A convenient approach for access to both carbapentofuranoses and carbahexopyranoses. Stereocontrolled synthesis of enantiopure Carba-D-ribofuranoses, Carba-D-arabinofuranoses and Carba-L-gulopyranose

Article abstract of DOI:10.1021/jo061717t

A new approach to carbasugars in enantiomerically pure form is reported. The key step involves ring-closing metathesis of dienols 6 derived from a (R)-(+)-glyceraldehyde derivative 4 to form the substituted cyclopentenol 9 and cyclohexenol 34a. Stereocont

Full text of DOI:10.1021/jo061717t

A Convenient Approach for Access to Both Carbapentofuranoses
and Carbahexopyranoses. Stereocontrolled Synthesis of Enantiopure
Carba-D-ribofuranoses, Carba-D-arabinofuranoses and
Carba-L-gulopyranose
Subrata Ghosh,* Tanurima Bhaumik, Niladri Sarkar, and Abhijit Nayek
Department of Organic Chemistry, Indian Association for the CultiVation of Science, JadaVpur,
Kolkata 700 032, India
ocsg@iacs.res.in
ReceiVed August 18, 2006
A new approach to carbasugars in enantiomerically pure form is reported. The key step involves ring-
closing metathesis of dienols 6 derived from a (R)-(+)-glyceraldehyde derivative 4 to form the substituted
cyclopentenol 9 and cyclohexenol 34a. Stereocontrolled addition of hydroxyl groups followed by
conversion of the ketal unit to hydroxymethyl group in these intermediates led to carbapentoses and
-hexoses. Stereoselectivity during introduction of hydroxyl groups arises through the steric hindrance
posed by the allylic substituents. A remarkable feature of the present approach is the accessibility of
both D- and L-series of carbapentoses as illustrated by the synthesis of â-D- and â-L-carbaribofuranoses
17 and 20, respectively. Carba-R-D-ribofuranose 25, the biosynthetic intermediate to the antibiotic
aristeromycin, has also been synthesized from the same cyclopentenol 9. Functional group manipulation
in the cyclopentenol 9a also enabled access to carbaarabinofuranose 32. The present synthetic strategy
can be extended for the synthesis of carbahexopyranose, as illustrated by the synthesis of carba-â-L-
gulopyranose 40b.
Introduction
which have considerable therapeutic potential in the management
of cancer, diabetes, and viral infections. Thus, development of
efficient routes for the synthesis of carbasugars continues to be
at the forefront of organic synthesis.4,5
Apart from the construction of highly oxygenated carbocycles,
stereocontrol in the synthesis of carbasugars is the major hurdle.
Synthetic investigations made so far toward carbapentoses
involve either transformation of carbohydrates4a-j with hydroxyl
groups of predefined stereochemistry or fragmentation of
norbornene derivatives.4k-n A few approaches involving con-
struction of cyclopentene derivatives5 followed by hydroxylation
have also been reported. A novel substrate-dependent dihy-
droxylation of cyclopentene has been reported recently by Miller
Carbocyclic analogues of pentoses and hexoses, often referred
to as carbasugars,1 are structural features present in many
biologically interesting molecules. Because of improved acid
and metabolic stability relative to their glycoside counterparts,
compounds containing carbasugar moieties are potential thera-
peutic agents.2 For example, a number of carbasugar-containing
nucleoside analogues exhibits promising antiviral activities. Also
oligosaccharide analogues containing carbasugar residues have
been reported to be efficient glycosyltransferase inhibitors3
(1) (a) Agrofoglio, L.; Suhas, E.; Farese, A.; Condom, R.; Challand, S.
R.; Earl, R. A.; Guedj, R. Tetrahedron 1994, 50, 10611. (b) Suami, T. Top.
Curr. Chem. 1990, 154, 257.
(2) (a) Crimmins, M. T. Tetrahedron 1998, 54, 9229. (b) De Clercq, E.
Nucleosides Nucleotides 1998, 17, 625. (c) Ferrero, M.; Gotor, V. Chem.
ReV. 2000, 100, 4319.
(3) (a) Ogawa, S.; Matsunaga, N.; Li, H.; Palcic, M. M. Eur. J. Org.
Chem. 1999, 3, 631. (b) Ogawa, S.; Furuya, T.; Tsunoda, H.; Hindsgaul,
O.; Stangier, K.; Palcic, M. M. Carbohydr. Res. 1995, 271, 197.
10.1021/jo061717t CCC: $33.50 © 2006 American Chemical Society
Published on Web 11/29/2006
J. Org. Chem. 2006, 71, 9687-9694
9687

Ghosh et al.
SCHEME 1
Results and Discussion
For entry into carbapentoses, cyclopentenol 9a (Scheme 2)
is required. Toward this end the (R)-(+)-glyceraldehyde deriva-
tive 4 was converted to a chromatographically separable 1:1
mixture of the unsaturated esters 5a and 5b following the
literature procedure.10e Conversion of the pure ester 5a to the
aldehyde 3a and reaction of the latter with vinyl magnesium
bromide gave a 1:1 mixture of the dienols 6a. Ring-closing
metathesis of the dienols 6a with Grubbs I Ru-catalyst (PCy3)2-
Cl2RudCHPh afforded a mixture of the cyclopentenols 7a.10f
The desired cyclopentenol 9a could however be obtained
predominantly in the following way. We anticipated that
reduction of the cyclopentenone, to be available from oxidation
of this mixture of cyclopentenols, would proceed from the side
opposite to the C-4 substituent to provide the desired cyclo-
pentenol predominantly. The mixture of the cyclopentenols 7a
was oxidized to give the ketone 8a in 96% yield. Reduction of
the ketone 8a with LiAlH4 gave a mixture of the cyclopentenols
9a along with its C-1 diastereomer in 16:1 ratio. The major
cyclopentenol 9a was obtained in 79% yield after column
chromatography. The stereochemical assignment to 9a was
based on the NOE (1.8%) between C1 and C4 hydrogens. In a
similar fashion the aldehyde 3b, prepared from the diastereoi-
someric ester 5b, was converted to the cyclopentenol 9b.
After successful synthesis of the cyclopentenols 9a and 9b,
we focused on their transformation to both â-D- and â-L-
carbaribofuranoses. The hydroxyl group in 9a and 9b was
protected to provide the benzyl ethers 10a and 10b, respectively.
Dihydroxylation of the cyclopentene derivative 10a was achieved
with OsO4 to produce exclusively the diol 11 in 90% yield.
Stereochemical assignment to the diol 11 was based on Kishi’s
principle,11 according to which hydroxylation took place from
the face of the double bond opposite to the alkoxy group. This
stereochemical assignment was further confirmed through
transformation of the diol 11 to carba-â-D-ribofuranose 17 (vide
infra). For completion of the synthesis, the diol 11 was protected
to afford the tribenzyl derivative 12. Acid-induced deketalization
of 12 afforded the diol 13. Periodate cleavage of the diol 13
followed by reduction of the resulting aldehyde 15 afforded the
polyoxygenated cyclopentane 16 in overall excellent yield.
Finally, hydrogenolysis led to carba-â-D-ribofuranose 17, [R]D
and co-workers.6 All of these investigations were mainly aimed
either at carbapentoses or at carbapyranoses, but there was no
general approach that can lead access to both carbapentoses and
carbahexoses.7
As part of our continued interest8 in the synthesis of
cyclopentane-containing molecules of biological interest, we
initiated a program to design a general approach that would
allow access to both carbapentofuranoses and carbahexopyra-
noses. We anticipated that carbaanalogues of pentoses and
hexoses could be prepared from the carbocyclic enols of the
general structure 1 (Scheme 1) on stereocontrolled introduction
of the hydroxyl groups. The ketal moiety at the allylic center
would be the source of chirality as well as the hydroxymethyl
group. The cyclic alkenols 1 would be available by ring-closing
metathesis9,10 of the dienols 2, which in turn would be available
from the unsaturated aldehyde 3 on addition of alkenyl metal
having the required number of methylenes for entry into either
carbapentoses or carbahexoses. The unsaturated aldehyde 3
would be available from (R)-(+)-glyceraldehyde derivative 4.
We herein report the results of our investigation based on this
concept.
(4) (a) Tadano, K.; Maeda, H.; Hoshino, M.; Iimura, Y.; Suami, T. J.
