Formal synthesis of D-myo-inositol 1,4,5-tris(dihydrogen phosphate): Cyclization by an unusual ene reaction and use of the Bu2SnCl2/Bu2SnH2 reagent for generating an equatorial alcohol

Article abstract of DOI:10.1021/jo990086i

D-Glucose was converted into the propargyl silane aldehyde 5, which, on treatment with camphorsulfonic acid, cyclized with retention of silicon. The allenic product (7) was elaborated via ketone 24 into 4, which had previously been converted into D-myo-inositol 1,4,5-tris(dihydrogen phosphate). Selective reduction of the advanced intermediate 24 was accomplished with Bu₂SnCl₂/Bu₂SnH₂, a reagent mixture that shows a very strong preference for generating equatorial alcohols. The cyclization step leading to allene 7 was studied by examining a number of model compounds; the unusual retention of silicon appears to be limited to highly oxygenated substrates, such as 5 and its all-benzyl analogue (27).

Full text of DOI:10.1021/jo990086i

J . Org. Chem. 1999, 64, 4397-4410
4397
F or m a l Syn th esis of D-m yo-In ositol 1,4,5-Tr is(d ih yd r ogen
p h osp h a te): Cycliza tion by a n Un u su a l En e Rea ction a n d Use of
th e Bu 2Sn Cl2/Bu 2Sn H2 Rea gen t for Gen er a tin g a n Equ a tor ia l
Alcoh ol
Derrick L. J . Clive,* Xiao He, Maarten H. D. Postema, and M. J effrey Mashimbye
Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Received J anuary 19, 1999
D-Glucose was converted into the propargyl silane aldehyde 5, which, on treatment with
camphorsulfonic acid, cyclized with retention of silicon. The allenic product (7) was elaborated via
ketone 24 into 4, which had previously been converted into D-myo-inositol 1,4,5-tris(dihydrogen
phosphate). Selective reduction of the advanced intermediate 24 was accomplished with Bu2SnCl2/
Bu2SnH2, a reagent mixture that shows a very strong preference for generating equatorial alcohols.
The cyclization step leading to allene 7 was studied by examining a number of model compounds;
the unusual retention of silicon appears to be limited to highly oxygenated substrates, such as 5
and its all-benzyl analogue (27).
In tr od u ction a n d Discu ssion
used for this purpose. In the case of glucose, the pyranose
ring was converted into the required carbocycle by
Ferrier9 rearrangement. Our synthesis is based on a type
of ene10,11 reaction for converting a linear chain into a
carbocycle. The plan was to convert D-glucose into acety-
lenic aldehyde (2), where the group R is chosen so as to
facilitate an ene reaction that would afford 3 (R′ ) H or
other atom). The latter seemed properly constituted for
elaboration into 4, which had been converted12 by others
into D-myo-inositol 1,4,5-tris(dihydrogen phosphate). How-
We report full details1 of a formal synthesis of D-myo-
inositol-1,4,5-tris(dihydrogen phosphate) (1) in optically
pure form, starting from D-glucose. Our approach il-
lustrates the use of the reagent system Bu2SnCl2/Bu2-
SnH2 for conversion of a cyclohexanone into the corre-
sponding equatorial alcohol in circumstances where
conventional reagents gave the axial isomer. The ketone
that we reduce was itself made by an unusual ene
reaction. We also describe a general survey of that ene
reaction and conclude that it probably works only for
highly oxygenated substrates.
Inositol phosphates play an essential role in the
coupling of cell surface receptors to cellular responses,
and the chemistry and biochemistry of these compounds
have been reviewed extensively.2 D-myo-Inositol 1,4,5-
tris(dihydrogen phosphate) (1) is a very important mes-
senger in the metabolism of calcium, and consequently,
it has been the object of a great deal of synthetic work.2,3
A resolution is usually employed in the synthesis of
optically pure 1,2,4 but there are a few methods by which
it has been obtained from compounds in the chiral pool;
(-)-quinic acid,5 D-pinnitol,6 and D-glucose7,8 have been
ever, compound 2 (R ) H) did not behave in the required
manner; little, if any, cyclization was observed under the
conditions we tried,13 and so we prepared the silicon-
substituted analogue 5 (≡ 2, R ) SiMe3), in the expecta-
tion that the ene pathway (Scheme 1) would be facili-
(7) Sato, K.; Bokura, M.; Taniguchi, M. Bull. Chem. Soc. J pn. 1994,
67, 1633-1640.
(8) Tethered versions of 1 have also been made from glucose: see
ref 3.
(9) Ferrier, R. J .; Middleton, S. Chem. Rev. 1993, 93, 2779-2831.
(10) Review on ene reaction: Snider, B. B. In Comprehensive
Organic Synthesis: Selectivity, Strategy, and Efficiency in Modern
Organic Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
New York, 1991; Vol. 5, pp 1-27.
(11) For use of an intramolecular pinacol coupling in inositol
synthesis, see: (a) Guidot, J . P.; Gall, T. Le; Mioskowski, C. Tetrahe-
dron Lett. 1994, 35, 6671-6674. (b) Chiara, J . L.; Mart´ın-Lomas, M.
Tetrahedron Lett. 1994, 35, 2969-2972.
(1) Preliminary communication: Clive, D. L. J .; He, X.; Postema,
M. H. D.; Mashimbye, M. J . Tetrahedron Lett. 1998, 39, 4231-4234.
(2) (a) Billington, D. C. The Inositol Phosphates; VCH: Weinheim,
1993. (b) Potter, B. V. L.; Lampe, D. Angew. Chem., Int. Ed. Engl. 1995,
34, 1933-1972.
(3) Tethered versions of inositol phosphates: Prestwich, G. D. Acc.
Chem. Res. 1996, 29, 503-513.
(4) (a) For an example of an enzymatic resolution, see: Ling, L.;
Ozaki, S. Tetrahedron Lett. 1993, 34, 2501-2504. (b) For an example
of chemical resolution, see: Aguilo´, A.; Mart´ın-Lomas, M.; Penade´s,
S. Tetrahedron Lett. 1992, 33, 401-404.
(5) Falk, J . R.; Yadagiri, P. J . Org. Chem. 1989, 54, 5851-5852.
(6) Tegge, W.; Ballou, C. E. Proc. Natl. Acad. Sci. U.S.A. 1989, 86,
94-98.
(12) (a) Racemic series: Yu, K.-L.; Fraser-Reid, B. Tetrahedron Lett.
1988, 29, 979-982. (b) Optically active series: Dreef, C. E.; Tuinman,
R. J .; Elie, C. J . J .; van der Marel, G. A.; van Boom, J . H. Recl. Trav.
Chim. Pays-Bas 1988, 107, 395-397.
10.1021/jo990086i CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/14/1999

4398 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
Sch em e 1a
Sch em e 2a
a
Pmb ) p-methoxybenzyl.
tated, either in the sense 5 f 614 (with subsequent
hydrolysis of the silyl ether) or with direct loss15 of the
silicon unit. This expectation was based on the fact that
allyl silanes are known18 to undergo cyclizations19 (see
eq 118a) formally related to the process we wanted. In the
a
(i) TrCl, pyridine, DMAP, 110 °C, 8 h, 80%; (ii) NaH, PmbCl,
0 °C to room temperature, then reflux, 24 h, 91%; (iii) t-BuOK,
DMSO, 100 °C, 1 h; (iv) HgCl2, HgO, acetone-water, room
temperature, 4 h, 88% from 10; (v) LiAlH4, THF, 0 °C to room
temperature, 4 h, 93%; (vi) t-BuMe2SiCl, Et3N, DMAP, CH2Cl2,
room temperature, 16 h, 99%; (vii) NaH, BnBr, 0 °C to room
temperature, then reflux, 24 h, 96%; (viii) Bu4NF, THF, room
temperature, 4 h, 92%; (ix) Swern oxidation, 89%; (x) Ph3P, CBr4,
CH2Cl2, -20 °C, then cool to -60 °C and add Et3N, then warm to
room temperature, 83%; (xi) n-BuLi, THF, -78 °C, 85%; (xii)
n-BuLi, HMPA, THF, -78 °C, Me3SiCH2OSO2CF3, room temper-
ature, overnight, 82%; (xiii) CSA, MeOH, CH2Cl2, room temper-
ature, 36 h, 94%; (xiv) Swern oxidation, 92%.
event, cyclization was now easily effected (in the presence
of camphorsulfonic acid), but the silicon unit did not
migrate, nor was it lost; instead, 5 was transformed
stereoselectively into 7.20
Aldehyde 5 was prepared as summarized in Scheme
2. D-Glucose was converted in three steps21 (76% overall)
into the allyl22 glucopyranosides 8. The C(6) primary
hydroxyl was protected by tritylation (8 f 9; TrCl,
pyridine, DMAP, 110 °C, 80%) and the remaining two
hydroxyls by conversion into their p-methoxybenzyl
ethers [9 f 10; p-MeOC6H4CH2Cl (PmbCl), NaH, THF,
reflux, 91%]. At that point deallylation could be effected
by the two-step method of double-bond isomerization,
using Wilkinson’s catalyst,23 or t-BuOK in hot (110 °C)
DMSO,24 followed by hydrolysis25 of the resulting enol
ethers, catalyzed by Hg2+ (HgCl2, HgO, acetone-water,
room temperature). Both procedures gave similar yields
overall [92% with use of (Ph3P)3RhCl and 88% with
t-BuOK], but the base-induced isomerization was more
economical. The resulting lactols (11) were reduced to the
glucitol 12 (LiAlH4, THF, 0 °C to room temperature,
93%), and the primary hydroxyl was silylated (12 f 13;
t-BuMe2SiCl, Et3N, DMAP, CH2Cl2, room temperature,
99%) so that the remaining secondary hydroxyl could be
benzylated (13 f 14; NaH, BnBr, THF, reflux, 96%).
Next, removal of the silyl group (14 f 15; Bu4NF, THF,
room temperature, 92%) and Swern oxidation (15 f 16;
89%) brought us to the appropriate stage for construction
of the ethynyl unit. This was initiated (16 f 17) by
sequential treatment with CBr4/Ph3P/Et3N (-60 °C to
room temperature, 83%) and n-BuLi (THF, -78 °C,
85%).26 Deprotonation of 17 with n-BuLi, and reaction
with Me3SiCH2OSO2CF3 (HMPA, THF, room tempera-
ture, 82%), then completed the required propargyl silane
(13) Thermolysis (140 °C, p-xylene): no cyclization. TFA in CH2Cl2
at 0 °C: decomposition. TFA in CHCl3 at room temperature: decom-
position. Camphorsulfonic acid in CH2Cl2 or CHCl3 at room temper-
ature: decomposition. Me2AlCl, CH2Cl2, -78 °C: little, if any cycliza-
tion product.
(14) For related cyclizations involving allyl silanes (with loss of
silicon), see: Schinzer, D. Synthesis 1988, 263-273.
(15) R,â-Unsaturated ketones incorporating a suitably located pro-
pargyl silane unit undergo cyclization with loss of silicon (see ref 16).
For a single example of cyclization onto a carbonyl, also with loss of
silicon, see ref 17.
(16) (a) Schinzer, D.; Dettmer, G.; Ruppelt, M.; So´lyom, S.; Steffen,
J . J . Org. Chem. 1988, 53, 3823-3828. (b) Schinzer, D.; Kabbara, J .;
Ringe, K. Tetrahedron Lett. 1992, 33, 8017-8018. (c) Schinzer, D.;
Ringe, K. Synlett 1994, 463-464. (d) Schinzer, D.; Ruppelt, M. Ber.
1991, 124, 247-248.
(17) Schinzer, D.; Panke, G. J . Org. Chem. 1996, 61, 4496-4497.
(18) E.g., (a) Asao, K.; Iio, H.; Tokoroyama, T. Tetrahedron Lett.
1989, 30, 6397-6400. (b) Yamamoto, Y.; Asao, N. Chem. Rev. 1993,
93, 2207-2293.
(19) For intermolecular reactions of propargyl silanes with electro-
philes, see: (a) Pornet, J .; Aubert, P.; Randrianoe´lina, B.; Miginiac,
L. Tetrahedron Lett. 1984, 25, 651-654. (b) Pornet, J .; Randrianoe´lina,
B.; Miginiac, L. J . Organomet. Chem. 1994, 481, 217-225.
(20) For cyclizations of allenyl silanes that occur with retention of
silicon, and for which the presence of the silicon substituent is essential,
see: (a) J in, J .; Smith, D. T.; Weinreb, S. M. J . Org. Chem. 1995, 60,
5366-5367. (b) Weinreb, S. M.; Smith, D. T.; J in, J . Synthesis 1998,
509-521. (c) Cf. Esch, P. M.; Hiemstra, H.; Speckamp, W. N.
Tetrahedron Lett. 1988, 29, 367-370.
(21) Fukase, K.; Matsumoto, T.; Ito, N.; Yoshimura, T.; Kotani, S.;
Kusumoto, S. Bull. Chem. Soc. J pn. 1992, 65, 2643-2654.
(22) Exploratory studies guided our choice of allyl glycosides, as we
found indications that hydrolysis of methyl glycosides was not possible
without loss of p-methoxybenzyl groups (which we wished to use for
protection of two of the hydroxyls).
(23) Corey, E. J .; Suggs, J . W. J . Org. Chem. 1973, 38, 3224.
(24) Cunningham, J .; Gigg, R.; Warren, C. D. Tetrahedron Lett.
1964, 1191-1196.
(25) Grigg, R.; Warren, C. D. J . Chem. Soc. C 1968, 1903-1911.
(26) Grandjean, D.; Pale, P.; Chuche, J . Tetrahedron Lett. 1994, 35,
3529-3530.

