Palladium-Mediated Cyclization on Carbohydrate Templates. 1. Synthesis of Enantiopure Bicyclic Compounds

Article abstract of DOI:10.1021/jo961881o

The bromo unsaturated carbohydrates 3a and 9 were prepared from ethyl 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranoside (1a) and (7) by deacetylation followed by monosilylation with TBDMSC1 and then alkylation with BrCH₂CBr=CH₂. The threo analogues 6 and 10 were obtained using the same methodology after inversion at C-4 via a Mitsunobu reaction. The N- and C-analogues 4b and 5 were prepared by palladium alkylation of the carbonate 2d with TsNHCH₂CBr=CH₂ and (CO₂Me)₂CHCH₂CBr=CH₂, respectively. Treatment of the unsaturated carbohydrates 3a and 9 with a catalytic amount of Pd(OAc)₂/PPhs in CH₃CN/H₂O in the presence of Bu₄NHSO₄ and NEt₃ afforded the bicyclic compound 14a. The N- and C-analogues 14b and 14c were obtained using the same conditions and starting, respectively, from 4b and 5. On the other hand, treatment of the threo derivatives 6 and 10 under these conditions gave the furanic structure 15. In the case of compound 3a, performing the reaction in the presence of sodium formate yielded the bicyclic 2-deoxy carbohydrate 17.

Full text of DOI:10.1021/jo961881o

J . Org. Chem. 1997, 62, 1341-1347
1341
P a lla d iu m -Med ia ted Cycliza tion on Ca r boh yd r a te Tem p la tes. 1.
Syn th esis of En a n tiop u r e Bicyclic Com p ou n d s
J ean-Flaubert Nguefack, Ve´ronique Bolitt, and Denis Sinou*
Laboratoire de Synthe`se Asyme´trique, UMR 5622, CPE Lyon, Universite´ Claude Bernard Lyon I, 43
boulevard du 11 Novembre 1918, 69622 Villeurbanne Ce´dex, France
Received October 4, 1996X
The bromo unsaturated carbohydrates 3a and 9 were prepared from ethyl 4,6-di-O-acetyl-2,3-
dideoxy-D-erythro-hex-2-enopyranoside (1a ) and (7) by deacetylation followed by monosilylation with
TBDMSCl and then alkylation with BrCH2CBrdCH2. The threo analogues 6 and 10 were obtained
using the same methodology after inversion at C-4 via a Mitsunobu reaction. The N- and
C-analogues 4b and 5 were prepared by palladium alkylation of the carbonate 2d with TsNHCH2-
CBrdCH2 and (CO2Me)2CHCH2CBrdCH2, respectively. Treatment of the unsaturated carbohy-
drates 3a and 9 with a catalytic amount of Pd(OAc)2/PPh3 in CH3CN/H2O in the presence of
Bu4NHSO4 and NEt3 afforded the bicyclic compound 14a . The N- and C-analogues 14b and 14c
were obtained using the same conditions and starting, respectively, from 4b and 5. On the other
hand, treatment of the threo derivatives 6 and 10 under these conditions gave the furanic structure
15. In the case of compound 3a , performing the reaction in the presence of sodium formate yielded
the bicyclic 2-deoxy carbohydrate 17.
