Asymmetric synthesis of (+)-allo-quercitol and (+)-talo-quercitol via free radical cycloisomerization of an enantiomerically pure alkyne-tethered aldehyde derived from a carbohydrate

Article abstract of DOI:10.1021/jo010455m

We describe for the first time the free radical cyclization of enantiomerically pure alkyne-tethered aldehydes obtained from a carbohydrate (6, 7). The synthesis of compounds 6 and 7 obtained from a derivative of D-ribose is reported. These radical precursors have been submitted to cyclization with tributyltin hydride plus azobisisobutyronitrile to yield, after ring closure, two carbocycles, respectively. These carbocycles have been obtained as mixtures of E and Z vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed ¹H NMR analysis. The specific transformation of 7-methoxymethoxy-2,2-dimethyl-4-methylene-5-tertbutyldimethylsilyloxy- (3aR,5S,7S,7aS)-perhydrobenzo[d] [1,3]dioxole into optically pure (+)-allo-quercitol and (+)-talo-quercitol is described. From these results, we conclude that under an appropriate choice of radical precursors and conditions, the synthesis of highly functionalized cyclohexane derivatives of biological interest is now available.

Full text of DOI:10.1021/jo010455m

8370
J . Org. Chem. 2001, 66, 8370-8378
Asym m etr ic Syn th esis of (+)-a llo-Qu er citol a n d (+)-ta lo-Qu er citol
via F r ee Ra d ica l Cycloisom er iza tion of a n En a n tiom er ica lly P u r e
Alk yn e-Teth er ed Ald eh yd e Der ived fr om a Ca r boh yd r a te$
J . S. Yadav,* Arup Maiti, A. Ravi Sankar,# and A. C. Kunwar#
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500007, India
yadav@iict.ap.nic.in
Received May 3, 2001
We describe for the first time the free radical cyclization of enantiomerically pure alkyne-tethered
aldehydes obtained from a carbohydrate (6, 7). The synthesis of compounds 6 and 7 obtained from
a derivative of D-ribose is reported. These radical precursors have been submitted to cyclization
with tributyltin hydride plus azobisisobutyronitrile to yield, after ring closure, two carbocycles,
respectively. These carbocycles have been obtained as mixtures of E and Z vinyltin isomers, but
with excellent diastereoselection at the new stereocenter formed during the ring closure. After
protodestannylation, only one diastereomer was detected and isolated. The absolute configuration
1
at the new stereocenter formed during the carbocyclization has been established by detailed H
NMR analysis. The specific transformation of 7-methoxymethoxy-2,2-dimethyl-4-methylene-5-tert-
butyldimethylsilyloxy-(3aR,5S,7S,7aS)-perhydrobenzo[d][1,3]dioxole into optically pure (+)-allo-
quercitol and (+)-talo-quercitol is described. From these results, we conclude that under an
appropriate choice of radical precursors and conditions, the synthesis of highly functionalized
cyclohexane derivatives of biological interest is now available.
In tr od u ction
Strategies for synthesizing such carbocycles from
carbohydrates have gained importance over the past
decade because of the readily available starting materials
and due to the high chirality content that can be
transformed into a variety of products, leading to the
construction of functionalized chiral carbocyclic building
blocks.8 The transformation of carbohydrate derivatives
into functionalized carbocycles has usually been achieved
by multistep protocols involving the initial conversion of
the carbohydrates into suitable functionalized open-chain
products, followed by ring closure using different proce-
dures.9-12 In particular, radical carbocyclization has been
recognized as a most efficient tool because it tolerates
high levels of substrate functionalization.10 In recent
years, there have been numerous examples of the use of
vinyl radical cyclization for the synthesis of five-
membered cyclitols.11 However, there are very few ex-
amples for the preparation of six-membered cyclitols
employing radical cyclization of a vinyl radical derived
from an alkyne.12 This is possibly due to the failure of
acyclic carbohydrate intermediates to yield cyclized
products.12b,c One of the reasons attributed is the fact that
Asymmetric syntheses of polyhydroxycyclohexane de-
rivatives are of interest due to their versatility as
synthetic intermediates, for their significant biological
activity, and for the structural challenge inherent in their
syntheses.1 “Quercitols”, a generic term used for cyclo-
hexanepentols, are the largest family of diastereoisomers
which can exist in 16 stereoisomeric forms, of which four
are symmetric, with the other 12 being grouped in six
pairs of enantiomers.2 (+)-Proto,3 (-)-proto,4 and (-)-vivo5
are the only optically active stereoisomeric forms found
in nature. So far, 10 possible diastereomers of quercitols
have been synthesized by different methods.1c In most
of the previous reports, the naturally available cyclitols
have been used as starting materials for the synthesis
of quercitols. However, the limited availability of chiral
sources has restricted their utility. The first synthesis
of (()-allo-quercitol and (+)-talo-quercitol was described
by McCasland6 starting from haloinositols. Recently
Balci7 et al. have synthesized (()-talo-quercitol. To the
best of our knowledge, no report is available on the
synthesis of (+)-allo-quercitol.
* To whom correspondence should be addressed. Telefax: +91 40
(6) (a) McCasland, G. E.; Furuta, S.; J ohnson, L. F.; Shoolery, J . N.
J . Am. Chem. Soc. 1961, 83, 2335. (b) Shoolery, J . N.; J ohnson, L. F.;
Furuta, S.; McCasland, G. E. J . Am. Chem. Soc. 1961, 83, 4243. (c)
McCasland, G. E.; Furuta, S.; Bartuska, V. J . Org. Chem. 1963, 28,
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Grau, A.; Marco-Contelles, J . Chem. Soc. Rev. 1998, 27, 155. (e) Fraser-
Reid, B.; Burgey, C. S.; Vollerthun, R. Pure Appl. Chem. 1998, 70, 285.
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7170512.
$
IICT Communication No. 4782.
Center for Nuclear Magnetic Resonance, Indian Institute of
#
Chemical Technology, Hyderabad-500007, India.
(1) (a) Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J .
Chem. Rev. 1996, 96, 1195. (b) Kiddle, J . J . Chem. Rev. 1995, 95, 2189.
(c) Hudlicky, T.; Cebulak, M. Cyclitols and Derivative; VCH: New York,
1993; pp 134-150.
(2) (a) McCasland, G. E. Adv. Carbohydr. Chem. 1965, 20, 11. (b)
McCasland, G. E.; Naumann, M. O.; Durham, L. J . J . Org. Chem. 1968,
33, 4220.
(3) Braconnot, H. Ann. Chim. Phys. 1849, 27, 392.
(4) Plouvier, V. C. R. Seances Acad. Sci. 1961, 253, 3047.
(5) Posternak, T. The Cyclitols, 1st ed.; Hermann: Paris, 1965; pp
103-107.
10.1021/jo010455m CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/10/2001

Cycloisomerization of an Alkyne-Tethered Aldehyde
J . Org. Chem., Vol. 66, No. 25, 2001 8371
Sch em e 1
such a cyclization is about 40 times slower than that of
the 5-hexenyl radical.13 Fraser-Reid et al. have reported
partial success using aldehyde functional groups as the
radical acceptor in 6-exo cyclizations.14 The efficiency may
be diminished by several factors; for example, the pres-
ence of oxygen R to the aldehyde may inhibit the reaction.
They concluded that care should be taken in choosing the
radical precursor for cyclization.12b With this information
in hand, we report the first examples of the 6-exo-trig
radical cycloisomerization of enantiomerically pure poly-
oxygenated alkyne-tethered aldehydes. This strategy
has resulted in a new and highly diastereoselective
method for the synthesis of (+)-allo-quercitol (6-deoxy-
D-allo-inositol) and (+)-talo-quercitol (1-deoxy-D-neo-
inositol).
(9) See reviews and recent references not included there: (a) Grove,
J . J . C.; Holzapfel, C. W. Tetrahedron Lett. 1997, 38, 7429. (b) Boiron,
A.; Zillig, P.; Faber, D.; Giese, B. J . Org. Chem. 1998, 63, 5877. (c)
Storch de Gracia, I.; Dietrich, H.; Bobo, S.; Chiara, J . L. J . Org. Chem.
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Tetrahedron Lett. 1998, 39, 7075. (g) Kapferer, P.; Sarabia, F.; Vasella,
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Shipman, M.; Sik, V. J . Chem. Soc., Perkin Trans. 1 1999, 3349. (i)
Clive, D. L. J .; He, X.; Postema, M. H. D.; Mashimbye, M. J . J . Org.
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Lett. 1999, 1, 1705. (l) Bobo, S.; Storch de Gracia, I.; Chiara, J . L.
Synlett 1999, 1551. (m) Marco-Contelles, J .; de Opazo, E. Tetrahedron
Lett. 1999, 40, 4445. (n) Boss, O.; Leroy, E.; Blaser, A.; Reymond, J .-
L. Org. Lett. 2000, 2, 151. (o) Sollogoub, M.; Mallet, J .-M.; Sinay, P.
Angew. Chem., Int. Ed. 2000, 39, 362. (p) Callam, C. S.; Lowary, T. L.
Org. Lett. 2000, 2, 167. (q) Carpintero, M.; J aramillo, C.; Fernandez-
Mayoralas, A. Eur. J . Org. Chem. 2000, 1285.
Sch em e 2a
(10) For excellent reviews on the radical cyclization reaction, see:
(a) Giese, B. Radicals in Organic Synthesis: Formation Of Carbon-
Carbon Bond; Pergamon: Oxford, 1986. (b) Curran, D. P. Synthesis
1988, 417, 489. (c) Curran, D. P. In Comprehensive Organic Chemistry;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1992; Vol. 4. (d)
Giese, B.; Kopping, B.; Gobel, T.; Dickhaut, J .; Thoma, G.; Kulicke, K.
J .; Tarach, F. Org. React. 1996, 48, ch. 2. (e) Motherwell, W. B.; Crich,
D. Free Radical Chain Reactions in Organic Synthesis; Academic
Press: London, 1992. (f) Ramaiah, M. Tetrahedron 1987, 43, 3541. (g)
Neumann, W. Synthesis 1987, 665.