D-myo-Inositol 1,4,5-Tris(dihydrogen phosphate)
J . Org. Chem., Vol. 64, No. 12, 1999 4399
Sch em e 3a
in MeOH-THF at a low temperature (-78 to 0 °C),
afforded (92%) the required equatorial alcohol 22, which
was easily benzylated (22 f 23; NaH, BnBr, THF, reflux,
87%). Ozonolysis of the allene required careful control,
and our optimized procedure calls for a deficiency of O3
in CH2Cl2-pyridine at -78 °C.31 This procedure allows
isolation of the ketone 24 in 80% yield [after correction
for recovered 23 (27%)]. Reduction of 24 in the correct
stereochemical sense (to the equatorial alcohol 25) re-
quired a good deal of effort, as formation of the undesired
axial alcohol was observed with all the conventional
hydride reducing agents we tried.32 Moreover, attempts33
to invert the axial into the equatorial alcohol proved
fruitless. We were eventually led to consider a stannane-
based method for reduction, because we expected the
intermediate radical34 (see 26) to abstract hydrogen from
a
(i) K2CO3, 3:1 MeOH-THF, reflux, 4 h, 86%; (ii) Dess-Martin
the conformation shown (with the bulky OSnR3 group
equatorial). Examination of the literature on the stan-
nane reduction of ketones brought to our attention the
use of Bu2SnHCl35 for reduction of R-alkoxy cyclohex-
anones to equatorial alcohols. The reagent is generated
in situ from Bu2SnH2 and Bu2SnCl2.36 An equilibrium is,
apparently, set up with Bu2SnHCl.37 When we used this
reagent system in THF at room temperature, we obtained
a 1:2 ratio of equatorial to axial alcohols. In refluxing
THF, the ratio improved to 2:1 in favor of the desired
equatorial alcohol, but in refluxing PhMe, only the
equatorial alcohol was formed (24 f 25, 88%). The
mechanism of reduction by Bu2SnHCl has been sug-
periodinane, CH2Cl2, 30 min, 84%; (iii) NaBH4, CeCl3‚7H2O, 1:10
THF-MeOH, -78 °C to 0 °C, 92%; (iv) NaH, BnBr, 0 °C to room
temperature, then reflux, 24 h, 87%; (v) O3 (<1 equiv), 1:6
pyridine-CH2Cl2, -78 °C, 80% after correction for recovered 23
(27%); (vi) 1:1 n-Bu2SnCl2/n-Bu2SnH2, PhMe, reflux, 24 h, 88%;
(vii) DDQ, 1:20 water-CH2Cl2, room temperature, 4 h, 70%.
unit (17 f 18). Finally, detritylation (18 f 19; camphor-
sulfonic acid, MeOH, room temperature) was accom-
plished in 94% yield, with no loss of the silyl group, and
Swern oxidation (92%) gave the key aldehyde 5 for ene
cyclization.
Our first experiments, in which 5 was exposed to
potentially suitable reagents (TiCl4, BF3‚Et2O, CF3CO2H,
TBAF27), were unpromising.28 Fortunately, however, a
sample of 5 that had been stored for a few days in a
mixture of CH2Cl2 and CDCl3 was examined, and we
found that the compound had been partially converted
into a new substance, which was subsequently fully
characterized as 7. A small amount of the corresponding
desilylated material (see 20 in Scheme 3) was also
isolated. The conditions for the unusual ring closure with
retention of silicon were optimized, it being found that
use of CSA in PhMe gave 7 in 91% yield.
Conversion of 7 into 4 required a number of apparently
simple operations: stereochemical inversion at C(3),
benzylation of the resulting alcohol, oxidative cleavage
of the exocyclic double bond at C(4), and reduction of the
resulting carbonyl to an equatorial alcohol. These opera-
tions proved unexpectedly troublesome. However, each
was eventually achieved in good yieldsbut only after
considerable effort to establish the proper choice and
sequence of reagents.
Our exploratory experiments suggested that the silyl
group should be removed first, and this was done by
treatment of 7 with K2CO3 in refluxing MeOH-THF (7
f 20, 86%). Oxidation, best29 carried out with the Dess-
Martin reagent in CH2Cl2, gave ketone 21 (84%), and
then reduction, using the NaBH4-CeCl3‚7H2O system30
(30) (a) Luche, J .-L. J . Am. Chem. Soc. 1978, 100, 2226-2227. (b)
Luche, J .-L.; Rodriguez-Hahn, L.; Crabbe´, P. J . Chem. Soc., Chem.
Commun. 1978, 601-602.
(31) Cf. (a) Slomp, G.; J r.; J ohnson, J . L. J . Am. Chem. Soc. 1958,
80, 915-921. (b) Boddy, I. K.; Boniface, P. J .; Cambie, R. C.; Craw, P.
A.; Huang, Z.-D.; Larsen, D. S.; McDonald, H.; Rutledge, P. S.;
Woodgate, P. D. Aust. J . Chem. 1984, 37, 1511-1529.
(32) E.g., various versions of the Meerwein-Ponndorf-Verley re-
duction [Al(OPr-i)3-i-PrOH; Sc(OSO2CF3)3-i-PrOH; Ce(OPr-i)3-i-PrOH]
and use of SmI2 in i-PrOH or THF-H2O gave complex mixtures; Al-
(OPr-i)2(OCOCF3) or BH3‚Me2S did not react; DIBAL, DIBAL/methy-
laluminum bis(2,6-di-tert-butylphenoxide) [MAD], NaBH4/MAD and
Bu4NBH4/MAD gave the axial alcohol; NaBH(OAc)3-AcOH apparently
gave an epimer mixture containing a trace (1H NMR) of the desired
equatorial alcohol. For relevant examples of reduction to equatorial
alcohols, see: (a) Evans, D. A.; Kaldor, S. W.; J ones, T. K.; Clardy, J .;
Stout, T. J . J . Am. Chem. Soc. 1990, 112, 7001-7031. (b) Corey, E. J .;
Hopkins, P. B.; Kim, S.; Yoo, S.-e.; Nambiar, K. P.; Falck, J . R. J . Am.
Chem. Soc. 1979, 101, 7131-7134.
(33) Treatment of the derived triflate with AcOK in DMF; AcOCs
in DMF; KOCHO, 18-crown-6 in DMF; CF3COONa, 18-crown-6 in DMF
gave none of the desired product. Use of AcOCs, 18-crown-6 in refluxing
PhH or of KO2 in DMSO-DMF (followed by treatment with Ph3P) each
gave a trace of the desired products. Use of KONO, 18-crown-6 in DMF,
followed by water at reflux, gave the equatorial alcohol in about 40%
yield. The system was prone to dehydration under Mitsunobu condi-
tions.
(34) Radical stannane reduction of ketones has been reported, but
is not an established synthetic method: Cf. (a) Kupchik, E. J . In
Organotin Compounds; Sawyer, A. K., Ed.; Dekker: New York, , 1971;
p 49. (b) Kuivila, H. G. Synthesis 1970, 499-509.
(35) (a) Martin, S. F.; J osey, J . A.; Wong, Y.-L.; Dean, D. W. J . Org.
Chem. 1994, 59, 4805-4820. (b) Shibata, I.; Yoshida, T.; Kawakami,
T.; Baba, A.; Matsuda, H. J . Org. Chem. 1992, 57, 4049-4051.
(36) (a) Neumann, W. P.; Pedain, J . Tetrahedron Lett. 1964, 2461-
2465. (b) Sawyer, A. K.; Brown, J . E.; Hanson, E. L. J . Organomet.
Chem. 1965, 3, 464-471.
(27) Cf. Pornet, J . Tetrahedron Lett. 1981, 22, 455-456.
(28) TFA, CH2Cl2, 0 °C: no reaction. BF3‚Et2O, CH2Cl2, -78 °C:
complex mixtures. TBAF, THF, 0 °C: complex mixtures. TiCl4, CH2-
Cl2, -78 °C: some cyclization (<39%) probably occurred.
(29) We also tried MnO2, PDC, PCC, Swern, TPAP-NMO.
(37) For the composition of the reagent, see: Davies, A. G.; Osei-
Kissi, D. K. J . Organomet. Chem. 1994, 474, C8-C10.

4400 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
gested38 to involve a radical process, but the reagent is
known39 to reduce R-(phenylseleno) ketones (albeit in
very poor yield) with preservation of the phenylseleno
group, and this behavior suggests that, at least in those
reactions, a radical mechanism is not involved. In our
case, the correlation between temperature and the axial/
equatorial ratio may reflect the operation of competing
ionic and radical mechanisms.
and used in natural product synthesis.44 However, related
cyclizations directly onto a carbonyl group have received
little attention, and we know of only one prior example
(see eq 5).17
Finally, having reached 25, oxidative removal of the
p-methoxybenzyl groups (DDQ, water-CH2Cl2, room
temperature, 70%) gave the target compound (4), which
is convertible12 by phosphorylation and deprotection into
D-myo-inositol 1,4,5-tris(dihydrogen phosphate) (1).
In principle, other inositol phosphates40 may be acces-
sible by the method described here, but we have not
tested this possibility. The outcome of any such attempts
would depend on the generality of both the ene cyclization
for other oxygenated acetylenes and the stereochemical
outcome of the stannane reduction. We have, however,
made a number of observations on the ene process.
In view of the unexpected retention of silicon in the
inositol work described above, we investigated the closure
of propargyl silanes onto aldehyde carbonyls (see Table
1) and have also examined corresponding cyclizations
with ketones and acetals.45 The reaction is a general route
to five- and six-membered carbocycles, but only in certain
situations is the silicon group retained.20
The starting materials 27-34 (see Table 1) were
prepared by standard reactions, as follows: 27 (Scheme
4), 28 (Scheme 5), 29 (Scheme 6), 30 (Scheme 7), 32
(Scheme 8), 34 (Scheme 9). Ketals 31 and 33 were made
by ketalization of 29 and 32 (see Supporting Information),
respectively.
In studying the ene reaction, we tried Lewis acids, as
well as CF3CO2H, CSA, and TBAF. With the highly
oxygenated substances 5 (Scheme 1) and 27 (Table 1,
entry 1) and ketals 31 and 33 (Table 1, entries 6 and 8),
the silicon unit is retained. The structure of 27a was
established by X-ray analysis, and the similarity of the
1H NMR signal for the vinyl hydrogen with the corre-
sponding signal for 7 suggested that 27a and 7 have the
same stereochemistry, and the fact that the hydroxyl in
7 is axial was subsequently confirmed by conversion of
7 into 4. The preferred conformation of 28a is tentatively
assigned as shown, based on the observation of a coupling
constant of >3 Hz for coupling46 between the CH(OH)
proton and the allene CH2. An equatorial hydrogen would
be associated with a J of 1.2 Hz.46 The stereochemical
assignments to 29a and 29b were made on the basis of
Obser va tion s on th e Closu r e of P r op a r gyl
Sila n es on to Ald eh yd e Gr ou p s
Several cases have been reported in which R,â-
unsaturated ketones incorporating a suitably located
propargyl silane unit undergo cyclization to afford allenes
that contain a spiro-fused or linearly fused bicyclic
structure, as illustrated in eqs 216a and 3.16a The silicon
group is lost41 during the cyclization, except in one case
(eq 4),42 where the expected product was accompanied
by a substance arising formally by [2 + 2] cycloaddition.
(41) For reactions of propargyl silanes in which the silicon unit
migrates to a new position, and is retained, see, for example: Dan-
heiser, R. L.; Dixon, B. R.; Gleason, R. W. J . Org. Chem. 1992, 57,
6094-6097.
(42) (a) Spence, J . D.; Lowrie, L. E.; Nantz, M. H. Tetrahedron Lett.
1995, 36, 5499-5502. (b) For the formation of (cyclobutylmethyl)silanes
in intermolecular reactions of allyl silanes, see: House, H. O.; Gaa, P.
C.; VanDerveer, D. J . Org. Chem. 1983, 48, 1661-1670, and references
therein.
(43) (a) For use of propargyl silanes in biomimetic polyene cycliza-
tions, see: J ohnson, W. S.; Plummer, M. S.; Pulla Reddy, S.; Bartlett,
W. R. J . Am. Chem. Soc. 1993, 115, 515-521. (b) For use of iminium
ions in the cyclization of propargyl silanes, see: Fischer, M. J .;
Overman, L. E. J . Org. Chem. 1990, 55, 1447-1459. Hiemstra, H.;
Speckamp, W. N. Tetrahedron Lett. 1983, 24, 1407-1410. Hiemstra,
H.; Fortgens, H. P.; Stegenga, S.; Speckamp, W. N. Tetrahedron Lett.
1985, 26, 3151-3154. Esch, P. M.; Hiemstra, H.; Klaver, W. J .;
Speckamp, W. N. Heterocycles 1987, 26, 75-79. Klaver, W. J .;
Moolenaar, M. J .; Hiemstra, H.; Speckamp, W. N. Tetrahedron 1988,
44, 3805-3818.
(44) (a) Review: Langkopf, E.; Schinzer, D. Chem. Rev. 1995, 95,
1375-1408. (b) Schinzer, D.; Ringe, K.; J ones, P. G.; Do¨ring, D.
Tetrahedron Lett. 1995, 36, 4051-4054. (c) Sole´, D.; Bonjoch, J .; Garc´ıa-
Rubio, S.; Suriol, R.; Bosch, J . Tetrahedron Lett. 1996, 37, 5213-5216.
(d) Klaver, W. J .; Hiemstra, H.; Speckamp, W. N. J . Am. Chem. Soc.
1989, 111, 2588-2595. (e) Hiemstra, H.; Klaver, W. J .; Speckamp, W.
N. Rec. Trav. Pays-Bas 1986, 105, 299-306.
Reactions such as those given in eqs 2 and 3, and
related processes,43 have been examined in some detail16
(38) Davies, A. G.; Kinart, W. J .; Osei-Kissi, D. K. J . Organomet.
Chem. 1994, 474, C11-C13.
(39) Aoki, I.; Nishibayashi, Y.; Uemura, S. Bull. Chem. Soc. J pn.
1995, 68, 337-340.
(45) (a) Cf. J ohnson, W. S.; Elliott, J . D.; Hanson, G. J . J . Am. Chem.
Soc. 1984, 106, 1138-1139. (b) For corresponding reaction of acetals
in the allyl silane series, see: Fleming, I.; Pearce, A. J . Chem. Soc.,
Perkin Trans 1 1981, 251-255.
(40) Cf. (a) Chung, S.-K.; Chang, Y.-T.; Sohn, K.-H. J . Chem. Soc.,
Chem. Commun. 1996, 163-164. (b) Bruzik, K. S.; Tsai, M.-D. J . Am.
Chem. Soc. 1992, 114, 6361-6374.
(46) Santelli, M. J . Chem. Soc., Chem. Commun. 1971, 938-939.

D-myo-Inositol 1,4,5-Tris(dihydrogen phosphate)
J . Org. Chem., Vol. 64, No. 12, 1999 4401
Ta ble 1
a
b
d
CSA, PhMe, room temperature, 5 h. ZnCl2, CH2Cl2, 0 °C, 2.5 h. c Preferred conformation of 28a is a tentative assignment. TFA,
CH2Cl2, -78 °C, 30 min. e ZnCl2, CH2Cl2, 0 °C, 3 h. f TFA, CH2Cl2, -78 °C, 1 h. TBAF, THF, 0 °C, 1 h. ZnCl2, CH2Cl2, 0 °C, 20 h; no
g
h
i
j
k
reaction. TFA, CH2Cl2, 0 °C, 12 h; no reaction. Me3SiOSO2CF3 (catalytic), CH2Cl2, -78 °C to room temperature, 11 h. Me3SiOSO2CF3
(catalytic), CH2Cl2, -78 °C, 3 h, yield corrected for recovered starting material. l A 1.2:1.0:1.3 mixture of 31 (corresponding to 13% recovery),
m
n
31b (corresponding to 12% yield), and 31c (corresponding to 16% yield). Me3SiOSO2CF3 (1 equiv), CH2Cl2, -78 °C, 3 h. CSA, CH2Cl2,
room temperature, 48 h. o Epimer mixture (55:45). Sc(OSO2CF3)3, MeNO2, room temperature, 12 h. Epimer mixture (1:1). ZnCl2,
p
q
r
s
t
CH2Cl2, room temperature, 24 h. ZnCl2, CH2Cl2, 0 °C to room temperature, 14 h. Me3SiOSO2CF3 (1 equiv), CH2Cl2, -78 °C, 1.5 h.
Epimer mixture (3:2). v CSA, CH2Cl2, room temperature, 20 h. Epimer mixture (1:7.2).
u
w

4402 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
Sch em e 4a
Sch em e 6a
a
(i) Dihydropyran, TsOH‚H2O, room temperature, 24 h, 66%
after correction for recovered 52 (36%); (ii) TsCl, pyridine, DMAP,
CH2Cl2, room temperature, 12 h, 63%; (iii) LiBr, acetone, reflux,
2 h, 95%; (iv) Me3SiCtCH, n-BuLi, THF, HMPA, -78 °C, then
room temperature, 12 h, 81%; (v) K2CO3, MeOH-THF, 0 °C,
6 h, then room temperature, 12 h, 94%; (vi) n-BuLi, THF, -78
°C, Me3SiCH2OSO2CF3, HMPA, room temperature, 10 h, 92%;
(vii) TsOH‚H2O, MeOH-water, reflux, 4 h, 89%; (viii) Swern,
90%.
Sch em e 7a
a
(i) MeMgBr, Et2O, 0 °C to room temperature, 2 h, 90%; (ii)
a
PCC, 3 Å molecular sieves, CH2Cl2, 25 min, 90%.
(i) NaOH, BnCl, 120 °C, 36 h, 87%; (ii) DMSO, t-BuOK, 100
°C, 1 h; HgO, HgCl2, acetone-water, 4 h, 88%; (iii) LiAlH4, THF,
0 °C to room temperature, 4 h, 95%; (iv) t-BuMe2SiCl, Et3N,
DMAP, CH2Cl2, room temperature, 16 h, 95%; (v) NaH, THF,
BnBr, reflux, 14 h, 94%; (vi) TBAF, THF, room temperature, 4 h,
97%; (vii) Swern, 89%; (viii) Ph3P, CBr4, CH2Cl2, -20 °C, then
cool to -60 °C and add Et3N, then warm to room temperature, 30
min, 76%; (ix) n-BuLi, THF, -78 °C, 2 h, 78%; (x) n-BuLi,
Me3SiCH2OSO2CF3, HMPA, THF, -78 °C to room temperature,
10 h, 78%; (xi) CSA, MeOH, room temperature, 24 h, 94%; (xii)
Swern, 84%.
Sch em e 8a
Sch em e 5a
a
(i) PCC, 3 Åmolecular sieves, CH2Cl2, 35 min, 82%; (ii) Ph3P,
CBr4, CH2Cl2, -20 °C, then cool to -60 °C and add Et3N, then
warm to room temperature, 30 min, 76%; (iii) n-BuLi, THF, -78
°C, 2 h, then room temperature, 30 min, 94%; (iv) n-BuLi, THF,
-78 °C, Me3SiCH2OSO2CF3, HMPA, room temperature, 10 h, 86%;
(v) TsOH‚H2O, MeOH-water, reflux, 3.5 h, 98%; (vi) PCC, 3 Å
molecular sieves, CH2Cl2, 30 min, 90%.
a
(i) Me3SiCtCH, n-BuLi, THF, HMPA, -78 °C, then room
temperature, 15 h, 94% after correction for recovered 47 (35%);
(ii) K2CO3, MeOH, 0 °C, 5 h, then room temperature, 12 h, 94%;
(iii) n-BuLi, THF, -78 °C, Me3SiCH2OSO2CF3, HMPA, room
temperature, 18 h, 91% after correction for recovered 49 (18%);
(iv) TsOH‚H2O, MeOH-water, reflux, 3 h, 93%; (v) Swern, 80%.
hydrogen [CH(OAc)]. The tentative stereochemical as-
signments to 30a and 30b were made on the basis that
the signal for C(5)H in 30a is at lower field than in 30b
(δ 3.14 versus 2.78). Similar arguments were used in the
case of 31b and 31c to make the tentative assignments
shown.47 The epimers of 32a and 33a were not separated,
and no stereochemical assignments were made for these
1H NMR measurements: Compound 29a has signals
centered at δ 3.14 [C(5)H] and 4.57 [C(1)H], while the
corresponding values for 29b are δ 2.71 [C(5)H] and 4.15
[C(1)H]. The signal at δ 4.15 has larger J values than
that at 4.57, as expected for an axial hydrogen. The
acetate derived from 29a has only small couplings (2.8
Hz) for the C(1)H signal, corresponding to an equatorial
(47) The sensitivity of the ratio 31a :31b:31c to changes in reaction
conditions is difficult to understand. We did not monitor the purity of
the Me3SiOSO2CF3 in these experiments.