In tr od u ction
prepared via palladium-mediated cyclization of the ap-
propriate glycals or pseudoglycals.4 Recently, the Pau-
son-Khand reaction was applied to the synthesis of bis-
annulated pyranosides.5 A palladium-mediated [3 + 2]
cycloaddition served as the key step in the synthesis of
cyclopentenones and cyclopentadienes.6
Palladium-catalyzed cyclization processes constitute a
widely used methodology for the stereospecific synthesis
of carbocyclic as well as heterocyclic derivatives, some-
times via cascade reactions.1 Most of these reactions are
based on an intramolecular Heck reaction and allow the
sequential formation of several carbon-carbon bonds in
a single step, even in a diastereo- and enantioselective
manner. This approach now competes well with the
radical-initiated cascade cyclization.2
Carbohydrates provide an abundant source of optically
active compounds with a variety of functional and ster-
eochemical features. In addition, they can be modified
to give versatile synthons. Although radical cyclization
has been extensively studied in carbohydrate chemistry,3
only a few examples of organometallic-induced reactions
have been reported to date. Enantiopure functionalized
cyclopentanes and their heterocyclic analogues were
We recently described an unexpected palladium-
catalyzed Heck-type cyclization in carbohydrate chem-
istry, providing bicyclic glycals and occurring via a
dealkoxypalladation pathway.7 These highly function-
alized and enantiomerically pure annulated glycals could
be useful intermediates for further transformations. In
the present paper, we report a more detailed investiga-
tion of this reaction.
Resu lts a n d Discu ssion
P r ep a r a tion of Un sa tu r a ted Sta r tin g Su ga r s. The
2,3-unsaturated glycosides 3, 6, 9, 10, and 13 used in this
study were prepared from easily accessible derivatives
of tri-O-acetyl-D-glucal. Deacetylation of ethyl 4,6-di-O-
acetyl-2,3-dideoxy-R-D-erythro-hex-2-enopyranoside (1a )8
in methanol followed by selective monoprotection of the
primary hydroxyl function with TBDMSCl, NEt3, and
imidazole gave the unsaturated compound 2a in 80%
yield (Scheme 1). Treatment of 2a with NaH and 2,3-
dibromopropene in THF at 60 °C led to the O-alkylated
sugar 3a in 70% yield. Subsequent desilylation of 3a
with Bu4NF in THF gave compound 3d in 85% yield.
Starting from tert-butyl and p-tert-butylphenyl 4,6-di-O-
acetyl-2,3-dideoxy-R-D-erythro-hex-2-enopyranosides (1b8
X Abstract published in Advance ACS Abstracts, February 15, 1997.
(1) (a) De Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl.
1994, 33, 2379. (b) Heumann, A.; Regnier, M. Tetrahedron 1995, 51,
975. (c) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1989, 23, 1173. (d)
Trost, B. M. Acc. Chem. Res. 1990, 23, 34. (e) Oppolzer, W. Angew.
Chem., Int. Ed. Engl. 1989, 28, 38. (f) Oppolzer, W. Pure Appl. Chem.
1988, 60, 39. (g) Grigg, R. J . Heterocycl. Chem. 1994, 31, 631. (h) Tsuji,
J . Palladium Reagents and Catalysts; Innovations in Organic Synthe-
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Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.;
Pergamon Press: Oxford, 1991; Vol. 5, p 46. (j) Negishi, E.; Coperet,
C.; Ma, S.; Liou, S. Y.; Liu, F. Chem. Rev. 1996, 96, 365. (k) Hegedus,
L. S. In Organometallics in Synthesis; Schlosser, M., Ed.; Wiley:
Chichester, 1994; p 383. (l) Hegedus, L. S. Transition Metals in the
Synthesis of Complex Organic Molecules; University Science Books:
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(2) (a) Giese, B. Radicals in Organic Synthesis: Formation of
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T. L. Chem. Rev. 1991, 91, 1237. (g) Hoffmann, H. M. R. Angew. Chem.,
Int. Ed. Engl. 1992, 31, 1332.
(4) . (a) Engelbrecht, G. J .; Holzapfel, C. W. Tetrahedron Lett. 1991,
32, 2161. (b) Holzapfel, C. W.; van der Merwe, T. L. Tetrahedron Lett.
1996, 37, 2303 and 2307.
(5) (a) Lindsell, W. E.; Preston, P. N.; Rettie, A. B. Carbohydr. Res.