(11) (a) Mariya, O.; Okawara, M.; Ueno, Y. Chem. Lett. 1984, 1437.
(b) Stork, G.; Mook, R., J r. Tetrahedron Lett. 1986, 27, 4529. (c)
Beckwith, A. L. J .; O’Shea, D. M. Tetrahedron Lett. 1986, 27, 4525.
(d) Stork, G.; Mook, R., J r. J . Am. Chem. Soc. 1987, 109, 2829. (e)
Nazoki, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. J pn. 1987, 60,
3415. (f) Enholm, E. J .; Burroff, J . A.; J aramillo, L. M. Tetrahedron
Lett. 1990, 31, 3727. (g) Nishida, A.; Takahashi, H.; Takeda, H.;
Takeda, N.; Yonemitsu, O. J . Am. Chem. Soc. 1990, 112, 902. (h)
Moufid, N.; Chapleur, Y. Tetrahedron Lett. 1991, 32, 1799. (i) Clive,
D. L. J .; Manning, H. W. J . Chem. Soc., Chem. Commun. 1993, 666.
(j) Marco-Contelles, J .; Destabel, C.; Chiara, J . L.; Bernabe, M.
Tetrahedron: Asymmetry 1995, 6, 1547. (k) Marco-Contelles, J .; Desta-
bel, C.; Gallego, P.; Chiara, J . L.; Bernabe, M. J . Org. Chem. 1996, 61,
1354. (l) Marco-Contelles, J .; Rodriguez, M. Tetrahedron Lett. 1998,
39, 6749. (m) Ryu, I.; Ogura, S.-i.; Minakata, S.; Komatsu, M.
Tetrahedron Lett. 1999, 40, 1515. (n) Alcaide, B.; Rodriguez-Campos,
I. M.; Rodriguez-Lopez, J .; Rodriguez-Vicente, A. J . Org. Chem. 1999,
64, 5377. (o) Tauh, P.; Fallis, A. G. J . Org. Chem. 1999, 64, 6960. (p)
Kiguchi, T.; Tajiri, K.; Ninomiya, I.; Naito, T. Tetrahedron 2000, 56,
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(12) (a) Fraser-Reid, B.; Vite, G. D.; Yeung, B.-W. A.; Tsang, R.
Tetrahedron Lett. 1988, 29, 1645. (b) Yeung, B.-W. A.; Alonso, R.; Vite,
G. D.; Fraser-Reid, B. J . Carbohydr. Chem. 1989, 8, 413. (c) Gomez,
A. M.; Danelon, G. O.; Valverde, S.; Lopez, J . C. J . Org. Chem. 1998,
63, 9626. (d) Keck, G. E.; Wager, T. T.; McHardy, S. F. J . Org. Chem.
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Chem. 1999, 64, 4465. (f) Chareyron, M.; Devin, P.; Fensterbank, L.;
Malacria, M. Synlett 2000, 83.
a
Reagents: (i) PPh3, CCl4, reflux; (ii) LAH, Et2O, 0 °C to room
temperature; (iii) LiNH2, liquid NH3; (iv) TrCl, Et3N, CH2Cl2, room
temperature; (v) TBDMSCl, imidazole, CH2Cl2, room temperature;
(vi) HCO2H, Et2O, 0 °C; (vii) MOMCl, (iPr)2NEt, CH2Cl2, room
temperature; (viii) TBAF, THF, room temperature; (ix) (COCl)2,
DMSO, Et3N, -78 °C.
Resu lts a n d Discu ssion
The synthetic approach used is described in Scheme
1. The essential aspects of this strategy include a Wittig-
type reaction on aldoses A, followed by some functional
group transformations, selective protections, and activa-
tions to afford the highly functionalized chiral, radical
precursors B. These compounds, upon treatment with a
tin hydride reagent, provide the vinyl radical,11 species
C, which leads to cyclitol derivatives D. These compounds
were conveniently designed for further synthetic ma-
nipulation to E. We therefore chose to prepare radical
precursors from D-(+)-ribose as shown in Scheme 2.
Accordingly, alcohol-ester 1, available from D-(+)-ribose,15
(13) (a) Beckwith, A. L. J . Tetrahedron 1981, 37, 3073. (b) Beckwith,
A. L. J .; Schiesser, C. H. Tetrahedron 1985, 41, 3925. (c) J enkins, P.
R.; Symons, M. C. R.; Booth, S. E.; Swain, C. J . Tetrahedron Lett. 1992,
33, 3543.
(14) See refs 12 and Tasang, R.; Dickson, J . K., J r.; Pak, H.; Walton,
R.; Fraser-Reid, B. J . Am. Chem. Soc. 1987, 107, 3484 and references
cited therein.

8372 J . Org. Chem., Vol. 66, No. 25, 2001
Yadav et al.
Sch em e 3
F igu r e 1.
(8E, 8Z and 9E, 9Z) was diastereomerically homogeneous
at the new stereocenter (C-5), formed during the cycliza-
tion. The strongly reduced conformational flexibility of
these carbocycles facilitated the stereochemical assign-
was converted to the corresponding chloride 2 in 88%
yield by refluxing it with triphenylphosphine in carbon
tetrachloride. Ester reduction using lithium aluminum
hydride afforded 3 in 90% yield which, upon treatment
with LiNH2 in liquid NH3,16 produced alkynediol 4a in
91% yield. Alkynediol 4a was converted into alkyne-
tethered aldehydes 6 and 7 by a four-step sequence in
high overall yield: (a) selective protection of the primary
hydroxyl group either as trityl (Tr) ether or tert-bu-
tyldimethylsilyl (TBDMS) ether to yield 4b and 5a ,
respectively; (b) tert-butyldimethylsilyl protection of the
secondary alcohol in 4b afforded 4c, and methoxymethyl
(MOM) protection of the same in 5a gave 5b; (c) selective
deprotection of trityl ether in 4c was effected by formic
acid17 and that of silyl ether in 5b was effected by TBAF
to afford alcohols 4d and 5c, respectively; (d) Swern
oxidation18 of 4d and 5c readily provided aldehydes 6 and
7, respectively. First, we took stable intermediate alkyne-
tethered aldehyde 6 for the investigation of radical
cyclization as shown in Scheme 3. Since under the
experimental conditions as described by Fraser-Reid12b
[tri-n-butyltin hydride (TBTH; 1.4 equiv), azobisisobu-
tyronitrile (AIBN; 0.1 equiv) in refluxing benzene (0.02
M) and slow addition of reagents (AIBN, TBTH) (ther-
modynamic conditions)] and the conditions described by
Oshima19a (Et3B as radical initiator19b) no cyclized prod-
ucts were obtained, we turned our attention to a change
in the reaction conditions. It was observed that at higher
concentrations of AIBN (0.6-0.8 equiv) and with addition
of the reagents (TBTH, AIBN) together (not via syringe
pump) and in high concentration (1.5 M) (kinetic condi-
tions), the cyclization was quite facile20 and afforded
substituted cyclohexyl stannane 8 in moderate yield,
which was a separable mixture of 8E (40%) and 8Z (8%)21
geometrical isomers. After this initial success, we tried
the reaction conditions on aldehyde 7, and, as expected,
the cyclization went smoothly in high yield (66%). This
time it was a separable mixture of 9E (56%) and 9Z
(10%)21 geometrical isomers. Each geometrical isomer
ments by inspection of the respective
1H NMR and 2-D
NOESY spectra. The structures were obtained from the
diagnostic data and derived from the measurements of
interproton coupling constants, detection of specific NOEs,
and by minimum energy calculations. We have carried
out extensive studies on products 8E, 8Z and 9E, 9Z (see
Experimental Section and Supporting Information). Be-
cause of the presence of an sp2 carbon, the six-membered
ring took on a distorted chair conformation in all the
cases. The presence of NOE between H3a
and H4a con-
firmed the E configuration in 8E. Long-range coupling
of J 6′-7a of 1.3 Hz implied a W coupling with both the
protons in an equatorial-coplanar disposition. We also
observed an allylic coupling between H4a and H3a of 1.1
Hz. Large vicinal coupling between H6 and H7 of 11.4 Hz,
NOEs between acetonide methyl (2a) with H3a, H7a, and
NOEs between acetonide methyl (2b) with H5 were also
consistent with the proposed structure. The absence of
NOE between H4a and H3a supported the Z configuration
in 8Z. The rest of the NOEs and couplings were consis-
tent with the proposed conformation. These observations
in combination with other couplings in the six-membered
ring suggested the S configuration at the new stereo-
center (C-5) formed during cyclization. This was further
confirmed at a later stage. The energy-minimized struc-
ture also supported our experimental values (see Sup-
porting Information). Similar trends were also observed
in the other cyclized products, 9E and 9Z (see Supporting
Information). The stereochemical outcome of the radical
cyclization could be rationalized using Beckwith’s guide-
lines,13b assuming that the major products came via a
transition state in which the radical species adopted a
chairlike conformation with most of the substituents in
the preferred pseudoequatorial positions, as shown in
Figure 1. The formation of the major E isomer was in
agreement with the results shown by Oshima.19 Both 9E
and 9Z isomers were stirred together with dry silica gel
in methylene chloride, causing protodestannylation11b to
produce 10 in 95% yield as a single product (Scheme 4).
Protection of 10 as a silyl ether afforded 11 in 82% yield.
The absolute configuration at the new stereocenter (C-
5) has been further confirmed as S (vide supra) after
careful analysis of the 2-D NOESY spectrum of 11. The
1H NMR data of 11 suggested a distorted chair conforma-
(15) Ohrui, H.; J ones, G. H.; Moffatt, J . G.; Maddox, M. L.;
Christensen, A. T.; Byram, S. K. J . Am. Chem. Soc. 1975, 97, 4602.
(16) (a) Yadav, J . S.; Chander, M. C.; J oshi, B. V. Tetrahedron Lett.
