Palladium-Mediated Cyclization on Carbohydrate Templates. 2. Synthesis of Enantiopure Tricyclic Compounds

Article abstract of DOI:10.1021/jo970817j

The bromo substituted unsaturated carbohydrates 3a-f were prepared from 3,4,6-tri-O-acetyl-D-glucal by Ferrier reaction with the appropriate allylic or homoallylic alcohol, deacetylation followed by monosilylation with TBDMSC1, and then alkylation with BrCH₂CBr=CH₂. The N- and C-analogues 4a,b were synthesized by palladium alkylation of the intermediate carbonate with TsNHCH₂CBr=CH₂ and (MeO₂C)_2,CHCH₂CBr=CH₂) respectively. Treatment of the unsaturated carbohydrates 3a, 4a, and 4b with a catalytic amount of Pd(OAc)₂/PPh₃ in CH₃CN/H₂O, in the presence of Bu₄NHSO₄ and NEt₃, afforded the tricyclic compounds 5, 6, and 7, respectively. Under the same conditions, the analogue tricyclic compounds 8, 9, and 10 were formed starting from 3b-d. In the case of compounds 3e and 3f, the formation of the bicyclic glucal 11 via an already described β-alkoxyelimination was only observed. Moreover, trapping of the σ-alkylpalladium intermediate obtained from 3e with an external nucleophile yielded the 2-deoxy carbohydrate 12 and the 2,3-unsaturated sugar 13, using respectively sodium formate and sodium tetraphenylborate.

Full text of DOI:10.1021/jo970817j

J . Org. Chem. 1997, 62, 6827-6832
6827
P a lla d iu m -Med ia ted Cycliza tion on Ca r boh yd r a te Tem p la tes. 2.
Syn th esis of En a n tiop u r e Tr icyclic Com p ou n d s
J ean-Flaubert Nguefack, Ve´ronique Bolitt, and Denis Sinou*
Laboratoire de Synthe`se Asyme´trique, Associe´ au CNRS, CPE Lyon, Universite´ Claude Bernard Lyon I,
43 Boulevard du 11 Novembre 1918 69622 Villeurbanne Ce´dex, France
Received May 7, 1997X
The bromo substituted unsaturated carbohydrates 3a -f were prepared from 3,4,6-tri-O-acetyl-D-
glucal by Ferrier reaction with the appropriate allylic or homoallylic alcohol, deacetylation followed
by monosilylation with TBDMSCl, and then alkylation with BrCH2CBrdCH2. The N- and
C-analogues 4a ,b were synthesized by palladium alkylation of the intermediate carbonate with
TsNHCH2CBrdCH2 and (MeO2C)2CHCH2CBrdCH2, respectively. Treatment of the unsaturated
carbohydrates 3a , 4a , and 4b with a catalytic amount of Pd(OAc)2/PPh3 in CH3CN/H2O, in the
presence of Bu4NHSO4 and NEt3, afforded the tricyclic compounds 5, 6, and 7, respectively. Under
the same conditions, the analogue tricyclic compounds 8, 9, and 10 were formed starting from 3b-
d . In the case of compounds 3e and 3f, the formation of the bicyclic glucal 11 via an already
described â-alkoxyelimination was only observed. Moreover, trapping of the σ-alkylpalladium
intermediate obtained from 3e with an external nucleophile yielded the 2-deoxy carbohydrate 12
and the 2,3-unsaturated sugar 13, using respectively sodium formate and sodium tetraphenylborate.
Carbohydrates are readily available, enantiopure ma-
terials possessing a variety of attractive functional and
stereochemical features. They are very useful intermedi-
ates for further synthetic transformations and particu-
larly for the synthesis of polycyclic enantiopure com-
pounds, such as furo- and pyrano[2,3-b]pyran, closely
related to the structural framework of many natural
products.1 In this field, the free-radical route is an
extremely efficient methodology for the cyclization of
carbohydrate derivatives. The different strategies in-
volve radicals located either on the carbohydrate and
leading to bicyclo[2,2,2] or -[2,2,1] systems2 or to fused
rings3 or on radicals located on a chain and cyclizing on
a double bond external4 or internal5 to the sugar ring and
allowing formation of bi- or tricyclic systems.
Pauson-Khand reaction7 of appropriate glycals have
been studied as tools in the synthesis of complex carbo-
and heterocyclic frameworks. These cyclizations gener-
ally occur with a high degree of stereoselectivity.
We recently described the use of an intramolecular
palladium-catalyzed Heck reaction in carbohydrate chem-
istry, leading to bicyclic glucals via an unusual dealkoxy-
palladation pathway.8 We also communicated prelimi-
nary results of a study concerning an easy access to
heterotricyclic systems via this cyclization reaction.9
In the present paper, we describe a full account of our
results concerning the applications and the limitations
of this methodology for the synthesis of functionalized
enantiopure heterotricyclic systems. It is to be noted
that, after our initial report on the use of the Heck-type
cyclization in carbohydrate chemistry, other authors have
described interesting results leading to enantiopure fused
furo- and pyrano[2,3-b]pyrans, using this strategy.10
In recent years, increasing attention has been devoted
to the organometallic-catalyzed cyclization of carbohy-
drates. Palladium-mediated cycloisomerization6 and the
Resu lts a n d Discu ssion
* To whom correspondance should be addressed. Fax: 33 (0)4 72
44 81 60. E-mail: sinou@univ-lyon1.fr.
P r ep a r a tion of th e Un sa tu r a ted Sta r tin g Ca r bo-
X Abstract published in Advance ACS Abstracts, September 15, 1997.
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A. H.; Valverde, S. J . Chem. Soc., Chem. Commun. 1992, 613.
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Rama Rao, A. V.; Yadav, J . S.; Rao, C. S.; Chandrasekhar, S. J . Chem.
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B.; J imeno, M. L. Tetrahedron Lett. 1992, 33, 5261. (e) Contelles, J .
M.; Mart`ınez-Grau, A.; Ripoll, M. M.; Cano, H.; Fo´ces-Fo´ces, C. J . Org.
Chem. 1992, 57, 403. (f) Araki, Y.; Endo, T.; Arai, Y.; Tanji, M.; Ishido,
Y. Tetrahedron Lett. 1989, 30, 2829. (g) Walton, R.; Fraser-Reid, B.
J . Am. Chem. Soc. 1991, 113, 5791. (h) Dickson, J . K.; Tsang, J r. R.;
Llera, J . H.; Fraser-Reid, B. J . Org. Chem. 1989, 54, 5350. (i) Yeung,
B. W. A.; Alonso, R. A.; Vite´, G. D.; Fraser-Reid, B. J . Carbohydr. Chem.
1989, 8, 413.
h yd r a t es. The requisite alkenyl 4,6-di-O-acetyl-2,3-
(5) (a) Lesueur, C.; Nouguier, R.; Bertrand, M. P.; Hoffmann, P.;
De Mesmaeker, A. Tetrahedron 1994, 50, 5369. (b) Bertrand, M. P.;
Lesueur, C.; Nouguier, R. Carbohydr. Lett. 1995, 1, 393. (c) Marco-
Contelles, J . Synth. Commun. 1994, 24, 1293. (d) Moufid, N.; Chap-
leur, Y.; Mayon, P. J . Chem. Soc., Perkin Trans. 1 1992, 991. (e)
Moufid, N.; Chapleur, Y.; Mayon, P. J . Chem. Soc., Perkin Trans. 1
1992, 999.