D-myo-Inositol 1,4,5-Tris(dihydrogen phosphate)
J . Org. Chem., Vol. 64, No. 12, 1999 4403
Sch em e 9a
with cold (4 °C) aqueous hydrochloric acid (0.5 M, 2 × 50 mL),
saturated aqueous NaHCO3 (1 × 50 mL), and brine (1 × 50
mL), dried, and evaporated. Flash chromatography of the
residue over silica gel (6 × 24 cm), using 2:8 EtOAc-hexane,
gave diols 9 (14.62 g, 80%) as a pure (1H NMR, 400 MHz),
yellow solid, which was a mixture of epimers: mp 47-52 °C;
[R]D ) 28.41 (c 1.45, CHCl3); FTIR (CHCl3 cast) 3463 (br) cm-1
;
1H NMR (CDCl3, 400 MHz) δ 2.15 (d, J ) 9.0 Hz, 0.64 H),
2.37 (d, J ) 0.9 Hz, 0.64 H), 2.42 (d, J ) 2.1 Hz, 0.36 H), 2.54
(d, J ) 2.3 Hz, 0.36 H), 3.28-3.43 (m, 3 H), 3.50-3.80 (m, 3
H), 4.02-4.20 (m, 1 H), 4.22-4.40 (m, 1 H), 4.75-4.82 (m, 1
H), 4.89-4.95 (m, 2 H), 5.20-5.25 (m, 1 H), 5.28-5.35 (m, 1
H), 5.89-6.01 (m, 1 H), 7.18-7.55 (m, 20 H); 13C NMR (CDCl3,
100.6 MHz) δ 63.8 (t′), 64.0 (t′), 68.3 (t′), 70.0 (t′), 70.4 (d′),
71.3 (d′), 71.4 (d′), 72.5 (d′), 74.1 (d′), 74.3 (d′), 74.7 (t′), 75.0
(t′), 82.9 (d′), 83.9 (d′), 86.8 (s′), 97.3 (d′), 101.6 (d′), 117.9 (t′),
127.0 (d′), 127.8 (d′), 127.9 (d′), 128.0 (d′), 128.5 (d′), 128.6 (d′),
133.7 (d′), 133.8 (d′), 138.6 (s′), 143.7 (s′), 143.8 (s′); exact mass
a
(i) MeMgBr, Et2O, 0 °C, 2 h, 90%; (ii) PCC, 3 Å molecular
sieves, CH2Cl2, 30 min, 92%.
Sch em e 10
(HR electrospray) m/z calcd for
575.240959, found 575.241310. Anal. Calcd for C35H36O6: C,
76.06; H, 6.57. Found: C, 75.82; H, 6.64.
C35H36NaO6 (M + Na)
2-P r op en yl 2,4-Bis-O-[(4-m eth oxyp h en yl)m eth yl]-3-O-
(p h en ylm et h yl)-6-O-(t r ip h en ylm et h yl)-D-glu cop yr a n o-
sid e (10). NaH (80% dispersion in oil, 10.0 g, 333.0 mmol) was
added portionwise to a stirred and cooled (0 °C) solution of
diols 9 (30.02 g, 54.38 mmol) in THF (450 mL) over 5 min.
The mixture was stirred (Ar atmosphere) for 30 min, and then
p-methoxybenzyl chloride (45.0 mL, 333.0 mmol) was added
neat in one portion by syringe. Stirring was continued at 0 °C
for 15 min. The cold bath was removed, and the solution was
allowed to warm to room temperature and then refluxed for
24 h. The mixture was cooled to 0 °C, and the excess of NaH
was carefully decomposed by addition of MeOH (ca. 50 mL).
The mixture was filtered through a pad (5 × 4 cm) of Celite
which was rinsed with Et2O (ca. 200 mL), and the solvent was
evaporated. Flash chromatography of the residue over silica
gel (6 × 35 cm), using 1.5:8.5 to 2:8 EtOAc-hexane, gave 10
(39.37 g, 91%) as a pure (1H NMR, 400 MHz), off-white solid,
which was a mixture of epimers: mp 41-43 °C; [R]D ) 8.8 (c
2.07, CHCl3); FTIR (CHCl3 cast) unexceptional; 1H NMR
(CDCl3, 400 MHz) δ 3.15-3.25 (m, 1 H), 3.35-3.50 (m, 1 H),
3.53-3.64 (m, 2 H), 3.73-3.87 (m, including singlets at δ 3.76,
3.77, 3.81 and 3.83, 7 H), 3.92-3.99 (m, 0.65 H), 4.05-4.12
(m, 0.65 H), 4.20-4.31 (m, 2.05 H), 4.46-4.56 (m, 0.65 H),
4.56-4.83 (m, 4 H), 4.86-4.98 (m, 2 H), 5.21-5.46 (m, 2 H),
5.92-6.13 (m, 1 H), 6.66-6.90 (m, 6 H), 7.21-7.41 (m, 16 H),
7.45-7.55 (m, 6 H); 13C NMR (CDCl3, 100.6 MHz) δ 55.2 (q′),
55.6 (q′), 62.5 (t′), 62.6 (t′), 68.0 (t′), 70.1 (t′), 70.5 (d′), 72.8
(t′), 74.6 (t′), 75.9 (t′), 77.6 (d′), 77.9 (d′), 79.9 (d′), 82.2 (d′),
82.3 (d′), 84.8 (d′), 86.3 (s′), 86.4 (s′), 95.3 (d′), 102.8 (d′), 113.6
(d′), 113.8 (d′), 117.3 (t′), 118.2 (t′), 126.8 (d′), 126.9 (d′), 127.5
(d′), 127.6 (d′), 127.8 (d′), 128.0 (d′), 128.1 (d′), 128.3 (d′), 128.4
(d′), 128.9 (d′), 129.2 (d′), 129.6 (d′), 129.8 (d′), 129.9 (d′), 130.1
(s′), 130.2 (s′), 130.5 (s′), 130.8 (s′), 133.9 (d′), 134.3 (d′), 138.7
(s′), 138.9 (s′), 144.0 (s′), 144.3 (s′), 159.2 (s′), 159.2 (s′), 159.3
(s′), 159.4 (s′); exact mass (HR electrospray) m/z calcd for
compounds or for 34a , which was also obtained as a
chromatographically inseparable mixture.
We interpret the formation of 31d and 33b according
to the process of Scheme 10, where the stereochemistry
shown for the intermediate allenic silanes is arbitrary.
Our experiments with 5 (Scheme 1), 27 (Table 1), and
2 (R ) H) show that the silicon unit is needed for the
cyclization to occur. Possibly, the transition state has a
partial positive charge on C(7) (see structure 5 for
numbering), and this is stabilized by the silicon unit,20
but it is not clear why in some cases (see Table 1) a proton
is lost rather than the trimethylsilyl group. Likewise, the
stereochemical outcomesOH and SiMe3 syn and OH
axialsfor 5 and 27 is also difficult to interpret.
The loss of the silicon unit in those cases where best
yields are obtained by use of TBAF (Table 1, entries 4,
7, and 9) is expected, as the process would be initiated
by F- attack on silicon.27
Although the mechanistic details are unclear, the
cyclization of ω-formyl propargyl silanes represents a
route to carbocycles that incorporate an allene48 append-
age; in favorable cases the yield is good and the reaction
can be highly stereoselective.
Exp er im en ta l Section
Gen er a l P r oced u r es. Unless stated to the contrary, the
general procedures used previously49 were followed. Optical
rotations were measured at room temperature.
C
51H52NaO8 (M + Na) 815.355989, found 815.355280. Anal.
Calcd for C51H52O8: C, 77.25; H, 6.61. Found: C, 77.39; H,
6.56.
The symbols s′, d′, t′, and q′ used for 13C NMR signals
indicate zero, one, two, or three attached hydrogens, respec-
tively. Where the number of 13C NMR signals is less than
expected, we assume that this is due to overlap of signals.
2-P r open yl 3-O-(P h en ylm eth yl)-6-O-(tr iph en ylm eth yl)-
D-glu cop yr a n osid e (9). Dry pyridine (130 mL) was added to
a dry 250 mL round-bottomed flask charged with triol 821,50
(10.32 g, 33.25 mmol), Ph3CCl (13.91 g, 49.89 mmol), and
DMAP (400 mg, 3.27 mmol). The mixture was heated at 110
°C for 8 h, cooled to room temperature, and evaporated. The
residue was dissolved in CH2Cl2 (200 mL), washed sequentially
2,4-Bis-O-[(4-m eth oxyp h en yl)m eth yl]-3-O-(p h en ylm e-
th yl)-6-O-(tr iph en ylm eth yl)-D-glu copyr an ose (11). (a) Use
of t-Bu OK. DMSO (45 mL) was added in one portion to a
suspension of 10 (9.68 g, 12.2 mmol) and t-BuOK (2.73 g, 24.4
mmol). The mixture was stirred to dissolve the solids and then
heated at 100 °C for 1 h. The solution was allowed to cool to
room temperature and then poured into water (150 mL). The
orange mixture was extracted with CH2Cl2 (4 × 50 mL), and
the combined organic extracts were washed with water (1 ×
40 mL) and brine (1 × 30 mL) and evaporated. The solid
residue was dissolved in 8:1 acetone-water (40 mL), and HgO
(3.96 g, 18.3 mmol) was added to the solution (stirring). A
solution of HgCl2 (4.97 g, 18.3 mmol) in 8:1 acetone-water
(15 mL) was added dropwise, and stirring was continued for
4 h at room temperature. The mixture was filtered through a
pad (5 × 4 cm) of Celite, and the pad was rinsed with acetone
(48) Chemistry of allenes. Schuster, H. F.; Coppola, G. M. Allenes
in Organic Synthesis; Wiley: New York, 1984.
(49) Clive, D. L. J .; Wickens, P. L.; Sgarbi, P. W. M. J . Org. Chem.
1996, 61, 7426-7437.
(50) Cf. Freudenberg, K.; Hochstetten, H. v.; Engels, H. Ber. 1925,
58, 666-671.