1988, 29, 2737. (b). Yadav, J . S.; Chander, M. C.; Rao, C. S. Tetrahedron
Lett. 1989, 30, 5455.
(17) Bessodes, M.; Komiotis, D.; Antonakis, K. Tetrahedron Lett.
1986, 27, 579.
(18) Mancuso, A. J .; Brownfain, D. S.; Swern, D. J . Org. Chem. 1979,
44, 4148.
(19) (a) Nozaki, K.; Oshima, K.; Utimoto, K. J . Am. Chem. Soc. 1987,
109, 2547. (b) During the course of our studies, a similar cyclization
reaction has been reported by Malacria et al. (see ref 12f). We have
applied their reaction conditions even at 80 °C but end up with an
unsuccessful result.
(20) (a) Devin, P.; Fensterbank, L.; Malacria, M. Tetrahedron Lett.
1998, 39, 833. (b) Beckwith, A. L. J .; Hay, B. P. J . Am. Chem. Soc.
1989, 111, 2674.
(21) We failed to get the minor isomers 8Z and 9Z in pure form. It
always contains some impurities. Prolonged silica gel column chro-
matographic separation yields protodestannylation.11b
tion. All the vicinal couplings, with the exception of J 6,7
,
were small, supporting the assigned absolute stereo-
chemistry at C-5. The characteristic NOE H5-acetonide
methyl (2b), H4a′-H5, H3a-H4a′′, and H3a-H7 were further
support for the assigned stereochemistry and structure.
The NOEs between H7a-CH2 of MOM and H7a-CH3 of
the MOM group confirmed that the bulky substituent
was equatorially placed. Two allylic couplings between

Cycloisomerization of an Alkyne-Tethered Aldehyde
J . Org. Chem., Vol. 66, No. 25, 2001 8373
Sch em e 4a
a
Reagents: (i) silica gel, room temperature; (ii) TBDMSCl,
imidazole, CH2Cl2, room temperature; (iii) OsO4, NMO, aqueous
acetone; (iv) NaIO4, aqueus THF; (v) NaBH4, MeOH, 0 °C/Dibal-
H, CH2Cl2, -78 °C.
F igu r e 2.
F igu r e 3. Preferred conformation for a few compounds, with
the most significant NOEs observed in the 2-D NOESY
spectrum.
H3a-H4a′ and H3a-H4a′′ of 1.6 Hz were also observed. The
observation of W coupling between H6′ and H7a further
corroborated the structure which was also consistent with
the energy-minimized structure (see Supporting Informa-
tion). Treatment of 11 with OsO4, NMO in 80% aqueous
acetone produced exclusively cyclohexitol 12 (85%). The
flagpole-flagpole interaction between H7 and C4-OH in
the 2-D NOESY spectrum suggested that 12 took a boat
conformation with an R configuration at the C4 stereo-
Sch em e 5a
center. The vicinal couplings J 6,7 ) 10.0 Hz and J 3a,7a
)
7.3 Hz were also consistent with the boat conformation.
The long-range coupling of 1.0 Hz between H6′ and H7a
suggested the equatorial-coplanar disposition of these
protons. The NOE between the acetonide methyl (2b) and
H5 further supported the boat conformation. The ob-
served stereochemical outcome of the dihydroxylation
reaction can be rationalized on the basis of the preferred
conformation of 11 (Figures 2 and 3) derived by a
minimum energy calculation (see Supporting Informa-
tion) in which the OsO4 attack took place from the less-
hindered exo face of the exocyclic double bond. Treatment
with NaIO4 in aqueous THF produced inosose 13 in 80%
yield. The final correlation between 13 and the quercitols
was carried out by stereoselective reduction of 13. As
expected, reduction of inosose 13 with NaBH4 in metha-
nol or with Dibal-H in CH2Cl2 was exo face-selective
giving exclusively (+)-allo-quercitol derivative 14 in 93-
a
Reagents: (i) DEAD, PPh3, p-nitrobenzoic acid, THF, room
temperature; (ii) NaOMe, MeOH.
95% isolated yield. The compound 14 was converted into
benzoate derivative 15 in 35% yield under Mitsunobu
conditions22 as shown in Scheme 5. Base treatment of
benzoate derivative 15 produced (+)-talo-quercitol de-
rivative 16 in 88% yield. These two derivatives of
quercitols 14 and 16 were characterized by NMR spec-
troscopy. To accommodate the bulky TBDMS group in
the equatorial position, the ring adopted boat conforma-
tions in both the cases. In 14, the flagpole-flagpole NOE
of H4-H7 confirms the S absolute configuration at the
(22) Mitsunobu, O. Synthesis 1981, 1.

8374 J . Org. Chem., Vol. 66, No. 25, 2001
Yadav et al.
(multiplet for unresolved lines), br (broad), etc. 13C spectra
were obtained with proton decoupling. The assignments were
carried out with the help of Nuclear Overhauser Effect
Spectroscopy (NOESY). Mass measurements were carried out
on either a Finnigan-MAT1020B or a MicroMass VG70-70H
mass spectrometer operating at 70 eV using the direct inlet
system and were given in mass units (m/z). The energy mini-
mization was performed using the Steepest descent method
with tripos force field default parameters in the SYBYL 6.7
program on an O2 workstation. Minimization was carried out
for a maximum of 1000 iterations or with the gradient criterion
of less than 0.05 kcal/mol between successive iterations,
whichever was earlier. This locates a local minimum close to
the starting configuration. The configurations were further
minimized with MOPAC software, for geometrical normaliza-
tion. This structure was taken as input for a MD run in search
of a much bigger conformational space. The protocol followed
is described below. A single interval of the 100 ps dynamics
run at 300 °K was carried out with a 1 fs time step. The results
of the dynamics run were saved after every 1 ps, resulting in
100 conformers. All these conformers were again minimized
as mentioned earlier. The SYBYL program selects unique
conformations (for structures see Supporting Information). For
tin-substituted compounds, the minimization was carried out
with the help of PCMODEL.24 Compound names were given
according to IUPAC nomenclature.
Unless otherwise stated, all nonaqueous reactions were
performed under an atmosphere of nitrogen in flame-dried
glassware equipped with a stir bar and a rubber septum.
Standard inert atmosphere techniques were used in handling
all air and moisture-sensitive reagents. Reactions were moni-
tored by analytical thin-layer chromatography (TLC) using
0.25 mm E.Merk precoated silica gel plates (60F254). The spots
were detected using UV light (254 nm), blowing I2, or by
dipping into anisaldehyde/sulfuric acid (A) or â-naphthol/
sulfuric acid (B) solution followed by charring on a hot plate.
Product purification by flash column chromatography (FCC)25
and dry flash column chromatography (DFC)26 were performed
using silica gel (100-200 mesh). Solutions in organic solvents
were dried over anhydrous sodium sulfate, and solvents were
evaporated with a Buchi rotary evaporator connected to a
water aspirator. Trace solvent was removed on a vacuum
pump. All compounds were stored at -5 °C in vials flushed
with nitrogen.
Sch em e 6a
a
Reagent: (i) 6 M HCl, MeOH, reflux; (ii) Ac2O, pyridine.
C-4 stereocenter. The couplings (J 4,5, J 5,6′, J 6′,7), the NOEs
between H5-acetonide methyl (2b) and between H6′-CH2
of MOM and H7a-CH3 of the MOM group, further
supported the boat conformation. In 16, despite not
observing the characteristic flagpole-flagpole NOE be-
tween the C4-OH and H7, NOE peaks between H5-
acetonide methyl (2b) and H7a-CH2 of the MOM group
suggested a boat conformation with the R configuration
at the C-4 stereocenter. Removal of protecting groups
from compounds 14 and 16 produced (+)-allo-quercitol
176b and (+)-talo-quercitol 19,6b respectively, in high
yields as shown in Scheme 6. These were acetylated to
get the pentaacetate derivative of the respective querci-
tols 18 and 20; the spectral data for these compounds
were in agreement with those reported earlier.6b
Con clu sion
We have described a new protocol for the preparation
of a highly functionalized cyclohexane derivative from
carbohydrates, which features the tri-n-butyltin hydride
mediated 6-exo-trig radical cycloisomerization of poly-
oxygenated, enantiomerically pure alkyne-tethered al-
dehyde. Carbocyclization is possible in good yield using
AIBN as the radical initiator. This procedure gives chiral,
highly functionalized vinyltin23 derivatives with large
potential synthetic applications, and the correct selection
of the radical precursor allows very high diastereoselec-
tion. In summary, the present method is to be very useful
for the synthesis of (+)-allo-quercitol and (+)-talo-quer-
citol.
Pyridine and triethylamine (Et3N) were dried over KOH.
Solvents were dried and purified in the following fashion:
toluene and benzene were distilled over P2O5, Et2O and THF
were distilled from sodium benzophenone ketyl, dichlo-
romethane (CH2Cl2) and dimethyl sulfoxide (DMSO) were
distilled from calcium hydride, and methanol was distilled
from magnesium methoxide.
Eth yl-2-[6-ch lor om eth yl-2,2-d im eth yl-(3a S,4S,6S,6a S)-
p er h yd r ofu r o[3,4-d ][1,3]d ioxol-4-yl] Aceta te (2). To a
stirred solution of alcohol ester 115 (10.0 g, 38.4 mmol) in dry
CCl4 (150 mL) was added triphenylphosphine (12.1 g, 46.2
mmol), and the reaction mixture was heated under reflux with
exclusion of moisture. Triphenylphosphine oxide commenced
to separate from the mixture after 15 min, and after 6 h, 2 g
of PdCO3 was added. The cooled solution was filtered, concen-
trated, and strongly cooled. A further portion of triphenylphos-
phine oxide that deposited was filtered, and the residue was
washed several times with ice-cold ether. The solution was
then concentrated, and the residue was charged on a silica
gel column and eluted with ether/hexane (5/95 to 20/80) to
afford chloro derivative 2 (9.4 g, 88%) as a colorless oil. Rf )
Exp er im en ta l Section
Gen er a l. Melting points were recorded on a Buchi R-535
apparatus. Infrared (IR) spectra were recorded on a Perkin-
Elmer Infrared 683 spectrophotometer with NaCl optics.