Org. Chem. 1987, 52, 1946. (b) Rassu, G.; Auzzas, L.; Pinna, L.; Zambrano,
V.; Battistini, L.; Zanurdi, F.; Marzocchi, L.; Acquotti, D.; Casiraghi, G. J.
Org. Chem. 2001, 66, 8070. (c) Tadano, K.; Maeda, H.; Hoshino, M.; Iimura,
Y.; Suami, T. Chem. Lett. 1986, 1081. (d) Callam, C. S.; Lowary, T. L.
Org. Lett. 2000, 2, 167. (e) Horneman, A. M.; Lundt, I. J. Org. Chem.
1998, 63, 1919. (f) Callam, C. S.; Lowary, T. L. J. Org. Chem. 2001, 66,
8961. (g) Tadano, K.; Kimura, H.; Hoshino, M.; Ogawa, S.; Suami, T. Bull.
Chem. Soc. Jpn. 1987, 60, 3673. (h) Tadano, K.; Hoshino, M.; Ogawa, S.;
Suami, T. J. Org. Chem. 1988, 53, 1427. (i) Tadano, K.; Hakuba, K.;
Kimura, H.; Ogawa, S. J. Org. Chem. 1989, 54, 276. (j) Yoshikawa, M.;
Yokokawa, Y.; Inoue, Y.; Yamaguchi, S.; Murukami, N.; Kitagawa, I.
Tetrahedron 1994, 50, 9961. (k) Marschner, C.; Penn, G.; Griengl, H.
Tetrahedron Lett. 1990, 31, 2873. (l) Mehta, G.; Reddy, D. S. Tetrahedron
Lett. 1999, 40, 9137. (m) Mehta, G.; Mohal, N. Tetrahedron Lett. 1999,
40, 5791. (n) Marschner, C.; Baumgartner, J.; Griengl, H. J. Org. Chem.
1995, 60, 5224.
1
+8.5 (c 1.7, MeOH) [lit.4k [R]D +8.0 (c 2.9, MeOH)]. H and
13C NMR spectra of the sample obtained in this way were
closely comparable to those reported in literature.4i Following
a similar protocol, dihydroxylation of the cyclopentene 10b
(9) For reviews on RCM reaction, see: (a) Schuster, M.; Blechert, S.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2036. (b) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413. (c) Pariya, C.; Jayaprakash, K. N.; Sarkar, A.
Coord. Chem. ReV. 1998, 168, 1. (d) Frustner, A. Angew. Chem., Int. Ed.
2000, 39, 3012. (e) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18. (f) Kotha, S.; Sreenivasachary, N. Indian J. Chem. 2001, 40B, 763. (g)
Grubbs, R. H. Tetrahedron 2004, 60, 7117. (h) Dieters, A.; Martin, S. F.
Chem. ReV. 2004, 104, 2199. (I) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.
Angew. Chem., Int. Ed. 2005, 44, 4490. (j) Ghosh, S.; Ghosh, S.; Sarkar,
N. J. Chem. Sci 2006, 118, 223.
(10) For our work on RCM reaction, see: (a) Holt, D. J.; Barker, W.
D.; Jenkins, P. R.; Davies, D. L.; Garratt, S.; Fawcett, J.; Rusell, D. R.;
Ghosh, S. Angew. Chem., Int. Ed. 1998, 37, 3298. (b) Haque, A.; Panda,
J.; Ghosh, S. Indian J. Chem. 1999, 38B, 8. (c) Holt, D. J.; Barker, W. D.;
Jenkins, P. R.; Panda, J.; Ghosh, S. J. Org. Chem. 2000, 65, 482. (d) Nayek,
A.; Banerjee, S.; Sinha, S.; Ghosh, S. Tetrahedron Lett. 2004, 45, 6457.
(e) Banerjee, S.; Ghosh, S.; Sinha, S.; Ghosh, S. J. Org. Chem. 2005, 70,
4199. (f) Nayek, A.; Sinha, S.; Bhaumik, T.; Ghosh, S. J. Mol. Catal. A:
Chem. 2006, 254, 85. (g) Ghosh, S.; Sinha, S.; Drew, M. G. B. Org. Lett.
2006, 8, 3781.
(5) (a) Shoberu, K. A.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1
1992, 2419. (b) Parry, R. J.; Haridas, K.; De Jong, R.; Johnson, C. R.
Tetrahedron Lett. 1990, 31, 7549.
(6) Jiang, M. X. -W.; Jin, B.; Gage, J. L.; Priour, A.; Savela, G.; Miller,
M. J. J. Org. Chem. 2006, 71, 4164 and references therein.
(7) (a) McCasland, G. E.; Furuta, S.; Durham, L. J. J. Org. Chem. 1966,
31, 1516. (b) Takahashi, T.; Kotsubo, H.; Iyobe, A.; Namiki, T.; Koizumi,
T. J. Chem. Soc., Perkin Trans. 1 1990, 3065. (c) Shing, T. K. M.; Cui, Y.;
Tang, Y. J. Chem. Soc., Chem. Commun. 1991, 756. (d) Dumortier, L.;
Vander Eycken, J.; Vandewalle, M. Synlett 1992, 245. (e) Mehta, G.; Mohal,
N. Tetrahedron Lett. 1998, 39, 3285. (f) Pingli, L.; Vandewalle, M. Synlett
1994, 228.
(8) (a) Ghosh, S.; Patra, D.; Saha, G. J. Chem. Soc., Chem. Commun.
1993, 783. (b) Ghosh, S.; Patra, D. Tetrahedron Lett. 1993, 34, 4565. (c)
Patra, D.; Ghosh, S. J. Org. Chem. 1995, 60, 2526. (d) Haque, A.; Ghatak,
A.; Ghosh, S.; Ghoshal, N. J. Org. Chem. 1997, 62, 5211. (e) Samajdar,
S.; Patra, D.; Ghosh, S. Tetrahedron 1998, 54, 1789. (f) Samajdar, S.;
Ghatak, A.; Ghosh, S. Tetrahedron Lett. 1999, 40, 4401. (g) Banerjee, S.;
Ghosh, S. J. Org. Chem. 2003, 68, 3981. (h) Sarkar, N.; Nayek, A.; Ghosh,
S. Org. Lett. 2004, 6, 1903.
(11) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40, 2247.
9688 J. Org. Chem., Vol. 71, No. 26, 2006

Access to Carbapentofuranoses and Carbahexopyranoses
SCHEME 2a
a For structures 3-12, 18, and 19: R1, R2 ) -(CH2)5- and for structures 3 and 5-8: a, R3 ) R-H; b, R3 ) â-H.
afforded the diol 18, which on benzylation gave the tribenzyl
derivative 19. Carba-â-L-ribofuranose 20, [R]D -6.2 (c 1.5,
MeOH), was then obtained from 19 following the protocol used
for the synthesis of 17. Thus, availability of the carbaribofura-
noses of both the D- and L-series from a single enantiomer, (R)-
(+)-glyceraldehyde derivative 4 is a remarkable advantage of
this approach. Further, hydrogenolysis of the tribenzyl derivative
13 afforded the carbaaldohexofuranose 14, a new class of
carbasugars for synthesis of which there is only a single report.4e
The cyclopentenol 9a can also be employed for synthesis of
the carba-R-D-ribofuranose. For this purpose it is necessary to
invert the configuration of the C-1 hydroxyl group. This was
achieved as delineated in Scheme 3. The cyclopentenol 9a was
converted to the silyl ether 21. Dihydroxylation of the cyclo-
pentene 21 followed by benzylation of the diol 22a gave the
dibenzyl ether 22b. The latter on desilylation gave the cyclo-
pentanol 22c. Oxidation of the cyclopentanol 22c with Jones
reagent afforded the ketone 23 in 87% yield. Reduction of the
ketone 23 with LiAlH4 took place from addition of the hydride
predominantly from the side opposite to C-2, C-3 benzyloxy
groups to afford the cyclopentanol 24 in 60% isolated yield with
9% yield of the diastereomeric cyclopentanol 22c. The ketal
group in 24 was then converted to a hydroxymethyl group using
the four-step protocol for conversion of 12 to 17 as described
in Scheme 2 to afford carba-R-D-ribofuranose 25, [R]D +42.4
1
(c 1.7, MeOH) [lit.5b [R]D +46.1 (c 0.8, MeOH)]. H NMR4h
and 13C NMR5b spectral data of the carbasugar 25 were closely
comparable to those reported in literature. The importance of
the carbasugar 25 as a biosynthetic intermediate to the antibiotic
aristeromycin 265b has already been established.
