A catalytic method for converting vinylic furanoses into cyclopentenones

Article abstract of DOI:10.1002/anie.200701663

(Chemical Equation Presented) From sugars to carbocycles: Pentacarbonyl iron is a cheap and efficient catalyst for mediating an isomerization- aldolization-dehydration sequence that converts vinyl sugars into cyclopentenones, which are very useful interme

Full text of DOI:10.1002/anie.200701663

Angewandte
Chemie
DOI: 10.1002/anie.200701663
Synthetic Methods
A Catalytic Method for Converting Vinylic Furanoses into
Cyclopentenones**
Julien Petrignet, Ireddy Prathap, Srivari Chandrasekhar, Jhillu Singh Yadav, and RenØ GrØe*
The conversion of carbohydrates into carbocycles is a very
useful strategy in organic synthesis since it affords function-
alized and optically active key intermediates for the total
synthesis of various types of bioactive molecules.[1] Further-
more, it is also an excellent route to carbasugars, which are of
pharmacological interest; noteworthy in this area are the
carbocyclic nucleosides.[2] Starting from the seminal Ferrier
reaction,[3] many methodologies have been developed
recently in order to perform such transpositions. They
involved Claisen rearrangements, either by thermal[4] or by
Scheme 1. Strategy for the transposition of vinyl sugars A into cyclo-
pentenones D.
titanium-catalyzed processes,[5] as well as 1,3 dipolar cyclo-
additions[6] and radical cyclizations.[7] Various metal-mediated
reactions have also been employed,[8] and the samarium-
promoted ring contractions have been very successful.[9] In
recent years, ring-closing metathesis (RCM)[10] has also
played a major role in this area.[11] Although these elegant
methods have proved to be very fruitful, only a fewof them
are catalytic reactions, proceeding under mild and neutral
reaction conditions and requiring cheap reagents. As an
extension of our work on the tandem isomerization–aldoliza-
tion reaction of allylic alcohols,[12] we have discovered a new
conversion of five-membered vinyl sugar derivatives into
cyclopentenones. Here, we describe our results in this field,
leading to the preparation of key intermediates for the
synthesis of several natural products, including prostaglandins
(PGs).
The strategy we have designed for this conversion is
indicated in Scheme 1. If our tandem reaction could be
applied, in an intramolecular manner, to the open form (A’)
of a vinyl sugar derivative A, it would give directly the aldol
product B and after crotonization the target cyclopentenone
D. An alternative possibility would be migration of the double
bond in sugar A to give the enol ether intermediate C. Then
ring opening to C’, followed by aldolization would give the
same aldol B and the desired cyclopentenone D.
The known vinyl derivative 1, easily available in three
steps and 43% overall yield from d-ribose,[13] was selected as
a first model to screen the different catalysts and optimize the
reaction conditions. In the presence of 5 mol% [Fe(CO)5] and
under irradiation for 1 h, 1 was converted (76% overall yield)
into a mixture of three aldol products 2 (67%), 3 (14%), and
4 (19%) (Scheme 2). These labile compounds could be
separated by chromatography, and their stereochemistry
was established from their NMR data. However, the crude
mixture of aldols was submitted directly to an elimination
reaction via the corresponding triflates to afford the target
enone 5, whose data were in agreement with literature,[14] in
70% overall yield from 1. It is worth noting that previous
syntheses of 5 involved multistep sequences. In particular, the
cyclopentenone without substituents on the double bond had
to be prepared first[11,15] and then subjected to iodination and
a Pd-catalyzed reaction with SnMe4 to introduce the methyl
group.[14] Nevertheless, both 5 and ent-5 have been used
already as key intermediates for the total synthesis of several
natural products.[14,16,17]
[*] J. Petrignet, Dr. I. Prathap, Dr. R. GrØe
Synth›se et Electrosynth›se Organiques
CNRS UMR 6510, UniversitØ de Rennes 1
Avenue du GØnØral Leclerc, 35042 Rennes Cedex (France)
Fax: (+33)2-2323-6978
E-mail: rene.gree@univ-rennes1.fr
Dr. S. Chandrasekhar, Dr. J. S. Yadav
Indian Institute of Chemical Technology
500007, Hyderabad (India)
[**] We thank IFCPAR/CEFIPRA for support (Project No. 7106) and Dr.
B. V. Rao for useful information on sugar 1. We thank P. GuØnot and
CRMPO (Rennes) for the analysis, D. GrØe for the NMR experi-
ments, and A. Lancou for preliminary experiments in these series.
Very fruitful discussions with Saibal Das are gratefully acknowl-
edged.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or fromthe author.
Scheme 2. Synthesis of cyclopentenone 5 starting fromvinyl sugar 1.
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From a mechanistic point of view, several aspects are isomerization, followed by treatment with TBAF, afforded
noteworthy. When the reaction was stopped before complete
directly in a one-pot process the desired cyclopentenone 5 in
52% overall yield from 1. The next intermediates, alkenes
10a and 10b, were prepared in 58% and 66% yields from 9 by