Proton magnetic resonance (1H NMR) and carbon magnetic
resonance (13C NMR) spectra were recorded on Varian Gemini-
200, Varian Unity-400, and Varian Inova-500 NMR spectrom-
1
eters in deuteriochloroform unless otherwise stated. In the H
0.49 (25% ether/hexane, A: black). [R]25 -11.06 (c 1.01,
NMR spectra, tetramethysilane (TMS) (δ 0 ppm) was used as
an internal reference, whereas for the 13C NMR spectra, CDCl3
(δ 77.0 ppm) was used as an internal reference. Chemical shifts
were reported in ppm downfield from TMS and were given on
the δ scale. The multiplicity, coupling constants (hertz), and
number of protons were indicated in parentheses and were
specified as s (singlet), d (doublet), t (triplet), q (quartet), m
D
1
CHCl3). IR γmax (film): 1730 (CdO) cm-1. H NMR (500 MHz,
CDCl3): δ 1.27 (t, J ) 7.0 Hz, 3H), 1.35 (s, 3H), 1.55 (s, 3H),
2.66 (d(ABq), J ) 5.6, 15.8, 6.8 Hz, 2H), 3.62 (d(ABq), J ) 4.5,
11.5, 5.3 Hz, 2H), 4.17 (q, J ) 7.2 Hz, 2H), 4.20 (ddd, J ) 4.1,
(24) PCMODEL. Gilbert, K. E.; Gajewski, J . J . Senna Software, Box
4076, Bloomington, IN 47402.
(23) Pereyer, M.; Quintard, J . P.; Rahm, A. Tin in Organic Synthesis;
Butterworth: London, 1986.
(25) Still, W. C.; Khan, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(26) Harwood, L. M. Aldrichimica Acta 1985, 18, 25.

Cycloisomerization of an Alkyne-Tethered Aldehyde
J . Org. Chem., Vol. 66, No. 25, 2001 8375
11.5, 5.3 Hz, 1H), 4.33 (ddd, J ) 4.5, 6.8, 10.1 Hz, 1H), 4.56
(dd, J ) 4.4, 6.6 Hz, 1H), 4.65 (dd, J ) 4.1, 6.6 Hz, 1H). 13C
NMR (125 MHz, CDCl3): δ 14.01, 25.34, 27.22, 38.29, 44.38,
60.54, 80.97, 82.75, 83.38, 84.07, 114.50, 170.10. MS m/z
(assignment, relative intensity): 265 (M+ + 2 - CH3, 20), 263
(M+ - CH3, 60), 235 (M+ - C3H7, 20), 43 (100). Anal. Calcd
for C12H19ClO5: C, 51.71; H, 6.87. Found: C, 51.59; H, 6.52.
2-[6-Ch lor om et h yl-2,2-d im et h yl-(3a S,4S,6S,6a S)-p er -
h yd r ofu r o[3,4-d ][1,3]d ioxol-4-yl]-1-eth a n ol (3). A suspen-
sion of LiAlH4 (1.1 g, 28.9 mmol) in dry ether (100 mL) was
cooled to 0 °C, and a solution of chloroester 2 (8.0 g, 28.8 mmol)
in ether was added slowly and allowed to attain room tem-
perature. The reaction mixture was stirred further for 30 min,
after which the reaction mixture was quenched with saturated
Na2SO4. The solution was filtered through a Celite pad and
washed thoroughly with hot chloroform, concentrated, and
purified by chromatography to give compound 3 (6.1 g, 90%)
ola n e (4c). TBDMSCl (0.62 g, 4.1 mmol) was added portion-
wise over 10 min to a stirred solution of 4b (1.5 g, 3.4 mmol)
and imidazole (1.4 g, 20.5 mmol) in dry CH2Cl2 (15 mL) at 0
°C under nitrogen. The reaction mixture was stirred at room
temperature for 48 h. The mixture was then diluted with CH2-
Cl2 (50 mL) and washed with water. The organic phase was
dried over Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by column chromatography
(eluent EtOAc:hexane 2:98) to give compound 4c (1.1 g, 56%)
as a colorless oil. Rf ) 0.35 (25% EtOAc/hexane, A: greenish
blue). [R]25 +26.81 (c 0.8, CHCl3). 1H NMR (500 MHz,
D
CDCl3): δ 0.12 (s, 6H), 0.88 (s, 9H), 1.36 (s, 3H), 1.60 (s, 3H),
2.17 (m, 2H), 2.59 (d, J ) 2.2 Hz, 1H), 3.26 (dt, J ) 6.3, 8.4
Hz, 1H), 3.39 (dt, J ) 6.5, 8.4 Hz, 1H), 3.95 (dd, J ) 5.2, 8.2
Hz, 1H), 4.31 (td, J ) 4.6, 8.2 Hz, 1H), 4.78 (dd, J ) 2.2, 5.2
Hz, 1H), 7.24 (m, 3H), 7.30 (m, 6H), 7.43 (m, 6H). 13C NMR
(125 MHz, CDCl3): δ -4.51, -4.13, 17.94, 25.82, 26.24, 27.54,
34.68, 59.73, 68.89, 69.42, 76.17, 80.32, 81.10, 86.61, 110.31,
126.79, 127.66, 128.74, 144.40. MS m/z (assignment, relative
intensity): 556 (M+, <1), 243 (100), 165 (35), 73 (78).
3-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-3-ter t-b u t yld im et h ylsilyloxy-1-p r op a n ol (4d ). To a
solution of 4c (1.0 g, 1.8 mmol) in Et2O was added a mixture
of HCO2H (2 mL)/Et2O (2 mL) at 0 °C, and after 1 min, 20 mL
of Et2O was added. The reaction mixture was washed succes-
sively with brine and NaHCO3 solution. The organic layer was
dried over Na2SO4 and evaporated under reduced pressure.
The crude product was purified by column chromatography
to yield 4d (0.37 g, 66%) as a colorless oil. Rf ) 0.48 (25%
EtOAc/hexane, A: green). [R]25D +15.9 (c 1.5, CHCl3). 1H NMR
(500 MHz, CDCl3): δ 0.12 (s, 3H), 0.13 (s, 3H), 0.88 (s, 9H),
1.36 (s, 3H), 1.54 (s, 3H), 1.98 (m, 2H), 2.55 (d, J ) 2.1 Hz,
1H), 3.83 (t, J ) 5.9 Hz, 2H), 4.04 (dd, J ) 8.5, 5.1 Hz, 1H),
4.27 (ddd, J ) 4.1, 5.1, 8.5 Hz, 1H), 4.79 (dd, J ) 2.1, 5.1 Hz,
1H). 13C NMR (125 Hz, CDCl3): δ -4.47, -3.89, 17.97, 25.82,
26.31, 27.50, 37.60, 59.01, 69.14, 70.48, 76.44, 80.08, 80.90,
110.66.
as a colorless oil. Rf ) 0.5 (50% EtOAc/hexane, A: green). [R]25
D
-18.95 (c 1.02, CHCl3). IR γmax (film): 3300-3450 (br s, OH)
cm-1. 1H NMR (500 MHz, CDCl3): δ 1.35 (s, 3H), 1.55 (s, 3H),
1.91 (m, 2H), 2.11 (t, J ) 5.7 Hz, 1H), 3.66 (d(ABq), J ) 11.6,
4.3, 15.2 Hz, 2H), 3.81 (q, J ) 5.7 Hz, 2H), 4.06 (dt, J ) 5.2,
7.9, 13.0 Hz, 1H), 4.18 (q, J ) 4.6, 9.0 Hz, 1H), 4.40 (dd, J )
5.3, 6.7 Hz, 1H), 4.63 (dd, J ) 3.9, 6.7 Hz, 1H). 13C NMR (125
MHz, CDCl3): δ 25.25, 27.13, 35.62, 44.38, 59.53, 82.45, 82.86,
83.13, 84.49, 114.62. MS m/z (assignment, relative intensity):
223 (M+ + 2 - CH3, 19), 221 (M+ - CH3, 58), 263 (13), 161
(40), 43 (100). Anal. Calcd for C10H17ClO4: C, 50.74; H, 7.24.
Found: C, 50.44; H, 7.03.
1-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-(1S)-p r op a n e-1,3-d iol (4a ). To a stirred suspension of
lithium amide (prepared from 1.1 g, 0.157 g atom of Li) in
liquid NH3 (70 mL) was added compound 3 (6.0 g, 25.4 mmol)
in dry THF (10 mL) over a period of 2 min. After being stirred
for 1 h, the reaction mixture was quenched with solid NH4Cl
(2.0 g), and ammonia was allowed to evaporate. The residue
portion was filtered and washed with hot chloroform. The
filtrate was evaporated under reduced pressure. The crude
product was purified by flash chromatography to give com-
pound 4a (4.63 g, 91%) as a colorless crystalline solid. Rf )
1-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-3-ter t-bu tyld im eth ylsilyloxy-(1S)-p r op a n e-1-ol (5a ).
TBDMSCl (2.9 g, 19.5 mmol) was added portionwise over 10
min to a stirred solution of alkynediol 4a (3.8 g, 19.0 mmol)
and imidazole (1.94 g, 28.5 mmol) in dry CH2Cl2 (50 mL) at 0
°C under nitrogen. The reaction mixture was stirred at room
temperature for 4 h. The mixture was then diluted with CH2-
Cl2 (50 mL) and washed with water. The organic layer was
dried (Na2SO4), filtered, and concentrated giving a residue
which was purified by chromatography. Elution with EtOAc/
hexane (5/95 to 10/90) gave compound 5a (4.75 g, 80%) as a
colorless liquid. Rf ) 0.64 (25% EtOAc/hexane, A: bluish
green). [R]25D +38.03 (c 1.0, CHCl3). IR γmax (film): 3330-3450
0.35 (80% EtOAc/hexane, A: green). mp 78 °C. [R]25 +30.16
D
(c 1.2, CHCl3). IR γmax (KBr): 3230-3450 (br s, OH’s), 3310
(s, C≡C-H), 2105 (w, C≡C) cm-1
.