4404 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
(50 mL). The combined filtrates were evaporated, and the
residue was dissolved in CH2Cl2 (100 mL), washed with 20%
aqueous NaI (1 × 100 mL) and brine (1 × 40 mL), dried, and
evaporated. Flash chromatography of the residue over silica
gel (6 × 20 cm), using 1.5:8.5 EtOAc-hexane, gave 11 (8.07 g,
88%) as a pure (1H NMR, 400 MHz), off-white solid, which
was a mixture of epimers: mp 61-63 °C; [R]D ) 7.8 (c 0.32,
777.340650. Anal. Calcd for C48H50O8: C, 76.37; H, 6.68.
Found: C, 76.15; H, 6.83.
1-O-[(1,1-Dim et h ylet h yl)d im et h ylsilyl]-2,4-b is-O-[(4-
m eth oxyp h en yl)m eth yl]-3-O-(p h en ylm eth yl)-6-O-(tr ip h -
en ylm eth yl)-D-glu citol (13). Et3N (4.05 mL, 29.0 mmol) was
added in one portion to a stirred solution of 12 (14.0 g, 18.6
mmol), DMAP (570 mg, 4.66 mmol), and t-BuMe2SiCl (4.18 g,
27.7 mmol) in CH2Cl2 (400 mL). Stirring was continued for 16
h, and the mixture was diluted with CH2Cl2 (200 mL) and
washed with brine (2 × 200 mL). The organic extracts were
dried and evaporated. Flash chromatography of the residue
over silica gel (6 × 25 cm), using 1:10 EtOAc-hexane, gave
13 (16.0 g, 99%) as a pure (1H NMR, 400 MHz), gummy solid:
1
CHCl3); FTIR (CDCl3 cast) 3428 (br) cm-1; H NMR (CDCl3,
400 MHz) δ 2.86 (d, J ) 2.1 Hz, 0.27 H), 3.07 (d, J ) 5.3 Hz,
0.64 H), δ 3.16-3.24 (m, 1 H), 3.40-3.47 (m, 1.35 H), 3.50-
3.66 (m, 2 H), 3.67-3.81 (m, including singlets at δ 3.74, 3.78,
3.81, 7 H), 3.84-4.02 (m, 0.65 H), 4.25 (d, J ) 10.1 Hz, 1 H),
4.57-4.63 (m, 1 H), 4.64-4.93 (m, 4.65 H), 5.30 (dd, J ) 2.8,
2.8 Hz, 0.28 H), 6.65-6.75 (m, 4 H), 6.80-6.87 (m, 2 H), 7.18-
7.39 (m, 16 H), 7.41-7.51 (m, 6 H); 13C NMR (CD3COCD3, 75.5
MHz) δ 55.4 (q′), 63.7 (t′), 63.8 (t′), 70.9 (d′), 72.5 (t′), 74.5 (t′),
74.8 (t′), 74.8 (t′), 75.3 (d′), 75.8 (t′), 75.9 (t′), 78.6 (d′), 78.7
(d′), 81.5 (d′), 82.6 (d′), 84.3 (d′), 85.6 (d′), 86.9 (s′), 91.5 (s′),
98.6 (d′), 114.1 (d′), 114.3 (d′), 114.4 (d′), 127.7 (d′), 128.0 (d′),
128.4 (d′), 128.5 (d′), 128.9 (d′), 129.6 (d′), 130.1 (d′), 130.2 (d′),
130.3 (d′), 130.3 (d′), 131.3 (s′), 131.4 (s′), 131.8 (s′), 132.1 (s′),
140.1 (s′), 140.3 (s′), 145.0 (s′), 145.0 (s′), 159.9 (s′), 160.0 (s′),
[R]D ) 3.93 (c 1.5, CHCl3); FTIR (CH2Cl2 cast) 3510 (br) cm-1
;
1H NMR (CDCl3, 400 MHz) δ 0.03 (s, 6 H), 0.88 (s, 9 H), 3.12
(d, J ) 4.8 Hz, 1 H), 3.27 (dd, J ) 9.5, 5.7 Hz, 1 H), 3.34 (dd,
J ) 9.8, 3.7 Hz, 1 H), 3.65-3.84 (m, including singlets at δ
3.78 and 3.79, 11 H), 3.95-4.04 (m, 1 H), 4.34 (d, J ) 11.0 Hz,
1 H), 4.38 (d, J ) 11.0 Hz, 1 H), 4.53 (d, J ) 11.4 Hz, 1 H),
4.55 (d, J ) 11.2, 1 H), 4.60 (d, J ) 11.4 Hz, 1 H), 4.64 (d, J )
11.2 Hz, 1 H), 6.73-6.80 (m, 2 H), 6.82-6.87 (m, 2 H), 6.95-
7.02 (m, 2 H), 7.21-7.35 (m, 16 H), 7.42-7.50 (m, 6 H); 13C
NMR (CDCl3, 75.5 MHz) δ -5.4 (q′), 18.2 (s′), 26.0 (q′), 55.2
(q′), 63.1 (t′), 65.0 (t′), 71.2 (d′), 72.5 (t′), 72.8 (t′), 74.0 (t′), 76.7
(d′), 78.3 (d′), 79.4 (d′), 86.6 (s′), 113.6 (d′), 113.7 (d′), 127.0
(d′), 127.7 (d′), 127.8 (d′), 128.3 (d′), 128.4 (d′), 128.8 (d′), 129.6
(d′), 129.7 (d′), 130.3 (s′), 130.7 (s′), 138.2 (s′), 144.0 (s′), 159.1
(s′); exact mass (HR electrospray) m/z calcd for C54H64NaO8Si
(M + Na) 891.426818, found 891.426920. Anal. Calcd for
160.1 (s′); exact mass (HR electrospray) m/z calcd for C48H48
-
NaO8 (M + Na) 775.324689, found 775.324710. Anal. Calcd
for C48H48O8: C, 76.57; H, 6.42. Found: C, 76.18; H, 6.41.
(b) Use of Wilk in son ’s ca ta lyst. (Ph3P)3RhCl (800.0 mg,
0.8464 mmol) and DABCO (398.0 mg, 3.55 mmol) were added
sequentially to a stirred solution of 10 (3.75 g, 4.73 mmol) in
a mixture of PhH (45 mL), EtOH (105 mL, 98%) and water
(15 mL). The mixture was stirred at room temperature for 1
h and then refluxed, open to the atmosphere, for 36 h. The
resulting brown solution was evaporated, and the residue was
dissolved in 9:1 acetone-water (150 mL). HgCl2 (14.4 g, 53.04
mmol) and yellow HgO (40 mg, 0.185 mmol) were added, and
the mixture was stirred at room temperature for 12 h,
evaporated, diluted with CH2Cl2 (100 mL), and filtered through
a pad (6 × 6 cm) of Celite. The pad was rinsed with CH2Cl2
(200 mL), and the combined filtrates were washed with 20%
aqueous NaI (1 × 60 mL). The aqueous layer was extracted
with CH2Cl2 (1 × 40 mL), and the combined organic extracts
were washed with brine (1 × 20 mL), dried, and evaporated.
Flash chromatography of the residue over silica gel (4 × 31
cm), using EtOAc-hexane mixtures (15% to 30% EtOAc), gave
11 (3.27 g, 92%) as a pure (1H NMR, 400 MHz) solid, which
was a mixture of epimers: mp 58-64 °C; [R]D ) 7.8 (c 0.32,
CHCl3).
C
54H64O8Si: C, 73.24; H, 7.42. Found: C, 73.32; H, 7.46.
1-O-[(1,1-Dim et h ylet h yl)d im et h ylsilyl]-2,4-b is-O-[(4-
m et h oxyp h en yl)m et h yl]-3,5-b is-O-(p h en ylm et h yl)-6-O-
(tr ip h en ylm eth yl)-D-glu citol (14). NaH (80% dispersion in
oil, 1.40 g, 46.0 mmol) was added in five portions to a stirred
and cooled (0 °C) solution of 13 (16.0 g, 18.4 mmol) in THF
(500 mL). The resulting mixture was stirred for 30 min, and
then BnBr (5.50 mL, 46.0 mmol) was added neat in one portion
by syringe. The cold bath was removed, and the mixture was
stirred for 1 h and then refluxed for 24 h. The resulting
mixture was cooled (0 °C), quenched with MeOH (50 mL),
diluted with brine (200 mL), and extracted with Et2O (3 × 300
mL). The combined organic extracts were washed with brine
(1 × 200 mL), dried, and evaporated. Flash chromatography
of the residue over silica gel (6 × 35 cm), using 5:95 to 1:10
EtOAc-hexane, gave 14 (17.0 g, 96%) as a pure (1H NMR, 400
MHz), thick syrup: [R]D ) 5.71 (c 2.38, CHCl3); FTIR (CH2Cl2
cast) unexceptional; 1H NMR (CDCl3, 400 MHz) δ -0.02 (d, J
) 2.5 Hz, 6 H), 0.86 (s, 9 H), 3.37 (dd, J ) 10.4, 5.6 Hz, 1 H),
3.56 (dd, J ) 10.3, 2.6 Hz, 1 H), 3.60-3.70 (m, 3 H), 3.71-
3.80 (m, including singlets at δ 3.74 and 3.76, 8 H), 4.01 (dd,
J ) 5.7, 5.7 Hz, 1 H), 4.35 (d, J ) 11.6 Hz, 1 H), 4.43-4.72
(m, 7 H), 6.68-6.76 (m, 4 H), 6.92-6.97 (m, 2 H), 7.16-7.32
(m, 21 H), 7.41-7.46 (m, 6 H); 13C NMR (CDCl3, 100.6 MHz)
δ -5.4 (q′), 18.2 (s′), 26.0 (q′), 55.2 (q′), 63.2 (t′), 63.9 (t′), 72.2
(t′), 72.8 (t′), 73.5 (t′), 74.5 (t′), 78.3 (d′), 78.6 (d′), 79.7 (d′),
80.2 (d′), 86.8 (s′), 113.5 (d′), 113.7 (d′), 126.9 (d′), 127.3 (d′),
127.8 (d′), 128.1 (d′), 128.2 (d′), 128.9 (d′), 129.5 (d′), 129.7 (d′),
130.9 (s′), 131.1 (s′), 138.8 (s′), 138.9 (s′), 144.1 (s′), 158.9 (s′),
2,4-Bis-O-[(4-m eth oxyp h en yl)m eth yl]-3-O-(p h en ylm e-
th yl)-6-O-(tr ip h en ylm eth yl)-D-glu citol (12). LiAlH4 (1.41
g, 37.2 mmol) was added in five portions to a stirred and cooled
(0 °C) solution of 11 (10.27 g, 13.65 mmol) in THF (200 mL).
The cold bath was removed, and stirring was continued for 4
h. The solution was recooled to 0 °C, and water (1.4 mL), 15%
aqueous NaOH (1.4 mL), and water (4.2 mL) were added
sequentially. The cold bath was removed, and the solution was
stirred for 30 min and then filtered through a pad (6 × 6 cm)
of Celite. The pad was rinsed with Et2O (500 mL), and the
combined filtrates were evaporated. Flash chromatography of
the residue over silica gel (6 × 20 cm), using 1:3 to 4:6 EtOAc-
hexane, gave 12 (9.64 g, 93%) as a pure (1H NMR, 400 MHz),
white solid: mp 44-46 °C; [R]D ) -6.78 (c 1.15, CHCl3); FTIR
(CHCl3 cast) 3460 (br) cm-1; 1H NMR (CDCl3, 400 MHz) δ 2.12
(t, J ) 6.5 Hz, 1 H), 3.12 (d, J ) 5.1 Hz, 1 H), 3.28 (dd, J )
9.5, 5.3 Hz, 1 H), 3.36 (dd, J ) 9.5, 4.3 Hz, 1 H), 3.50-3.57
(m, 1 H), 3.65-3.72 (m, 1 H), 3.73-3.86 (m, including singlets
at δ 3.78, 3.79, 9 H), 4.01-4.08 (m, 1 H), 4.33 (d, J ) 11.0 Hz,
1 H), 4.35 (d, J ) 11.0 Hz, 1 H), 4.48-4.60 (m, 3 H), 4.67 (d,
J ) 11.3 Hz, 1 H), 6.75-6.80 (m, 2 H), 6.81-6.85 (m, 2 H),
6.97-7.03 (m, 2 H), 7.17-7.34 (m, 16 H), 7.42-7.49 (m, 6 H);
13C NMR (CD3COCD3, 75.5 MHz) δ 55.5 (q′), 62.5 (t′), 66.5 (t′),
71.8 (d′), 73.0 (t′), 73.3 (t′), 74.9 (t′), 79.1 (d′), 80.1 (d′), 81.0
(d′), 87.3 (s′), 114.2 (d′), 114.3 (d′), 127.7 (d′), 128.1 (d′), 128.5
(d′), 128.6 (d′), 129.0 (d′), 129.7 (d′), 130.2 (d′), 131.6 (s′), 132.0
(s′), 140.0 (s′), 145.3 (s′), 160.0 (s′); exact mass (HR electro-
spray) m/z calcd for C48H50NaO8 (M + Na) 777.340339, found
159.0 (s′); exact mass (HR electrospray) m/z calcd for C61H70
-
NaO8Si (M + Na) 981.473768 found 981.474400. Anal. Calcd
for C61H70O8Si: C, 76.38; H, 7.36. Found: C, 76.50; H, 7.51.
2,4-Bis-O-[(4-m et h oxyp h en yl)m et h yl]-3,5-b is-O-(p h e-
n ylm eth yl)-6-O-(tr ip h en ylm eth yl)-D-glu citol (15). TBAF
(1 M in THF, 17.75 mL, 17.75 mmol) was added in one portion
by syringe to a stirred solution of 14 (16.67 g, 17.40 mmol) in
THF (340 mL). The mixture was stirred for 4 h at room
temperature, diluted with Et2O (150 mL), and washed with
water (1 × 150 mL). The aqueous layer was extracted with
Et2O (2 × 90 mL), and the combined organic extracts were
washed with brine (1 × 150 mL), dried, and evaporated. Flash
chromatography of the residue over silica gel (6 × 35 cm), using
2:8 to 3:7 EtOAc-hexane, gave 15 (13.50 g, 92%) as a pure
(1H NMR, 400 MHz), white solid: mp 41-43 °C; [R]D ) -11.90
(c 2.66, CH2Cl2); FTIR (CH2Cl2 cast) 3476 cm-1
;
1H NMR
(CDCl3, 400 MHz) δ 2.12 (br s, 1 H), 3.41 (dd, J ) 11.3, 3.8

D-myo-Inositol 1,4,5-Tris(dihydrogen phosphate)
J . Org. Chem., Vol. 64, No. 12, 1999 4405
Hz, 1 H), 3.51-3.61 (m, 2 H), 3.61-3.79 (m, including singlets
at δ 3.74 and 3.77, 8 H), 3.79-3.88 (m, 2 H), 4.08 (dd, J ) 4.4,
4.4 Hz, 1 H), 4.42 (d, J ) 11.3 Hz, 1 H), 4.45-4.55 (m, 4 H),
4.61 (br s, 2 H), 4.75 (d, J ) 11.3 Hz, 1 H), 6.75 (d, J ) 8.0 Hz,
2 H), 6.80 (d, J ) 8.0 Hz, 2 H), 7.00 (d, J ) 8.5 Hz, 2 H), 7.16-
7.35 (m, 21 H), 7.43-7.50 (m, 6 H); 13C NMR (CDCl3, 100.6
MHz) δ 55.2 (q′), 61.9 (t′), 63.2 (t′), 72.2 (t′), 73.3 (t′), 74.4 (t′),
78.0 (d′), 78.8 (d′), 79.1 (d′), 79.3 (d′), 86.9 (s′), 113.5 (d′), 113.8
(d′), 127.0 (d′), 127.4 (d′), 127.6 (d′), 127.8 (d′), 128.2 (d′), 128.3
(d′), 128.8 (d′), 129.6 (d′), 129.7 (d′), 130.4 (s′), 130.5 (s′), 138.4
(s′), 138.7 (s′), 144.0 (s′), 159.1 (s′), 159.2 (s′); exact mass (HR
electrospray) m/z calcd for C55H56NaO8 (M + Na) 867.387289,
found 867.387600. Anal. Calcd for C55H56O8: C, 78.17; H 6.68.
Found: C, 78.14; H, 6.74.
128.9 (d′), 129.7 (s′), 129.7 (d′), 129.9 (d′), 130.8 (s′), 137.6 (d′),
138.3 (s′), 138.8 (s′), 144.1 (s′), 159.0 (s′), 159.4 (s′); exact mass
(HR electrospray) m/z calcd for C56H5479Br81BrNaO7 (M + Na)
1021.211350, found 1021.211970. Anal. Calcd for C56H54O7-
Br2: C, 67.34; H, 5.45. Found: C, 67.40; H, 5.41.
(b) 1,2-Did eoxy-3,5-bis-O-[(4-m eth oxyp h en yl)m eth yl]-
4,6-bis-O-(p h en ylm eth yl)-7-O-(tr ip h en ylm eth yl)-D-glu co-
h ep t-1-yn itol (17). n-BuLi (2.5 M in hexane, 1.30 mL, 3.25
mmol) was added dropwise to a stirred and cooled (-78 °C)
solution of the above dibromo alkene (1.62 g, 1.62 mmol) in
THF (40 mL). Stirring at -78 °C was continued for 2 h, and
then water (2.0 mL) was added. The cold bath was removed,
and stirring was continued for 30 min. The mixture was
diluted with Et2O (20 mL), washed with brine (2 × 10 mL),
dried, and evaporated. Flash chromatography of the residue
over silica gel (1.5 × 25 cm), using 2:8 EtOAc-hexane, gave
17 (1.15 g, 85%) as a pure (1H NMR, 300 MHz), white solid:
mp 43-45 °C; [R]D ) 23.4 (c 0.65, CH2Cl2); FTIR (CH2Cl2 cast)
2,4-Bis-O-[(4-m et h oxyp h en yl)m et h yl]-3,5-b is-O-(p h e-
n ylm eth yl)-6-O-(tr ip h en ylm eth yl)-D-glu cose (16). DMSO
(0.91 mL, 12.8 mmol) was added dropwise to a stirred and
cooled (-78 °C) solution of (COCl)2 (0.84 mL, 9.62 mmol) in
CH2Cl2 (40 mL). After 20 min 15 (2.69 g, 3.19 mmol) in CH2-
Cl2 (7 mL plus 3 mL as a rinse) was added by syringe over 1
min. Stirring was continued for 30 min at -78 °C, and then
Et3N (3.65 mL, 26.2 mmol) was added dropwise over ca. 2 min.
The cold bath was removed, and stirring was continued for 6
h. The mixture was diluted with water (2 mL) and CH2Cl2 (50
mL), washed with brine (1 × 20 mL), dried, and evaporated.
Flash chromatography of the residue over silica gel (3 × 25
cm), using 1:9 to 2:8 EtOAc-hexane, gave 16 (2.39 g, 89%) as
a pure (1H NMR, 400 MHz), white solid: mp 46-48 °C; [R]D
1
3281 cm-1; H NMR (CDCl3, 300 MHz) δ 2.64 (d, J ) 2.4 Hz,
1 H), 3.24 (dd, J ) 10.2, 4.7 Hz, 1 H), 3.63 (dd, J ) 10.2, 2.3
Hz, 1 H), 3.73-3.87 (m, including singlets at δ 3.77 and 3.78,
7 H), 4.04 (dd, J ) 7.5, 3.2 Hz, 1 H), 4.26-4.42 (m, 3 H), 4.44-
4.56 (m, 4 H), 4.72 (d, J ) 11.6 Hz, 1 H), 4.79 (d, J ) 11.2 Hz,
1 H), 4.89 (d, J ) 11.6 Hz, 1 H), 6.65-6.75 (m, 2 H), 6.77-
6.93 (m, 4 H), 7.14-7.38 (m, 21 H), 7.38-7.52 (m, 6 H); 13C
NMR (CDCl3, 75.5 MHz) δ 55.3 (q′), 62.7 (t′), 71.0 (d′), 71.0
(t′), 71.9 (t′), 74.2 (t′), 74.8 (t′), 76.3 (s′), 78.4 (d′), 78.5 (d′), 81.0
(d′), 81.1 (s′), 86.7 (s′), 113.5 (d′), 113.8 (d′), 126.9 (d′), 127.3
(d′), 127.3 (d′), 127.8 (d′), 128.1 (d′), 128.3 (d′), 128.9 (d′), 129.6
(s′), 129.7 (d′), 129.9 (d′), 130.8 (s′), 138.7 (s′), 139.0 (s′), 144.1
(s′), 159.0 (s′), 159.3 (s′); exact mass (HR electrospray) m/z calcd
for C56H54NaO7 (M + Na) 861.376724, found 861.377150.
1,2,3-Tr id eoxy-4,6-b is-O-[(4-m et h oxyp h en yl)m et h yl]-
5,7-bis-O-(p h en ylm eth yl)-1-(tr im eth ylsilyl)-8-O-(tr ip h e-
n ylm eth yl)-D-glu co-oct-2-yn itol (18). n-BuLi (2.5 M in
hexane, 0.61 mL, 1.53 mmol) was added over 30 s to a stirred
and cooled (-78 °C) solution of 17 (1.15 g, 1.37 mmol) in THF
(35 mL). Stirring at -78 °C was continued for 1 h, and then
Me3SiCH2OSO2CF3 (0.35 mL, 1.75 mmol) and HMPA (1.0 mL,
5.75 mmol) were added, each in one portion. The cold bath
was removed, and stirring was continued for 8 h. The mixture
was diluted with Et2O (40 mL) and washed with brine (1 ×
20 mL). The aqueous layer was extracted with Et2O (2 × 20
mL), and the combined organic extracts were dried and
evaporated. Flash chromatography of the residue over silica
gel (1.5 × 25 cm), using 1:9 EtOAc-hexane, gave 18 (1.04 g,
82%) as a pure (1H NMR, 400 MHz), gummy solid: [R]D ) 19.4
) 0.600 (c 1.50, CHCl3); FTIR (CH2Cl2 cast) 1727 cm-1 1H
;
NMR (CDCl3, 400 MHz) δ 3.28 (dd, J ) 10.3, 4.7 Hz, 1 H),
3.64 (dd, J ) 10.3, 2.7 Hz, 1 H), 3.70-3.79 (m, including
singlets at δ 3.72 and 3.74, 7 H), 3.82 (d, J ) 5.2 Hz, 1 H),
4.02-4.10 (m, 2 H), 4.24 (d, J ) 10.3 Hz, 1 H), 4.30-4.43 (m,
4 H), 4.49 (d, J ) 11.6 Hz, 1 H), 4.71 (dd, J ) 21.9, 11.6 Hz,
2 H), 6.62-6.65 (m, 2 H), 6.75-6.82 (m, 4 H), 7.04-7.10 (m, 2
H), 7.15-7.23 (m, 14 H), 7.23-7.36 (m, 5 H), 7.40-7.45 (m, 6
H), 9.64 (s, 1 H); 13C NMR (CDCl3, 75.5 MHz) δ 55.2 (q′), 55.3
(q′), 62.7 (t′), 72.2 (t′), 72.8 (t′), 73.1 (t′), 74.0 (t′), 76.6 (d′), 78.8
(d′), 80.0 (d′), 80.8 (d′), 86.9 (s′), 113.4 (d′), 113.9 (d′), 127.0
(d′), 127.3 (d′), 127.5 (d′), 127.9 (d′), 128.1 (d′), 128.4 (d′), 128.9
(d′), 129.6 (s′), 129.7 (d′), 130.0 (s′), 130.2 (d′), 137.9 (s′), 138.6
(s′), 144.0 (s′), 159.0 (s′), 159.5 (s′), 201.1 (d′); exact mass (HR
electrospray) m/z calcd for C55H54NaO8 (M + Na) 865.371639,
found 865.371920. Anal. Calcd for C55H54O8: C, 78.36; H, 6.46.
Found: C, 78.01; H, 6.52.
1,2-Did eoxy-3,5-bis-O-[(4-m eth oxyp h en yl)m eth yl]-4,6-
bis-O-(ph en ylm eth yl)-7-O-(tr iph en ylm eth yl)-D-glu co-h ept-
1-yn it ol (17). (a ) 1,1-Dib r om o-1,2-d id eoxy-3,5-b is-O-[(4-
m et h oxyp h en yl)m et h yl]-4,6-b is-O-(p h en ylm et h yl)-7-O-
(tr ip h en ylm eth yl)-D-glu co-h ep t-1-en itol. A solution of CBr4
(1.36 g, 4.10 mmol) in CH2Cl2 (20 mL) was added at a fast
dropwise rate to a stirred and cooled (-20 °C) solution of Ph3P
(1.07 g, 4.08 mmol) in CH2Cl2 (20 mL). The resulting mixture
was stirred for 15 min at -20 °C, and then a solution of 16
(1.73 g, 2.05 mmol) and Et3N (0.28 mL, 2.05 mmol) in CH2Cl2
(20 mL) was added dropwise at -60 °C. The cold bath was
removed, and the solution was allowed to warm to room
temperature. After 30 min, the mixture was filtered through
a pad (3 × 3 cm) of flash chromatography silica gel which was
rinsed with Et2O (50 mL), and the combined filtrates were
evaporated. Flash chromatography of the residue over silica
gel (1.5 × 25 cm), using 1:9 EtOAc-hexane, gave the required
dibromo alkene (1.70 g, 83%) as a pure (1H NMR, 300 MHz),
white solid: mp 39-41 °C; [R]D ) 17.1 (c 1.52, CHCl3); FTIR
(CHCl3 cast) unexceptional; 1H NMR (CDCl3, 300 MHz) δ
3.36-3.46 (m, 2 H), 3.65-3.75 (m, including singlet at δ 3.73,
5 H), 3.78 (s, 3 H), 4.07 (dd, J ) 5.5, 5.5 Hz, 1 H), 4.22 (dd, J
) 8.4, 4.6 Hz, 1 H), 4.31 (d, J ) 11.4 Hz, 1 H), 4.41 (d, J )
11.7 Hz, 1 H), 4.51-4.64 (m, 5 H), 4.70 (d, J ) 11.6 Hz, 1 H),
6.60 (d, J ) 8.5 Hz, 1 H), 6.72 (d, J ) 8.5 Hz, 2 H), 6.81 (d, J
) 9.0 Hz, 2 H), 6.99 (d, J ) 9.0 Hz, 2 H), 7.18-7.36 (m, 21 H),
7.40-7.50 (m, 6 H); 13C NMR (CDCl3, 75.5 MHz) δ 55.2 (q′),
63.2 (t′), 70.9 (t′), 72.4 (t′), 73.9 (t′), 75.0 (t′), 78.6 (d′), 79.0
(d′), 79.6 (d′), 79.7 (d′), 86.7 (s′), 92.3 (s′), 113.5 (d′), 113.8 (d′),
126.9 (d′), 127.4 (d′), 127.6 (d′), 127.8 (d′), 128.2 (d′), 128.3 (d′),
(c 1.17, CH2Cl2); FTIR (CH2Cl2 cast) 2212 cm-1 1H NMR
;
(CDCl3, 400 MHz) δ 0.14 (s, 9 H), 1.64 (dd, J ) 3.2, 2.2 Hz, 2
H), 3.21 (dd, J ) 10.3, 4.7 Hz, 1 H), 3.60 (dd, J ) 10.3, 2.2 Hz,
1 H), 3.75 (s, 3 H), 3.76 (s, 3 H), 3.80-3.85 (m, 1 H), 3.98 (dd,
J ) 8.0, 2.9 Hz, 1 H), 4.26 (d, J ) 11.5 Hz, 1 H), 4.29 (dd, J )
8.0, 2.9 Hz, 1 H), 4.35 (d, J ) 10.5 Hz, 1 H), 4.45-4.52 (m, 4
H), 4.69 (d, J ) 11.6 Hz, 1 H), 4.77 (d, J ) 11.1 Hz, 1 H), 4.91
(d, J ) 11.7 Hz, 1 H), 6.65-6.69 (m, 2 H), 6.75-6.81 (m, 2 H),
6.82-6.86 (m, 2 H), 7.13-7.32 (m, 21 H), 7.41-7.50 (m, 6 H);
13C NMR (CDCl3, 75.5 MHz) δ -1.8 (q′), 7.4 (t′), 55.2 (q′), 62.8
(t′), 70.6 (t′), 71.9 (s′), 71.9 (d′), 74.3 (t′), 74.7 (t′), 76.0 (t′), 78.5
(d′), 78.8 (d′), 81.7 (d′), 86.7 (s′), 86.8 (s′), 113.4 (d′), 113.7 (d′),
126.9 (d′), 127.1 (d′), 127.2 (d′), 127.2 (d′), 127.7 (d′), 128.0 (d′),
128.2 (d′), 128.9 (d′), 129.7 (d′), 129.8 (d′), 130.2 (s′), 130.9 (s′),
138.9 (s′), 139.4 (s′), 144.2 (s′), 158.9 (s′), 159.2 (s′); exact mass
(HR electrospray) m/z calcd for C60H64NaO7Si (M + Na)
947.431903, found 947.432090. Anal. Calcd for C60H64O7Si: C,
77.89; H, 6.97. Found: C, 77.81; H, 7.23.
1,2,3-Tr id eoxy-4,6-b is-O-[(4-m et h oxyp h en yl)m et h yl]-
5,7-bis-O-(p h en ylm eth yl)-1-(tr im eth ylsilyl)-D-glu co-oct-
2-yn itol (19). CSA (40.0 mg, 0.172 mmol) in MeOH (5 mL)
was added in one portion to a stirred solution of 18 (1.17 g,
1.27 mmol) in CH2Cl2 (50 mL). Stirring was continued for 36
h, Et3N (1 mL) was added, and the solution was evaporated.
Flash chromatography of the residue over silica gel (1.5 × 25
cm), using 2:8 EtOAc-hexane, gave 19 (0.82 g, 94%) as a pure
(1H NMR, 400 MHz) oil: [R]D ) 37.59 (c 3.20, CH2Cl2); FTIR
1
(CH2Cl2 cast) 3492, 2212 cm-1; H NMR (CDCl3, 400 MHz) δ