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2161.
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Marco-Contelles, J . J . Org. Chem. 1996, 61, 7666. (c) Voelter, W.; Al-
Abed, Y.; Al- Tel, T.; Naz, N. Tetrahedron Lett. 1994, 35, 8581. (d)
Voelter, W.; Al-Abed, Y.; Al-Tel, T.; Ficher, R.; Hiller, W.; Naz, N. J .
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Commun. 1995, 1893. (b) Nguefack, J .-F.; Bolitt, V.; Sinou,D. J . Org.
Chem. 1997, 62, 1341.
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59.
(10) (a) Tenaglia, A.; Karl, F. Synlett 1996, 327. (b) For the free-
radical-mediated cyclization of dodecan-1,6-dien-11-ynes in carbohy-
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here, see: Marco-Contelles, J . J . Chem. Soc., Chem. Commun. 1996,
2629.
S0022-3263(97)00817-7 CCC: $14.00 © 1997 American Chemical Society

6828 J . Org. Chem., Vol. 62, No. 20, 1997
Nguefack et al.
Sch em e 1a
a
Reagents and conditions: (1) ROH, BF3‚OEt2, rt; (2) cat. MeONa, MeOH, quant; (3) TBDMSCl, NEt3, imidazole, CH2Cl2, rt, 24 h; (4)
NaH, BrCH2CBrdCH2, THF, 60 °C, 24 h; (5) ClCO2Me, DMAP, py, CH2Cl2, 0 °C to rt, 24 h; (6) for compound 4a (4b): TsNHCH2CBrdCH2
[(MeO2C)2CHCH2CBrdCH2], Pd2dba3, dppb, THF, 60 °C, 24 h.
Sch em e 2
Sch em e 3
dideoxy-R-D-erythro-hex-2-enopyranosides (1a -f) were
obtained in 40-75% yield from 3,4,6-tri-O-acetyl-D-glucal
and the appropriate unsaturated alcohol using Ferrier’s
procedure (Scheme 1).11 Deacetylation of 1a -f using a
catalytic amount of sodium methoxide in methanol af-
forded the diols, which were treated with TBDMSCl,
NEt3, and imidazole, in dichloromethane to give the
monosilylated carbohydrates 2a -f in 60-76% yield.
Treatment of 2a -f with NaH and 2,3-dibromopropene
in THF at 60 °C gave the 4-O-alkylated carbohydrates
3a -f in 63-84% yield.
Reaction of the unsaturated carbohydrate 2a with
methyl chloroformate gave the corresponding carbonate
which was directly treated with TsNHCH2CBrdCH2 or
(MeO2C)2CHCH2CBrdCH2 in THF at 60 °C in the pres-
ence of tris(dibenzylidene acetone)dipalladium(0) and 1,4-
bis(diphenylphosphino)butane (dppb) and led respectively
to the 4-N-alkylated carbohydrate 4a (90% yield) and to
the 4-C-alkylated carbohydrate 4b (65% yield).
P a lla d iu m -Med ia ted Cycliza tion . The cyclization
of compounds 3a -f and 4a ,b was performed under the
previously described conditions8b in the presence of
Pd(OAc)2, PPh3, Bu4NHSO4, and NEt3, at 80 °C in
CH3CN/H2O (1/1) as the solvent.
Using these conditions, the unsaturated carbohydrate
3a was transformed into the tricyclic compound 5, after
24 h, in 75% yield (Scheme 2). This compound 5 shows
characteristic chemical shifts, particularly at δ 5.59, 4.06,
3.60, 3.66, and 3.20 ppm, respectively, for the hydrogen
atoms H-1, H-4, H-8, H-3, and H-9, with coupling
constants J 1,9 ) 6.6, J 9,8 ) 7.4, J 8,4 ) 7.4, and J 4,3 ) 7.4
Hz, characteristic of a cis-syn-cis arrangement.7d More-
over, this relative stereochemistry was confirmed by NOE
experiments. Irradiation of the H-9 signal at δ 3.20 ppm
gave an enhancement of the signals corresponding to H-1
and H-8 of 16 and 12%, respectively, while irradiation of
the H-8 signal showed an enhancement of the signals of
H-9 and H-4 of 3% and 11%, respectively.
The N-tosyl derivative 4a and the C-substituted car-
bohydrate 4b gave under these conditions the tricyclic
aza compound 6 and carba compound 7, in 80 and 78%
yield, respectively (Scheme 2). The 1H and 13C NMR
spectra (see Experimental Section) are again character-
istic of a cis-syn-cis junction of the cycles.
We then studied the influence of the aglycon’s struc-
ture, particularly the degree and the position of the
substitution on the double bond in our cyclization reac-
tion.
The unsaturated sugars 3b and 3c gave respectively
the tricyclic compounds 8 and 9 in 77% and 78% yield
(Scheme 3). For compound 8, the main 1H NMR char-
acteristics are the signals of the hydrogen atoms H-1,
H-9, H-8, and H-4 at δ 5.52, 2.38, 2.90, and 3.34 ppm,
respectively, with the coupling constants J 1,9 ) 6.8, J 9,8
) 6.0, J 8,4 )8.8, and J 4,3 ) 10.0 Hz. For compound 9,
the chemical shifts for H-1, H-9, H-8, and H-4 are at δ
(11) Ferrier, R. J .; Prasad, M. J . J . Chem. Soc. (C) 1969, 570.
5.54, 2.58, 2.90, and 3.21 ppm, respectively, with J 1,9 )

Palladium-Mediated Cyclization of Carbohydrates
J . Org. Chem., Vol. 62, No. 20, 1997 6829
Sch em e 4
Sch em e 5
6.8, J 9,8 ) 6.4, and J 8,4 ) 9.7 Hz. These values are again
in agreement with a cis-syn-cis relationship of the three
cycles.7d The exo configuration of the vinyl group and so
the cis relationship between H-9 and the vinyl group was
expected from the high coupling constants (10.5 and 11.0
Hz) between H-9 and the allylic proton H-10. This
stereochemistry was confirmed by NOE experiments. For
product 8, irradiation of the H-9 signal at δ 2.38 ppm
shows an enhancement of the signals of H-1 (13.7%), H-8
(8.9%), and H-4 (2.5%) and more important, of the signals
corresponding to the vinylic protons CHd at δ 5.58 ppm
(8.7%) and dCH2 at δ 5.06 ppm (2%) and no enhancement
of the signal of the allylic proton H-10 at δ 3.06 ppm.
For compound 9, irradiation of the H-9 signal at δ 2.58
ppm shows again an enhancement of the signals of H-1
(13.9%), H-8 (8.7%), H-4 (1.9%), of the vinylic proton at
δ 4.85 ppm (2.0%), and also of the methyl group at δ 1.66
ppm (7.7%); no enhancement of the allylic hydrogen H-10
was observed.
complex, the formation of the endo σ-alkylpalladium
being disfavored due to some steric effects. Compounds
8 and 9 are formed by the usual â-hydride elimination
pathway. For compound 10, the cyclization leads to the
exo σ-alkylpalladium complex; however, the â-hydride
elimination which is a syn-elimination process only leads
to the Z isomer 10.