1H NMR (500 MHz,
CDCl3): δ 1.36 (s, 3H), 1.52 (s, 3H), 1.84 (dddd, J ) 8.7, 14.7,
4.2, 8.2 Hz, 1H), 2.05 (dddd, J ) 3.1, 14.7, 6.8, 3.2 Hz, 1H),
2.25 (br s, 1H), 2.64 (d, J ) 2.2 Hz, 1H), 2.92 (br s, 1H), 3.93
(m, 2H), 4.00 (dd, J ) 5.9, 8.7 Hz, 1H), 4.19 (dt, J ) 3.1, 8.7
Hz, 1H), 4.92 (dd, J ) 2.2, 5.9 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 25.86, 27.41, 35.47, 60.80, 68.14, 71.00, 76.29, 80.08,
110.73. MS m/z (assignment, relative intensity): 185 (M+
CH3, 13), 149 (12), 43 (100). Anal. Calcd for C10H16O4: C, 59.99;
H, 8.05. Found: C, 59.55; H, 7.89.
-
1
(br s, OH), 3310 (s, C≡C-H), 2108 (w, C≡C) cm-1. H NMR
(500 MHz, CDCl3): δ 0.09 (s, 6H), 0.90 (s, 9H), 1.35 (s, 3H),
1.53 (s, 3H), 1.78 (dddd, J ) 4.1, 8.7, 14.5, 8.5 Hz, 1H), 2.03
(dddd, J ) 2.4, 3.8, 6.1, 14.5 Hz, 1H), 2.58 (d, J ) 2.10 Hz,
1H), 3.64 (d, J ) 3.3 Hz, 1H), 3.91 (ddd, J ) 3.8, 8.1, 4.1 Hz,
1H), 3.97 (m, 2H), 4.19 (ddt, J ) 2.4, 3.3, 8.6 Hz, 1H), 4.92
(dd, J ) 2.1, 5.7 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ -5.59,
18.06, 25.80, 26.06, 27.50, 35.14, 62.16, 68.49, 71.38, 75.69,
80.00, 80.33, 110.50. MS m/z (assignment, relative intensity):
299 (M+ - CH3, 4), 131 (100), 75 (60). Anal. Calcd for C16H30O4-
Si: C, 61.11; H, 9.61. Found: C, 61.05; H, 9.67.
1-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-3-tr ip h en ylm eth yloxy-(1S)-p r op a n e-1-ol (4b). To a
stirred solution of alkynediol 4a (0.8 g, 4 mmol) in dry CH2Cl2
(12 mL) was added dropwise Et3N (0.57 mL, 6 mmol) at 0 °C.
TrCl (1.2 g, 4.3 mmol) was added portionwise to this reaction
mixture. The reaction mixture was stirred at room tempera-
ture for 1 h. Then 10 mL of water was added to the mixture
and extracted with CH2Cl2. The organic layer was dried (Na2-
SO4), concentrated, and purified by dry column chromatogra-
phy to provide 4b (1.67 g, 90%) as a colorless semisolid. Rf )
0.35 (25% EtOAc/hexane, A: blue). [R]25D +14.18 (c 1.1, CHCl3).
4-(1-Eth yn yl)-5-(1-m eth oxym eth oxy-3-ter t-bu tyldim eth -
ylsilyloxy-(1S )-p r op yl)-2,2-d im e t h yl-(4R ,5S )-1,3-d iox-
ola n e (5b). (iPr)2NEt (12.5 mL, 71.5 mmol) was added
dropwise to a stirred and cooled (0 °C) solution of alcohol 5a
(4.5 g, 14.3 mmol) in CH2Cl2 (50 mL). After 15 min, meth-
oxymethylene chloride (MOMCl) (3.25 mL, 57.2 mmol) was
added dropwise over a period of 10 min, and stirring was
continued for 1 h. The cold bath was removed, and stirring
was continued for 12 h. The reaction mixture was diluted with
water (10 mL) and extracted with CH2Cl2. The combined
organic extracts were washed with brine, dried, and evapo-
rated. The residue was purified by flash chromatography
(eluent EtOAc:hexane 4:96) gave compound 5b (3.8 g, 75%)
as a colorless liquid. Rf ) 0.85 (10% EtOAc/hexane, A: green).
IR γmax (film): 3370 (br s, OH) cm-1 1H NMR (500 MHz,
.
CDCl3): δ 1.28 (s, 3H), 1.49 (s, 3H), 1.87 (dddd, J ) 4.4, 7.1,
8.3, 14.7 Hz, 1H), 2.14 (dddd, J ) 2.6, 6.9, 4.7, 14.7 Hz, 1H),
2.55 (d, J ) 2.3 Hz, 1H), 3.26 (d, J ) 4.2 Hz, 1H), 3.41 (m,
2H), 3.83 (dd, J ) 5.6, 8.6 Hz, 1H), 4.11 (ddt, J ) 2.6, 4.2, 8.5
Hz, 1H), 4.87 (dd, J ) 2.3, 5.6 Hz, 1H), 7.24 (m, 3H), 7.30 (m,
6H), 7.43 (m, 6H). 13C NMR (125 MHz, CDCl3): δ 26.00, 27.51,
33.29, 62.16, 68.47, 70.86, 75.73, 79.82, 80.31, 87.50, 110.59,
127.13, 127.93, 128.58, 143.74. MS m/z (assignment, relative
intensity): 442 (M+, <1), 243 (CPh3, 100), 183 (12), 165 (30).
4-[1-ter t-Bu tyld im eth ylsilyloxy-3-tr ip h en ylm eth yloxy-
(1S)-p r op yl]-5-(1-eth yn yl-2,2-d im eth yl-(4R,5R)-1,3-d iox-

8376 J . Org. Chem., Vol. 66, No. 25, 2001
Yadav et al.
[R]25 +22.35 (c 1.04, CHCl3). IR γmax (film): 3320 (s, C≡C-
Gen er a l P r oced u r e for Ra d ica l Cycliza tion . A solution
of AIBN (1.0 mmol) and tributyltin hydride (3.0 mmol) in dry
degassed benzene (2 mL) was added to a degassed solution of
alkyne-tethered aldehyde (1.5 mmol) in dry degassed benzene
(1.5 M) at reflux under nitrogen. After being heated at reflux
for 2 h (monitored by TLC), the solution was concentrated at
reduced pressure. The resulting residue was diluted with
acetonitrile, and the acetonitrile phase was washed with
hexane and concentrated at reduced pressure. Purification of
the residue by medium-pressure column chromatography
eluting with EtOAc/hexane (0/100 to 20/80) gave the cyclized
products. Yields were shown in Scheme 3.
D
H), 2120 (w, C≡C) cm-1. H NMR (500 MHz, CDCl3): δ 0.06
1
(s, 3H), 0.062 (s, 3H), 0.90 (s, 9H), 1.35 (s, 3H), 1.53 (s, 3H),
1.87 (qd, J ) 6.3, 12.5, 14.2 Hz, 1H), 2.06 (ddt, J ) 3.9, 7.5,
14.2 Hz, 1H), 2.54 (d, J ) 2.3 Hz, 1H), 3.39 (s, 3H), 3.80 (m,
1H), 4.06 (dd, J ) 3.9, 6.3 Hz, 1H), 4.10 (ABq, J ) 7.5, 12.9
Hz, 2H), 4.73 (ABq, J ) 6.6, 17.3 Hz, 2H), 4.87 (dd, J ) 2.3,
5.4 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ -5.38, -5.35, 18.23
25.91, 27.28, 35.03, 55.90, 59.13, 68.47, 75.04, 76.04, 79.47,
80.47, 96.95, 110.21. MS m/z (assignment, relative intensity):
343 (M+ - CH3, 5), 131 (100), 45 (90). Anal. Calcd for C18H34O5-
Si: C, 60.30; H, 9.69. Found: C, 60.39; H, 9.60.
4-[1-Tr ibu tyltin sta n n yl-(Z)-m eth ylid en e]-7-ter t-bu tyl-
d im e t h y ls ily lo x y -2,2-d im e t h y l-(3a R ,5S ,7S ,7a S )-p e r -
h yd r oben zo[d ][1,3]d ioxol-5-ol (8Z). 4-[1-Tr ibu tyltin sta n -
n yl-(E)-m et h ylid en e]-7-ter t-b u t yld im et h ylsilyl-oxy-2,2-
d im eth yl-(3a R,5S,7S,7a S)-p er h yd r oben zo[d ][1,3]d ioxol-
3-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-3-m eth oxym eth oxy-1-p r op a n ol (5c). To a solution of 5b
(3.5 g, 9.77 mmol) in dry THF (20 mL) was added Bu4NF (1.0
M solution in dry THF, 12.7 mL, 1.3 mmol) at 0 °C, and the
resulting solution was allowed to warm to room temperature.
The mixture was stirred for 3 h. Saturated NH4Cl solution (5
mL) was added, and the reaction mixture was stirred for few
minutes. It was then diluted with water and extracted with
EtOAc. The combined organic layers were washed with brine,
dried, and evaporated under reduced pressure. The crude
product was purified by flash chromatography; elution with
EtOAc/hexane (10/90 to 40/60) gave 5c (2.27 g, 95%) as a
colorless oil. Rf ) 0.43 (50% EtOAc/hexane; A, green; B, brown).