the CM reaction. Then, starting from 10a and following the
same sequence as above, the desired cyclopentenone 8a was
obtained in 42% yield.
However, under the same conditions, the alkene 10b did
not afford the expected cyclopentenone 8b but instead the
corresponding carboxylic acid 8b’ in 52% overall yield. A
mechanistic proposal to explain the formation of this
derivative is given in Scheme 4. After migration of the
conversion (after 30 min), it was possible to isolate by
chromatography a small amount (5%) of the labile isomer-
ized enol ether 6, in addition to the aldol products and the
starting material. This indicates that the process could occur,
at least in part, through intermediates of type C. In this case,
the transposition would have analogies with the Ferrier
rearrangement.[1,3] However, it is well known that the latter
process is not suitable for the transformation of furanosides
into cyclopentane derivatives,[1] contrary to the results
obtained with our new system. Furthermore, it has been
clearly established also that the direct aldol cyclization of
ketoaldehydes is difficult to perform for the preparation of
cyclopentenones of this type.[1a] Finally, as far as the catalysts
are concerned, the lactol 1 was found to be unreactive towards
two other catalysts known to mediate the intermolecular
isomerization–aldolization reaction [NiHCl(dppe)] (dppe =
1,2-bis(diphenylphosphanyl)ethane)[12d] as well as [RhH-
(PPh3)3].[12b]
To extend the scope of this reaction, we set out to
introduce R2 substituents on the methyl group of the cyclo-
pentenone. Towards this goal, the cross-metathesis reaction
(CM)[10] of lactol 1 appeared the method of choice, and two
representative substituents were selected (R2 = Ph and R2 =
CO2Me). Using the 2nd generation Grubbs catalyst,[10b] the
CM reaction afforded the desired alkenes 7a and 7b in
moderate yields (44% and 56% respectively, Scheme 3).
However, starting from these compounds, the transposition
into the target cyclopentenones afforded only lowyields of
the corresponding aldols in the case of 7a and mostly
degradation products starting from 7b. Therefore a comple-
mentary strategy was considered through an isomerization–
Mukaiyama aldol process.[18] To check the possible use of this
tandem process, the silyl ether 9 was first prepared in 92%
yield by protection of lactol 1. The iron-carbonyl-catalyzed
Scheme 4. Mechanistic proposal for the formation of 8b’.
double bond, the silyl ether is deprotected to give an
alcoholate in equilibrium with the corresponding enolate,
which is suitable for an intramolecular aldol reaction. The
intermediate aldolate can react with the ester function to
form the lactone 11. Then, abstraction of the acidic proton
with concomitant ring opening of the lactone and acidification
gives carboxylic acid 8b’.[19]
A second series of cyclopentenones was of interest to us,
the 4-alkoxy-substituted derivatives, since they are extremely
useful precursors of PGs. The vinyl sugar 16 was selected as
the starting material for studying the transposition. This lactol
was prepared in four steps and 58% overall yield from the
known aldehyde 12,[20] as indicated in Scheme 5.[21]
Scheme 3. Synthesis of cyclopentenones 5 and 8 starting fromvinyl
sugar 1. Conditions: a) TBSCl, imidazole, CH2Cl2, RT, 16 h, 93%;
b) Styrene or methyl acrylate, 2nd generation Grubbs catalyst (5%),
CH2Cl2, 408C, 6 h, 7a (44%), 7b (56%), 10a (58%), 10b (66%, as a
86:14 E/Z mixture); c) [Fe(CO)5] (5 mol%), hn, THF; d) [Fe(CO)5]
(5 mol%), hn, THF then TBAF (1 equiv) À788C to RT, 1 h, overall yield
8a (42%), 8b’ (52%). TBS=tert-butyldimethylsilyl, TBAF=tetrabutyl-
ammonium fluoride.
Scheme 5. Synthesis of vinyl sugar 16. Conditions: a) Ph3P+CH3,BrÀ,
tBuOK, THF, 08C, 2 h, 94%; b) H2SO4, MeOH, 608C, 12 h, 85%;
c) NaH, BnBr, THF, 408C, 6 h, 90%; d) H2O, AcOH, 708C, 12 h, 80%.
Bn=benzyl.
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Under the same conditions as described for 1, vinyl sugar
16 gave a complex mixture of aldols 17, which were submitted
directly to the elimination conditions to afford the desired
cyclopentenone 18 in 88% overall yield (Scheme 6). Starting
analogues, as already demonstrated by the preparation of 5, 8,
[25]
18, and 21. The development of newcatalysts
and the
extension of this reaction to other sugar derivatives are
currently under investigation in our groups.
Received: April 16, 2007
Published online: July 2, 2007
Keywords: aldol reaction · carbocycles · carbohydrates · iron ·
.
prostaglandins
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Scheme 6. Synthesis of cyclopentenones 18 and 21 and PGs precur-
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acrylate, 2nd generation Grubbs catalyst (5%), CH2Cl2, 408C, 6 h,
85%; d) tetramethylguanidine, CH3NO2, 08C, 2 h, 72%; e) LiAlH-
(OtBu)3, THF, 508C, 2 h, 55%.
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corresponding cyclopentenones. This method appears com-
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approach the CH2R2 substituent is already introduced,
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Communications
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