Since the compound 3e gave the bicyclic compound 11
under the standard conditions, we tried to trap the
σ-alkylpalladium intermediate C by an external nucleo-
phile, using Grigg’s methodology,12 expecting the forma-
tion of a tricyclic structure. The use of sodium formate
as the trapping reagent in the case of compound 3e gave
a mixture of bicyclic compounds 11 and 12, in 10% and
56% yield, respectively. The main 1H NMR character-
istics of the deoxycarbohydrate 12 are the signals of H-1
(δ 4.85 ppm), H-2 (δ 1.68 and 2.68 ppm), H-3 (δ 2.73 and
2.80 ppm), and H-4 (δ 3.95 ppm) and, more important,
Cyclization of the unsaturated carbohydrate 3d gave
the tricyclic compound 10 in 79% yield (Scheme 3). The
cis-syn-cis relationship of the three cycles is confirmed
1
by the H NMR spectrum, particularly by the coupling
constants J 1,9 ) 6.5, J 9,8 ) 6.8, and J 8,4 ) 6.9 Hz. The Z
configuration of the cinnamyl moiety was determined by
NOE experiments. Effectively, enhancement of the H-9
signal (3.8%) was observed by irradiation of the ethylenic
proton of the cinnamyl moiety at δ 6.8 ppm.
When the reaction was extended to the unsaturated
carbohydrates 3c and 3f (Schemes 3 and 4), only the
bicyclic compound 11 was obtained in 72% and 78% yield,
respectively.
Discu ssion
the coupling constants J 1,2 ) 6.0 Hz and 5.2 Hz, J 2,2
)
The mechanism of this cyclization starts with the
formation of a σ-vinylpalladium intermediate A by oxida-
tive addition of compound 3 or 4 to the palladium(0)
complex (Scheme 5). An association-insertion process,
involving the unsaturation of the pyranose moiety, gives
a new σ-alkylpalladium species B. Another association-
insertion sequence involving the double bond of the
aglycon moiety leads to the formation of the σ-alkylpal-
ladium complex C via a 5-exo-trig process. In the case
of 3a -d and 4, a â-hydride elimination occurs leading
to the tricyclic compounds 5-10. For 3e, there is no
hydrogen atom available for the â-hydride elimination
and so the σ-alkylpalladium intermediate B leads to the
bicyclic compound 11 via a â-dealkoxypalladation reac-
tion, as shown in the preceeding paper.8b Concerning the
cyclization of substrate 2f, the formation of the bicyclic
compound 11 instead of a tricyclic one indicates that
6-exo-trig cyclization is disfavored versus â-dealkoxy-
palladation.
14.3 Hz, J 2,3 ) 9.3 and 6.2 Hz, and J 3,4 ) 7.3 Hz. The
formation of the bicyclic 12 indicates that, in this
particular case, the σ-alkylpalladium intermediate C is
less favored than B, probably due to some steric effects
(Scheme 5).
When the cyclization of 3e was carried out in the
presence of sodium tetraphenylborate as the trapping
reagent, a mixture of compounds 11 and 13 was obtained
in 60% and 20% yield, respectively. Compound 13 was
formed by trapping of the vinylpalladium intermediate
A via a Suzuki-type reaction, and we never observed any
compound resulting from the trapping of intermediate
B. This result indicates the difficulty of trapping this
intermediate B by a large nucleophile (Scheme 6). There
is a competition with the â-dealkoxypalladation reaction,
which is favored in this case.
Con clu sion
The exo stereochemistry of compounds 8 and 9 or the
Z stereochemistry for compound 10 can be explained by
the mechanism proposed for the cyclization (Scheme 7).
Starting from carbohydrates 3b-d , the approach of the
palladium complex is to the double bond of the aglycon,
and so the cyclization leads to the exo σ-alkylpalladium
The results reported here give a new insight into
palladium-mediated cyclization in sugar chemistry. Thus,
cyclization of unsaturated carbohydrates stereospecifi-
(12) Grigg, R.; Dorrity, M. J.; Malone, J. F.; Sridharan, V.; Sukirthal-
ingham, S. Tetrahedron Lett. 1990, 31, 1343.

6830 J . Org. Chem., Vol. 62, No. 20, 1997
Nguefack et al.
Sch em e 6
Sch em e 7
mmol), and 0.05 equiv of imidazole (30 mg, 0.43 mmol) in
CH2Cl2 (30 mL) at room temperature for ca. 24 h (until TLC
analysis showed no more starting material). After addition
of 25 mL of water and extraction with 3 × 30 mL of CH2Cl2,
the organic layer was dried. After evaporation of the solvent
under reduced pressure, the residue was purified by column
chromatography using petroleum ether/ethyl acetate as the
eluent to give compounds 2a -f.
cally gave the corresponding tricyclic systems. The
reaction conditions are very mild and the yields good. The
versatility of the pyranoside templates opens many
synthetic possibilities, as well as the use of functionalized
unsaturated chains. These endeavors as well as the use
of these enantiopure synthons for the conversion to
natural products will be reported in due course.
P r ep a r a tion of Alk en yl 4-O-(2′-Br om op r op -2′-en yl)-6-
O-(ter t-bu tyld im eth ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-
2-en op yr a n osid es (3a -f). To the 4-hydroxyl compound 2
(1.22 mmol) in 12 mL of dry THF was added 54 mg (1.34 mmol)
of NaH (60%). The solution was stirred for 1 h at 60 °C and
488 mg (2.44 mmol) of 2,3-dibromopropene was added. After
being stirred at 60 °C for 14 h, the solution was cooled, and
the reaction was quenched with 10 mL of H2O and extracted
with 3 × 15 mL of Et2O. After being dried, the solvent was
removed under reduced pressure and the crude product was
purified by column chromatography with petroleum ether/ethyl
acetate as the eluent to afford the O-alkylated compound 3.
Allyl 4-O-(2′-Br om op r op -2′-en yl)-6-O-(ter t-bu tyld im e-
t h ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-en op yr a n osid e
(3a ): yield 82%; oil; Rf 0.47 (petroleum ether/ethyl acetate 10/
1); [R]20D +86.3 (c 1.0, CH2Cl2); 1H NMR (200 MHz) δ 6.06 (brd,
1H, J ) 10.2 Hz), 5.94 (dddd, 1H, J ) 5.1, 6.3, 10.3, 17.2 Hz),
5.82 (dd, 1H, J ) 1.5, 3.0 Hz), 5.79 (ddd, 1H, J ) 2.1, 2.6, 10.2
Hz), 5.61 (dd, 1H, J ) 0.9, 1.5 Hz), 5.30 (ddd, 1H, J ) 1.6, 3.0,
17.2 Hz), 5.20 (ddd, 1H, J ) 1.4, 3.0, 10.3 Hz), 5.02 (brdd, 1H,
J ) 1.4, 2.6 Hz), 4.29 (ddt, 1H, J ) 1.6, 5.1, 12.7 Hz), 4.23 (d,
1H, J ) 13.9 Hz), 4.14 (d, 1H, J ) 13.9 Hz), 4.08 (ddt, 1H, J
) 1.2, 6.3, 12.7 Hz), 4.03-4.00 (m, 1H), 3.80-3.79 (m, 3H),
0.92 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H); 13C NMR (50 MHz) δ
134.2, 130.5, 129.3, 127.2, 118.0, 117.3, 93.5, 73.0, 70.7, 70.6,
69.0, 62.9, 26.1, 18.5, -5.0, -5.1. Anal. Calcd for C18H31O4-
SiBr: C, 51.54; H, 7.45. Found: C, 51.50; H, 7.28.