The cyclopentanol 22c can be used for entry into the arabino
series. It is interesting to note that whereas Jones oxidation of
the cyclopentanol 22c gave the cyclopentanone 23, Swern
oxidation gave the cyclopentenone 27 in excellent yield (Scheme
4). Triethylamine used during Swern oxidation probably facili-
tated elimination of the benzyloxy group â to the carbonyl of
the initially formed cyclopentanone 23. Hydroboration of the
enone 27 gave a mixture of the diols, which on chromatography
afforded the pure diols 29a (20%) and 30a (54%). The moderate
stereoselectivity observed during this reaction may be rational-
ized as follows. Reduction of carbonyl group in conjugated
enone with diborane generally proceeds12 at a faster rate to form
(12) Stefanovic, M.; Lajsic, S. Tetrahedron Lett. 1967, 8, 1777.
J. Org. Chem, Vol. 71, No. 26, 2006 9689

Ghosh et al.
SCHEME 3a
allylic alcohols 28a and 28b, with the latter predominating.
Subsequent addition of borane to the alkene units in these
alcohols occurred exclusively from the opposite face of the C-4
substituent leading to the diols 29a and 30a. For completion of
the synthesis of the carbaarabinofuranoses, the diols 29a and
30a were benzylated to afford 29b and 30b, respectively. Each
of the benzyloxy cyclopentanes 29b and 30b were subjected to
the four-step protocol already described for conversion of 12
to carba-â-D-ribofuranose 17, to give carba-R-D-arabinofuranose
31, [R]D +44.5 (c 1.5, MeOH) [lit.4i (for ent-31) [R]D -40.5 (c
0.84, MeOH)] and carba-â-D-arabinofuranose 32, [R]D +9.2 (c
1.5, MeOH) [lit.4g [R]D +9.7 (c 0.7, MeOH)]. 1H and 13C NMR
spectral data of the carbasugars 31 and 32 were also comparable
to those reported in literature.4i,n
The above protocol can be extended for access to carbahex-
opyranoses as illustrated by the synthesis of 5a-carba-â-L-
gulopyranose. Toward this end, the aldehyde 3b was allowed
to react with allyl zinc to afford a diastereoisomeric mixture of
the alcohols 33 (Scheme 5). Ring-closing metathesis of this
dienol mixture with Grubbs’ first generation catalyst afforded
the cyclohexenols 34a and 34b in excellent yield. The cyclo-
hexenol 34a could be exclusively obtained by oxidation of the
mixture of the cyclohexenols 34a and 34b to the cyclohexenone
34c followed by its reduction with LiAlH4. NOE (1.8%) between
C-1 and C-5 hydrogens in the acetate 34d derived from 34a
confirmed the syn stereochemical assignment. For introduction
of the hydroxyl groups, the cyclohexenol 34a was subjected to
epoxidation with m-CPBA. A mixture of products was obtained
from which no desired epoxide could be isolated. However,
epoxidation of the acetate 34d with m-CPBA proceeded
smoothly to produce in 89% yield an inseparable mixture of
the oxiranes 35 and the diastereoisomer 36. An attempt to
convert these oxiranes to the corresponding allylic alcohols using
the procedure (Ph2Se2/NaBH4/30% H2O2) of Sharpless and
Lauer13 led to isolation of the ene-diol 38a in 41% yield. During
this reaction, the oxirane ring in 36 remained unchanged and
produced only the deacetylated epoxide 37 in 29% yield. The
inertness of the oxirane ring in 36 toward nucleophilic opening
may be explained as follows. Opening of the oxirane ring in
36 requires the nucleophile to approach from the opposite face
of the epoxide ring, which is hindered by the bulky ketal
substituent. The hydroxyl groups in the cyclohexenediol 38a
were protected to provide the benzyl ether 38b. Dihydroxylation
with OsO4 led exclusively the cis-diol 39a. The stereochemical
assignment to the diol 39a follows from its conversion to the
known gulopyranose 40b as stated below. The diol 39a was
benzylated, and the ketal unit in tetrabenzylated derivative 39b
was converted to the hydroxymethyl group using the four-step
protocol used in the synthesis of carbafuranoses to afford carba-
a For structures 21-24: R1, R2 ) -(CH2)5-.
SCHEME 4a
25
â-L-gulopyranose 40b. The pentaacetate 40c, [R]D +21.5 (c
2.0, CHCl3) [lit.7f [R]20 +20.5 (c 1.0, CHCl3)] obtained from
D
acetylation of 40b displayed 1H NMR spectral data comparable
to those reported in literature.7f
Conclusion
We have developed a new synthetic approach that provided
access to both carbapentoses and carbahexoses in enantiomeri-
cally pure form. A ring-closing metathesis of dienols derived
from (R)-(+)-glyceraldehyde derivative afforded the basic
carbocyclic units, which on stereoselective hydroxylation gave
aFor structures 27-30: R1, R2 ) -(CH2)5-.
allylic alcohol. Thus reaction of the enone 27 probably
proceeded through preferential addition of diborane to an
initially formed carbonyl-borane complex from the face opposite
to the C-4 substituent leading to a mixture of the nonisolable
(13) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95, 2697.
9690 J. Org. Chem., Vol. 71, No. 26, 2006

Access to Carbapentofuranoses and Carbahexopyranoses
SCHEME 5a
a For structures 3b and 33-39: R1, R2 ) -(CH2)5-.
(20 mL). After stirring at that temperature for 1 h, the reaction
mixture was quenched by sequential addition of water (0.26 mL),
aqueous NaOH solution (15%, 0.26 mL), and water (0.78 mL) and
allowed to attain room temperature. After stirring at room temper-
ature for 15 min, the white solid formed was filtered off. The solid
was washed thoroughly with diethyl ether. The combined ether layer
was dried. Removal of solvent in vacuo followed by column
chromatography of the residual mass with silica gel (100-200
mesh) using ether/petroleum ether (1:3) as eluent afforded the
cyclopentenol derivatives 9a (1.1 g, 79%) and its C-1 diastereomer
(70 mg, 5%) as viscous liquid.
9a. Rf ) 0.54 (EtOAc/petroleum ether 1:1); [R]22D -90.5 (c 5.1,
CHCl3); 1H NMR δ 1.37 (2H, br s, CH2), 1.56-1.57 (8H, m, CH2),
2.26-2.36 (2H, m, CH2), 2.73-2.77 (2H, m), 3.70 (1H, dd, J )
6.5, 8.0 Hz, OCH2), 4.04 (1H, dd, J ) 6.3, 7.7 Hz, OCH2), 4.10-
4.15 (1H, m, OCH), 4.62-4.64 (1H, m, C1-H), 5.88 (1H, dd, J )
2.2, 5.5 Hz, dCH), 6.01-6.02 (1H, m, dCH); 13C NMR δ 24.1
(CH2), 24.3 (CH2), 25.4 (CH2), 35.1 (CH2), 36.2 (CH2), 37.5 (CH2),
47.0 (CH), 67.4 (OCH2), 75.8 (OCH), 77.8 (OCH), 110.2 (C), 133.1
(CH), 136.8 (CH); HRMS (ESI) calcd for C13H20O3Na (M + Na)+,
247.1310; found, 247.1343.
the carbasugars. The synthesis of both the D- and L-series of
carbaribofuranoses from a single enantiomer of glyceraldehyde
derivative is the most remarkable feature of the present
approach.