1
5-ol (8E). 8Z. Rf ) 0.55 (25% EtOAc/ hexane, B: brown). H
NMR (500 MHz, CDCl3): δ 0.06 (s, 6H), 0.88 (t, J ) 7.2 Hz,
9H), 0.90 (s, 9H), 1.30 (m, 9H), 1.34 (s, 3H), 1.45 (s, 3H), 1.50
(m, 9H), 2.08 (dddd, J ) 4.1, 5.6, 1.1, 13.4 Hz, 1H), 2.40 (ddd,
J ) 11.1, 8.3, 13.4, 1H), 3.78 (ddd, J ) 2.8, 5.6, 11.1 Hz, 1H),
4.25 (ddd, J ) 2.8, 7.5, J ) 1.1 Hz, 1H), 4.47 (dd, J ) 7.5, 1.8
Hz, 1H), 4.58 (dt, J ) 8.3, 4.1 Hz, 1H), 6.16 (d, J ) 1.8 Hz,
1H).
1
[R]25 +6.48 (c 1.1, CHCl3). IR γmax (film): 3200-3450 (br s,
8E. Rf ) 0.6 (25% EtOAc/hexane, B: brown). H NMR (500
D
OH), 3310 (s, C≡C-H), 2106 (w, C≡C) cm-1
.
1H NMR (500
MHz, CDCl3): δ 0.06 (s, 6H), 0.90 (t, J ) 7.1 Hz, 9H), 0.91 (s,
9H), 1.30 (m, 9H), 1.35 (s, 3H), 1.44 (s, 3H), 1.46 (m, 9H), 1.78
(ddt, J ) 5.1, 3.6, 13.3 Hz, 1H), 2.19 (ddd, J ) 11.4, 5.1, 13.3
Hz, 1H), 4.18 (ddd, J ) 5.1, 11.4, 3.3 Hz, 1H), 4.25 (ddd, J )
3.3, 5.9, 1.3 Hz, 1H), 4.44 (dt, J ) 5.1, 3.6 Hz, 1H), 4.63 (dd,
J ) 5.9, 1.1 Hz, 1H), 6.18 (d, J ) 1.1 Hz, 1H).
MHz, CDCl3): δ 1.36 (s, 3H), 1.54 (s, 3H), 1.95 (m, 1H), 2.11
(m, 1H), 2.38 (br s, 1H), 2.58 (d, J ) 2.2 Hz, 1H), 3.39 (s, 3H),
3.83 (m, 2H), 4.12 (m, 2H), 4.76 (ABq, J ) 6.6 Hz, 2H), 4.89
(dd, J ) 2.2, 5.2 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 25.84,
27.20, 34.81, 55.95, 58.95, 68.36, 76.34, 76.38, 79.08, 80.33,
97.12, 110.39. MS m/z (assignment, relative intensity): 229
(M+ - CH3, 8), 125 (60), 45 (100), 43 (100). Anal. Calcd for
4-[1-Tr ib u t ylt in st a n n yl-(Z)-m et h ylid en e]-7-m et h oxy-
m et h oxy-2,2-d im et h yl-(3a R,5S,7S,7a S)-p er h yd r ob en zo-
[d ][1,3]d ioxol-5-ol (9Z). 4-[1-Tr ibu tyltin sta n n yl-(E)-m eth -
yliden e]-7-m eth oxym eth oxy-2,2-dim eth yl-(3aR,5S,7S,7aS)-
p er h yd r oben zo[d ][1,3]d ioxol-5-ol (9E). 9Z. Rf ) 0.51 (25%
EtOAc/hexane, B: brown). [R]25D +51.4 (c 1.01, CHCl3). IR γmax
C
12H20O5: C, 59.00; H, 8.25. Found: C, 58.89; H, 8.12.
Gen er a l P r oced u r e for Oxid a tion of Alk yn e-Teth er ed
Alcoh ols. To a solution of oxalyl chloride (1.5 mmol) in dry
CH2Cl2 (10 mL) at -78 °C was added DMSO (1.6 mmol) in
CH2Cl2 (1 mL) over 1 min, and the mixture was stirred for 20
min. A solution of alcohol (1.0 mmol) in CH2Cl2 (2 mL) was
added dropwise over 1 min. After 1 h of stirring at -78 °C,
Et3N (6.0 mmol) was added, and the resulting white slurry
was stirred further for 20 min and allowed to warm slowly to
room temperature. The mixture was diluted with water and
extracted with CH2Cl2. The organic layer was washed several
times with water, dried, and concentrated under reduced
pressure at very low temperature. Rapid flash chromatography
of the residue gave aldehyde in good yield.
(film): 3350-3450 (br s, OH) cm-1 1H NMR (500 MHz,
.
CDCl3): δ 0.88 (t, J ) 7.4 Hz, 9H), 1.28 (m, 9H), 1.3 (m, 9H),
1.41 (s, 3H), 1.54 (s, 3H), 1.79 (dddd, J ) 3.3, 5.3, 13.6, 1.0
Hz, 1H), 2.47 (ddd, J ) 11.3, 8.1, 13.6 Hz, 1H), 3.38 (s, 3H),
3.74 (ddd, J ) 3.3, 5.5, 11.3 Hz, 1H), 4.49 (ddd, J ) 7.6, 3.3,
1.0 Hz, 1H), 4.59 (d, J ) 7.6 Hz, 1H), 4.66 (m, 1H), 4.70 (ABq,
J ) 6.8 Hz, 2H), 6.27 (d, J ) 1.8 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 10.60, 13.62, 27.27, 27.30, 29.09, 29.12, 33.80, 55.39,
67.24, 71.32, 76.63, 79.49, 95.12, 109.62, 128.52, 153.01.
9E. Rf ) 0.48 (25% EtOAc/hexane, B: brown). [R]25 -2.92
D
(c 1.09, CHCl3). IR γmax (film): 3350-3450 (br s, OH) cm-1
.
1H NMR (500 MHz, CDCl3): δ 0.88 (t, J ) 7.4 Hz, 9H), 1.28
(m, 9H), 1.3 (m, 9H), 1.41 (s, 3H), 1.54 (s, 3H), 2.02 (dddd, J )
1.03, 3.6, 4.4, 13.4 Hz, 1H), 2.18 (dt, J ) 4.3, 2.2, 13.4 Hz,
1H), 3.41 (s, 3H), 4.18 (ddd, J ) 3.6, 5.0, 12.2 Hz, 1H), 4.47
(ddd, J ) 5.0, 5.7, 1.0 Hz, 1H), 4.49 (dt, J ) 4.3, 4.4, 1.0 Hz,
1H), 4.73 (dd, J ) 1.48, 5.7 Hz, 1H), 4.75 (ABq, J ) 6.8, 10.8
Hz, 2H), 6.28 (d, J ) 1.48 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 10.97, 13.64, 25.74, 27.20, 27.28, 29.20, 29.28, 33.56,
55.44, 70.45, 71.72, 76.31, 78.02, 95.62, 109.62, 130.96, 152.79.
MS m/z (assignment, relative intensity): 533 (M+, 7), 515 (M
- H2O, 20), 177 (100). Anal. Calcd for C24H46O5Sn: C, 54.06;
H, 8.69. Found: C, 54.27; H, 8.59.
3-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-3-ter t-bu tyld im eth ylsilyloxy-1-p r op a n a l (6). A solution
of alcohol 4d (0.35 g, 1.1 mmol) was oxidized using the general
procedure to give aldehyde 6 (0.3 g, 89%) as a colorless oil. Rf
) 0.55 (25% EtOAc/hexane, A: violet). [R]25 +38.6 (c 2.3,
D
CHCl3). 1H NMR (200 MHz, CDCl3): δ 0.07 (s, 3H), 0.11 (s,
3H), 0.8 (s, 9H), 1.38 (s, 3H), 1.42 (s, 3H), 2.58 (d, J ) 2.1 Hz,
1H), 2.74 (m, 2H), 4.03 (dd, J ) 5.2, 7.8 Hz, 1H), 4.56 (dt, J )
5.3, 7.8 Hz, 1H), 4.79 (dd, J ) 5.3, 2.1 Hz, 1H), 9.82 (t, J ) 2.3
Hz, 1H). 13C NMR (50 MHz, CDCl3): δ -4.53, -4.20, 17.89,
25.69, 26.08, 27.27, 48.87, 67.89, 68.55, 76.71, 80.42, 110.59,
200.44.
3-[5-(1-E t h yn yl)-2,2-d im et h yl-(4S,5R)-1,3-d ioxola n -4-
yl]-3-m eth oxym eth oxy-1-p r op a n a l (7). A solution of alcohol
5c (2.0 g, 8.19 mmol) was oxidized using the general procedure
to give aldehyde 7 (1.78 g, 90%) as a colorless oil which
decomposes on standing. So it was immediately used for the
7 -M e t h o x y m e t h o x y -2 ,2 -d i m e t h y l -4 -m e t h y l e n e -
(3a R,5S,7S,7a S)-p er h yd r ob en zo[d ][1,3]d ioxol-5-ol (10).
The mixture of compounds 9Z and 9E (2 g, 3.75 mmol) was
stirred together with silica gel (150 g) in CH2Cl2 (300 mL) for
48 h. The reaction mixture was filtered, washed with CH2Cl2,
concentrated, and purified by flash chromatography to yield
compound 7 (0.85 g, 95%) as a colorless oil. Rf ) 0.35 (50%
next step. Rf ) 0.43 (25% EtOAc/hexane; A, violet; B, green).
1
[R]25 +2.2 (c 2.1, CHCl3). H NMR (500 MHz, CDCl3): δ 1.32
D
(s, 3H), 1.50 (s, 3H), 2.58 (d, J ) 3.0 Hz, 1H), 2.76 (ddd, J )
2.7, 7.0, 16.9 Hz, 1H), 2.86 (ddd, J ) 4.2, 1.6, 16.9 Hz, 1H),
3.31 (s, 3H), 4.17 (dd, J ) 6.1, 7.3 Hz, 1H), 4.42 (dt, J ) 4.2,
7.0, 7.3 Hz, 1H), 4.71 (ABq, J ) 6.9 Hz, 2H), 4.89 (dd, J ) 6.1,
3.0 Hz, 1H), 9.79 (dd, J ) 1.6, 2.7 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 25.66, 27.09, 46.70, 55.77, 68.13, 73.92, 76.57, 78.74,
79.82, 97.26, 110.62, 200.19.