Exp er im en ta l Section
Gen er a l Meth od s a n d Ma ter ia ls. All reactions were
monitored by thin-layer chromatography carried out on 0.2 mm
silica gel plates (60 F-254, Merck). Compounds were visual-
ized under UV light (254 nm) or by spraying with a H2SO4
solution and heating. Column chromatography was performed
on silica gel 60 (40-63 mesh ASTM, Macherey-Nagel). NMR
spectra were obtained in CDCl3 and chemical shifts are given
in ppm on the δ scale from internal tetramethylsilane. THF
was distilled from sodium/benzophenone, purged, and kept
under a nitrogen atmosphere. Reactions involving palladium
complexes were carried out in a Schlenck tube under a
nitrogen atmosphere. 3,4,6-Tri-O-acetyl-D-glucal, 2,3-dibro-
mopropene, Bu4NHSO4, TBDMSCl, DMAP, propenol, (E)-but-
2-enol, 3-methylbut-2-enol, (E)-3-phenylprop-2-enol, 2-meth-
ylprop-2-enol, but-3-en-1-ol, Pd(OAc)2, Pd2(dba)3, dppb, NaBPh4,
and HCO2Na were purchased from Aldrich Chemical. Tosyl(2-
bromoprop-2-enyl)amine,13 and 1,1-bis(methoxycarbonyl)-3-
bromobut-3-ene14 were prepared by known procedures.
Sta n d a r d P r ep a r a tion of Alk en yl 4,6-Di-O-a cetyl-2,3-
dideoxy-r-D-er yth r o-h ex-2-en opyr an osides (1a-f). To 3,4,6-
tri-O-acetyl-D-glucal (5 g, 18.5 mmol) in 25 mL of benzene were
added 2 equiv (37.0 mmol) of the allylic or homoallylic alcohol
and 0.5 equiv (9.25 mmol, 1.15 mL) of BF3‚OEt2. The resulting
mixture was stirred at room temperature until TLC showed
no more starting glucal. After addition of Na2CO3 (5 g) and
filtration of the solid, the solvent was evaporated under
reduced pressure. The residue was purified by column chro-
matography on silica gel with petroleum ether/ethyl acetate
as the eluent, to give compounds 1a -f.
(E)-Bu t-2-en yl 4-O-(2′-Br om op r op -2′-en yl)-6-O-(ter t-bu -
t yld im et h ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-en op y-
r a n osid e (3b): yield 67%; oil; Rf 0.72 (petroleum ether/ethyl
1
acetate 5/1); [R]20 +78.2 (c 1.1, CH2Cl2); H NMR (200 MHz)
D
δ 6.05 (brd, 1H, J ) 10.2 Hz), 5.94 (brs, 1H), 5.80 (ddd, 1H, J
) 2.3, 2.4, 10.2 Hz), 5.70-5.65 (m, 2H), 5.60 (brs, 1H), 5.01
(brs, 1H), 4.26-3.78 (m, 8H), 1.72 (dd, 3H, J ) 1.0, 6.1 Hz),
0.92 (s, 9H), 0.10 (s, 6H); 13C NMR (50 MHz) δ 129.4, 130.3,
129.9, 127.2, 127.3, 117.8, 93.2, 72.9, 70.7, 70.4, 68.6, 62.9, 26.0,
18.5, 17.9, -5.1, -5.2. Anal. Calcd for C19H33O4SiBr: C,
52.64; H, 7.67. Found: C, 53.06; H, 7.58.
St a n d a r d P r ep a r a t ion of Alk en yl 6-O-(ter t-Bu t yld i-
m et h ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-en op yr a n o-
sid es (2a -f). The corresponding diacetate (8.66 mmol) was
treated with a catalytic amount of sodium methoxide in
methanol (100 mL) at room temperature. After evaporation
of the solvent, the free hydroxyl unsaturated glycoside was
obtained in quantitative yield and used without further
purification. This diol was treated with 1.25 equiv of TBDM-
SCl (1.62 g, 10.77 mmol), 1.3 equiv of NEt3 (1.6 mL, 11.2
3-Met h ylb u t -2-en yl 4-O-(2′-Br om op r op -2′-en yl)-6-O-
(ter t-bu tyld im eth ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-
en op yr a n osid e (3c): yield 66%; oil; Rf 0.76 (petroleum ether/
1
ethyl acetate 5/1); [R]20 +73.5 (c 1.0, CH2Cl2); H NMR (200
D
(13) Bussas, R.; Kresze, G. Liebigs Ann. Chem. 1980, 629.
(14) Grigg, R.; Stevenson, P.; Worakun, T. Tetrahedron 1988, 44,
2033.
MHz) δ 6.04 (brd, 1H, J ) 10.2 Hz), 5.94 (dd, 1H, J ) 0.9, 2.5
Hz), 5.78 (ddd, 1H, J ) 2.1, 2.5, 10.2 Hz), 5.60 (dd, 1H, J )

Palladium-Mediated Cyclization of Carbohydrates
J . Org. Chem., Vol. 62, No. 20, 1997 6831
0.9, 1.6 Hz), 5.41-5.32 (m, 1H), 5.01 (brd, 1H, J ) 1.2, 2.5
Hz), 4.30-3.82 (m, 8H), 1.75 (s, 3H), 1.70 (s, 3H), 0.93 (s, 9H),
0.10 (s, 6H); 13C NMR (50 MHz) δ 137.9, 130.4, 129.5, 127.5,
120.7, 117.9, 93.3, 73.0, 70.8, 70.5, 64.4, 63.0, 26.0, 25.9, 18.6,
18.1, -5.0, -5.2. Anal. Calcd for C20H35O4SiBr: C, 53.68; H,
7.88. Found: C, 53.76; H, 7.99.
+34.3 (c 1.05, CH2Cl2); 1H NMR (200 MHz) δ 6.01 (brd, 1H, J
) 10.4 Hz), 5.96 (dddd, 1H, J ) 5.5, 6.3, 10.6, 17.1 Hz), 5.79
(brdd, 1H, J ) 2.4, 10.4 Hz), 5.36 (ddd, 1H, J ) 1.6, 2.9, 17.1
Hz), 5.09 (ddd, 1H, J ) 1.4, 2.9, 10.6 Hz), 5.01 (dd, 1H, J )
1.5, 9.5 Hz), 4.89 (dd, 1H, J ) 1.0, 2.3 Hz), 4.36 (ddt, 1H, J )