1994, 254, 311. (b) Marco-Contelles, J . Tetrahedron Lett. 1994, 35,
5059. (c) Naz, N.; Al-Tel, T. H.; Al-Abed, Y.; Voelter, W. Tetrahedron
Lett. 1994, 35, 8581. (d) Naz, N.; Al-Tel, T. H.; Al-Abed, Y.; Voelter,
W.; Ficker, R.; Hiller, W. J . Org. Chem. 1996, 61, 3250.
(6) Trost, B. M.; Sevanne, P.; Mignani, S.; Acemogen, M. J . Am.
Chem. Soc. 1989, 111, 7487.
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Lesueur, C.; Nouguier, R.; Bertrand, M. P.; Hoffmann, P.; De Mes-
maeker, A. Tetrahedron 1994, 50, 5369.
(7) Nguefack, J .-F; Bolitt, V.; Sinou, D. J . Chem. Soc., Chem.
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S0022-3263(96)01881-6 CCC: $14.00 © 1997 American Chemical Society

1342 J . Org. Chem., Vol. 62, No. 5, 1997
Nguefack et al.
Sch em e 1a
a
Reagents and conditions: (a) cat. MeONa, MeOH, quant; (b) TBDMSCl, NEt3, imidazole, CH2Cl2, rt, 24 h, 80%; (c) pyridine, DMAP
ClCO2Me, CH2Cl2, rt, 24 h, 75%; (d) NaH, BrCH2CBrdCH2, THF, 60 °C, 24 h, 70%; (e) Bu4NF, THF, 25 °C, 1.5 h, 85%; (f) for compound
4a (4b), TsNHCH2CBrdCH2), (BnNHCH2CBrdCH2), Pd2dba3, dppb, THF, 60 °C, 24 h, 87% (66%); for compound 5, (MeO2C)2CHCH2CBrdCH2,
Pd2dba3, dppb, THF, 60 °C, 6 h, 80%; (g) PPh3, ClCH2CO2H, toluene, 0 °C, 15 min, then DEAD, 0 °C, 30 min, rt, 24 h; (h) cat. MeONa,
MeOH, rt, 20 h, 62% (overall yield g + h); (i) NaH, BrCH2CBrdCH2, THF, 60 °C, 20 h, 65%.
and 1c9 ), the same sequence led to the O-alkylated
unsaturated carbohydrates 3b and 3c.
Deacetylation of 4,6-di-O-acetyl-1,5-anhydro-2,3-dideoxy-
D-erythro-hex-2-enitol (11), obtained from 1a according
to Grynkiewicz’s procedure,12 in methanol in the presence
of sodium methoxide followed by selective monosilylation
of the diol as previously described gave compound 12 in
68% yield. The unsaturated carbohydrate 13 was pre-
pared from 12 by alkylation with 2,3-dibromopropene in
80% yield (Scheme 3).
Treatment of the carbonate 2d , obtained from the
unsaturated carbohydrate 2a , with TsNHCH2CBrdCH2
or BnNHCH2CBrdCH2 in THF at 60 °C in the presence
of tris(dibenzylideneacetone)dipalladium(0) and 1,4-bis-
(diphenylphosphino)butane (dppb) led to the N-alkylated
carbohydrates 4a and 4b in 87% and 66% yield, respec-
tively. The C-alkylated analogue 5 was prepared in 80%
yield using the same methodology and (MeO2C)2CHCH2-
CBrdCH2 as the alkylating reagent (Scheme 1).
Compound 6 was synthesized from the pseudoglucal
2a in a two-step sequence, involving inversion of config-
uration at C-4 of 2a via a Mitsunobu reaction,10 followed
by alkylation of the resulting alcohol with 2,3-dibro-
mopropene as previously described (Scheme 1).