EtOAc/hexane, B: brown). [R]25 +44.03 (c 1.01, CHCl3). IR
D
γmax (film): 3330-3450 (br, OH) cm-1
.
1H NMR (500 MHz,
CDCl3): δ 1.40 (s, 3H), 1.50 (s, 3H), 1.97 (dddd, J ) 1.2, 4.0,
5.4, 13.5 Hz, 1H), 2.22 (ddd, J ) 5.3, 11.8, 13.5 Hz, 1H), 3.41
(s, 3H), 4.08 (ddd, J ) 3.4, 5.4, 11.8 Hz, 1H), 4.50 (ddd, J )
1.2, 3.4, 6.0 Hz, 1H), 4.60 (dd, J ) 5.3, 4.0 Hz, 1H), 4.74 (ABq,
J ) 6.9, 12.4 Hz, 2H), 4.744 (dt, J ) 1.4, 6.0 Hz, 1H), 5.28 (dt,

Cycloisomerization of an Alkyne-Tethered Aldehyde
J . Org. Chem., Vol. 66, No. 25, 2001 8377
J ) 1.4, 2.7 Hz, 1H), 5.31 (dt, J ) 1.4, 2.7 Hz, 1H). 13C NMR
(125 MHz, CDCl3): δ 25.40, 26.97, 33.31, 55.45, 69.10, 70.59,
76.08, 76.24, 95.51, 109.86, 114.63, 146.16. MS m/z (assign-
ment, relative intensity): 229 (M+ - CH3, 20), 95 (15), 45 (100).
Anal. Calcd for C12H20O5: C, 59.00; H, 8.25. Found: C, 58.95;
H, 8.31.
4-ol (14). Meth od A. NaBH4 (16.5 mg, 0.45 mmol) was added
to a solution of inosose 13 (150 mg, 0.41 mmol) in methanol (2
mL) at 0 °C under nitrogen atmosphere. The reaction mixture
was stirred for 45 min at 0 °C before quenching with a few
drops of saturated Na2SO4 solution. The solvent was evapo-
rated under reduced pressure and directly charged over a dry
silica gel column for purification to give 14 (0.14 g, 93%) as a
colorless oil.
7-Met h oxym et h oxy-2,2-d im et h yl-4-m et h ylen e-5-ter t-
bu tyld im eth ylsilyloxy-(3a R,5S,7S,7a S)-p er h yd r oben zo-
[d ][1,3]d ioxole (11). To a stirred solution of 10 (0.5 g, 2.05
mmol) and imidazole (0.82 g, 12 mmol) in 10 mL of CH2Cl2
was added TBDMSCl (0.36 g, 2.4 mmol) at 0 °C. The reaction
mixture was stirred at room temperature for 12 h. The mixture
was then diluted with CH2Cl2 and washed with water. The
organic layer was dried (Na2SO4), filtered, and concentrated.
The crude product was purified by flash chromatography to
give 10 (0.6 g, 82%) as a colorless oil. Rf ) 0.51 (10% EtOAc/
Meth od B. To a stirred solution of 13 (150 mg, 0.41 mmol)
in CH2Cl2 was added Dibal-H (0.33 mL, 1.5 M solution in
toluene, 0.49 mmol) at -78 °C. After 30 min, the reaction
mixture was quenched with a few drops of water and stirred
for a few minutes. Then the mixture was filtered through a
Celite pad, concentrated under reduced pressure, and purified
by silica gel column chromatography to give 14 (143 mg, 95%).
Rf ) 0.45 (25% EtOAc/hexane, B: red). [R]25 +45.56 (c 0.98,
D
hexane, B: red). [R]25 +44.48 (c 1.2, CHCl3). 1H NMR (500
CHCl3). IR γmax (film): 3380 (br s, OH) cm-1
.
1H NMR (500
D
MHz, CDCl3): δ 0.04 (s, 3H), 0.08 (s, 3H), 0.89 (s, 9H), 1.40 (s,
3H), 1.50 (s, 3H), 1.92 (dddd, J ) 1.2, 4.3, 5.4, 12.7 Hz, 1H),
2.10 (ddd, J ) 4.8, 11.5, 12.7 Hz, 1H), 3.40 (s, 3H), 4.12 (ddd,
J ) 3.4, 5.4, 11.5 Hz, 1H), 4.49 (ddd, J ) 1.2, 5.9, 3.4 Hz, 1H),
4.53 (dd, J ) 4.3, 4.8 Hz, 1H), 4.69 (dt, J ) 1.6, 5.9 Hz, 1H),
4.74 (s, 2H), 5.12 (s, 1H), 5.17 (br s, 1H). 13C NMR (125 MHz,
CDCl3): δ -5.21, -5.01, 17.98, 25.50, 25.62, 27.08, 29.56,
34.88, 55.21, 69.93, 70.86, 76.03, 76.12, 95.47, 109.58, 113.13,
MHz, CDCl3): δ 0.10 (s, 6H), 0.90 (s, 9H), 1.39 (s, 3H), 1.55 (s,
3H), 1.79 (dddd, J ) 1.0, 6.1, 4.4, 13.5 Hz, 1H), 2.26 (ddd, J )
10.9, 7.1, 13.5 Hz, 1H), 2.36 (d, J ) 4.2 Hz, 1H), 3.40 (s, 3H),
3.56 (dt, J ) 4.05, 4.2, 7.8 Hz, 1H), 4.02 (ddd, J ) 3.3, 6.1,
10.9 Hz, 1H), 4.07 (dt, J ) 4.1, 7.8, 4.4, 7.1 Hz, 1H), 4.45 (dd,
J ) 4.1, 7.3 Hz, 1H), 4.54 (ddd, J ) 3.3, 7.3, 1.0 Hz, 1H), 4.71
(s, 2H). 13C NMR (125 MHz, CDCl3): δ -4.81, -4.61, 17.97,
24.22, 25.76, 25.91, 32.39, 55.43, 69.07, 69.46, 70.77, 74.56,
75.09, 95.38, 109.65. MS m/z (assignment, relative intensity):
363 (M+ + 1, 1), 276 (6), 273 (8), 215 (10), 91 (90), 45 (100).
Anal. Calcd for C17H34O6Si: C, 56.32; H, 9.45. Found: C, 56.44;
H, 9.32.
146.32. MS m/z (assignment, relative intensity): 359 (M+
+
1, 1), 244 (M+ + 1 - Si(CH3)2C(CH3)3, 15). Anal. Calcd for
C
18H34O5Si: C, 60.30; H, 9.56. Found: C, 59.95; H, 9.44.
4-H yd r oxy-4-h yd r oxym et h yl-7-m et h oxym et h oxy-2,2-
dim eth yl-5-ter t-bu tyldim eth ylsilyloxy-(3aS,4S,5S,7S,7aS)-
p er h yd r oben zo[d ][1,3]d ioxol-4-ol (12). A solution of osmi-
um tetroxide in toluene (0.05 M, 0.56 mL, 0.28 mmol) and
NMO (0.558 g, 4.13 mmol) was added to a stirred solution of
compound 11 (0.5 g, 1.39 mmol) in acetone (16 mL)/water (4
mL). The reaction mixture was stirred at room temperature
in the dark for 24 h. Sodium bisulfite (0.5 g) was added, and
the reaction mixture was stirred for another 1 h, dried over
Na2SO4, filtered through a Celite pad, and concentrated under
reduced pressure. The diol was purified by flash chromatog-
raphy. Elution with EtOAc/hexane (15/85 to 40/60) gave 12
(0.45 g, 85%) as a colorless oil. Rf ) 0.48 (50% EtOAc/hexane,
B: brown). [R]25D +33.67 (c 0.59, CHCl3). IR γmax (film): 3320-
7-Meth oxym eth oxy-2,2-d im eth yl-4-(4-n itr op h en ylca r -
b on yloxy)-5-ter t-b u t yld im et h ylsilyloxy-(3a S,4S,5S,7S,-
7a S)-p er h yd r oben zo[d ][1,3]d ioxol (15). Diethylazodicar-
boxylate (DEAD) (0.09 mL, 0.56 mmol) was added dropwise
to a solution of 14 (0.1 g, 0.28 mmol), triphenylphosphine (0.15
g, 0.56 mmol), and p-nitrobenzoic acid (0.094 g, 0.56 mmol) in
THF (1.5 mL) at room temperature. After stirring for 24 h at
room temperature, the solvent was removed under reduced
pressure. The residue was taken up in ether and washed
successively with saturated aqueous NaHCO3 and brine. After
drying and evaporation, the residue was purified by flash
chromatography yielding benzoate ester 15 (0.048 g, 35%) as
a colorless oil. Rf ) 0.32 (15% EtOAc/hexane, B: brown). [R]25
D
3450 (br, OH’s) cm-1. H NMR (400 MHz, CDCl3): δ 0.05 (s,
+39.26 (c 0.5, CHCl3). 1H NMR (500 MHz, CDCl3): δ 0.003 (s,
6H), 0.87 (s, 9H), 1.41 (s, 3H), 1.58 (s, 3H), 1.65 (m, 1H), 2.02
(m, 1H), 3.43 (s, 3H), 3.59 (m, 1H), 4.34 (m, 2H), 4.48 (dd, J )
4.9, 7.92 Hz, 1H), 4.59 (dt, J ) 1.0, 4.39 Hz, 1H), 4.77 (ABq, J
) 7.0, 12.5 Hz, 2H), 8.22-8.32 (m, 4H). 13C NMR (125 MHz,
CDCl3): δ -5.09, 25.57, 26.31, 28.10, 29.69, 32.56, 39.02, 55.6,
68.18, 69.97, 76.25, 77.60, 96.07, 123.53, 130.91, 139.50,
179.91. Anal. Calcd for C24H37NO9Si: C, 56.34; H, 7.29; N, 2.74.
Found: C, 56.15; H, 7.05; N, 2.67.