1.6, 5.5, 12.8 Hz), 4.18 (ddt, 1H, J ) 1.4, 6.3, 12.8 Hz), 3.98-
3.76 (m, 3H), 0.91 (s, 9H), 0.08 (s, 6H); 13C NMR (50 MHz) δ
135.0, 132.0, 128.0, 117.4, 93.7, 70.6, 69.3, 69.2, 62.6, 52.9, 25.9,
18.2, -5.4, -5.3. Anal. Calcd for C17H30O6Si: C, 56.95; H,
8.43. Found: C, 56.61; H, 8.40.
Allyl 4-[N-Tosyl-N-(2′-br om op r op -2′-en yl)a m in o]-6-O-
(ter t-bu tyld im eth ylsilyl)-2,3,4-tr id eoxy-r-D-er yth r o-h ex-
2-en op yr a n osid e (4a ): yield 90%; oil; Rf 0.45 (petroleum
ether/ethyl acetate 5/1); [R]20D +120.4 (c 1.3, CH2Cl2); 1H NMR
(300 MHz) δ 7.45 (d, 2H, J ) 8.3 Hz), 7.32 (d, 2H, J ) 8.3 Hz),
6.00 (brd, 1H, J ) 10.3 Hz), 6.00-5.86 (m, 1H), 5.85 (ddd, 1H,
J ) 2.6, 2.8, 10.3 Hz), 5.63 (brd, 1H, J ) 1.7 Hz), 5.26 (ddd,
1H, J ) 1.6, 1.6, 17.2 Hz), 5.19 (brs, 1H), 5.17 (ddd, 1H, J )
1.6, 1.6, 10.3 Hz), 4.95 (d, 1H, J ) 3.0 Hz), 4.37 (brd, 1H, J )
9.7 Hz), 4.24 (ddd, 1H, J ) 1.6, 5.2, 12.6 Hz), 4.21 (d, 1H, J )
17.1 Hz), 3.99 (brdd, 1H, J ) 6.6, 12.6 Hz), 3.95 (ddd, 1H, J )
1.8, 6.5, 9.7 Hz), 3.87 (dd, 1H, J ) 1.8, 11.3 Hz), 3.76 (d, 1H,
J ) 17.1 Hz), 3.60 (dd, 1H, J ) 6.5, 11.3 Hz), 2.36 (s, 3H),
0.91 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H); 13C NMR (50 MHz) δ
144.5, 137.1, 135.4, 131.3, 130.3, 127.9, 127.6, 127.4, 118.7,
118.2, 93.4, 86.5, 69.1, 68.7, 63.2, 53.5, 25.9, 21.7, 18.4, -5.1,
-5.2. Anal. Calcd for C25H38O5SSiNBr: C, 52.43; H, 6.68; N,
2.44. Found: C, 52.34; H, 6.64; N, 2.48.
Allyl 6-O-(ter t-Bu tyld im eth ylsilyl)-4-[1′,1′-bis(m eth ox-
ycar bon yl)-3′-br om obu t-3′-en yl]-2,3,4-tr ideoxy-r-D-er yth r o-
h ex-2-en op yr a n osid e (4b): yield 65%; oil; Rf 0.45 (petroleum
ether/ethyl acetate 10/1); [R]20D +94.6 (c 1.2, CH2Cl2); 1H NMR
(200 MHz) δ 6.07 (dd, 1H, J ) 4.4, 10.6 Hz), 5.94 (dd, 1H, J )
10.4, 17.3 Hz), 5.85 (ddd, 1H, J ) 1.6, 2.7, 10.6 Hz), 5.75 (d,
1H, J ) 1.8 Hz), 5.68 (d, 1H, J ) 1.8 Hz), 5.28 (brd, 1H, J )
17.3 Hz), 5.15 (brdd, 1H, J ) 1.3, 10.4 Hz), 5.13 (brd, 1H, J )
1.3 Hz), 4.30-4.17 (m, 2H), 3.99 (brdd, 1H, J ) 6.0, 12.9 Hz),
3.77 (s, 3H), 3.75 (s, 3H), 3.84-3.75 (m, 2H), 3.24 (brd, 1H, J
) 15.9 Hz), 3.15 (brd, 1H, J ) 15.9 Hz), 2.88 (dd, 1H, J ) 2.1,
4.3 Hz), 0.91 (s, 9H), 0.08 (s, 6H); 13C NMR (50 MHz) δ 170.6,
170.1, 135.4, 130.3, 127.9, 127.6, 122.8, 117.5, 93.0, 73.4, 69.2,
64.9, 60.8, 53.5, 53.2, 44.2, 37.9, 26.7, 19.0, -4.6, -4.7. Anal.
Calcd for C23H37O7SiBr: C, 51.77; H, 6.98. Found: C, 52.01;
H, 6.90.
Sta n d a r d P a lla d iu m (0)-Med ia ted Cycliza tion P r ocess.
The 2,3-unsaturated glycoside (0.96 mmol) in 7.5 mL of
acetonitrile and 1.5 mL of water was stirred in the presence
of Pd(OAc)2 (21 mg, 0.095 mmol), PPh3 (50 mg, 0.19 mmol),
NEt3 (340 mL, 2.39 mmol), and Bu4NHSO4 (324 mg, 0.95
mmol) at 80 °C until TLC analysis showed that all the starting
material was consumed (15-24 h). After addition of 10 mL
of water, the mixture was extracted with 4 × 20 mL of ethyl
ether. Evaporation of the solvent under reduced pressure gave
an oil which was purified by column chromatography.
(1S,3S,4S,8R,9S)-3-[[(ter t-Bu tyld im eth ylsilyl)oxy]m e-
t h y l ] - 7 , 1 0 - b i s ( m e t h y l e n e ) - 2 , 5 , 1 2 - t r i o x a t r i -
cyclo[7,3,0,04,8]d od eca n e (5): yield 75%; oil; Rf 0.41 (petro-
leum ether/ethyl acetate 10/1); [R]20D +52.6 (c 1.1, CH2Cl2); 1H
NMR (400 MHz) δ 5.59 (d, 1H, J ) 6.6 Hz), 5.29 (ddd, 1H, J
) 2.5, 2.5, 2.5 Hz), 5.25 (ddd, 1H, J ) 2.5, 2.5, 2.5 Hz), 5.19
(ddd, 1H, J ) 2.1, 2.1, 2.1 Hz), 4.98 (ddd, 1H, J ) 2.1, 2.2, 2.2
Hz), 4.68 (dddd, 1H, J ) 2.3, 2.3, 2.4, 13.0 Hz), 4.45 (ddd, 1H,
J ) 1.9, 2.7, 13.6 Hz), 4.43 (ddd, 1H, J ) 2.1, 3.8, 13.0 Hz),
4.31 (dddd, 1H, J ) 1.1, 2.6, 3.5, 13.6 Hz), 4.06 (dd, 1H, J )
7.4, 7.4 Hz), 3.86 (dd, 1H, J ) 2.8, 11.4 Hz), 3.75 (dd, 1H, J )