Deacetylation of ethyl 4,6-di-O-acetyl-2,3-dideoxy-â-D-
erythro-hex-2-enopyranoside (7), prepared from tri-O-
acetyl-D-glucal by the method of Baer et al.,11 using a
catalytic amount of sodium methoxide in methanol af-
forded the diol, which was treated with TBDMSCl, NEt3,
and imidazole in CH2Cl2 to give the monosilylated
carbohydrate 8 in 68% yield. Standard alkylation of this
compound with 2,3-dibromopropene as already described
gave ethyl 4-O-(2′-bromoprop-2′-enyl)-6-O-(tert-butyldim-
ethylsilyl)-2,3-dideoxy-â-D-erythro-hex-2-enopyranoside (9)
in 72% yield (Scheme 2). Inversion of configuration at
C-4 of compound 8 using the Mitsunobu procedure,10
followed by alkylation with 2,3-dibromopropene led to the
epimerized analogue 10 in 52% yield (Scheme 2).
P a lla d iu m -Med ia ted Cycliza tion . As previously
described,7 an attempt to trap the transient bicyclic
σ-alkylpalladium species resulting from a Heck reaction
of carbohydrate 3a in the presence of Pd(OAc)2, PPh3,
Bu4NBr, Na2CO3, and NaBPh4 in acetonitrile-water
failed, leading instead to the formation of the unexpected
unsaturated bicycle 14a (Scheme 4). Table 1 summarizes
some of the results obtained in the improvement of this
methodology. Firstly, it should be noticed that there is
no reaction without base (Table 1, entry 1). Among the
bases used, triethylamine gave the highest yields (com-
pare Table 1, entries 2 and 3, 4 and 5). Both quaternary
ammonium salts (bromide and hydrogenosulfate) were
equally effective in this reaction. Most importantly, the
nature of the phosphine seemed crucial for the cyclization
reaction. While the diphosphines used gave very low
yields (Table 1, entries 10-12), monophosphines gave
chemical yields in 14a of up to 77%, the most effective
being trifurylphosphine (Table 1, entry 9). While there
is no appreciable difference between triphenylphosphine
and tris(2-methylphenyl)phosphine (Table 1, entries 5
and 7), the more basic tris(4-methoxyphenyl)phosphine
gave a less efficient catalyst (Table 1, entry 8).
(9) Frappa, I.; Sinou, D. Synth. Commun. 1995, 25, 2941.
(10) Sa¨ıah, M.; Bessodes, M.; Antonakis, K. Tetrahedron Lett. 1992,
33, 4317.
(11) Baer, H. H.; Hanna, Z. S. Can. J . Chem. 1981, 59, 889.
(12) Grynkiewicz, G. Carbohydr. Res. 1984, 128, C9.

Synthesis of Enantiopure Bicyclic Compounds
J . Org. Chem., Vol. 62, No. 5, 1997 1343
Sch em e 2a
a
Reagents and conditions: (a) cat. MeONa, MeOH, quant; (b) TBDMSCl, NEt3, imidazole, CH2Cl2, rt, 1.5 h, 68%; (c) NaH,
BrCH2CBrdCH2, THF, 60 °C, 24 h, 72%; (d) PPh3, ClCH2CO2H, toluene, 0 °C, 15 min, then DEAD, 0 °C, 30 min, rt, 24 h; (e) cat. MeONa,
MeOH, rt, 24 h, 56% (overall yield d + e); (f) NaH, BrCH2CBrdCH2, THF, 60 °C, 24 h, 76%.
