Efficient synthesis of fused perhydrofuro[2,3-b]pyrans (and furans) by ring opening of 1,2-cyclopropanated sugar derivatives

Article abstract of DOI:10.1021/ol070177z

Figure presented An efficient method has been developed for the construction of fused perhydrofuro{2,3-b]pyrans by dlastereoselective ring opening of 1,2-cyclopropanated sugar derivatives. The methodology has been successfully applied to the synthesis of

Full text of DOI:10.1021/ol070177z

ORGANIC
LETTERS
2007
Vol. 9, No. 7
1331-1334
Efficient Synthesis of Fused
Perhydrofuro[2,3-b]pyrans (and Furans)
by Ring Opening of 1,2-Cyclopropanated
Sugar Derivatives
Shrutisagar Dattatraya Haveli, Perali Ramu Sridhar, Perumal Suguna, and
Srinivasan Chandrasekaran*
Department of Organic Chemistry, Indian Institute of Science,
Bangalore-560012, India
scn@orgchem.iisc.ernet.in
Received January 23, 2007
ABSTRACT
An efficient method has been developed for the construction of fused perhydrofuro[2,3-b]pyrans by diastereoselective ring opening of 1,2-
cyclopropanated sugar derivatives. The methodology has been successfully applied to the synthesis of fused perhydrofuro[2,3-b]pyrano-
γ-
butyrolactone derivatives.
A wide range of linear-fused perhydrofuro[2,3-b]pyran or
furan ring systems are encountered in a number of biologi-
cally active natural product structures. A few approaches are
available for the construction of this kind of fused motif;
these involve radical cyclization of substituted furans1 or
pyrans,2 cycloadditions,3 intramolecular dehydration reac-
tions,4 acid-catalyzed cyclization of hydroxyacetals,5 and
spontaneous intramolecular ketalization of acyclic dihy-
droxyaldehydes.6 However, these strategies suffer from harsh
reaction conditions, multistep reactions, and low overall yield.
We recently reported an efficient methodology for the
synthesis of 2-C-branched glyco-amino-acids by ring opening
of 1,2-cyclopropanecarboxylated sugar derivatives.7 Logi-
cally, a similar strategy can be utilized for the construction
of fused perhydrofuro[2,3-b]pyran/furan ring systems by
trapping the intermediate oxonium ion in an intramolecular
fashion. In this report we describe the synthesis of perhy-
drofuro[2,3-b]pyran ring systems with defined stereochem-
istry, inherently present in the cyclopropanated sugar
precursor, using NIS-mediated ring opening of 1,2-cyclo-
propanated sugar derivatives8 (Scheme 1). Additionally
(1) (a) Mayer, S.; Prandi, J.; Bamhaoud, T.; Bakkas, S.; Guillou, O.
Tetrahedron 1998, 54, 8753. (b) Harrison, T.; Pattenden, G.; Myers, P. L.
Tetrahedron Lett. 1988, 29, 3869.
(2) (a) Ami, E.; Rajesh, S.; Wang, J.; Kimura, T.; Hayashi, Y.; Kiso,
Y.; Ishida, T. Tetrahedron Lett. 2002, 43, 2931. (b) Yanada, R.; Koh, Y.;
Nishimori, N.; Matsumura, A.; Obika, S.; Mitsuya, H.; Fujii, N.; Takemoto,
Y. J. Org. Chem. 2004, 69, 2417. (c) Inoue, A.; Shinokubo, H.; Oshima,
K. Org. Lett 2000, 2, 651. (d) Mikami, S.; Fujita, K.; Nakamura, T.;
Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K. Org. Lett. 2001,
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Beau, J. M. Tetrahedron Lett. 1988, 29, 3691.
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K. A. Chem. Commun. 2000, 459. (c) Sugita, Y.; Kawai, K.; Yokoe, I.
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I.; Tadano, K.-I. J. Org. Chem. 2000, 65, 8595. (b) Quaedflieg, P. J. L. M.;
Kesteleyn, B. R. R.; Wigerinck, P. B. T. P.; Voyvaerts, N. M. F.; Vijn, R.
J.; Liebregts, C. S. M.; Kooistra, J. H. M. H.; Cusan, C. Org. Lett. 2005,
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Soc., Perkin Trans 1. 1995, 2103.
(7) Sridhar, P. R.; Ashalu, K. C.; Chandrasekaran, S. Org. Lett. 2004, 6,
1777 and references cited therein.
10.1021/ol070177z CCC: $37.00
© 2007 American Chemical Society
Published on Web 03/03/2007