4.8, 11.4 Hz), 3.66 (ddd, 1H, J ) 2.8, 4.8, 7.8 Hz), 3.22-3.17
(m, 1H), 3.00 (dddd, 1H, J ) 1.1, 3.0, 7.4, 7.4 Hz), 0.80 (s, 9H),
0.09 (s, 3H), 0.08 (s, 3H); 13C NMR (75 MHz) δ 149.4, 147.1,
107.7, 107.1, 102.9, 77.1, 73.6, 73.5, 72.8, 64.7, 42.8, 41.1, 26.0,
18.5, -5.3, -5.2. Anal. Calcd for C18H30O4Si: C, 63.86; H,
8.93. Found: C, 63.88; H, 8.91.
(E)-3-P h en ylp r op -2-en yl 4-O-(2′-Br om op r op -2′-en yl)-6-
O-(ter t-bu tyld im eth ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-
2-en op yr a n osid e (3d ): yield 63%; oil; Rf 0.61 (petroleum
ether/ethyl acetate 10/1); [R]20D +49.6 (c 0.95, CH2Cl2); 1H NMR
(200 MHz) δ 7.40-7.21 (m, 5H), 6.62 (brd, 1H, J ) 15.9 Hz),
6.30 (ddd, 1H, J ) 5.6, 6.6, 15.9 Hz), 6.07 (brd, 1H, J ) 10.2
Hz), 5.93 (ddd, 1H, J ) 1.4, 1.5, 1.5 Hz), 5.81 (ddd, 1H, J )
2.1, 2.5, 10.2 Hz), 5.60 (dd, 1H, J ) 0.8, 1.4 Hz), 5.08 (dd, 1H,
J ) 1.2, 2.4 Hz), 4.43 (ddd, 1H, J ) 1.3, 5.6, 12.6 Hz), 4.24
(ddd, 1H, J ) 1.2, 6.6, 12.6 Hz), 4.20-4.13 (m, 2H), 4.07 (brd,
1H, J ) 12.2 Hz), 3.97-3.80 (m, 3H), 0.92 (s, 9H), 0.09 (s, 6H);
13C NMR (50 MHz) δ 132.9, 130.7, 128.7, 127.8, 127.3, 126.6,
125.8, 118.1, 93.5, 73.1, 70.8, 70.7, 68.6, 62.9, 26.2, 18.6, -5.0,
-5.1. Anal. Calcd for C24H35O4SiBr: C, 58.17; H, 7.12.
Found: C, 58.63; H, 6.99.
2-Meth ylp r op -2-en yl 4-O-(2′-Br om op r op -2′-en yl)-6-O-
(ter t-bu tyld im eth ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-
en op yr a n osid e (3e): yield 68%; oil; Rf 0.73 (petroleum ether/
1
ethyl acetate 5/1); [R]20 +65.2 (c 1.1, CH2Cl2); H NMR (200
D
MHz) δ 6.07 (ddd, 1H, J ) 1.1, 1.2, 10.2 Hz), 5.94 (dd, 1H, J
) 1.5, 3.0 Hz), 5.82 (ddd, 1H, J ) 2.1, 2.5, 10.2 Hz), 5.61 (dd,
1H, J ) 0.9, 2.1 Hz), 5.00 (s, 2H), 4.90 (s, 1H), 4.27-3.81 (m,
8H), 1.56 (s, 3H), 0.92 (s, 9H), 0.11 (s, 3H), 0.10 (s, 3H); 13C
NMR (50 MHz) δ 141.8, 129.4, 130.4, 127.2, 117.9, 112.3, 93.3,
73.0, 71.7, 70.7, 70.6, 62.8, 26.0, 19.7, 18.4, -5.1, -5.3. Anal.
Calcd for C19H33O4SiBr: C, 52.64; H, 7.67. Found: C, 53.02;
H, 7.58.
Bu t -3-en yl 4-O-(2′-Br om op r op -2′-en yl)-6-O-(ter t-b u -
tyld im eth ylsilyl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-en op yr a -
n osid e (3f): yield 84%; oil; Rf 0.47 (petroleum ether/ethyl
acetate 10/1); [R]20D +18.6 (c 1.0, CH2Cl2); 1H NMR (200 MHz)
δ 6.04 (brd, 1H, J ) 10.2 Hz), 5.94 (dd, 1H, J ) 1.6, 3.1 Hz),
5.91-5.78 (m, 1H), 5.79 (ddd, 1H, J ) 2.2, 2.8, 10.2 Hz), 5.61
(dd, 1H, J ) 1.0, 1.6 Hz), 5.12 (ddd, 1H, J ) 1.7, 3.4, 17.3 Hz),
5.05 (brdd, 1H, J ) 3.4, 10.2 Hz), 4.99 (brs, 1H), 4.23 (brd,
1H, J ) 13.8 Hz), 4.15 (brd, 1H, J ) 13.8 Hz), 4.07-3.78 (m,
5H), 3.54 (dt, 1H, J ) 6.8, 9.6 Hz), 2.41-2.30 (m, 2H), 0.91 (s,
9H), 0.09 (s, 6H); 13C NMR (50 MHz) δ 135.3, 129.5, 130.4,
127.4, 118.1, 116.6, 94.4, 73.1, 70.8, 70.6, 67.9, 63.0, 34.4, 26.2,
18.6, -5.0, -5.1. Anal. Calcd for C19H33O4SiBr: C, 52.65; H,
7.67. Found: C, 52.99; H, 7.76.
P r ep a r a t ion of Allyl 6-O-(ter t-Bu t yld im et h ylsilyl)-4-
[N-tosyl-N-(2′-br om op r op -2′-en yl)a m in o]-2,3,4-tr id eoxy-
r-D-er yth r o-h ex-2-en op yr a n osid e (4a ) a n d Allyl 6-O-(ter t-
Bu t yld im e t h ylsilyl)-4-[1′,1′-b is(m e t h oxyca r b on yl)-3′-
b r o m o b u t -3′-e n y l]-2,3,4-t r id e o x y -r-D -er yt h r o-h e x -2-
en op yr a n osid e (4b). To a solution of 2a (6.94 mmol) in 60
mL of CH2Cl2 at room temperature were added 170 mg (1.4
mmol) of DMAP, 2.8 mL (34.7 mmol) of pyridine, and 2.7 mL
(34.7 mmol) of methylchloroformate. The mixture was stirred
for 24 h at room temperature. After addition of 60 mL of a
water solution of CuSO4‚5H2O, the product was extracted with
4 × 50 mL of Et2O. The organic layer was dried, the solvent
was removed under reduced pressure, and the crude product
was purified by column chromatography with petroleum ether/
ethyl acetate 3/1 as the eluent to give the carbonate (75%). To
a solution of this carbonate (1.44 mmol) in 10 mL of dry THF
was added 838 mg (2.89 mmol) of TsNHCH2CBrdCH2 or 726
mg (2.89 mmol) of (MeO2C)2CHCH2CBrdCH2, and the cata-
lytic system obtained by reacting Pd2(dba)3 (33 mg, 0.036
mmol) and dppb (31 mg, 0.072 mmol) in 10 mL of THF was
added. The mixture was stirred at 60 °C for 24 h and
quenched with 10 mL of H2O. After extraction with 3 × 15
mL of Et2O, the organic layer was dried. The solvent was
removed under reduced pressure to give an oil which was
purified by column chromatography using petroleum ether/
ethyl acetate as the eluent to give 4a or 4b.
(1S,3S,4S,8R,9S)-3-[[(ter t-Bu tyld im eth ylsilyl)oxy]m e-
t h y l ]-7 ,1 0-b i s (m e t h y l e n e )-5-N -t o s y l -2 ,1 2 -d i o x a -5 -
a za tr icyclo[7,3,0,04,8]d od eca n e (6): yield 80%; oil; Rf 0.30
Allyl 6-O-(ter t-Bu t yld im et h ylsilyl)-4-O-(m et h oxyca r -
bon yl)-2,3-dideoxy-r-D-er yth r o-h ex-2-en opyr an oside: yield
(petroleum ether/ethyl acetate 10/1); [R]20 +33.6 (c 1.33,
D
75%; oil; Rf 0.70 (petroleum ether/ethyl acetate 5/1); [R]20
CH2Cl2); H NMR (400 MHz) δ 7.68 (d, 2H, J ) 8.2 Hz), 7.32
1
D

6832 J . Org. Chem., Vol. 62, No. 20, 1997
Nguefack et al.