Sch em e 3a
Ta ble 1. In flu en ce of Ba se, Ad d ed Sa lt a n d P h osp h in e
on th e P a lla d iu m (0)-Ca ta lyzed Cycliza tion of 3a to 14a a
conversion time yieldb
entry base
added salt
Bu4NBr
phosphine
PPh3
PPh3
PPh3
(%)
(h)
(%)
1
2
3
4
5
no
traces
48
0
Na2CO3 Bu4NBr
NEt3 Bu4NBr
Na2CO3 Bu4NHSO4 PPh3
100
100
100
100
100
100
24 43
24 61
24 39
10 72
15 72
15 70
40 63
NEt3
Bu4NHSO4 PPh3
Bu4NHSO4 PPh3
Bu4NHSO4 P(C6H4-2-Me)3
6c NEt3
7
8
9
NEt3
NEt3
NEt3
Bu4NHSO4 P(C6H4-4-OMe)3 100
Bu4NHSO4 P(2-furyl)3 100
4
77
10 NEt3
11 NEt3
12 NEt3
Bu4NHSO4 Ph2P(CH2)4PPh2 20
Bu4NHSO4 Ph2P(CH2)3PPh2 30
24 traces
24 10
24 32
a
Reagents and conditions: (a) cat. MeONa, MeOH, quant; (b)
Bu4NHSO4 dppfd
50
TBDMSCl, NEt3, imidazole, CH2Cl2, rt, 17 h, 77%; (c) NaH,
BrCH2CBrdCH2, THF, 60 °C, 20 h, 80%.
a
Standard conditions: 3a (0.50 mmol) in CH3CN (15 mL) and
H2O (3 mL) in the presence of Pd(OAc)2 (0.05 mmol), the phosphine
(0.10 mmol for monophosphines or 0.05 mmol for diphosphines),
the added salt (0.50 mmol), and the base (1.22 mmol) were heated
Sch em e 4
b
at 80 °C for the indicated time. Isolated yield after column
chromatography on silica gel. c Pd(acac)2 was used instead of
d
Pd(OAc)2. 1,1′-Bis(diphenylphosphino)ferrocene.
at δ 4.10 ppm with J 3,4) 7.4 Hz and J 4,5 ) 7.4 Hz, the
former value being typical of cis stereochemistry in such
bicyclic structures. Additional features of interest in
compound 14a are the 13C chemical shifts of C-1, C-2,
and C-3 at δ 143.16, 99.67, and 38.43, respectively.
A similar reaction performed with the unprotected
carbohydrate 3d gave the bicyclic compound 14d in 68%
yield; the coupling constant J 3,4 ) 7.6 Hz is again in
agreement with a cis-fused bicyclic structure.
Whatever the conditions used, the N-benzyl derivative
4b failed to give the cyclized product; this is probably
due to the complexation of the σ-vinylpalladium inter-
mediate by the nitrogen atom. However, the N-tosyl
unsaturated carbohydrate 4a gave the bicyclic aza-
compound 14b in 81% yield (Scheme 4); this different
reactivity could be due to the unavailability of the
nitrogen lone pair for coordination to the palladium as a
result of its incorporation into a sulfonamide function.
The 1H NMR spectrum showed signals at δ 6.42 and 4.79
ppm for the vinylic protons H-1 (dd) and H-2 (dd) and at
When the cyclization was performed under the stan-
dard conditions (CH3CN-H2O, Bu4NHSO4, NEt3, 80 °C)
on tert-butylglycoside 3b and (p-tert-butylphenyl)glyco-
side 3c, the same bicyclic derivative 14a was also
obtained, but in lower yields (20 and 30%, respectively),
the reaction being in this case sluggish. The same
bicyclic compound 14a was also formed in 66% chemical
yield by intramolecular cyclization of dihydropyran 13
under the same conditions.
Compound 14a showed characteristic chemical shifts
and coupling constants, particularly at δ 6.30 and 4.80
ppm for the olefinic protons H-1 and H-2, with coupling
constants J 1,2 ) 6.0 Hz, J 1,3 ) 1.7 Hz, and J 2,3 ) 4.3 Hz.
The hydrogen atom H-4 appeared as a doublet of doublets
δ 2.43-2.40 ppm for H-3 with a coupling constant J 3,4
)
7.6 Hz, again characteristic of the cis-fused bicyclic
structure. In the 13C NMR spectrum the chemical shifts
for C-1, C-2, and C-3 are found as expected at δ 144.07,
98.22, and 38.59 ppm, respectively.