4406 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
0.13 (s, 9 H), 1.55 (d, J ) 2.5 Hz, 2 H), 2.07 (dd, J ) 7.5, 4.0
Hz, 1 H), 3.66-3.86 (m, including singlets at δ 3.78 and 3.79,
10 H), 4.15 (dd, J ) 7.0, 4.0 Hz, 1 H), 4.28 (d, J ) 11.7 Hz, 1
H), 4.43-4.49 (m, 3 H), 4.56 (d, J ) 11.6 Hz, 1 H), 4.64 (s, 2
H), 4.77 (d, J ) 11.2 Hz, 1 H), 4.93 (d, J ) 11.3 Hz, 1 H), 6.78-
6.84 (m, 4 H), 7.15-7.32 (m, 14 H); 13C NMR (CDCl3, 100.6
MHz) δ -1.9 (q′), 7.4 (t′), 55.2 (q′), 60.3 (t′), 70.5 (t′), 71.2 (t′),
71.6 (d′), 74.6 (t′), 74.9 (t′), 75.4 (s′), 79.0 (d′), 79.0 (d′), 81.5
(d′), 87.0 (s′), 113.6 (s′), 113.7 (s′), 127.3 (d′), 127.5 (d′), 127.6
(d′), 128.0 (d′), 128.1 (d′), 128.4 (d′), 129.7 (d′), 130.0 (s′), 130.6
(s′), 138.3 (s′), 138.9 (s′), 159.2 (s′); exact mass (HR electro-
spray) m/z calcd for C41H50NaO7Si (M + Na) 705.322353, found
705.321500.
6,7,8-Tr id eoxy-3,5-b is-O-[(4-m et h oxyp h en yl)m et h yl]-
2,4-bis-O-(p h en ylm eth yl)-8-(tr im eth ylsilyl)-L-gu lo-oct-6-
yn ose (5). DMSO (0.43 mL, 6.06 mmol) was added dropwise
to a stirred and cooled solution (-78 °C) of (COCl)2 (0.40 mL,
4.58 mmol) in CH2Cl2 (30 mL). After 20 min 19 (1.02 g, 1.50
mmol) in CH2Cl2 (10 mL) was added by syringe over 1 min.
Stirring was continued for 30 min at -78 °C, and then Et3N
(1.72 mL, 12.3 mmol) was added. After a further 30 min, the
cold bath was removed and stirring was continued for 6 h. The
mixture was diluted with water (5 mL) and CH2Cl2 (20 mL),
washed with brine (20 mL), dried, and evaporated. Flash
chromatography of the residue over silica gel (2 × 20 cm), using
1:10 to 2:8 EtOAc-hexane, gave 5 (0.94 g, 92%) as a pure (1H
NMR, 400 MHz) oil: [R]D ) 33.38 (c 1.33, CHCl3); FTIR (CH2-
Cl2, cast) 2212, 1733 cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.14
(s, 9 H), 1.56 (d, J ) 2.5 Hz, 2 H), 3.77 (s, 3 H), 3.78 (s, 3 H),
3.82 (dd, J ) 8.0, 4.5 Hz, 1 H), 4.02 (dd, J ) 5.0, 2.0 Hz, 1 H),
4.22-4.27 (m, 2 H), 4.40-4.58 (m, 6 H), 4.76 (d, J ) 11.7 Hz,
1 H), 4.90 (d, J ) 11.5 Hz, 1 H), 6.77-6.86 (m, 4 H), 7.15 (d,
J ) 9.0 Hz, 2 H), 7.18-7.34 (m, 12 H), 9.64 (d, J ) 2.0 Hz, 1
H); 13C NMR (CDCl3, 100.6 MHz) δ -1.8 (q′), 7.3 (t′), 55.3 (q′),
70.6 (t′), 71.3 (d′), 72.3 (t′), 74.2 (t′), 75.0 (t′), 75.2 (s′), 80.4
(d′), 81.5 (d′), 83.9 (d′), 87.0 (s′), 113.7 (d′), 113.8 (d′), 127.6
(d′), 127.8 (d′), 127.8 (d′), 128.3 (d′), 128.4 (d′), 129.8 (d′), 129.9
(d′), 130.0 (s′), 130.1 (s′), 137.5 (s′), 138.5 (s′), 159.3 (s′), 201.3
(d′); exact mass (HR electrospray) m/z calcd for C41H48NaO7Si
(M + Na) 703.306703, found 703.306590.
3.80 (s, 6 H), 3.88 (dd, J ) 6.9, 2.8 Hz, 1 H), 3.98 (dd, J ) 6.6,
6.6 Hz 1 H), 4.25 (ddd, J ) 6.2, 2.7, 2.7 Hz, 1 H), 4.49 (d, J )
10.7 Hz, 1 H), 4.52-4.78 (m, 8 H), 4.97-5.11 (m, 2 H), 6.78-
6.87 (m, 4 H), 7.20-7.41 (m, 14 H); 13C NMR (CDCl3, 75.5
MHz) δ 55.2 (q′), 68.9 (d′), 71.9 (t′), 72.3 (t′), 72.4 (t′), 74.3 (t′),
77.5 (d′), 78.5 (t′), 79.0 (d′), 80.0 (d′), 101.8 (s′), 113.7 (d′), 127.5
(d′), 127.7 (d′), 127.8 (d′), 128.3 (d′), 129.4 (d′), 129.5 (d′), 130.6
(s′), 130.8 (s′), 138.5 (s′), 138.8 (s′), 159.1 (s′), 205.8 (s′); exact
mass (HR electrospray) m/z calcd for C38H40NaO7 (M + Na)
631.267174, found 631.266900.
(3S,4R,5S,6S)-2-E t h en ylid en e-3,5-bis[(4-m et h oxyp h e-
n yl)m eth oxy]-4,6-bis(ph en ylm eth oxy)cycloh exan on e (21).
A solution of 20 (296.7 mg, 0.488 mmol) in CH2Cl2 (6 mL) was
added to a stirred suspension of Dess-Martin periodinane
(289.6 mg, 0.693 mmol) in CH2Cl2 (12 mL). The mixture was
stirred for 30 min, diluted with Et2O (18 mL), and poured into
saturated aqueous NaHCO3 (18 mL) containing Na2S2O3 (4.5
g). The mixture was stirred for 5 min. Et2O (20 mL) was added,
and the layers were separated. The Et2O layer was washed
with saturated aqueous NaHCO3 (20 mL), water (20 mL), and
brine (10 mL), dried, and evaporated. Flash chromatography
of the residue over silica gel (1 × 25 cm), using 3:7 EtOAc-
hexane, gave 21 (248.3 mg, 84%) as a pure (1H NMR, 400
MHz), gummy solid: [R]D ) -13.7 (c 1.30, acetone); FTIR (CH2-
Cl2 cast) 1960, 1708 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 3.77
(s, 3 H), 3.78 (s, 3 H), 3.87 (dd, J ) 5.6, 2.3 Hz, 1 H), 3.98 (dd,
J ) 4.8, 4.8 Hz, 1 H), 4.27 (d, J ) 2.5 Hz, 1 H), 4.38 (ddd, J )
5.6, 4.1, 4.1 Hz, 1 H), 4.45-4.57 (m, 6 H), 4.66 (d, J ) 11.2
Hz, 1 H), 4.86 (d, J ) 11.9 Hz, 1 H), 5.41 (dd, J ) 14.9, 4.0 Hz,
1 H), 5.43 (dd, J ) 14.9, 4.0 Hz, 1 H), 6.80-6.91 (m, 4 H),
7.17-7.41 (m, 14 H); 13C NMR (CDCl3, 75.5 MHz) δ 55.3 (q′),
72.0 (t′), 72.3 (t′), 72.6 (t′), 72.6 (t′), 76.7 (d′), 77.4 (d′), 81.2
(d′), 81.8 (d′), 82.1 (t′), 104.3 (s′), 113.7 (d′), 113.8 (d′), 127.8
(d′), 127.8 (d′), 127.9 (d′), 127.9 (d′), 128.4 (d′), 128.5 (d′), 129.6
(d′), 129.6 (d′), 129.9 (s′), 130.1 (s′), 137.8 (s′), 159.3 (s′), 159.4
(s′), 194.6 (s′), 211.2 (s′); exact mass (HR electrospray) m/z calcd
for C38H38NaO7 (M + Na) 629.251524, found 629.251915.
4-Deoxy-4-eth en ylid en e-1,5-bis-O-[(4-m eth oxyp h en yl)-
m et h yl]-2,6-b is-O-(p h en ylm et h yl)-D-m yo-in osit ol (22).
CeCl3‚7H2O (0.42 g, 1.13 mmol) was added in one portion to a
stirred solution of 21 (0.63 g, 1.04 mmol) in 1:10 THF-MeOH
(126 mL). After 10 min, the mixture was cooled to -78 °C,
and NaBH4 (42.8 mg, 1.13 mmol) was added. Stirring was
continued at -78 °C for 1 h and then at 0 °C (ice bath) for 4
h. The reaction was quenched with saturated aqueous NH4Cl
(25 mL), and the mixture was diluted with water (25 mL),
evaporated, and extracted with Et2O (3 × 25 mL). The
combined organic extracts were washed with brine (1 × 20
mL), dried, and evaporated. Flash chromatography of the
residue over silica gel (1.5 × 20 cm), using 3:7 EtOAc-hexane,
gave 22 (0.58 g, 92%) as a pure (1H NMR, 300 MHz), gummy
solid: [R]D ) 56.3 (c 2.05, CH2Cl2); FTIR (CH2Cl2 cast) 3479,
1970 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.66 (d, J ) 11.0 Hz,
1 H), 3.53 (dd, J ) 8.2, 2.5 Hz, 1 H), 3.80 (s, 3 H), 3.81 (s, 3
H), 3.89-3.96 (m, 2 H), 4.00 (dd, J ) 8.0, 8.0 Hz, 1 H), 4.06
(ddd, J ) 10.8, 3.0, 3.0 Hz, 1 H), 4.49 (d, J ) 10.9 Hz, 1 H),
4.57-4.80 (m, 5 H), 4.83 (d, J ) 11.0 Hz, 1 H), 4.98 (d, J )
11.8 Hz, 1 H), 5.11-5.22 (m, 2 H), 6.78-6.86 (m, 4 H), 7.22-
7.41 (m, 14 H); 13C NMR (CDCl3, 75.5 MHz) δ 55.3 (q′), 67.9
(d′), 72.4 (t′), 72.9 (t′), 73.8 (t′), 75.1 (t′), 77.4 (d′), 78.3 (d′),
79.8 (d′), 81.2 (d′), 81.6 (t′), 103.8 (s′), 113.7 (d′), 113.8 (d′), 127.5
(d′), 127.5 (d′), 127.5 (d′), 127.9 (d′), 128.3 (d′), 128.3 (d′), 129.4
(d′), 129.8 (d′), 130.3 (s′), 130.4 (s′), 138.8 (s′), 138.9 (s′), 159.2
(s′), 203.2 (s′); exact mass (HR electrospray) m/z calcd for
(Ra)-5-Deoxy-2,4-bis-O-[(4-m eth oxyp h en yl)m eth yl]-1,3-
bis-O-(p h en ylm eth yl)-5-[(tr im eth ylsilyl)eth en ylid en e]-L-
ch ir o-in ositol (7). CSA (64 mg, 0.28 mmol) was added to a
stirred solution of 5 (0.90 g, 1.32 mmol) in PhMe (200 mL).
Stirring was continued for 2.5 h, Et3N (2 mL) was added, and
the solution was evaporated. Flash chromatography of the
residue over silica gel (1.5 × 20 cm), using 2:8 EtOAc-hexane,
gave 7 (0.82 g, 91%) as a pure (1H NMR, 300 MHz), gummy
solid: [R]D ) -0.504 (c 4.96, CHCl3); FTIR (CH2Cl2 cast) 3441,
1947 cm-1; 1H NMR (CDCl3, 300 MHz) δ 0.16 (s, 9 H), 1.97 (br
s, 1 H), 3.74 (dd, J ) 6.6, 2.7 Hz, 1 H), 3.80 (s, 6 H), 3.89 (dd,
J ) 6.2, 2.9 Hz, 1 H), 3.97 (dd, J ) 6.0, 6.0 Hz, 1 H), 4.23 (dd,
J ) 5.5, 2.6 Hz, 1 H), 4.46 (d, J ) 11.2 Hz, 1 H), 4.52 (d, J )
11.5 Hz, 1 H), 4.54-4.76 (m, 7 H), 5.35 (dd, J ) 2.7, 2.7 Hz, 1
H), 6.78-6.87 (m, 4 H), 7.21-7.40 (m, 14 H); 13C NMR (CDCl3,
75.5 MHz) δ -0.9 (q′), 55.2 (q′), 68.4 (d′), 71.3 (t′), 72.1 (t′),
72.2 (t′), 73.8 (t′), 77.2 (d′), 78.0 (d′), 79.4 (d′), 86.4 (d′), 95.5
(s′), 113.6 (d′), 127.5 (d′), 127.8 (d′), 128.2 (d′), 128.3 (d′), 129.3
(d′), 129.4 (d′), 130.8 (s′), 130.8 (s′), 138.6 (s′), 159.0 (s′), 206.5
(s′); exact mass (HR electrospray) m/z calcd for C41H48NaOSi
(M + Na) 703.306703, found 703.306710. Anal. Calcd for
C
41H48OSi: C, 72.32; H, 7.11. Found: C, 72.25; H, 7.11.
5-Deoxy-5-eth en ylid en e-2,4-bis-O-[(4-m eth oxyp h en yl)-
m et h yl]-1,3-bis-O-(p h en ylm et h yl)-L-ch ir o-in osit ol (20).
Powdered K2CO3 (∼325 mesh, 0.880 g, 6.37 mmol) was added
in one portion to a stirred solution of 7 (1.45 g, 2.13 mmol) in
3:1 MeOH-THF (280 mL), and the resulting mixture was
refluxed for 4 h, cooled, diluted with Et2O (50 mL), and filtered
through a pad (2.5 × 2 cm) of flash chromatography silica gel,
using Et2O (50 mL) as a rinse. The combined filtrates were
evaporated, and flash chromatography of the residue over
silica gel (2 × 25 cm), using 3:7 EtOAc-hexane, gave 20 (1.12
g, 86%) as a pure (1H NMR, 300 MHz) oil: [R]D ) 23.1 (c 1.06,
CHCl3); FTIR (CH2Cl2 cast) 3440, 1959 cm-1; 1H NMR (CDCl3,
300 MHz) δ 2.14 (br s, 1 H), 3.76 (dd, J ) 6.1, 2.9 Hz, 1 H),
C
38H40NaO7 (M + Na) 631.267174, found 631.267670.
4-Deoxy-4-eth en ylid en e-1,5-bis-O-[(4-m eth oxyp h en yl)-
m eth yl]-2,3,6-tr is-O-(p h en ylm eth yl)-D-m yo-in ositol (23).
NaH (80% dispersion in oil, 34.2 mg, 1.14 mmol) was added
in one portion to a stirred and cooled (0 °C) solution of 22
(0.580 g, 0.954 mmol) in THF (40 mL). After 30 min, BnBr
(0.14 mL, 1.14 mmol) was added neat in one portion, the cold
bath was removed, and the mixture was stirred for 1 h and
then refluxed for 24 h. The resulting mixture was cooled (0
°C) and quenched with MeOH (5 mL), diluted with brine (10
mL), and extracted with Et2O (3 × 20 mL). The combined