Experimental Section
(4S)-4-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]cyclopent-2-en-1-
one 8a. To a magnetically stirred solution of the mixture of the
cyclopentenol derivatives 7a, prepared by ring-closing metathesis
of the dienol mixture 6a according to the previously published
procedure,10f (350 mg, 1.56 mmol) in acetone (10 mL) was added
dropwise Jones reagent (1.2 mL) at 0 °C till the color of the reagent
persisted. After stirring at that temperature for an additional 30 min,
the reaction mixture was diluted with water (2 mL) and extracted
with diethyl ether (2 × 15 mL). The combined organic layer was
washed sequentially with aqueous NaOH solution (20%, 5 × 1 mL)
and water (5 × 1 mL) and dried. Removal of the solvent in vacuo
followed by column chromatography using ether/petroleum ether
(1:6) as eluent afforded the cyclopentenone derivative 8a (333 mg,
1
96%): IR 1715.0 cm-1; H NMR δ 1.41 (2H, br s, CH2), 1.53-
C-1 Diastereomer of 9a. Rf ) 0.49 (EtOAc/petroleum ether 1:1);
1.64 (8H, m, CH2), 2.04 (1H, dd, J ) 2.4, 18.6 Hz, CH2), 2.45
(1H, dd, J ) 6.6, 18.9 Hz, CH2), 3.08-3.14 (1H, m, CH), 3.67-
3.73 (1H, m), 3.98-4.09 (2H, m), 6.26 (1H, dd, J ) 1.8, 5.4 Hz,
dCH), 7.77 (1H, dd, J ) 2.4, 5.4 Hz, dCH); 13C NMR δ 23.7
(CH2), 23.9 (CH2), 25.0 (CH2), 34.6 (CH2), 36.4 (CH2), 36.9 (CH2),
45.4 (CH), 67.2 (OCH2), 77.3 (OCH), 110.3 (C), 135.3 (CH), 165.1
(CH), 208.5 (CO); HRMS (ESI) calcd for C13H18O3Na (M + Na)+,
245.1154; found, 245.1112.
1
[R]22 -161.7 (c 2.9, CHCl3); H NMR δ 1.40 (2H, br s, CH2),
D
1.52-1.68 (8H, m, CH2), 1.75-1.93 (2H, m, CH2), 3.03-3.09 (2H,
m), 3.58 (1H, t, J ) 6.9 Hz), 3.87 (1H, dd, J ) 6.4, 13.0 Hz),
3.97-4.02 (1H, m), 4.87-4.90 (1H, m, C1-H), 5.92-5.94 (1H,
m, dCH), 6.05-6.08 (1H, m, dCH); 13C NMR δ 23.8 (CH2), 24.0
(CH2), 25.1 (CH2), 34.9 (CH2), 36.1 (CH2), 36.4 (CH2), 48.3 (CH),
67.5 (OCH2), 76.9 (OCH), 78.9 (OCH), 109.7 (C), 134.6 (CH),
136.5 (CH); HRMS (ESI) calcd for C13H20O3Na (M + Na)+,
247.1310; found, 247.1313.
Reduction of Ketone 8a. (1R,4S)-4-[(2S)-1,4-Dioxaspiro[4.5]-
dec-2-yl]cyclopent-2-en-1-ol 9a and its C-1 Diastereoisomer. To
a stirred suspension of LiAlH4 (260 mg, 6.84 mmol) in diethyl ether
(15 mL) at -60 °C was added dropwise a solution of the
cyclopentenone derivative 8a (1.38 g, 6.22 mmol) in diethyl ether
(2S)-2-[(1S,4R)-4-(Benzyloxy)cyclopent-2-en-1-yl]-1,4-
dioxaspiro[4.5]decane 10a. To a magnetically stirred suspension
of NaH (60 mg, 1.25 mmol, 50% in oil), freed from adhering oil
J. Org. Chem, Vol. 71, No. 26, 2006 9691

Ghosh et al.
1
by repeated washing with petroleum, in dry THF (3 mL) at 0 °C
was added dropwise a solution of the alcohol 9a (140 mg, 0.63
mmol) in dry THF (3 mL) under N2 atmosphere. The mixture was
allowed to stir at room temperature for 2 h, and then to it was
added HMPA (0.3 mL) dropwise followed by benzyl bromide (0.15
mL, 1.25 mmol). After stirring for an additional 12 h at room
temperature, the reaction mixture was cooled to 0 °C and quenched
by adding cold water (1 mL). Usual workup of the reaction mixture
followed by column chromatography using ether/petroleum ether
(1:4) as eluent afforded the benzyl ether 10a (180 mg, 92%) as a
colorless viscous liquid: [R]23D -23.9 (c 1.5, CHCl3); 1H NMR δ
1.39-1.49 (2H, m, CH2), 1.56-1.63 (8H, m, CH2), 2.27 (2H, td,
J ) 7.7, 13.7 Hz, CH2), 2.74-2.77 (1H, m, CH), 3.66 (1H, ddd, J
) 3.4, 5.9, 9.3 Hz), 3.94-4.04 (3H, m), 4.51 (1H, d, J ) 11.9 Hz,
PhCH2), 4.56 (1H, d, J ) 12.0 Hz, PhCH2), 5.94 (1H, td, J ) 2.0,
5.7 Hz, dCH), 6.03 (1H, td, J ) 1.7, 5.8 Hz, dCH), 7.25-7.34
(5H, m, ArH); 13C NMR δ 23.8 (CH2), 24.0 (CH2), 25.1 (CH2),
32.2 (CH2), 34.9 (CH2), 36.5 (CH2), 48.0 (CH), 67.3 (OCH2), 70.9
(OCH2) 78.8 (OCH), 83.7 (OCH), 109.5 (C), 127.5 (CH), 127.7
(CH), 128.3 (CH), 132.4 (CH), 135.9 (CH), 138.5 (C); HRMS (ESI)
calcd for C20H26O3Na (M + Na)+, 337.1780; found, 337.1784.
(1R,2R,3R,5S)-3-(Benzyloxy)-5-[(2S)-1,4-dioxaspiro[4.5]dec-
2-yl]cyclopentane-1,2-diol 11. To a magnetically stirred solution
of the cyclopentene derivative 10a (160 mg, 0.51 mmol) in acetone/
water (4:1, 7.5 mL) at room temperature was added N-methylmor-
pholine N-oxide monohydrate (207 mg, 1.53 mmol) followed by a
catalytic amount of OsO4. After the reaction mixture stirred at room
temperature for 14 h, acetone was removed under reduced pressure.
The residual mass was extracted with chloroform (2 × 10 mL),
washed with brine (2 × 2 mL), and dried. Removal of solvent in
vacuo followed by column chromatography using ethyl acetate/
13 (96 mg, 71%): [R]24 +44.7 (c 1.5, CHCl3); H NMR δ 1.33
D
(1H, ddd, J ) 4.2, 8.5, 13.0 Hz, CH2), 2.21-2.31 (1H, m, CH),
2.37 (1H, t, J ) 8.3 Hz, CH2), 2.75 (2H, br s, OH), 3.45 (1H, dd,
J ) 5.7, 11.7 Hz, OCH2), 3.59 (2H, dd, J ) 3.0, 11.7 Hz, OCH2,
OCH), 3.88 (1H, dd, J ) 1.9, 4.5 Hz), 3.95 (2H, dd, J ) 4.7, 7.7
Hz), 4.39-4.60 (6H, m, PhCH2), 7.29-7.34 (15H, m, ArH); 13C
NMR δ 30.5 (CH2), 42.1 (CH), 65.1 (OCH2), 71.25 (OCH2), 71.27
(OCH2), 71.7 (OCH2), 75.0 (OCH), 80.0 (OCH), 80.1 (OCH), 81.3
(OCH), 127.5 (CH), 127.70 (CH), 127.72 (CH), 127.8 (CH), 127.9
(CH), 128.0 (CH), 128.3 (CH), 128.37 (CH), 128.38 (CH), 137.3
(C), 137.9 (C), 137.9 (C); HRMS (ESI) calcd for C28H33O5 (M +
H)+, 449.2328; found, 449.2328.
(1R,2S,3R,4R)-4-[(1S)-1,2-Dihydroxyethyl]cyclopentane-1,2,3-
triol (Carba-â-D-allofuranose) 14. A solution of the diol 13 (16
mg, 0.03 mmol) in dry methanol (2 mL) containing Pd-C (10%)
was stirred under hydrogen atmosphere at room temperature for
20 h. The catalyst was filtered off, and removal of solvent in vacuo
afforded the alcohol 14 (6 mg, 94%): [R]24 -7.5 (c 0.5, CH3-
D
OH); 1H NMR (CD3OD) δ 1.25-1.33 (1H, m), 2.03 (1H, m), 2.12-
2.22 (1H, m), 3.54-3.70 (4H, m), 3.96-3.98 (1H, m), 4.10 (1H,
m); 13C NMR (CD3OD) δ 33.7 (CH2), 45.9 (CH), 66.0 (OCH2),
73.7 (OCH), 75.5 (OCH), 76.5 (OCH), 79.6 (OCH); HRMS (ESI)
calcd for C7H14O5Na (M + Na)+, 201.0739; found, 201.0723.