1
(d, 2H, J ) 8.2 Hz), 5.62 (d, 1H, J ) 6.8 Hz), 5.16 (ddd, 1H, J
) 2.1, 2.1, 2.3 Hz), 5.04 (m, 2H), 4.96 (brd, 1H, J ) 2.1 Hz),
4.81 (ddd, 1H, J ) 2.3, 4.6, 12.7 Hz), 4.36 (brd, 1H, J ) 12.7
Hz), 4.29 (dd, 1H, J ) 4.3, 11.9 Hz), 4.06-4.01 (m, 3H), 3.81
(dd, 1H, J ) 7.1, 7.1 Hz), 3.68 (ddd, 1H, J ) 2.0, 2.0, 15.1 Hz),
2.97 (dd, 1H, J ) 7.0, 7.2 Hz), 2.81 (brdd, 1H, J ) 7.4, 7.4 Hz),
2.51 (s, 3H), 0.91 (s, 9H), 0.09 (s, 6H); 13C NMR (75 MHz) δ
146.0, 143.9, 143.5, 132.7, 129.7, 128.2, 108.8, 108.6, 101.4,
72.8, 71.9, 64.6, 57.1, 55.3, 43.7, 41.8, 25.9, 21.5, 18.4, -4.9,
-5.0. Anal. Calcd for C25H37O5SSiN: C, 61.05; H, 7.58; N,
2.86. Found: C, 60.84; H, 7.64; N, 2.70.
CH2Cl2); H NMR (300 MHz) δ 7.32 (d, 2H, J ) 7.6 Hz), 7.21
(dd, 1H, J ) 7.3, 7.6 Hz), 7.07 (d, 2H, J ) 7.3 Hz), 6.68 (ddd,
1H, J ) 2.3, 2.4, 2.5 Hz), 5.65 (d, 1H, J ) 6.5 Hz), 5.31 (ddd,
1H, J ) 1.7, 2.5, 2.5 Hz), 5.20 (ddd, 1H, J ) 1.8, 2.0, 2.0 Hz),
5.01 (ddd, 1H, J ) 2.6, 2.8, 13.6 Hz), 4.64 (ddd, 1H, J ) 1.4,
1.7, 13.6 Hz), 4.42 (ddd, 1H, J ) 2.3, 4.0, 13.5 Hz), 4.29 (ddd,
1H, J ) 2.2, 2.4, 13.5 Hz), 4.08 (dd, 1H, J ) 6.1, 6.9 Hz), 3.83
(dd, 1H, J ) 2.7, 11.5 Hz), 3.79 (dd, 1H, J ) 4.7, 11.5 Hz),
3.71 (ddd, 1H, J ) 2.7, 4.7, 6.1 Hz), 3.32 (brdd, 1H, J ) 6.5,
6.8 Hz), 3.05 (brdd, 1H, J ) 6.8, 6.9 Hz), 0.90 (s, 9H), 0.09 (s,
3H), 0.08 (s, 3H); 13C NMR (50 MHz) δ 148.8, 139.5, 137.3,
128.5, 128.2, 126.9, 124.2, 101.1, 76.9, 73.1, 72.3, 71.7, 64.7,
43.8, 42.1, 26.0, 18.5, -5.1, -5.2. Anal. Calcd for
C24H34O4Si: C, 69.52; H, 8.26. Found: C, 70.01; H, 8.32.
Sta n d a r d Ta n d em P a lla d iu m (0)-Med ia ted Cycliza -
tion /Ion -Ca p tu r e P r oced u r e. Compound 3e (1.01 mmol)
was allowed to react under the previously described conditions
for palladium(0)-catalyzed cyclization in the presence of added
NaBPh4 (691 mg, 1.21 mmol) or HCO2Na (75 mg, 1.11 mmol),
respectively for 15 h at 60 °C or 24 h at 80 °C. The usual
workup gave the pure product after column chromatography.
(2-Meth ylp r op -2-en yl) 2,3,4-Tr id eoxy-2′,3′,4′,5′-tetr a h y-
d r o-6-O-(ter t-bu tyld im eth ylsilyl)-4′-m eth ylen e-r-D-r ibo-
h exop yr a n osid o[4,3-b]fu r a n (12): yield 56%; oil; Rf 0.40
(1S,3S,4R,8R,9S)-3-[[(ter t-Bu tyld im eth ylsilyl)oxy]m e-
th yl]-5,5-bis(m eth oxyca r bon yl)-7,10-bis(m eth ylen e)-2,12-
d ioxa tr icyclo[7,3,0,04,8]d od eca n e (7): yield 78%; oil; Rf 0.26
(petroleum ether/ethyl acetate 10/1); [R]20 +74.5 (c 1.15,
D
1
CH2Cl2); H NMR (400 MHz) δ 5.54 (d, 1H, J ) 5.8 Hz), 5.27
(ddd, 1H, J ) 2.2, 2.2, 2.4 Hz), 5.17 (ddd, 1H, J ) 1.7, 1.9, 2.2
Hz), 5.08 (ddd, 1H, J ) 1.6, 1.8, 2.1 Hz), 4.96 (ddd, 1H, J )
1.9, 2.1, 2.3 Hz), 4.59 (ddd, 1H, J ) 2.4, 4.3, 13.1 Hz), 4.38
(brd, 1H, J ) 13.1 Hz), 3.87 (ddd, 1H, J ) 2.2, 4.4, 5.8 Hz),
3.80 (dd, 1H, J ) 2.2, 11.5 Hz), 3.72 (s, 3H), 3.66 (s, 3H), 3.59
(dd, 1H, J ) 5.8, 11.5 Hz), 3.43 (ddd, 1H, J ) 1.5, 1.8, 15.9
Hz), 3.21-3.19 (m, 3H), 2.77 (ddd, 1H, J ) 2.3, 2.4, 15.9 Hz),
0.89 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR (75 MHz) δ
172.2, 169.8, 147.6, 146.5, 108.7, 108.4, 102.0, 72.6, 72.3, 65.3,
61.4, 53.0, 52.3, 44.5, 43.6, 41.4, 40.6, 25.9, 18.3, -5.2, -5.4.
Anal. Calcd for C23H36O7Si: C, 61.03; H, 8.01. Found: C,
61.40; H, 8.20.