D-myo-Inositol 1,4,5-Tris(dihydrogen phosphate)
J . Org. Chem., Vol. 64, No. 12, 1999 4407
organic extracts were washed with brine (1 × 20 mL), dried,
and evaporated. Flash chromatography of the residue over
silica gel (2 × 25 cm), using 2:8 EtOAc-hexane, gave 23 (0.580
g, 87%) as a pure (1H NMR, 300 MHz), white solid: mp 100-
101 °C; [R]D ) 1.50 (c 1.60, CHCl3); FTIR (CH2Cl2 cast) 1965
water (10 mL) and brine (10 mL), dried, evaporated. Flash
chromatography of the residue over silica gel (1 × 10 cm), using
1:1 EtOAc-hexane, gave 4 (23.5 mg, 70%) as a pure (1H NMR,
400 MHz), white solid: mp 122-123 °C; [R]D ) 10.3 (c 1.73,
CHCl3); lit.52 mp 117-119 °C; [R]16 ) 15.5 (c 1, CHCl3); lit.53
D
cm-1; H NMR (CDCl3, 300 MHz) δ 3.29 (dd, J ) 9.5, 2.5 Hz,
mp 117-119 °C; [R]D ) 12.4 (c ) 0.8, CHCl3); lit.54 mp 121-
1
1 H), 3.69-3.74 (m, 1 H), 3.75-3.84 (m, including singlets at
δ 3.80 and 3.81, 7 H), 3.97-4.06 (m, 2 H), 4.44 (d, J ) 11.9
Hz, 1 H), 4.50-4.59 (m, 3 H), 4.75-4.96 (m, 6 H), 5.14-5.30
(m, 2 H), 6.78-6.87 (m, 4 H), 7.18-7.43 (m, 19 H); 13C NMR
(CDCl3, 75.5 MHz) δ 55.3 (q′), 71.9 (t′), 72.2 (t′), 73.1 (t′), 73.4
(t′), 75.9 (t′), 76.1 (d′), 76.5 (d′), 78.1 (d′), 80.1 (d′), 81.8 (t′),
83.1 (d′), 101.3 (s′), 113.8 (d′), 127.1 (d′), 127.4 (d′), 127.4 (d′),
127.6 (d′), 127.8 (d′), 128.0 (d′), 128.1 (d′), 128.3 (d′), 128.4 (d′),
129.3 (d′), 129.8 (d′), 130.5 (s′), 130.7 (s′), 138.3 (s′) 139.3 (s′),
139.4 (s′) 159.2 (s′), 159.3 (s′), 202.8 (s′); exact mass (HR
electrospray) m/z calcd for C45H46NaO7 (M + Na) 721.314124,
found 721.316612.
1,5-Bis-O-[(4-m eth oxyp h en yl)m eth yl]-2,3,6-tr is-O-(p h e-
n ylm eth yl)-D-epi-4-in osose (24). The apparatus described51
by Rubin was used for this experiment. A cold (-78 °C),
saturated solution of ozone in CH2Cl2 (21.5 mL) was trans-
ferred to a stirred and cooled (-78 °C) solution of 23 (188.1
mg, 0.269 mmol) and pyridine (3.2 mL) in CH2Cl2 (20 mL).31
The mixture was stirred for 30 min and then evaporated. Flash
chromatography of the residue over silica gel (1 × 20 cm), using
2:8 EtOAc-hexane, gave 24 [109.1 mg, 80% (after correction
for recovered starting material (50.5 mg, 27%)] as a pure (1H
NMR, 400 MHz), white solid: mp 150-151 °C; [R]D ) 24.1 (c
1.12, CHCl3); FTIR (CH2Cl2 cast) 1740 cm-1; 1H NMR (CDCl3,
400 MHz) δ 3.68 (dd, J ) 9.4, 2.1 Hz, 1 H), 3.80 (s, 3 H), 3.82
(s, 3 H), 3.93-3.99 (m, 2 H), 4.10 (dd, J ) 2.1, 2.1 Hz, 1 H),
4.19 (dd, J ) 9.4, 9.4 Hz, 1 H), 4.47 (d, J ) 11.9 Hz, 1 H),
4.50-4.59 (m, 3 H), 4.78-4.91 (m, 6 H), 6.81-6.88 (m, 4 H),
7.17-7.41 (m, 19 H); 13C NMR (CDCl3, 75.5 MHz) δ 55.3 (q′),
55.3 (q′), 72.2 (t′), 72.5 (t′), 73.2 (t′), 73.7 (t′), 75.8 (d′), 75.9
(t′), 79.8 (d′), 81.4 (d′), 82.6 (d′), 83.7 (d′), 113.8 (d′), 127.4 (d′),
127.6 (d′), 127.8 (d′), 128.0 (d′), 128.0 (d′), 128.1 (d′), 128.3 (d′),
128.5 (d′), 129.4 (d′), 129.8 (s′), 129.9 (d′), 130.1 (s′), 137.4 (s′),
138.3 (s′), 138.8 (s′), 159.3 (s′), 159.4 (s′), 201.7 (s′); exact mass
123 °C; [R]25D ) 10 (c 1, CHCl3); FTIR (CH2Cl2 cast) 3439 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 2.37 (br d, J ) 6.1 Hz, 1 H), 2.68
(br s, 2 H), 3.27 (dd, J ) 9.8, 2.4 Hz, 1 H), 3.47 (dd, J ) 9.1,
9.1 Hz, 1 H), 3.52 (br d, J ) 9.0 Hz, 1 H), 3.68 (dd, J ) 9.3, 9.3
Hz, 1 H), 4.01 (dd, J ) 9.4, 9.4 Hz, 1 H), 4.08 (dd, J ) 2.5, 2.5
Hz, 1 H), 4.58 (d, J ) 11.6 Hz, 1 H), 4.69 (d, J ) 11.6 Hz, 1 H),
4.72 (d, J ) 11.4 Hz, 1 H), 4.84 (d, J ) 11.3 Hz, 1 H), 4.88 (d,
J ) 11.3 Hz, 1 H), 4.93 (d, J ) 11.4 Hz, 1 H), 7.28-7.40 (m,
15 H); 13C NMR (CDCl3, 75.5 Hz) δ 72.6 (t′), 72.6 (d′), 72.6
(d′), 74.8 (t′), 74.9 (d′) 75.1 (t′), 76.4 (d′), 80.3 (d′), 81.8 (d′),
127.8 (d′), 127.9 (d′), 127.9 (d′), 128.1 (d′), 128.5 (d′), 128.6 (d′),
128.6 (d′), 137.7 (s′), 138.5 (s′), 138.6 (s′); exact mass (HR
electrospray) m/z calcd for C27H30NaO6 (M + Na) 473.194009,
found 473.194360.
(Ra )-5-Deoxy-1,2,3,4-tetr a k is-O-(p h en ylm eth yl)-5-[(tr i-
m eth ylsilyl)eth en ylid en e]-L-ch ir o-in ositol (27a ). CSA (6.0
mg, 0.026 mmol) was added to a stirred solution of 27 (96.9
mg, 0.156 mmol) in PhMe (20 mL). Stirring was continued for
5 h, Et3N (1 mL) was added, and the solution was evaporated.
Flash chromatography of the residue over silica gel (1.5 × 20
cm), using 1:9 EtOAc-hexane, gave 27a (70.8 mg, 73%) as a
pure (1H NMR, 360 MHz), white solid: FTIR (CH2Cl2 cast)
1
3386, 1948 cm-1; H NMR (CDCl3, 360 MHz) δ 0.08 (s, 9 H),
1.86 (br s, 1 H), 3.75 (dd, J ) 6.8, 3.0 Hz, 1 H), 3.89 (dd, J )
6.2, 3.0 Hz, 1 H), 3.99 (dd, J ) 5.8, 5.8 Hz, 1 H), 4.23 (dd, J )
5.5, 2.6 Hz, 1 H), 4.48-4.72 (m, 8 H), 4.78 (d, J ) 11.6 Hz, 1
H), 5.33 (dd, J ) 2.8, 2.8 Hz, 1 H), 7.20-7.40 (m, 20 H); 13C
NMR (CDCl3, 75.5 MHz) δ -0.8 (q′), 68.3 (d′), 71.6 (t′), 72.3
(t′), 72.6 (t′), 73.8 (t′), 77.6 (d′), 78.4 (d′), 79.4 (d′), 79.6 (d′),
86.6 (d′), 95.4 (s′), 127.4 (d′), 127.5 (d′), 127.6 (d′), 127.7 (d′),
127.9 (d′), 128.3 (d′), 128.3 (d′), 128.4 (d′), 138.6 (s′), 138.6 (s′),
138.65 (s′), 138.70 (s′), 206.5 (s′); exact mass (HR electrospray)
m/z calcd for C39H44NaO5Si (M + Na) 643.285573, found
643.286700. Crystal data: compound 27a crystallizes in the
monoclinic space group P21 (No. 4) with a ) 11.401 (2) Å, b )
12.219 (2) Å, c ) 13.716 (2) Å, â ) 108.353 (10)°, V ) 1813.6
(5) Å3, Z ) 2, Fcalcd ) 1.137 g cm-3, µ ) 0.105 mm-1. X-ray
diffraction data were collected on a Siemens P4/RA instrument
with Mo KR radiation (λ ) 0.71073 Å) at -60 °C. The final
model, with 6315 unique data used and 407 parameters varied,
converged to values of R1 (Fo) ) 0.0810 (for 3100 data with
(HR electrospray) m/z calcd for
711.293389, found 711.293620.
C43H44NaO8 (M + Na)
1,5-Bis-O-[(4-m eth oxyp h en yl)m eth yl]-2,3,6-tr is-O-(p h e-
n ylm eth yl)-D-m yo-in ositol (25). A solution of n-Bu2SnCl2
(279 mg, 0.918 mmol) in PhMe (5 mL) was added to a stirred
solution of n-Bu2SnH2 (216 mg, 0.918 mmol) in PhMe (5 mL),
and the mixture was stirred at room temperature for 15 min.
A solution of 24 (63.3 mg, 0.0920 mmol) in PhMe (6 mL) was
added, and the resulting solution was refluxed for 24 h and
then cooled to room temperature. MeOH (2 mL) was added,
and the solvents were evaporated. Flash chromatography of
the residue over silica gel (1 × 15 cm), using 2:8 EtOAc-
hexane, gave 25 (56.2 mg, 88%) as a pure (1H NMR, 300 MHz),
gummy solid: [R]D ) 8.00 (c 2.26, CHCl3); FTIR (CH2Cl2 cast)
3473 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.40 (br s, 1 H), 3.17
(dd, J ) 9.8, 2.2 Hz, 1 H), 3.35 (dd, J ) 9.0, 9.0 Hz, 1 H), 3.36
(dd, J ) 9.0, 2.4 Hz, 1 H), 3.79 (s, 3 H), 3.81 (s, 3 H), 4.00 (dd,
J ) 2.2, 2.2 Hz, 1 H), 4.02 (dd, J ) 9.6, 9.6 Hz, 1 H), 4.15 (dd,
J ) 9.6, 9.6 Hz, 1 H), 4.52-4.63 (m, 4 H), 4.73-4.94 (m, 6 H),
6.80-6.90 (m, 4 H), 7.18-7.42 (m, 19 H); 13C NMR (CDCl3,
75.5 MHz) δ 55.3 (q′), 72.3 (t′), 72.6 (t′), 73.0 (d′), 73.8 (d′),
74.1 (t′), 75.0 (t′), 75.8 (t′), 80.2 (d′), 80.9 (d′), 81.5 (d′), 83.3
(d′), 113.8 (d′), 113.9 (d′), 127.4 (d′), 127.5 (d′), 127.8 (d′), 127.9
(d′), 128.0 (d′), 128.2 (d′) 128.3 (d′), 128.5 (d′), 129.3 (d′), 129.6
(d′), 130.5 (s′), 131.1 (s′), 138.1 (s′), 139.0 (s′), 139.0 (s′), 159.2
(s′), 159.3 (s′); exact mass (HR electrospray) m/z calcd for
2
Fo > 2σ(Fo2)) and wR2 (Fo2) ) 0.2366 (all data). The absolute
stereochemistry of the molecule was not established from the
structural results alone but was assigned on the basis of the
known stereochemistry of its chemical precursors.
2-Eth en ylid en ecycloh exa n ol (28a ).55 (a ) Use of Zn Cl2.
A solution of 28 (40.0 mg, 0.204 mmol) in CH2Cl2 (10 mL) was
added to a stirred and cooled (0 °C) suspension of ZnCl2 (61.0
mg, 0.45 mmol) in CH2Cl2 (20 mL). Stirring was continued for
2.5 h, and water (10 mL) was then added. After 2 min, the
organic phase was washed with saturated aqueous NaHCO3
(10 mL), water (10 mL), and brine (10 mL), dried (MgSO4) and
evaporated. Flash chromatography of the residue over silica
gel (1.5 × 15 cm), using 2:8 EtOAc-hexane, gave 28a (16.7
mg, 66%) as a pure (1H NMR, 300 MHz), colorless oil: FTIR
(CH2Cl2 cast) 3381, 1961 cm-1; 1H NMR (CD2Cl2, 300 MHz) δ
1.28-1.46 (m, 3 H), 1.58-1.72 (m, 1 H), 1.72-1.84 [m, 2 H,
including doublet at δ 1.79 (J ) 4.5 Hz, 1 H) which disappeared
on exchange with D2O)], 1.90-2.07 (m, 2 H), 2.30-2.42 (m, 1
H), 3.93-4.04 (m, 1 H), 4.76-4.88 (m, 2 H), [irradiation of the
C
43H46NaO8 713.309039, found 713.309230.
2,3,6-Tr is-O-(p h en ylm eth yl)-D-m yo-in ositol (4). DDQ
(52) Ozaki, S.; Kondo, Y.; Shiotani, N.; Ogasawara, T.; Watanabe,
Y. J . Chem. Soc., Perkin Trans. 1 1992, 729-737.
(53) Sato, K.; Sakuma, S.; Muramatsu, S.; Bokura, M. Chem. Lett.
1991, 1473-1474.
(55.9 mg, 0.246 mmol) was added in one portion to a stirred
solution of 25 (51.5 mg, 0.0746 mmol) in CH2Cl2 (20 mL) and
water (1 mL). Stirring was continued for 4 h, and the solution
was then washed with saturated aqueous NaHCO3 (10 mL),
(54) Desai, T.; Gigg, J .; Gigg, R.; Payne, S. Carbohydr. Res. 1992,
225, 209-228.
(55) (a) Ortiz de Montellano, P. R. J . Chem. Soc., Chem. Commun.
1973, 709-710. (b) Alexakis, A.; Marek, I.; Mangeney, P.; Normant,
J . F. Tetrahedron 1991, 47, 1677-1696.
(51) Rubin, M. B. J . Chem. Educ. 1964, 41, 388.