(1S,2R,3S,4R)-2,3,4-Tris(benzyloxy)cyclopentanecar-
baldehyde 15. To a magnetically stirred ice-cold solution of the
diol 13 (80 mg, 0.18 mmol) in methanol/water (3:1, 1.6 mL) was
added NaIO4 (76 mg, 0.36 mmol) in multiple portions. The reaction
mixture was allowed to stir at 0 °C for 30 min. The precipitated
white solid was filtered off after washing it thoroughly with diethyl
ether. Usual workup of the filtrate afforded the aldehyde 15 (70
mg, 94%): IR 1722.3 cm-1; 1H NMR δ 1.91-1.99 (1H, m, CH2),
2.34 (1H, ddd, J ) 6.6, 10.6, 14.3 Hz, CH2), 3.05-3.12 (1H, m,
CH), 3.89 (1H, t, J ) 3.3 Hz), 4.03-4.06 (1H, m), 4.27 (1H, dd,
J ) 4.6, 6.4 Hz), 4.45-4.87 (6H, m, PhCH2), 7.28-7.35 (15H, m,
ArH), 9.72 (1H, s, CHO); 13C NMR δ 27.5 (CH2), 53.3 (CH), 71.2
(OCH2), 72.0 (OCH2), 72.1 (OCH2), 79.0 (OCH), 80.3 (OCH), 81.1
(OCH), 127.5 (CH), 127.61 (CH), 127.65 (CH), 127.70 (CH),
127.73 (CH), 128.28(CH), 128.31 (CH), 137.7 (C), 137.9 (C), 138.0
(C), 201.7 (CHO); HRMS (ESI) calcd for C27H28O4Na (M + Na)+,
439.1885; found 439.1832.
petroleum ether (2:3) afforded the cis-diol 11 (159 mg, 90%): [R]23
D
+1.2 (c 1.5, CHCl3); 1H NMR δ 1.26 (1H, ddd, J ) 5.6, 9.6, 13.1
Hz, CH2), 1.39 (2H, br s, CH2), 1.57-1.61 (8H, m, CH2), 1.98-
2.09 (1H, m, CH), 2.17 (1H, td, J ) 8.3, 13.3 Hz, CH2), 3.13 (1H,
br s, OH), 3.32 (1H, br s, OH), 3.60 (1H, dd, J ) 6.0, 7.0 Hz),
3.86 (1H, dt, J ) 2.0, 7.4 Hz), 4.0-4.12 (4H, m), 4.51 (1H, d, J )
11.8 Hz, PhCH2), 4.57 (1H, d, J ) 11.8 Hz, PhCH2), 7.24-7.38
(5H, m, ArH); 13C NMR δ 23.7 (CH2), 23.9 (CH2), 24.9 (CH2),
30.4 (CH2), 34.8 (CH2), 36.2 (CH2), 45.1 (CH), 67.9 (OCH2), 71.5
(OCH2), 75.4 (OCH), 75.8 (OCH), 78.9 (OCH), 82.7 (OCH), 109.7
(C), 127.5 (CH), 128.2 (CH), 138.0 (C); HRMS (ESI) calcd for
C20H28O5Na (M + Na)+, 371.1834; found, 371.1840.
[(1R,2R,3S,4R)-2,3,4-Tris(benzyloxy)cyclopent-1-yl]metha-
nol 16. To a magnetically stirred ice-cold solution of the aldehyde
15 (70 mg, 0.17 mmol) in methanol (1.8 mL) under argon
atmosphere was added NaBH4 (13 mg, 0.34 mmol) in small
portions, and the mixture was allowed to stir for 30 min at 0 °C.
The reaction mixture was quenched with water. Usual workup of
the residual mass obtained after evaporation of methanol under
reduced pressure followed by column chromatography using ethyl
acetate/petroleum ether (1:3) as eluent afforded the alcohol 16 (67
mg, 95%): [R]20D +33.0 (c1.5, CHCl3); 1H NMR δ 1.30 (1H, ddd,
J ) 4.9, 7.9, 13.1 Hz, CH2), 2.21-2.31 (1H, m), 2.35-2.43 (2H,
m), 3.56-3.63 (2H, m, OCH2), 3.80 (1H, dd, J ) 4.9, 7.1 Hz),
3.86 (1H, dd, J ) 3.1, 4.7 Hz), 4.00 (1H, ddd, J ) 3.1, 4.9, 7.6
Hz), 4.43-4.61 (6H, m, PhCH2), 7.23-7.35 (15H, m, ArH); 13C
NMR δ 30.1 (CH2), 42.5 (CH), 65.1 (OCH2), 71.3 (OCH2), 71.5
(OCH2), 71.7 (OCH2), 80.8 (OCH), 81.07 (OCH), 81.09 (OCH),
127.5 (CH), 127.56 (CH), 127.58 (CH), 127.59 (CH), 127.78 (CH),
127.80 (CH), 128.2 (CH), 128.27 (CH), 128.31 (CH), 138.06 (C),
138.09 (C), 138.2 (C); HRMS (ESI) calcd for C27H30O4Na (M +
Na)+, 441.2042; found, 441.2041.
(2S)-2-[(1R,2R,3S,4R)-2,3,4-tris(Benzyloxy)cyclopent-1-yl]-1,4-
dioxaspiro[4.5]decane 12. Following the procedure for the ben-
zylation of the alcohol 9a, the cis-diol 11 (140 mg, 0.40 mmol)
was benzylated with benzyl bromide (0.19 mL, 1.61 mmol) to afford
the benzyl ether 12 (180 mg, 85%) as a colorless viscous liquid:
[R]23D -16.8 (c 1.5, CHCl3); 1H NMR δ 1.22-1.30 (1H, m, CH2),
1.39 (2H, br s, CH2), 1.49-1.61 (8H, m, CH2), 2.17-2.33 (2H, m,
CH2, CH), 3.62 (1H, dd, J ) 6.6, 6.9 Hz), 3.81 (1H, t, J ) 5.4
Hz), 3.92-4.02 (3H, m), 4.13 (1H, dd, J ) 6.6, 13.2 Hz), 4.52-
4.66 (6H, m, PhCH2), 7.23-7.39 (15H, m, ArH); 13C NMR δ 23.7
(CH2), 23.9 (CH2), 25.1 (CH2), 29.5 (CH2), 34.8 (CH2), 36.4 (CH2),
43.7 (CH), 67.2 (OCH2), 71.2 (OCH2), 71.6 (OCH2), 71.7 (OCH2),
77.1 (OCH), 78.3 (OCH), 81.0 (OCH), 82.9 (OCH), 109.5 (C),
127.36 (CH), 127.40 (CH), 127.43 (CH), 127.5 (CH), 127.6 (CH),
128.0 (CH), 128.12 (CH), 128.14 (CH), 128.2 (CH), 138.3 (C),
138.4 (C); HRMS (ESI) calcd for C34H41O5 (M + H)+, 529.2954;
found, 529.2917.
