-1,2-cyclohexanediamino manganase(III) triflate.
Reaction conditions and regioselectivity for the porphyrin-based
catalytic rearrangement of epoxides were investigated with trans-
2-(tert-butyldimethylsiloxy)methyl-3-phenyloxirane, 1a, as a model
substrate in a variety of solvents with a series of high-valent
metalloporphyrin catalysts, such as Fe(TPP)ClO4, Mn(TPP)ClO4,
and Cr(TPP)ClO4. The representative results are shown in Table
1. As reported previously, an Fe(TPP)ClO4-dioxane catalyst system
exclusively promoted the hydrogen migration of 1a to give ketone
2a in a quantitative yield (entry 1).7a On the other hand, the use of
Cr(TPP)ClO4 (1 mol %) in dichloroethane at 83 °C preferentially
brought about the alkyl migration of 1a, affording 87% yield of
the desired aldehyde 3a along with the ketone 2a in 11% yield
(entry 4). Changing the catalyst from Cr(TPP)ClO4 to Cr(TPP)-
OTf further improved the reactivity and regioselectivity of the
rearrangement, providing aldehyde 3a as the sole isolable product
in 97% yield under the optimal conditions (entry 5). Attempts for
the rearrangement of 1a with other Lewis acid catalysts, such as
B(C6F5)3 12 and chromium and manganese salen complexes,13 which
have been known to catalyze ring-opening reactions of epoxides,
were, however, unsuccessful under the reaction conditions examined
(entries 6-9). The Cr(TPP)OTf-catalyzed rearrangement in dichlo-
roethane can also be applied successfully to a variety of epoxides
such as trialkyl-substituted epoxides, spiroepoxides, and bicyclic
epoxides (Table 2, entries 1-4), furnishing the corresponding
aldehydes in good yields.
We next explored the stereoselectivity of the Cr(TPP)OTf-
dichloroethane catalyst system with various optically active epoxy
silyl ethers (Table 2, entries 5-10). As a whole, a facile and highly
stereoselective migration of the alkyl groups to give the corre-
sponding aldehydes was observed. Optically pure phenyl-substituted
epoxy silyl ethers 1b-1d were converted to the corresponding
optically active â-siloxy aldehydes 3b-3d as the sole isolable
products in high yields via highly stereoselective anti migration of
the siloxymethyl groups to the Câ of the oxirane moieties. Likewise,
stereoselective migration of the siloxymethyl groups took place in
the rearrangement of epoxy geraniol and nerol derivatives, 1e and
1f, the same aldehyde 3e being obtained in high yields without
any loss of optical purity.
9
9554
J. AM. CHEM. SOC. 2004, 126, 9554-9555
10.1021/ja047104k CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Cr(TPP)OTf-Catalyzed Rearrangement of Epoxides to
previously reported Fe(TPP)X (X ) OTf or ClO4)-catalyzed
isomerization of epoxides 1 into ketones 2 via hydrogen migration
(route A in Scheme 1):7a ketones 2 and aldehydes 3 can selectively
be prepared from epoxides 1 in a highly controlled manner by means
of a simple choice of Fe(III) and Cr(III) central metal ions of the
porphyrin catalysts. Elucidation of the precise mechanism for the
present rearrangement and other uses of the Cr(TPP)OTf catalyst
in synthetic chemistry are now under active investigation.
Aldehydesa
Acknowledgment. We thank the Japan Society for the Promo-
tion of Science for financial support, a Grant-in-Aid for Scientific
Research (C) (KAKENHI 16590020).
Supporting Information Available: Experimental details, char-
acterization data, NMR spectra, and HPLC traces. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
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a Reaction conditions: 1 mol % Cr(TPP)OTf, ClCH2CH2Cl, 83 °C;
enantiomeric excess was determined by chiral HPLC analysis or 300 MHz
1H NMR Mosher’s ester analysis; The absolute configuration was deter-
mined by comparison of the optical rotations with those of authentic
samples.4b,5c b Isolated yield. c Recovery of the starting epoxide, 22%.
d Recovery of the starting epoxide, 28%. e 20 mol % Cr(TPP)OTf was used.
An R,â-disubstituted epoxy alcohol derivative 1g was also
susceptible toward the rearrangement, though an increase of catalyst
loading (20 mol %) and a longer reaction time were required to
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in 85% yield with minimal racemization.14
In summary, catalytic and regio- and stereoselective rearrange-
ment of epoxides 1 to aldehydes 3 via alkyl migration (route B in
Scheme 1) can now be realized using a high-valent metalloporphyrin
complex, Cr(TPP)OTf, in low catalyst loading (1-20 mol %). The
yield and regio- and stereoselectivity of the catalytic process are
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