4408 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
dCH2 signal caused the width of the CH(OH) multiplet to
decrease by 6.6 Hz.]; 13C NMR (CD2Cl2, 75.5 MHz) δ 23.9 (t′),
26.8 (t′), 29.7 (t′), 36.2 (t′), 69.0 (d′), 78.2 (s′), 107.2 (s′), 201.1
(s′); exact mass m/z calcd for C8H12O 124.08881, found
124.08886.
(b) Use of CF 3CO2H. TFA (0.05 mL, 0.65 mmol) was added
dropwise to a stirred and cooled (-78 °C) solution of 28 (50.0
mg, 0.255 mmol) in CH2Cl2 (40 mL). The mixture was stirred
for 30 min, Et3N (0.05 mL) was added, and stirring was
continued for 10 min. Evaporation of the solvent and flash
chromatography of the residue over silica gel (1.5 × 15 cm),
using 2:8 EtOAc-hexane, gave 28a (15.0 mg, 47%) as a pure
(1H NMR, 300 MHz), colorless oil, identical with material
obtained in the previous experiment.
powdered molecular sieves (4 Å, 2.50 g). The mixture was
stirred at 0 °C for 1 h, diluted with Et2O (ca. 20 mL), and
filtered through a pad (2.5 × 2 cm) of flash chromatography
silica gel, using Et2O (ca. 50 mL) as a rinse. Evaporation of
the solvent, and flash chromatography of the residue over silica
gel (2 × 15 cm), using 1.5:8.5 EtOAc-hexane, gave 30a (35.0
mg, 67%) and 30b (4.0 mg, 8%), each as a pure (1H NMR, 300
MHz), colorless oil.
Alcohol 30a : FTIR (CH2Cl2 cast) 3355, 1958 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 1.41 (s, 3 H), 1.46-1.70 [m, 3 H, including
singlet at δ 1.51 (1 H)], 1.95-2.10 (m, 2 H), 2.34 (ddd, J )
13.8, 4.8, 2.4 Hz, 1 H), 2.55-2.71 (m, 1 H), 3.14 (dddd, J )
12.2, 12.2, 3.4, 3.4 Hz, 1 H), 4.75 (dd, J ) 9.9, 4.5 Hz, 1 H),
4.79 (dd, 9.9, 4.0 Hz, 1 H), 7.15-7.37 (m, 5 H); 13C NMR
(CDCl3, 75.5 MHz) δ 28.0 (t′), 29.4 (q′), 33.9 (t′), 39.2 (d′), 47.5
(t′), 70.1 (s′), 76.0 (t′), 106.1 (s′), 126.1 (d′), 127.0 (d′), 128.5
tr a n s-2-Eth en ylid en e-5-p h en ylcycloh exa n ol (29a ). (a )
Use of Zn Cl2. A solution of 29 (30.2 mg, 0.110 mmol) in CH2-
Cl2 (5 mL) was added to a stirred and cooled (0 °C) suspension
of ZnCl2 (20.0 mg, 0.147 mmol) in CH2Cl2 (15 mL). Stirring
was continued for 3 h, and the mixture was filtered through a
pad (4 × 2 cm) of flash chromatography silica gel which was
rinsed with Et2O (30 mL). Evaporation of the combined
filtrates, and flash chromatography of the residue over silica
(1.5 × 15 cm), using 2:8 EtOAc-hexane, gave 29a (12.3 mg,
56%) as a pure (1H NMR, 300 MHz), colorless oil: FTIR (CH2-
Cl2 cast) 3216, 1958 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.56-
1.74 (m, 2 H), 1.83 (br t, J ) 13.0 Hz, 1 H), 1.99 (br d, J )
12.6 Hz, 1 H), 2.12 (br d, J ) 13.0 Hz, 1 H), 2.30 (ddd, J )
13.0, 3.1, 3.1 Hz, 1 H), 2.51-2.68 (m, 1 H), 3.14 (dddd, J )
13.0, 13.0, 3.1, 3.1 Hz, 1 H), 4.57 (br s, 1 H), 4.71 (d, J ) 4.5
Hz, 2 H), 7.13-7.36 (m, 5 H); 13C NMR (CDCl3, 75.5 MHz) δ
26.2 (t′), 33.9 (t′), 37.1 (d′), 40.8 (t′), 69.9 (d′), 74.5 (s′), 102.2
(t′), 126.2 (d′), 127.0 (d′), 128.5 (d′), 146.3 (s′), 203.9 (s′); exact
mass m/z calcd for C14H16O 200.12012, found 200.12035. The
(d′), 146.3 (s′), 202.8 (s′); exact mass m/z calcd for C15H18
O
214.13577, found 214.13574.
Alcohol 30b: FTIR (CH2Cl2 cast) 3442, 1960 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 1.49 (s, 3 H), 1.58 (dddd, J ) 12.7, 12.7,
12.7, 4.2 Hz, 1 H), 1.77 (br dd, J ) 12.7, 12.7 Hz, 1 H), 1.94-
2.11 [m, 3 H, including singlet at δ 2.07 (1 H)], 2.24-2.39 (m,
1 H), 2.50 (ddd, J ) 12.7, 4.8, 2.2 Hz, 1 H), 2.78 (dddd, J )
12.7, 12.7, 3.4, 3.4 Hz, 1 H), 4.92 (dd, J ) 9.9, 4.3 Hz, 1 H),
4.99 (dd, J ) 9.9, 3.9 Hz, 1 H), 7.17-7.37 (m, 5 H); 13C NMR
(CDCl3, 75.5 MHz) δ 26.8 (q′), 29.3 (t′), 34.6 (t′), 42.0 (d′), 48.6
(t′), 70.1 (s′), 79.2 (t′), 109.9 (s′), 126.4 (d′), 126.9 (d′), 128.6
(d′), 145.5 (s′), 200.2 (s′); exact mass m/z calcd for C15H18
O
214.13577, found 214.13536.
tr a n s-2-Eth en ylid en e-5-p h en ylcycloh exa n ol (31a ) [≡
29a ]. Use of a Ca ta lytic Am ou n t of Me3SiOSO2CF 3 a t -78
°C to Room Tem p er a tu r e. Me3SiOSO2CF3 (0.0062 M in CH2-
Cl2, 0.20 mL, 0.00124 mmol) was added dropwise to a stirred
and cooled (-78 °C) solution of 31 (3.5 mg, 0.011 mmol) in
CH2Cl2 (5 mL). Stirring was continued for 6 h, the cold bath
was removed, and stirring was continued for another 5 h. The
mixture was poured into saturated aqueous NaHCO3 (ca. 3.0
mL) and extracted with Et2O (2 × 5 mL). The combined organic
extracts were washed with water (5 mL) and brine (5 mL),
dried (MgSO4), and evaporated. Flash chromatography of the
residue over silica gel (1 × 10 cm), using 2:10 EtOAc-hexane,
gave 31a (1.7 mg, 77%) as a pure (1H NMR, 300 MHz),
colorless oil, identical with material (29a ) obtained from 29.
tr a n s-1-E t h en ylid en e-2-m et h oxy-4-p h en ylcycloh ex-
a n e (31b) a n d cis-1-Eth en ylid en e-2-m eth oxy-4-p h en yl-
cycloh exa n e (31c). Use of 1.1 equ iv of Me3SiOSO2CF 3 a t
-78 °C. Me3SiOSO2CF3 (0.0517 M in CH2Cl2, 2.75 mL, 0.142
mmol) was added dropwise to a stirred and cooled (-78 °C)
solution of 31 (39.4 mg, 0.124 mmol) in CH2Cl2 (30 mL).
Stirring was continued for 3 h, saturated aqueous NaHCO3
(10 mL) was added, the cold bath was removed, and stirring
was continued for 30 min. The mixture was extracted with
CH2Cl2 (2 × 10 mL), and the combined organic extracts were
washed with water (20 mL) and brine (20 mL), dried (MgSO4),
and evaporated. Flash chromatography of the residue over
silica gel (1.5 × 15 cm), using 0.5:9.5 EtOAc-hexane, gave 31b
(15.3 mg, 58%) as a pure (1H NMR, 300 MHz), colorless oil
and 31c (7.1 mg, 27%) as a pure (1H NMR, 300 MHz), colorless
oil.
1
derived acetate (see Supporting Information) showed in its H
NMR spectrum (300 MHz, CDCl3) a signal for C(1)H at δ 5.57
(dd, J ) 2.8, 2.8 Hz), and we conclude, therefore, that the
acetate is axial.
(b) Use of CF 3CO2H. TFA (0.01 mL, 0.13 mmol, in 1.0 mL
CH2Cl2) was added dropwise to a stirred and cooled (-78 °C)
solution of 29 (31.7 mg, 0.116 mmol) in CH2Cl2 (25 mL). The
mixture was stirred for 1 h, Et3N (0.05 mL) was added, and
stirring was continued for 10 min. Evaporation of the solvent,
and flash chromatography of the residue over silica gel (1.5 ×
12 cm), using 2:8 EtOAc-hexane, gave 29a (10.8 mg, 46%) as
a pure (1H NMR, 300 MHz), colorless oil, identical with
material obtained by use of ZnCl2.
tr a n s-2-Eth en ylid en e-5-p h en ylcycloh exa n ol (29a ) a n d
cis-2-Eth en ylid en e-5-p h en ylcycloh exa n ol (29b). Use of
Bu 4NF . TBAF (1 M in THF, 0.51 mL, 0.51 mmol) was added
dropwise to a stirred and cooled (0 °C) mixture of 29 (93.0 mg,
0.342 mmol) in THF (40 mL) and powdered molecular sieves
(4 Å, 2.50 g). The mixture was stirred at 0 °C for 1 h, diluted
with Et2O (20 mL), and filtered through a pad (2.5 × 2 cm) of
flash chromatography silica gel, using Et2O (50 mL) as a rinse.
Evaporation of the solvent, and flash chromatography of the
residue over silica gel (3 × 20 cm), using 1.5:8.5 EtOAc-
hexane, gave 29a (14.0 mg, 20%) as a pure (1H NMR, 300
MHz), colorless oil, which was identified by comparison of its
1H NMR spectrum with that of material obtained by use of
ZnCl2, and 29b (25.5 mg, 37%) as a pure (1H NMR, 300 MHz),
Compound 31b: FTIR (CH2Cl2 cast) 1960 cm-1 1H NMR
;
1
colorless oil: FTIR (CH2Cl2, cast) 3396, 1962 cm-1; H NMR
(CDCl3, 300 MHz) δ 1.64 (dddd, J ) 12.6, 12.6, 12.6, 4.2 Hz, 1
H), 1.81 (ddd, J ) 13.1, 13.1, 2.8 Hz, 1 H), 1.91-2.02 (m, 1 H),
2.13-2.23 (m, 1 H), 2.28 (br ddd, J ) 13.1, 13.1, 3.4 Hz, 1 H),
2.33-2.48 (m, 1 H), 3.06 (dddd, J ) 12.6, 12.6, 3.2, 3.2 Hz, 1
H), 3.33 (s, 3 H), 3.98 (dd, J ) 2.8, 2.8 Hz, 1 H), 4.72 (d, J )
4.2 Hz, 2 H), 7.17-7.37 (m, 5 H); 13C NMR (CDCl3, 100.6 MHz)
δ 26.3 (t′), 34.0 (t′), 37.7 (d′), 39.9 (t′), 55.6 (d′), 73.6 (t′), 78.6
(q′), 98.7 (s′), 126.1 (d′), 127.0 (d′), 128.4 (d′), 146.5 (s′), 204.9
(CDCl3, 300 MHz) δ 1.47-1.66 (m, 2 H), 1.90-2.01 [(m, 2 H,
including doublet at δ 1.96 (J ) 4.9 Hz, 1 H)], 2.11-2.27 (m,
1 H), 2.35 (dddd, J ) 11.9, 4.8, 2.8, 1.6 Hz, 1 H), 2.56 (ddd, J
) 13.0, 5.1, 2.3 Hz, 1 H), 2.71 (dddd, J ) 11.9, 11.9, 2.8, 2.8
Hz, 1 H), 4.09-4.21 (m, 1 H), 4.94-5.08 (m, 2 H), 7.18-7.35
(m, 5 H); 13C NMR (CDCl3, 75.5 MHz) δ 29.8 (t′), 34.2 (t′), 42.6
(d′), 43.2 (t′), 68.3 (d′), 80.2 (t′), 106.7 (s′), 126.4 (d′), 126.8 (d′),
128.6 (d′), 145.4 (s′), 199.8 (s′); exact mass m/z calcd for C14H16
O
(s′); exact mass m/z calcd for
C
15H18O 214.13577, found
200.12012, found 200.12021.
214.13534.
t r a n s-2-E t h e n ylid e n e -1-m e t h yl-5-p h e n ylcycloh e x-
a n ol (30a ) a n d cis-2-Eth en ylid en e-1-m eth yl-5-p h en ylcy-
cloh exa n ol (30b). Use of Bu 4NF . TBAF (1 M in THF, 0.31
mL, 0.31 mmol) was added dropwise to a stirred and cooled (0
°C) mixture of 30 (70.0 mg, 0.244 mmol) in THF (40 mL) and
Compound 31c: FTIR (CH2Cl2 cast) 1962 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 1.51-1.72 (m, 2 H), 1.90-2.00 (m, 1 H),
2.08-2.22 (m, 1 H), 2.29-2.39 (m, 1 H), 2.49 (ddd, J ) 13.2,
4.3, 2.3 Hz, 1 H), 2.69 (dddd, J ) 12.3, 12.3, 2.8, 2.8 Hz, 1 H),
3.48 (s, 3 H), 3.69-3.79 (m, 1 H), 4.88 (ddd, 9.2, 4.2, 3.9 Hz, 1