(1S)-1-[(1R,2R,3S,4R)-2,3-4-Tris(benzyloxy)cyclopent-1-yl]e-
thane-1,2-diol 13. A mixture of the cyclopentane derivative 12 (160
mg, 0.30 mmol) and aqueous acetic acid (80%, 2.5 mL) was stirred
at room temperature for 17 h. The resulting solution was diluted
with ethyl acetate (10 mL) and washed repeatedly with aqueous
NaOH solution (20%, 5 × 1.5 mL) to make it just alkaline (pH
paper). The organic layer was washed with brine (2 × 1 mL), dried,
and concentrated, and the residual mass was column chromato-
graphed using ethyl acetate/petroleum ether (2:3) to afford the diol
Synthesis of Dienols 6b. To a magnetically stirred solution of
vinyl magnesium bromide [prepared by addition of vinyl bromide
(3.3 g, 31 mmol) in THF (40 mL) to magnesium turnings (370
mg, 15.5 mmol)] was added a solution of the aldehyde 3b (690
mg, 3.1 mmol) in THF (8 mL) and refluxed gently for 1 h. The
reaction mixture was allowed to attain room temperature, then
cooled to 0 °C, quenched by water (4 mL), and filtered. Organic
phase was washed with brine (3 × 4 mL) and dried. Removal of
solvent in vacuo followed by column chromatography using ether/
9692 J. Org. Chem., Vol. 71, No. 26, 2006

Access to Carbapentofuranoses and Carbahexopyranoses
petroleum ether (1:4) as eluent afforded the alcohol 6b (550 mg,
BH3 gas thus liberated was subsequently bubbled through a solution
of the cyclopentenone derivative 27 (330 mg, 1.01 mmol) in THF
(20 mL) at -10 °C till complete disappearance of the starting
cyclopentenone derivative. The reaction mixture was then warmed
to 20 °C and was diluted with THF (10 mL). To the magnetically
stirred reaction mixture, cooled to -10 °C was added dropwise
aqueous NaOH solution (3 N, 7 mL) to make it alkaline (pH paper)
followed by H2O2 (30%, 7 mL). The reaction mixture was allowed
to attain room temperature very slowly when the two layers
separated. The organic layer was separated, and the aqueous layer
was extracted with ether (2 × 10 mL). The two organic layers were
combined and washed with water (4 × 2 mL) and brine (2 × 2
mL) and dried, and the solvent was removed in vacuo. The residual
mass was column chromatographed using ethyl acetate/petroleum
ether (3:7) as eluent to afford the alcohols 29a (70 mg, 20%) and
30a (190 mg, 54%).
29a. [R]23D -5.1 (c 0.3, CHCl3); 1H NMR δ 1.39-1.40 (2H, m,
CH2), 1.48-1.71 (8H, m, CH2), 2.06-2.22 (3H, m, CH2, CH), 2.98
(2H, br s, OH), 3.61 (1H, dd, J ) 4.9, 6.5 Hz), 3.75 (1H, dd, J )
4.4, 6.3 Hz), 3.97-4.07 (3H, m), 4.11 (1H, dd, J ) 4.4, 10.5 Hz),
4.65 (1H, d, J ) 11.8 Hz, PhCH2), 4.82 (1H, d, J ) 11.8 Hz,
PhCH2), 7.26-7.39 (5H, m, ArH); 13C NMR δ 23.8 (CH2), 24.1
(CH2), 25.0 (CH2), 32.2 (CH2), 35.0 (CH2), 36.3 (CH2), 45.8 (CH),
68.0 (OCH2), 72.1 (OCH2), 74.4 (OCH), 79.4 (OCH), 80.1 (OCH),
91.3 (OCH), 109.9 (C), 127.7 (CH), 127.8 (CH), 128.4 (CH), 138.4
(C); HRMS (ESI) calcd for C20H28O5Na (M + Na)+, 371.1834;
found, 371.1846.
30a. [R]23D -1.9 (c 0.8, CHCl3); 1H NMR δ 1.30-1.40 (2H, m,
CH2), 1.53-1.64 (8H, m, CH2), 1.80-1.86 (2H, m, CH2), 2.01-
2.11 (1H, m, CH), 2.68 (1H, br s, OH), 2.78 (1H, br s, OH), 3.61
(1H, dd, J ) 6.2, 7.8 Hz), 3.70 (1H, dd, J ) 5.5, 7.2 Hz), 4.02-
4.15 (3H, m), 4.25 (1H, t, J ) 7.7 Hz), 4.68 (1H, d, J ) 11.8 Hz,
PhCH2), 4.81 (1H, d, J ) 11.7 Hz, PhCH2), 7.26-7.38 (5H, m,
ArH); 13C NMR δ 23.8 (CH2), 24.1 (CH2), 25.0 (CH2), 31.7 (CH2),
34.9 (CH2), 36.4 (CH2), 44.8 (CH), 67.9 (OCH2), 68.9 (OCH), 72.2
(OCH2), 79.3 (OCH), 79.9 (OCH), 85.0 (OCH), 109.9 (C), 127.9
(CH), 128.5 (CH), 137.9 (C); HRMS (ESI) calcd for C20H29O5 (M
+ H)+, 349.2015; found, 349.2029.
(4R,6S)-6-[(2S)-1,4-Dioxa-spiro[4.5]dec-2-yl]octa-1,7-dien-4-
ol and Its C-4 Diastereoisomer 33. A solution of allyl bromide
(1.0 g, 8.37 mmol) in THF (10 mL) was added dropwise to a stirred
suspension of commercial zinc dust (0.4 g, 6.69 mmol) in THF (5
mL) at room temperature, and the mixture was stirred for 1 h to
produce a clear solution. A solution of the aldehyde 3b (1.25 g,
5.58 mmol) in THF (15 mL) was added dropwise to this solution
at room temperature and stirred for 1 h. The reaction mixture was
then cooled to 0 °C and quenched with a few drops of water. Usual
workup of the reaction mixture followed by column chromatography
using ether/petroleum ether (1:6) as eluent afforded an inseparable
mixtures of dienols 33 (1.23 g, 83%) in a ca. 1:1 ratio: 1H NMR
δ (for both diastereoisomers) 1.35 (2H, br s), 1.47-1.53 (1H, m),
1.58 (4H, br s), 1.62 (4H, br s), 1.72-1.82 (1H, m), 2.23-2.29
(2H, m), 2.33-2.40 (1H, m), 2.60 (1H, br s), 3.62-3.73 (2H, m),
3.85-3.97 (2H, m), 5.05-5.10 (4H, m), 5.52-5.59 (1H, m), 5.80-
5.87 (1H, m); 13C NMR δ (for both isomers) 23.9 (CH2), 24.0
(CH2), 24.1 (CH2), 25.10 (CH2), 25.15 (CH2), 35.2 (CH2), 35.3
(CH2), 36.4 (CH2), 36.5 (CH2), 39.7 (CH2), 39.8 (CH2), 41.4 (CH2),
42.68 (CH2), 42.70 (CH2), 45.6 (CH), 46.3 (CH), 68.1 (CH2), 68.2
(CH2), 68.9 (CH), 69.1 (CH), 78.0 (CH), 78.3 (CH), 109.9 (C),
110.0 (C), 117.0 (CH2), 117.2 (CH2), 117.5 (CH2), 117.6 (CH2),
135.0 (CH), 135.1 (CH), 138.0 (CH), 138.2 (CH); HRMS (ESI)
calcd for C16H26O3Na (M + Na)+, 289.1780; found, 289.1779.
1
70%) as a mixture of two diastereoisomers: IR 3445.0 cm-1; H
NMR (of the diastereoisomeric mixture) δ 1.33 (4H, br s), 1.42-
1.55 (18H, m), 1.74-1.87 (2H, m), 2.18-2.30 (1H, m), 2.33-
2.46 (1H, m), 2.82 (2H, br s), 3.52-3.60 (2H, m), 3.84-3.91 (4H,
m), 4.11-4.21 (2H, m), 4.99-5.20 (8H, m), 5.47-5.56 (2H, m),
5.77-5.85 (2H, m); 13C NMR (for one isomer from the mixture)
δ 24.2 (CH2), 24.2 (CH2), 25.4 (CH2), 35.5 (CH2), 36.7 (CH2), 39.8
(CH2), 45.4 (CH), 68.2 (OCH2), 71.4 (OCH), 78.3 (OCH), 110.3
(C), 115.4 (CH2), 117.5 (CH2), 138.3 (CH), 140.9 (CH) and (for
the other isomer) δ 24.2 (CH2), 24.2 (CH2), 25.4 (CH2), 35.5 (CH2),
36.7 (CH2), 40.1 (CH2), 46.1 (CH), 68.4 (OCH2), 70.9 (OCH), 78.4
(OCH), 110.3 (C), 114.1 (CH2), 117.7 (CH2), 138.2 (CH), 141.9
(CH); HRMS (ESI) calcd for C15H24O3Na (M + Na)+, 275.1623;
found, 275.1627.
(1S,4R)-4-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]cyclopent-2-en-1-
ol 9b and Its C-1 Diastereoisomer. A solution of the above diene
mixture 6b (370 mg, 1.47 mmol) in dry dichloromethane(12 mL)
was degassed by bubbling argon through it. To it was added Grubbs’
first generation catalyst (44 mg, 0.05 mmol) in one portion. The
resulting pink solution was stirred at room temperature under argon
atmosphere for 24 h. The residual mass obtained after removal of
solvent was chromatographed using ether/petroleum ether (1:3) as
eluent to afford the pure cyclopentenol derivative 7b (280 mg, 85%)
as a 1:1 diastereoisomeric mixture.