(petroleum ether/ethyl acetate 10/1); [R]20 +107.5 (c 0.9,
D
CH2Cl2); 1H NMR (500 MHz) δ 5.02 (ddd, 2H, J ) 2.1, 2.1, 2.2
Hz), 4.95 (brs, 1H), 4.85 (dd, 1H, J ) 5.2, 6.0 Hz), 4.84 (brs,
1H), 4.45 (ddd, 1H, J ) 1.9, 3.7, 13.2 Hz), 4.31 (brd, 1H, J )
13.2 Hz), 4.14 (brd, 1H, J ) 12.9 Hz), 3.95 (dd, 1H, J ) 7.3,
8.4 Hz), 3.87 (dd, 1H, J ) 1.8, 11.0 Hz), 3.83 (brd, 1H, J )
12.9 Hz), 3.69 (dd, 1H, J ) 6.4, 11.0 Hz), 3.64 (ddd, 1H, J )
1.8, 6.4, 8.4 Hz), 2.74 (brdd, 1H, J ) 6.2, 9.3 Hz), 2.03 (ddd,
1H, J ) 5.2, 6.2, 14.3 Hz), 1.87 (ddd, 1H, J ) 6.0, 9.3, 14.3
Hz), 1.68 (s, 3H), 0.87 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H); 13C
NMR (50 MHz) δ 149.9, 142.2, 111.1, 104.9, 96.2, 76.6, 72.4,
70.5, 70.4, 64.3, 39.0, 30.9, 26.1, 19.6, 18.6, -5.2. Anal. Calcd
for C19H32O4Si: C, 64.73; H, 9.15. Found: C, 64.97; H, 9.04.
2-Meth ylp r op -2-en yl 6-O-(ter t-Bu tyld im eth ylsilyl)-4-O-
(2′-p h en ylp r op -2′-en yl)-2,3-d id eoxy-r-D-er yth r o-h ex-2-
en op yr a n osid e (13): yield 20%; oil; Rf 0.44 (petroleum ether/
(1S,3S,4S,8R,9S,10S)-3-[[(ter t-Bu tyld im eth ylsilyl)oxy]-
m e t h y l ] -7 -m e t h y l e n e -1 0 -v i n y l -2 ,5 ,1 2 -t r i o x a t r i -
cyclo[7,3,0,04,8]d od eca n e (8): yield 77%; oil; Rf 0.30 (petro-
leum ether/ethyl acetate 10/1); [R]20D +81.2 (c 1.0, CH2Cl2); 1H
NMR (500 MHz) δ 5.58 (ddd, 1H, J ) 8.2, 10.1, 17.1 Hz), 5.52
(d, 1H, J ) 6.8 Hz), 5.08 (ddd, 1H, J ) 2.0, 2.0, 2.6, Hz), 5.06
(dd, 1H, J ) 1.6, 17.1 Hz), 4.96 (ddd, 1H, J ) 1.9, 1.9, 2.0 Hz),
4.89 (dd, 1H, J ) 1.6, 10.1 Hz), 4.44 (dddd, 1H, J ) 1.8, 1.9,
2.1, 13.5 Hz), 4.30 (ddd, 1H, J ) 2.0, 2.1, 13.5 Hz), 4.14-4.07
(m, 2H), 3.87 (dd, 1H, J ) 4.9, 11.7 Hz), 3.82-3.72 (m, 2H),
3.34 (dd, 1H, J ) 8.8, 10.0 Hz), 3.06 (dddd, 1H, J ) 8.2, 8.4,
10.1, 10.5 Hz), 2.90 (brdd, 1H, J ) 6.0, 8.8 Hz), 2.38 (ddd, 1H,
J ) 6.0, 6.8, 10.5 Hz), 0.87 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H);
13C NMR (50 MHz) δ 147.4, 139.3, 115.5, 107.2, 101.9, 77.3,
72.3, 72.1, 71.8, 64.8, 45.3, 44.7, 41.3, 26.1, 18.6, -5.1. Anal.
Calcd for C19H32O4Si: C, 64.73; H, 9.15. Found: C, 65.17; H,
9.39.
ethyl acetate 10/1); [R]20 +95.8 (c 0.8, CH2Cl2); 1H NMR (200
D
MHz) δ 7.31-7.49 (m, 5H), 6.05 (brd, 1H, J ) 10.2 Hz), 5.79
(ddd, 1H, J ) 2.1, 2.2, 10.2 Hz), 5.53 (d, 1H, J ) 0.9 Hz), 5.34
(d, 1H, J ) 0.9 Hz), 4.99 (brs, 2H), 4.89 (brs, 1H), 4.55 (d, 1H,
J ) 12.8 Hz), 4.40 (d, 1H, J ) 12.8 Hz), 4.17 (d, 1H, J ) 12.6
Hz), 4.02-4.08 (m, 1H), 3.95 (d, 1H, J ) 12.6 Hz), 3.66-3.83
(m, 3H), 1.56 (s, 3H), 0.89 (s, 9H), 0.04 (s, 3H), 0.03 (s, 3H).
Anal. Calcd for C25H38O4Si: C, 69.72; H, 8.89. Found: C,
69.25; H, 8.98.
(1S,3S,4S,8R,9S,10S)-3-[[(ter t-Bu tyld im eth ylsilyl)oxy]-
m e t h y l]-7-m e t h y le n e -10-(p r o p -1′-e n -2′-y l)-2,5,12-t r i-
oxa tr icyclo[7,3,0,04,8]d od eca n e (9): yield 78%; oil; Rf 0.32
(petroleum ether/ethyl acetate 10/1); [R]20 +103.4 (c 1.3,
D
1
CH2Cl2); H NMR (300 MHz) δ 5.54 (d, 1H, J ) 6.8 Hz), 5.06
(ddd, 1H, J ) 2.0, 2.1, 2.6 Hz), 4.96 (ddd, 1H, J ) 1.8, 1.9, 2.0
Hz), 4.85 (brs, 1H), 4.70 (dd, 1H, J ) 1.5, 1.6 Hz), 4.49 (brd,
1H, J ) 13.5 Hz), 4.27 (ddd, 1H, J ) 1.9, 2.1, 13.5 Hz), 4.11-
4.05 (m, 2H), 3.88 (dd, 1H, J ) 2.1, 9.6 Hz), 3.84 (ddd, 1H, J
) 2.1, 4.0, 8.7 Hz), 3.81 (dd, 1H, J ) 4.0, 9.6 Hz), 3.42 (dd,
1H, J ) 8.6, 9.7 Hz), 3.21 (ddd, 1H, J ) 9.0, 9.2, 11.0 Hz),
2.90 (brdd, 1H, J ) 6.4, 9.7 Hz), 2.58 (ddd, 1H, J ) 6.4, 6.8,
11.0 Hz), 1.66 (s, 3H), 0.90 (s, 9H), 0.085 (s, 3H), 0.08 (s, 3H);
13C NMR (50 MHz) δ 147.8, 143.5, 113.5, 106.7, 101.9, 79.1,
77.2, 72.1, 72.0, 64.9, 48.3, 41.4, 40.7, 26.1, 18.6, 18.3, -5.1,
-5.0. Anal. Calcd for C20H34O4Si: C, 65.53; H, 9.34. Found:
C, 65.07; H, 9.97.
Ack n ow led gm en t . Financial support from the
CNRS, MESR, and MESRES for a fellowship (J .-F.N.)
is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for compounds 1a -f and
2a -f, as well as copies of 1H and 13C NMR spectra with
complete peak assignments for new compounds having mi-
croanalyses which did not come within 0.4% for C and/or H
calculated values are also avalaible (16 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
(1S,3S,4S,8R,9S)-3-[[(ter t-Bu tyld im eth ylsilyl)oxy]m e-
t h y l ]-7 -m e t h y l e n e -1 0 (E )-b e n z y l i d e n e -2 ,5 ,1 2 -t r i -
oxa tr icyclo[7,3,0,04,8]d od eca n e (10): yield 79%; oil; Rf 0.57
(petroleum ether/ethyl acetate 10/1); [R]20 +111.4 (c 0.95,
J O970817J
D