D-myo-Inositol 1,4,5-Tris(dihydrogen phosphate)
J . Org. Chem., Vol. 64, No. 12, 1999 4409
H), 4.91 (ddd, 9.2, 3.2, 3.2 Hz, 1 H), 7.16-7.37 (m, 5 H); 13C
NMR (CDCl3, 75.5 MHz) δ 30.6 (t′), 34.6 (t′), 40.5 (t′), 43.0 (d′),
57.4 (d′), 77.1 (t′), 78.6 (q′), 103.5 (s′), 126.4 (d′), 126.8 (d′), 126.8
(d′), 128.5 (d′), 145.5 (s′), 201.5 (s′); exact mass m/z calcd for
Use of Zn Cl2. A solution of 32 (50.9 mg, 0.197 mmol) in CH2-
Cl2 (5 mL) was added to a stirred and cooled (0 °C) suspension
of ZnCl2 (59.1 mg, 0.434 mmol) in CH2Cl2 (35 mL). The mixture
was stirred for 2.5 h, the cold bath was removed, and stirring
was continued for 12 h. The mixture was diluted with Et2O
(ca. 20 mL) and filtered through a pad (2 × 2 cm) of flash
chromatography silica gel, using Et2O (ca. 40 mL). Evaporation
of the combined filtrates, and flash chromatography of the
residue over silica gel (2 × 15 cm), using first hexane and then
2:8 EtOAc-hexane, gave 32a (10.1 mg, 26%) as a colorless oil,
which was a 55:45 mixture of epimers, identified by its 1H
NMR spectrum (CDCl3, 360 MHz), and 32b (25.0 mg, 62%) as
a pure (1H NMR, 360 MHz), colorless oil. Compound 32b:
FTIR (CH2Cl2 cast) unexceptional; 1H NMR (CDCl3, 360 MHz)
δ 2.57-2.71 (m, 2 H), 2.93-3.06 (m, 2 H), 3.57-3.67 (m, 1 H),
5.25 (br s, 1 H), 5.35 (br s, 1 H), 6.22 (br s, 1 H), 7.18-7.37 (m,
5 H); 13C NMR (CDCl3, 75.5 MHz) δ 41.3 (t′), 41.6 (t′), 44.2
(d′), 112.6 (t′), 126.2 (d′), 126.9 (d′), 128.6 (d′), 132.2 (d′), 136.3
(s′), 139.5 (s′), 146.4 (s′); exact mass m/z calcd for C13H1337Cl
206.06763, found 206.06751.
tr a n s- a n d cis-1-Eth en ylid en e-2-m eth oxy-4-p h en ylcy-
clop en ta n e (33a ). Me3SiOSO2CF3 (0.0517 M in CH2Cl2, 4.34
mL, 0.224 mmol) was added dropwise to a stirred and cooled
(-78 °C) solution of 33 (62.0 mg, 0.204 mmol) in CH2Cl2 (30
mL). Stirring was continued for 1.5 h, saturated aqueous
NaHCO3 (10 mL) was added, and the cold bath was removed.
The mixture was stirred for 30 min and extracted with CH2-
Cl2 (2 × 15 mL). The combined organic extracts were washed
with water (20 mL) and brine (20 mL), dried (MgSO4), and
evaporated. Flash chromatography of the residue over silica
gel (1.5 × 20 cm), using 1:10 EtOAc-hexane, gave 33a (36.4
mg, 89%) as a colorless oil, which was as a 3:2 mixture of
epimers: FTIR (CH2Cl2 cast) 1958 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.76-1.96 (m, 1 H), 2.26 (br dd, J ) 13.2, 6.0 Hz, 0.6
H), 2.43-2.80 (m, 1.8 H), 2.91-3.20 (m, 1 H), 3.38 (s, 1.8 H),
3.43 (s, 1.2 H), 3.45-3.57 (m, 0.6 H), 4.32 (br d, J ) 5.1 Hz,
0.6 H), 4.41-4.48 (m, 0.4 H), 4.83-4.90 (m, 2 H), 7.17-7.37
(m, 5 H); 13C NMR (CDCl3, 75.5 MHz) δ 37.0 (t′), 38.0 (t′), 40.7
(t′), 42.0 (t′), 42.7 (d′), 42.9 (d′), 56.0 (q′), 56.8 (q′), 76.2 (t′),
76.9 (t′), 82.9 (d′), 84.0 (d′), 102.0 (s′), 103.0 (s′), 126.3 (d′), 126.4
(d′), 127.1 (d′), 128.5 (d′), 128.5 (d′), 143.7 (s′), 144.2 (s′), 203.9
(s′), 205.0 (s′); exact mass calcd for C14H16O 200.12012, found
200.12014.
C
15H18O 241.13577, found 214.13551.
tr a n s-2-Eth en yliden e-5-ph en ylcycloh exan ol (31a),tr a n s-
1-E t h en ylid en e-2-m et h oxy-4-p h en ylcycloh exa n e (31b ),
a n d cis-1-Eth en ylid en e-2-m eth oxy-4-p h en ylcycloh exa n e
(31c). Use of a Ca ta lytic Am ou n t of Me3SiOSO2CF 3 a t -78
°C. Me3SiOSO2CF3 (0.0062 M in CH2Cl2, 0.18 mL, 0.0011
mmol) was added dropwise to a stirred and cooled (-78 °C)
solution of 31 (3.4 mg, 0.011 mmol) in CH2Cl2 (5 mL). Stirring
was continued for 3 h, saturated aqueous NaHCO3 (ca. 3.0 mL)
was added, the cold bath was removed, and stirring was
continued for ca. 30 min. The mixture was extracted with Et2O
(2 × 5 mL), and the combined organic extracts were washed
with water (5 mL) and brine (5 mL), dried (MgSO4), and
evaporated. Flash chromatography of the residue over silica
gel (1 × 10 cm), using 2:10 EtOAc-hexane, gave 31a (0.9 mg,
48% based on conversion) as a pure (1H NMR, 300 MHz),
colorless oil, and a mixture (1.0 mg) of 31b, 31c, and unreacted
31 in a ratio of 31:31b:31c ) 1.2:1:1.3] as a colorless oil.
Compounds 31b, 31c, and 31 were not further separated,
identification being made through the 1H NMR spectrum of
the mixture.
Tr im e t h yl[(4-p h e n yl-1-cycloh e xe n -1-yl)e t h yn yl]si-
la n e (31d ). CSA (15.0 mg, 0.0645 mmol) was added in one
portion to a stirred solution of 31 (20.0 mg, 0.0629 mmol) in
CH2Cl2 (30 mL). Stirring was continued for 48 h, Et3N (1 mL)
was added, and the solution was evaporated. Flash chroma-
tography of the residue over silica gel (1.5 × 10 cm), using
1:20 EtOAc-hexane, gave 31d (6.1 mg, 38%) as a pure (1H
NMR, 360 MHz), colorless oil: FTIR (CH2Cl2 cast) 2144 cm-1
;
1H NMR (CDCl3, 360 MHz) δ 0.02 (s, 9 H), 1.70-1.82 (m, 1
H), 1.91-2.00 (m, 1 H), 2.17-2.46 (m, 4 H), 2.71-2.82 (m, 1
H), 6.24-6.29 (m, 1 H), 7.16-7.34 (m, 5 H); 13C NMR (CDCl3,
75.5 MHz) δ 0.1 (q′), 29.5 (t′), 29.8 (t′), 33.8 (t′), 39.1 (d′), 91.7
(s′), 106.8 (s′), 120.8 (s′), 126.3 (d′), 126.9 (d′), 128.5 (d′), 135.6
(d′), 146.4 (s′); exact mass m/z calcd for C17H22Si 254.14908,
found 254.14893.
cis- a n d tr a n s-2-Eth en ylid en e-4-p h en ylcyclop en ta n ol
(32a ). (a ) Use of Bu 4NF . TBAF (1 M in THF, 0.27 mL, 0.27
mmol) was added dropwise to a stirred and cooled (0 °C)
mixture of 32 (46.5 mg, 0.18 mmol) in THF (60.0 mL) and
powdered 3 Å molecular sieves (1.50 g). The mixture was
stirred at 0 °C for 1 h, diluted with Et2O (ca. 20 mL), and
filtered through a pad (2.5 × 2 cm) of flash chromatography
silica gel, which was rinsed with Et2O (ca. 50 mL). Evaporation
of the combined filtrates, and flash chromatography of the
residue over silica gel (2 × 15 cm), using 2:8 EtOAc-hexane,
gave 32a (26.3 mg, 78%) as a colorless oil, which was a 55:45
Tr im e t h yl[(4-p h e n yl-1-cyclop e n t e n -1-yl)e t h yn yl]si-
la n e (33b). A solution of 33 (31.7 mg, 0.104 mmol) in CH2Cl2
(ca. 2 mL) was added to a stirred solution of CSA (26.6 mg,
0.115 mmol) in CH2Cl2 (30 mL). Stirring was continued for 20
h, Et3N (1 mL) was added, and the solution was evaporated.
Flash chromatography of the residue over silica gel (1.5 × 15
cm), using 5:100 EtOAc-hexane, gave 33b (8.6 mg, 34%) as a
pure (1H NMR, 360 MHz), colorless oil: FTIR (CH2Cl2 cast)
1
1
mixture of epimers: FTIR (CH2Cl2 cast) 3356, 1959 cm-1; H
2146 cm-1; H NMR (CDCl3, 300 MHz) δ 0.21 (s, 9 H), 2.42-
NMR (CDCl3, 300 MHz) δ 1.73-2.00 (m, 2 H), 2.17-2.27 (m,
0.45 H), 2.45-2.60 (m, 1 H), 2.63-2.79 (m, 0.55 H), 2.79-2.92
(m, 0.55 H), 2.92-3.05 (m, 0.45 H), 3.05-3.19 (m, 0.55 H),
3.49-3.62 (m, 0.45 H), 4.78-5.04 (m, 3 H), 7.18-7.39 (m, 5
H); 13C NMR (CDCl3, 75.5 MHz) δ 37.1 (t′), 37.3 (t′), 41.6 (d′),
42.7 (d′), 43.1 (t′), 43.5 (t′), 73.9 (d′), 74.7 (d′), 77.8 (t′), 79.3
(t′), 106.8 (s′), 106.9 (s′), 126.4 (d′), 126.5 (d′), 127.0 (d′), 127.1
(d′), 128.5 (d′), 128.6 (d′), 143.4 (s′), 143.7 (s′), 202.4 (s′), 203.7
2.62 (m, 2 H), 2.78-2.93 (m, 2 H), 3.46 (dddd, J ) 8.4, 8.4,
8.4, 8.4 Hz, 1 H), 6.10-6.19 (m, 1 H), 7.15-7.34 (m, 5 H); 13
C
NMR (CDCl3, 75.5 MHz) δ 0.1 (q′), 41.8 (t′), 43.5 (d′), 44.5 (t′),
95.6 (s′), 102.1 (s′), 123.9 (s′), 126.2 (d′), 126.9 (d′), 128.5 (d′),
138.0 (d′), 146.2 (s′); exact mass calcd for C16H20Si 240.13342,
found 240.13362.
cis-2-Eth en yliden e-1-m eth yl-4-ph en ylcyclopen tan ol an d
tr a n s-2-E t h en ylid en e-1-m et h yl-4-p h en ylcyclop en t a n ol
(34a ). TBAF (1 M in THF, 0.14 mL, 0.14 mmol) was added
dropwise to a stirred and cooled (0 °C) mixture of 34 (31.2 mg,
0.114 mmol) in THF (40 mL) and powdered 3 Å molecular
sieves (0.50 g). The mixture was stirred at 0 °C for 1 h.
Saturated aqueous NH4Cl (ca. 10 mL) was added, and after 5
min, the organic phase was washed with water (10 mL) and
brine (10 mL), dried (MgSO4), and evaporated. Flash chroma-
tography of the residue over silica gel (1.5 × 12 cm), using
1.5:8.5 EtOAc-hexane, gave 34a (20.2 mg, 88%) as a colorless
oil, which was a 1:7.2 mixture of epimers: FTIR (CH2Cl2 cast)
(s′); exact mass m/z calcd for
C13H14O 186.10446, found
186.10406.
(b) Use of Sc(OSO2CF 3)3. Aldehyde 32 (32.9 mg, 0.128
mmol) in MeNO2 (5 mL) was added to a stirred solution of
Sc(OSO2CF3)3 in MeNO2 (10 mL). Stirring was continued for
12 h, and the mixture was poured into brine (ca. 15 mL) and
extracted with CH2Cl2 (3 × 10 mL). The combined organic
extracts were dried (MgSO4) and evaporated. Flash chroma-
tography of the residue over silica gel (1.5 × 15 cm), using
2:10 EtOAc-hexane, gave 32a (16.8 mg, 70%) as a colorless
oil, which was a 1:1 mixture of epimers. The structures were
identified by examination of the 1H NMR spectrum (CDCl3,
300 MHz) of the mixture.
1
3367, 1958 cm-1; H NMR (CDCl3, 400 MHz) δ 1.50 (s, 3 H),
1.60 (br s, 0.12 H), 1.65 (br s, 0.88 H), 1.80 (dd, J ) 12.7, 12.7
Hz, 0.88 H), 2.09 (dd, J ) 12.2, 12.2 Hz, 0.12 H), 2.29 (ddd, J
) 12.8, 6.2, 1.7 Hz, 1 H), 2.55-2.67 (m, 0.88 H), 2.73-2.92
(m, 0.24 H), 2.97-3.08 (m, 0.88 H), 3.16 (dddd, J ) 11.5, 11.5,
cis- a n d tr a n s-2-Eth en ylid en e-4-p h en ylcyclop en ta n ol
(32a) an d 1-(1-Ch lor oeth en yl)-4-ph en ylcyclopen ten e (32b).

4410 J . Org. Chem., Vol. 64, No. 12, 1999
Clive et al.
7.0, 7.0 Hz, 0.12 H), 3.50-3.62 (m, 0.88 H), 4.88-5.01 [m, 2
H, including two sets of doublets at δ 4.93 (J ) 3.4 Hz) and δ
4.94 (J ) 3.4 Hz)], 7.18-7.36 (m, 5 H); 13C NMR (CDCl3, 75.5
MHz) δ 27.1 (q′), 28.9 (q′), 37.7 (t′), 37.8 (t′), 42.5 (d′), 49.3 (t′),
79.2 (t′), 79.6 (t′), 110.5 (s′), 126.3 (d′), 126.5 (d′), 127.0 (d),
127.1 (d′), 128.47 (d′), 128.54 (d′), 143.6 (s′), 143.7 (s′), 201.5
(s′), 202.1 (s′); exact mass calcd for C14H16O 200.12012, found
200.12000.
for Research Development, Pretoria, South Africa.
M.J .M. was on sabbatical leave from the University of
Venda, Northern Province, South Africa. We thank a
referee for advice on the mechanism of the Bu2SnCl2/
Bu2SnH2 reduction.
Su p p or tin g In for m a tion Ava ila ble: Procedures for mak-
ing 27, 28, 28a -acetate, 29-32, 32b, 33-46, 48-51, and 53-
66, NMR spectra for compounds not analyzed, and X-ray data
on 27a . This material is available free of charge via the
Internet at http://pubs.acs.org.
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada for finan-
cial support. M.H.D.P. held an NSERC Graduate Fel-
lowship and M.J .M. a Fellowship from the Foundation
J O990086I