The mixture of the cyclopentenol derivatives 7b (362 mg, 1.62
mmol) was oxidized with Jones reagent, as described for oxidation
of 7a, to the cyclopentenone derivative 8b (310 mg, 86%): IR
1716.5 cm-1; 1H NMR δ 1.26-1.33 (2H, m, CH2), 1.47-1.55 (8H,
m, CH2), 2.19 (1H, dd, J ) 2.3, 18.8 Hz, CH2), 2.39 (1H, dd, J )
6.5, 18.8 Hz, CH2), 3.10-3.15 (1H, m, CH), 3.55 (1H, dd, J )
6.5, 8.2 Hz, OCH2), 4.01 (1H, dd, J ) 6.6, 8.2 Hz, OCH2), 4.17
(1H, dd, J ) 6.3, 11.6 Hz, OCH), 6.21 (1H, dd, J ) 2.0, 5.6 Hz,
dCH), 7.51 (1H, dd, J ) 2.5, 5.7 Hz, dCH); 13C NMR δ 23.5
(CH2), 23.7 (CH2), 24.9 (CH2), 34.3 (CH2), 35.8 (CH2), 36.3 (CH2),
44.4 (CH), 66.4 (OCH2), 75.7 (OCH), 109.9 (C), 135.7 (CH), 163.5
(CH), 208.7 (CO); HRMS (ESI) calcd for C13H18O3Na (M + Na)+,
245.1154; found, 245.1179.
Following the procedure for the reduction of the cyclopentenone
derivative 8a, the cyclopentenone derivative 8b (310 mg, 1.40
mmol) was reduced with LiAlH4 (58 mg, 1.54 mmol) at -60 °C
to the cyclopentenol derivative 9b (272 mg, 75%) and its C-1
diastereoisomer (18 mg, 5%) as viscous liquid.
9b. Rf ) 0.55 (EtOAc/petroleum ether 1:1); [R]24D +33.0 (c 1.7,
CHCl3); 1H NMR δ 1.32-1.38 (2H, m, CH2), 1.48-1.66 (8H, m,
CH2), 2.21 (2H, ddd, J ) 7.2, 8.2, 14.1 Hz, CH2), 2.40-2.42 (1H,
m, OH), 2.78-2.82 (1H, m, CH), 3.57 (1H, t, J ) 7.9 Hz, OCH2),
4.03 (1H, dd, J ) 6.5, 7.9 Hz, OCH2), 4.12-4.18 (1H, m, OCH),
4.61-4.63 (1H, m, C1-H), 5.80 (1H, dd, J ) 2.2, 5.6 Hz, dCH),
5.95-5.98 (1H, m, dCH); 13C NMR δ 23.6 (CH2), 23.9 (CH2),
25.1 (CH2), 33.9 (CH2), 34.6 (CH2), 35.8 (CH2), 46.2 (CH), 67.7
(OCH2), 75.3 (OCH), 75.5 (OCH), 109.8 (C), 134.4 (CH), 135.5
(CH); HRMS (ESI) calcd for C13H20O3Na (M + Na)+, 247.1310;
found, 247.1299.
C-1 Diastereomer of 9b. Rf ) 0.50 (EtOAc/petroleum ether 1:1);
[R]24D +131.8 (c 2.3, CHCl3); 1H NMR δ 1.33-1.40 (2H, m, CH2),
1.48-1.60 (8H, m, CH2), 1.84 (1H, ddd, J ) 3.2, 8.0, 11.2 Hz,
CH2), 2.08 (1H, ddd, J ) 4.7, 7.2, 12.0 Hz, CH2), 3.06-3.12 (2H,
m), 3.51-3.58 (1H, m), 3.94-4.01 (2H, m), 4.87-4.90 (1H, m,
C1-H), 5.81 (1H, dd, J ) 1.9, 5.5 Hz, dCH), 5.92-5.95 (1H, m,
dCH); 13C NMR δ 23.7 (CH2), 23.9 (CH2), 25.1 (CH2), 34.8 (CH2),
36.2 (CH2), 36.4 (CH2), 47.9 (CH), 67.0 (OCH2), 76.9 (OCH), 77.9
(OCH), 109.5 (C), 134.9 (dCH) 135.7 (dCH); HRMS (ESI) calcd
for C13H20O3Na (M + Na)+, 247.1310; found, 247.1333.
(1S,2R,3R,4S)-2-(Benzyloxy)-4-[(2S)-1,4-dioxaspiro[4.5]dec-2-
yl]cyclopentane-1,3-diol 29a and (1R,2R,3R,4S)-2-(Benzyloxy)-
4-[(2S)-1,4-dioxaspiro[4.5]dec-2-yl]cyclopentane-1,3-diol 30a. To
a magnetically stirred solution of BF3‚OEt2 (5 mL) in diglyme (20
mL) at 45 °C was added NaBH4 (1.0 g) in small portion, and the
(5R)-5-[(2S)-1,4-Dioxa-spiro[4.5]dec-2-yl]-cyclohex-3-enone 34c.
A solution of diastereoisomeric dienols 33 (1.1 g, 4.14 mmol) in
dichloromethane (50 mL) was treated with Grubbs’ first generation
catalyst (90 mg, 0.11 mmol) under argon atmosphere and stirred
at room temperature for 3 h. The residual mass obtained after
removal of solvent was chromatographed using ether/petroleum
J. Org. Chem, Vol. 71, No. 26, 2006 9693

Ghosh et al.
ether (1:4) to afford an inseparable mixture of cyclohexenols 34a
and 34b (0.88 g, 89%) in a ca. 1:1 ratio.
s, CH3 of other isomer), 2.23-2.54 (4H, m), 2.99-3.01 (1H, m),
3.07-3.08 (1H, m), 3.12-3.19 (1H, m), 3.29-3.31 (1H, m), 3.73
(1H, dd, J ) 7.5, 7.2 Hz), 3.87-3.92 (1H, m), 4.06-4.14 (3H, m),
4.23 (1H, dd, J ) 12.6, 6.6 Hz), 4.67-4.73 (1H, m), 4.83-4.91
(1H, m); 13C NMR (for both isomers) δ 21.1 (CH3), 21.2 (CH3),
23.7 (CH2), 23.8 (CH2), 23.9 (CH2), 25.1 (CH2), 27.0 (CH2), 28.8
(CH2), 29.4 (CH2), 30.6 (CH2), 34.5 (CH2), 35.1 (CH2), 36.0 (CH2),
36.2 (CH2), 37.6 (CH), 38.2 (CH), 49.7 (CH), 51.8 (CH), 52.8 (CH),
53.8 (CH), 66.6 (CH2), 66.7 (CH2), 67.8 (CH), 68.6 (CH), 76.6
(CH), 77.2 (CH), 109.4 (C), 109.8 (C), 170.1 (CO), 170.4 (CO);
HRMS (ESI) calcd for C16H24O5Na (M + Na)+, 319.1521; found,
319.1528.
A solution of cyclohexenols 34a and 34b (0.4 g, 1.68 mmol)
was oxidized through Swern oxidation following the procedure for
the synthesis of the aldehyde 3b with oxalyl chloride (0.23 mL,
2.69 mmol), DMSO (0.36 mL, 5.04 mmol), and triethylamine (1.4
mL, 10.08 mmol) to afford the cyclohexenone 34c (280 mg, 71%)
as a colorless oil: IR (neat) νmax 1718 cm-1; 1H NMR δ 1.36 (2H,
br s), 1.51 (4H, br s), 1.54-1.59 (4H, m), 2.44-2.61 (2H, m),
2.74-2.78 (1H, m), 2.85-2.90 (2H, m), 3.62-3.69 (1H, m), 3.98-
4.05 (2H, m), 5.74-5.79 (1H, m), 5.84-5.91 (1H, m); 13C NMR
δ 23.7 (CH2), 23.9 (CH2), 25.1 (CH2), 34.6 (CH2), 35.9 (CH2), 39.8
(CH2), 40.4 (CH), 40.9 (CH2), 66.6 (CH2), 77.5 (CH), 110.0 (C),
126.4 (CH), 127.4 (CH), 209.0 (CO); HRMS (ESI) calcd for
C14H21O3 (M + H)+, 237.1491; found, 237.1470.