1
3H), 0.07 (s, 3H), 0.85 (s, 9H), 1.29 (s, 3H), 1.43 (s, 3H), 1.72
(dddd, J ) 1.0, 4.9, 6.4, 13.5 Hz, 1H), 2.09 (ddd, J ) 8.1, 10.0,
13.5 Hz, 1H), 2.33 (d, J ) 10.0 Hz, 1H), 2.79 (s, 1H), 3.32 (s,
3H), 3.47 (dd, J ) 10.0, 11.5 Hz, 1H), 3.58 (d, J ) 11.5 Hz,
1H), 4.13 (dd, J ) 4.9, 8.1 Hz, 1H), 4.24 (d, J ) 7.3 Hz, 1H),
4.26 (ddd, J ) 3.2, 6.4, 10.0 Hz, 1H), 4.44 (ddd, J ) 1.0, 7.3,
3.2 Hz, 1H), 4.64 (s, 2H). 13C NMR (125 MHz, CDCl3): δ -5.01,
-4.25, 17.89, 24.04, 25.77, 26.24, 32.91, 55.33, 66.41, 67.03,
70.43, 72.58, 74.66, 77.64, 95.73, 109.44. MS m/z (assignment,
relative intensity): 394 (M+ + 1), 377 (M+ + 1 - CH3, 5), 245
(40), 75 (55), 45 (100). Anal. Calcd for C18H36O7Si: C, 55.07;
H, 9.24. Found: C, 55.75; H, 9.65.
7-Meth oxym eth oxy-2,2-d im eth yl-5-ter t-bu tyld im eth yl-
silyloxy-(3a S,5S,7S,7a S)-p er h yd r oben zo[d ][1,3]d ioxol-4-
on e (13). To a stirred solution of the diol 12 (0.4 g, 1.02 mmol)
in THF (2 mL)/water (2 mL) was added sodium periodate (0.32
g, 1.5 mmol) portionwise. The reaction mixture was stirred
for 2 h at room temperature. The reaction mixture was
extracted with EtOAc, concentrated under reduced pressure,
and purified by flash chromatography to provide inosose 13
7-Meth oxym eth oxy-2,2-d im eth yl-5-ter t-bu tyld im eth yl-
silyloxy-(3aR,4S,5S,7S,7aS)-per h ydr oben zo[d][1,3]dioxol-
4-ol (16). To a stirred solution of 15 (0.048 g, 0.094 mmol) in
0.5 mL of methanol was added sodium methoxide (30%
solution in MeOH, 0.1 mL). The mixture was stirred for 30
min and then quenched with water. The solvent was evapo-
rated under reduced pressure and directly charged over a dry
silica gel column for purification. Elution with EtOAc/hexane
(5/95 to 20/80) gave 0.03 g of 16 as a colorless oil. Rf ) 0.42
(25% EtOAc/hexane, B: red). [R]25 +38.87 (c 0.48, CHCl3).
D
1H NMR (500 MHz, CDCl3): δ 0.10 (s, 3H), 0.11 (s, 3H), 0.90
(s, 9H), 1.39 (s, 3H), 1.55 (s, 3H), 1.94 (dddd, J ) 1.0, 6.1, 4.8,
13.5 Hz, 1H), 2.00 (ddd, J ) 4.2, 10.5, 13.5 Hz, 1H), 2.12 (br
s, 1H), 3.40 (s, 3H), 3.62 (dd, J ) 3.1, 5.7 Hz, 1H), 4.13 (t, J )
5.7 Hz, 1H), 4.14 (ddd, J ) 4.8, 4.4, 3.1 Hz, 1H), 4.28 (ddd, J
) 3.6, 6.1, 10.5 Hz, 1H), 4.46 (ddd, J ) 5.7, 3.6, 1.0 Hz, 1H),
4.73 (s, 2H). Anal. Calcd for C17H34O6Si: C, 56.32; H, 9.45.
Found: C, 56.34; H, 9.49.
(0.3 g, 80%). Rf ) 0.72 (25% EtOAc/hexane, B: reddish brown).
1
[R]25 +64.45 (c 1.02, CHCl3). H NMR (500 MHz, CDCl3): δ
D
0.04 (s, 3H), 0.10 (s, 3H), 0.89 (s, 9H), 1.42 (s, 3H), 1.48 (s,
3H), 2.21 (m, 2H), 3.42 (s, 3H), 4.18 (dd, J ) 2.8, 4.0 Hz, 1H),
4.52 (ddd, J ) 3.1, 6.4, 9.8 Hz, 1H), 4.71 (m, 2H), 4.77 (s, 2H).
13C NMR (125 MHz, CDCl3): δ -5.24, -5.12, 17.97, 25.55,
25.93, 26.91, 29.63, 34.29, 55.49, 69.39, 74.11, 76.37, 78.17,
96.19, 110.83, 205.24. MS m/z (assignment, relative inten-
sity): 360 (M+ + 2), 242 (20), 184 (30), 46 (100). Anal. Calcd
for C17H32O6Si: C, 56.64; H, 8.95. Found: C, 56.57; H, 8.55.
7-Meth oxym eth oxy-2,2-d im eth yl-5-ter t-bu tyld im eth yl-
silyloxy-(3aR,4R,5S,7S,7aS)-per h ydr oben zo[d][1,3]dioxol-
(1a ,2a ,3a ,4a ,5b)-P en t a h yd r oxycycloh exa n e [(+)-a llo-
Qu er citol] (17). To a stirred solution of 14 (0.15 g, 0.42 mmol)
in methanol (2 mL) was added a 6 M HCl solution (1 mL),
and it was heated to 60 °C. After 4 h, all the solvent was
removed under reduced pressure, and the crude product was
purified by flash column chromatography (35% CHCl3-IPA)

8378 J . Org. Chem., Vol. 66, No. 25, 2001
Yadav et al.
to afford 17 (0.645 g, 95%) as a colorless solid. Rf ) 0.5 (50%
Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 20.60, 20.79, 20.89,
66.70, 67.17, 67.93, 68.34, 68.97, 169.43, 169.6, 169.72, 169.75,
169.78.
CHCl3-IPA). mp >200 °C (lit.6a 262 °C for DL isomer). [R]25
D
1
+23.3 (c 0.36, water). H NMR (500 MHz, D2O): δ 1.52 (ddd,
J ) 3.1, 9.4, 13.9 Hz, 1H), 2.05 (ddd, J ) 4.4, 5.9, 13.9 Hz,
1H), 3.49 (dd, J ) 2.9, 8.2 Hz, 1H), 3.73 (t, J ) 3.1 Hz, 1H),
3.93 (dd, J ) 2.9, 3.1 Hz, 1H), 3.97 (ddd, J ) 8.2, 9.3, 4.4 Hz,
1H), 3.99 (ddd, J ) 5.9, 3.1, 3.2 Hz, 1H). 13C NMR (500 MHz,
D2O): δ 34.21, 63.69, 67.12, 70.20, 71.34, 73.02. Anal. Calcd
for C6H12O5: C, 43.90; H, 7.73. Found: C, 43.79; H, 7.33.
(1a ,2a ,3a ,4a ,5b )-P en t a a cet oxycycloh exa n e [(+)-a llo-
Qu er citol P en ta a ceta te] (18). To a stirred solution of 17
(0.05 g, 0.3 mmol) in 0.5 mL of pyridine was added acetic
anhydride (0.1 mL). The reaction mixture was stirred at room
temperature for 8 h and cooled to 0 °C. After addition of 5 mL
of water, the water phase was extracted with ether (4 × 5 mL).
The combined organic extract was washed with NaHCO3
solution (1 mL) and water and then dried over Na2SO4. The
solvent was evaporated under reduced pressure, and the crude
product was purified by flash column chromatography to afford
18 (0.1 g, 90%) as a colorless solid. Rf ) 0.5 (50% EtOAc/
hexane, B: brown). mp 114 °C (lit.6a mp 94 °C for DL isomer).
IR γmax (KBr): 1238, 1369, 1739, 2925, 3467 cm-1. [R]25D +11.6
(1a ,2a ,3a ,4b,5b)-P en ta h yd r oxycycloh exa n e [(+)-ta lo-
Qu er citol] (19). Compound 16 (30 mg) was treated with acid
to remove protecting groups as described above to give (+)-
talo-quercitol 19 (14 mg, 97%) as a colorless solid. Rf ) 0.45
(50% CHCl3-IPA). mp >200 °C (lit.6a mp 246-248 °C dec).
[R]25 +56.4 (c 0.2, water) [lit.6a +62 (c 0.5, water)]. Further
D
data are in accord with the literature.7
(1a ,2a ,3a ,4b ,5b )-P en t a a cet oxycycloh exa n e [(+)-ta lo-
Qu er citol P en ta a ceta te] (20). (+)-talo-Quercitol 19 (10 mg)
was submitted to acetylation as described above to give (+)-
talo-quercitol pentaacetate 20 (19.8 mg, 90%) as a colorless
solid. Rf ) 0.6 (50% EtOAc/hexane). [R]25 +24 (c 0.2, CHCl3)
D
[lit.6a +28 (c 1, CHCl3)]. mp 172-178 °C dec (lit.6a mp 182-
183 °C). Further data are in accord with the literature.7
Ack n ow led gm en t. A.M. thanks CSIR, New Delhi,
India, for financial assistance.
Su p p or tin g In for m a tion Ava ila ble: Energy-minimized
structures of compounds 8E, 8Z, 9E, 9Z, 11, 12, 14, 16. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
(c 1.02, CHCl3). H NMR (400 MHz, CDCl3): δ 1.84 (dddd, J
) 3.5, 7.4, J ) 1.5, 14.3 Hz, 1H), 2.070 (s, 6H), 2.073 (s, 3H),
2.08 (s, 3H), 2.09 (s, 3H), 2.30 (ddd, J ) 4.1, 7.6, 14.3 Hz, 1H),
5.12 (dd, J ) 3.4, 7.6 Hz, 1H), 5.30 (m, 3H), 5.40 (t, J ) 3.5
J O010455M