Scheme 1. NIS Mediated Ring Opening of 1,2-Cyclopropanated Sugar Derivatevs
we also describe an efficient method for the construction of
perhydrofuro[2,3-b]pyrano-γ-butyrolactone derivatives under
similar reaction conditons.
have a R-[1,2-b]-cis-bicyclic stereochemistry.2f,g The stere-
ochemistry at C1 and C2 was defined on the basis of the
stereochemistry present in the 1,2-cyclopropanated sugar
precursors. The configuration of the iodide in the product
has been assigned based on nOe experiments between the
C3 and C7 hydrogens (carbohydrate nomenclature).
Cyclopropanation of tri-O-benzyl-D-glucal 1 was carried
out by using methyl diazoacetate (MDA) in dichloromethane
with catalytic rhodium acetate (23 °C, 90 min) to furnish
the corresponding 1,2-cyclopropane carboxylated sugar
derivative 2 in 59% yield.9 LAH reduction of 2 in anhydrous
ether at 0 °C afforded 1,5-anhydro-2-deoxy-1,2-C-(exo-
hydroxymethylmethylene)-3,4,6-tri-O-benzyl-R-D-glucitol 3
in 90% yield. Treatment of alcohol 3 with N-iodosuccinimide
(CH3CN, 4 Å MS, 23 °C, 36 h) furnished the expected
perhydrofurano[2,3-b]pyran derivative 4 along with an
unexpected oxidized product, perhydrofuro[2,3,b]pyrano-γ-
butyrolactone 5 (2:3 ratio).
However, in the reaction of 16 with NIS under similar
reaction conditions the product 17 was obtained as a 1:1
mixture of diastereomers.
Table 1. Synthesis of Linear Perhydrofuro[2,3-b]pyran Ring
Systems by NIS-Mediated Ring Opening of 1,2-Cyclopropanated
Sugar Derivatives
Formation of the lactone 5 can be accounted for by the in
situ oxidation of primary alcohol to the corresponding
carboxylic acid, which can be an active competitor for the
NIS-mediated ring opening reaction. It has been found that
by changing the solvent from acetonitrile to dichloromethane,
the required perhydrofuro[2,3-b]pyran derivative 4 was
obtained as the exclusive product in 62% yield.
The generality of this methodology has been demonstrated
by extending this reaction to a number of other sugar deriv-
atives. The cyclopropyl methanols 7, 10, 13, and 16 were
readily obtained in high yield by LAH reduction of the cor-
responding cyclopropanated esters 6, 9, 12, and 15, respec-
tively. The alcohols 7, 10, and 13 on treatment with 1 equiv
of NIS (CH2Cl2, 23 °C, ∼36 h) gave rise to the corresponding
perhydrofuro[2,3-b]pyran derivatives 8, 11, and 14, respec-
tively, in good yield (58% to 66%) and with very high
diastereoselectivity at the newly formed stereocenters (Table
1). The coupling constant for the anomeric proton (J ≈ 4.2
Hz) in all the products showed that the fused ring systems
(8) For a review on the preparation and ring opening of cyclopropanated
carbohydrates, see: Cousins, G. S.; Hoberg. J. O. Chem. Soc. ReV. 2000,
29, 165.
(9) Timmers, C. M.; Leeuwenburgh, M. A.; Verheijen, J. C.; van der
Marel, G.; van Boom, J. H. Tetrahedron: Asymmetry 1996, 7, 49.
a Isolated yield after column chromatography. Yield of iodoethers based
on the corresponding alcohol precursors.
1332
Org. Lett., Vol. 9, No. 7, 2007