Acetic Acid (1R,5R)-5-[(2S)-1,4-dioxa-spiro[4.5]dec-2-yl]-cy-
clohex-3-enyl Ester 34d. The cyclohexenone 34c (280 mg, 1.19
mmol) was reduced with LiAIH4 (50 mg, 1.30 mmol) at -60 °C,
following the procedure for the reduction of 8a, to afford exclusively
the cyclohexenol 34a (260 mg, 92%) as a colorless viscous liquid:
[R]25D +47.9 (c 0.9, CHCl3); 1H NMR δ 1.22-1.37 (3H, m), 1.51
(4H, br s), 1.55-1.60 (4H, m), 1.97-2.00 (1H, m), 2.05-2.09 (1H,
m), 2.33-2.38 (2H, m), 2.51 (1H, br s), 3.60-3.66 (1H, m), 3.88-
3.91 (1H, m), 3.94-4.05 (2H, m), 5.45-5.51 (1H, m), 5.66-5.73
(1H, m); 13C NMR δ 23.7 (CH2), 23.9 (CH2), 25.1 (CH2), 34.7
(CH2), 34.8 (CH2), 34.9 (CH2), 36.0 (CH2), 39.3 (CH), 66.4 (CH2),
66.8 (CH), 78.1 (CH), 109.4 (C), 126.3 (CH), 126.8 (CH); HRMS
(ESI) calcd for C14H22O3Na (M + Na)+, 261.1467; found, 261.1487.
To a magnetically stirred solution of the cyclohexenol 34a (260
mg, 1.09 mmol) in dichloromethane (10 mL) at 0 °C was added
dropwise acetic anhydride (0.17 mL, 1.86 mmol), triethyl amine
(0.34 mL, 2.40 mmol), and 4-(dimethylamino)pyridine (4-DMAP;
10 mg). The reaction mixture was then allowed to stir under argon
atmosphere for 2 h at room temperature. Solvent was evaporated,
and the residual mass was extracted with ether (30 mL). The ether
layer was then washed with water (2 mL) followed by brine (2
mL) and dried. Removal of solvent under reduced pressure followed
by column chromatography using ether/petroleum ether (1:9)
(1R,3S,5S,6S)-5-[(2S)-1,4-Dioxa-spiro[4.5]dec-2-yl]-7-oxa-
bicyclo[4.1.0]heptan-3-ol 37 and (1R,4S,5R)-5-[(2S)-1,4-dioxa-
spiro[4.5]dec-2-yl]-cyclohex-2-ene-1,4-diol 38a. To a magnetically
stirred solution of diphenyl diselenide (125 mg, 0.4 mmol) in
absolute ethanol (1.5 mL) was added sodium borohydride (26 mg,
0.69 mmol) in portions, and stirring was continued until the bright
yellow solution turned colorless. A solution of epoxides 35 and 36
(170 mg, 0.57 mmol) in absolute ethanol (1.5 mL) was added
dropwise to the reaction mixture, and the reaction mixture was
stirred at room temperature for 2 h. The reaction mixture was cooled
to 0 °C, and THF (2.5 mL) was added followed by addition of
H2O2 (30%) (0.6 mL) over a period of 3 min. The reaction mixture
was left to attain room temperature and then refluxed at 70 °C for
1.5 h. The resulting slurry was diluted with water (2 mL) and
extracted with ether (3 × 5 mL). The organic phase was washed
with aqueous Na2CO3 (10%, 2 × 2 mL), dried, and concentrated.
Column chromatography of the residual mass using ethyl acetate/
petroleum ether (3:5) afforded the epoxy alcohol 37 (42 mg, 29%)
1
as a colorless viscous liquid: IR(neat) νmax 3421 cm-1; H NMR
δ 1.40 (2H, br s), 1.50-1.63 (9H, m), 1.77-1.81 (1H, m), 2.24-
2.36 (2H, m), 2.37-2.48 (2H, m), 3.00-3.01 (1H, m), 3.29-3.30
(1H, m), 3.71-3.76 (1H, m), 3.95-4.02 (2H, m), 4.07-4.12 (1H,
m); 13C NMR δ 23.7 (CH2), 23.9 (CH2), 25.1 (CH2), 34.2 (CH2),
34.5 (CH2), 36.0 (CH2), 36.7 (CH2), 37.5 (CH), 53.1 (CH), 54.4
(CH), 64.5 (CH), 66.6 (CH2), 76.6 (CH), 109.9 (C); HRMS (ESI)
calcd for C14H22O4Na (M + Na)+, 277.1416; found, 277.1439. The
cyclohexenediol 38a (60 mg, 41%) was also produced as a white
crystalline solid: mp 142 °C; [R]25D +32.1 (c 0.5, CHCl3); IR (KBr)
afforded the corresponding acetate 34d (280 mg, 92%) as a colorless
1
oil: [R]25 +53.6 (c 1.8, CHCl3); IR(neat): νmax 1732 cm-1; H
D
ν
max 3246.0 cm-1; 1H NMR δ 1.40 (2H, br s), 1.59 (4H, br s), 1.61
NMR δ 1.24-1.43 (3H, m), 1.56 (4H, br s), 1.68 (4H, br s), 2.02
(3H, s, -OCOCH3), 2.03-2.15 (2H, m), 2.39-2.44 (1H, m), 2.52-
2.58 (1H, m), 3.61-3.68 (1H, m), 3.92-4.03 (2H, m), 4.92-5.01
(1H, m), 5.46-5.49 (1H, m), 5.68-5.73 (1H, m); 13C NMR δ 21.3
(CH3), 23.8 (CH2), 23.9 (CH2), 25.1 (CH2), 31.2 (CH2), 31.3 (CH2),
34.8 (CH2), 36.1 (CH2), 39.3 (CH), 66.6 (CH2), 69.8 (CH), 78.1
(CH), 109.4 (C), 126.3 (CH), 126.5 (CH), 170.5 (CO); HRMS (ESI)
calcd for C16H24O4Na (M + Na)+, 303.1572; found, 303.1528.
Epoxidation of Acetate 34d. To a magnetically stirred cold (0
°C) solution of the acetate 34d (170 mg, 0.61 mmol) in 1,2-
dichloroethane (4.5 mL) was added m-CPBA (209 mg, 1.21 mmol)
in one portion. After stirring at room temperature for 8 h, the
reaction mixture was cooled to 0 °C and quenched by adding
saturated Na2SO3 solution, extracted with ether (30 mL), and
washed with ice-cold 2% NaOH solution (w/v) (3 × 2 mL) and
dried. Evaporation of the solvent followed by column chromatog-
raphy using ether/petroleum ether (1:6) afforded an inseparable
mixture (2:3) of epoxides 35 and 36 (160 mg, 89%) as a colorless
viscous liquid: IR(neat) νmax 1728 cm-1; 1H NMR δ (for mixture
of diastereomers) 1.23-1.42 (6H, m), 1.59 (8H, br s), 1.62 (8H, br
s), 1.70-1.84 (4H, m), 2.02 (3H, s, CH3 of one isomer), 2.03 (3H,
(4H, br s), 1.65-1.68 (2H, m), 2.11-2.17 (1H, m), 2.45 (1H, br
s), 2.54 (1H, br s), 3.78 (1H, dd, J ) 7.0, 6.8 Hz), 4.05-4.07 (1H,
m), 4.10-4.30 (3H, m), 5.82-5.91 (2H, m); 13C NMR δ 23.8
(CH2), 24.0 (CH2), 25.1 (CH2), 29.0 (CH2), 34.8 (CH2), 36.3 (CH2),
41.1 (CH), 64.9 (CH), 67.0 (CH2), 67.5 (CH), 76.4 (CH), 109.5
(C), 129.1 (CH), 135.1 (CH); HRMS (ESI) calcd for C14H22O4Na
(M + Na)+, 277.1416; found, 277.1461.
Acknowledgment. Financial support from the Department
of Science and Technology, Government of India is gratefully
acknowledged. T.B. and N.S. wish to thank CSIR, New Delhi
for Senior Research Fellowships.
Supporting Information Available: General methods and
procedures along with spectral data for compounds 3b, 10b, 17-
25, 27, 29b, 30b, 31, 32, 38b, 39a,b, and 40a-c and copies of 1H,
13C NMR and DEPT spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO061717T
9694 J. Org. Chem., Vol. 71, No. 26, 2006