Scheme 2. Synthesis of the Furofuryl Glycal Ring System
There are many natural products that contain the perhy-
b]pyrano-γ-butyrolactone derivative 5 as a single diastere-
omer in excellent yield (94%). There are some reports that
cleverly use the acid-catalyzed rearrangement strategy for the
formation of fused tetrahydrofuro[2,3-b]furano-γ-butyrolac-
tone motif,13 by using donor-acceptor 1,2-cyclopropane car-
boxylated derivatives. The present strategy is complementary
to the existing methods and it is useful since it incorporates
an additional chiral center in the molecule under milder
conditions which can be used for further transformations.
The methodology has been validated by applying it to a
few other 1,2-cyclopropanecarboxylic acid derivatives. Thus,
treatment of cyclopropane carboxylic acids 24, 26, 28, and
30 with NIS/CH3CN (4 Å MS, 10 h) gave rise to the
corresponding iodobutyrolactones 25, 27, 29, and 31, re-
spectively, in very good yield (83-92%) with very high di-
astereoselectivity at the newly formed stereocenters (Table 2).
drofurofuran core such as clerodin and caryoptin10 which
show insect anti-feedant properties. With this in mind, the
methodology was subsequently extended to the cyclopro-
panated tetrahydrofuran derivatives. The dihydrofuran de-
rivative 1811 was treated with methyl diazoacetate in the
presence of Rh2(OAc)4 to give the cyclopropanated ester 19
as a major product. Reduction of 19 with LAH gave rise to
the required alcohol 20 in 98% yield. Compound 20 when
subjected to the ring opening and cyclization reaction
conditions (NIS 1 equiv, CH2Cl2, 25 °C, 36 h) led to the
formation of perhydrofuro[2,3-b]furan derivative 21 in 65%
yield as a mixture of diastereomers (9:1). This mixture was
subjected to dehydrohalogenation with DBU (THF, reflux,
14 h) as a base to obtain the corresponding furofuryl glycal
22 in 78% yield (Scheme 2).
The low reactivity and moderate yield of these reactions
with all the cyclopropyl methanol derivatives studied so far
may be attributed to the lack of neighboring group participa-
tion and donor-acceptor functionality in the cyclopropane
ring systems.12 Consequently, we decided to incorporate these
two features in the substrates to check the selectivity and
yield under similar reaction conditons. Toward this end, 1,2-
cyclopropane carboxylic acid 23 was synthesized by base hy-
drolysis of the 1,2-cyclopropane carboxylate 2 (Scheme 3).
Table 2. Synthesis of Linear Perhydrofuro[2,3-b]pyrano-γ-
butyrolactone Ring Systems by NIS-Mediated Ring Opening of
Sugar Derived 1,2-Cyclopropancarboxylic Acids
Scheme 3. Synthesis of Fused
Perhydrofuro[2,3-b]pyrano-γ-butyrolactone
Treatment of carboxylic acid 23 with NIS/CH3CN (4 Å MS,
10 h) furnished the corresponding 3-iodoperhydrofuro[2,3-
a Isolated yield after column chromatography. Yield of iodolactones based
on the corresponding carboxylic acid precursors.
(10) (a) van Beek, T. A.; de Groot, A. TraV. Chim. Pays-Bas 1986, 105,
513. (b) Merritt, A. T.; Ley, S. V. Nat. Prod. Rep. 1992, 9, 243.
(11) Kim, C.; Hoang, R.; Theodorakis, A. Org. Lett. 1999, 1, 1295.
Org. Lett., Vol. 9, No. 7, 2007
1333

In conclusion, we have developed an efficient method for
the stereoselective construction of linear-fused perhydrofuro-
[2,3-b]pyran motifs using NIS-mediated ring opening and
cyclization of 1,2-cyclopropanated sugar derivatives. We also
describe herein a general method for the synthesis of fused
perhydrofuro[2,3-b]pyrano-γ-butyrolactone systems under
similar reaction conditions using sugar-derived 1,2-cyclo-
propanecarboxylic acids. Application of this methodology
for the synthesis of caryoptin is underway.
Acknowledgment. S.D.H. thanks the University Grants
Commission, India, for a Senior Research Fellowhip and
S.C.N. thanks DST, New Delhi for a J. C. Bose National
Fellowship.
Supporting Information Available: 1H and 13C NMR
data for cyclopropyl methanols (3, 7, 10, 13, 16, 20),
cyclopropane carboxylic acids (23, 28),d fused bicycles (4,
8, 11, 14, 17, 21), and fused lactones (5, 25, 27, 29, 31).
This material is available free of charge via the Internet at
http://pubs.acs.org.
(12) For reviews on donor - acceptor cyclopropanes: (a) Reissig, H.-U.;
Zimmer, R. Chem. ReV. 2003, 103, 1151. (b) Reissig, H.-U. Top. Curr.
Chem. 1988, 144, 73. (c) Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61,
321.
(13) (a) Kim, C.; Hoang, R.; Theodorakis, E. A. Org. Lett. 1999, 1, 1295.
(b) Kim, C.; Brady, T.; Kim, S. H.; Theodorakis, E. A. Synth. Commun.
2004, 34, 1951. (c) Weisser, R.; Yue, W.; Reiser, O. Org. Lett. 2005, 7,
5353.
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