Finally, the cyclization process was extended to the
C-substituted analogue 5, which gave the bicyclic com-
pound 14c in 80% chemical yield. This compound again

1344 J . Org. Chem., Vol. 62, No. 5, 1997
Nguefack et al.
Sch em e 5
Sch em e 8
Sch em e 6
However, using sodium formate, known as a good
hydrogen donor, as the trapping reagent under the
standard cyclization conditions led very nicely to the
2-deoxy carbohydrate 17 in 62% yield. This compound
17 showed characteristic chemical shifts and coupling
constant values for the anomeric proton at δ 4.89 ppm
and J 1,2 ) 5.6 Hz and J 1,3 ) 6.9 Hz. Additionnal
characteristics are the 13C NMR chemical shifts of C-1,
C-2, and C-3 at δ 96.75, 31.43, and 39.10 ppm, respec-
tively.
Sch em e 7a
a
Reagents and conditions: (a) NEt3, Bu4NHSO4, Pd(OAc)2,
PPh3, NaBPh4, CH3CN/H2O 5/1, 60 °C, 24 h, 38% (14) and 20%
(16); (b) NEt3, Bu4NHSO4, Pd(OAc)2, PPh3, HCO2Na, CH3CN/H2O
5/1, 80 °C, 24 h, 62%.
Discu ssion
From a mechanistic point of view, the cyclization
process starts with the formation of a σ-vinylpalladium
intermediate by oxidative addition of compound 3 or 9
to the palladium(0) complex, followed by an association-
insertion reaction leading to a new σ-alkylpalladium
species (Scheme 8). We believe that the oxygen atom of
the aglycon is coordinated to the metal; such hydroxyl
or alkoxy coordination was recently proposed by J effery14
and Cacchi et al.15 In the case of derivative 9, this
complexation could prevent the syn relationship between
the anomeric proton and the palladium fragment re-
quired for the usual â-hydride elimination and so could
hamper this â-hydride elimination. Such an unsaturated
compound arising from â-elimination was never observed
in this case.
This complexation seems crucial for the next step,
which is a dealkoxypalladation. There are few examples
of dehydroxypalladation in the literature, including
σ-bonded palladium(II) intermediates of tetrahydro-
furans,16 and, to our knowledge, only two cases of
â-alkoxyelimination processes.17 The main role of this
chelation is demonstrated by comparing the results
obtained with substrates 3a , 3b, and 3c: the two last
compounds gave lower yields, probably due to the dif-
ficulty of the complexation of the aglycon oxygen atom
to the palladium. Chelating diphosphines performed
poorly in our cyclization reaction, probably also by
preventing the coordination of the aglycon to the pal-
ladium, resulting in poor cyclization yields. Finally, the
fact that trifurylphosphine is more efficient than triph-
enylphosphine is in good agreement with our hypothesis;
showed typical chemical shifts for both H-1 and H-2 at δ
6.12 and 4.55 ppm and a coupling constant J 3,4 ) 9.1 Hz
(Scheme 4).
To study the mechanism of this intramolecular cycliza-
tion, we extended this reaction to three other substrates,
6, 9, and 10.
Under the standard conditions of cyclization, the
unsaturated â-glycoside 9 was transformed into the
bicyclic compound 14a in 50% chemical yield (Scheme
5).
On the other hand, both ethyl R- and â-4-O-(2′-
bromoprop-2′-enyl)-6-O-(tert-butyldimethylsilyl)-2,3-
dideoxy-D-threo-hex-2-enopyranoside (6) and (10) led to
the formation of the same compound 15 in 57 and 67%
yield, respectively, which has an E double bond config-
uration (Scheme 6). The 1H NMR spectrum showed a
doublet at δ 6.34 ppm and a doublet of doublets at δ 4.80
ppm for the hydrogen atoms -CHdCHOEt, the coupling
constant J ) 12.7 Hz being typical of an E configuration
of the double bond.13 The presence of the hydroxyl
function is shown by the observation of a doublet at δ
2.40 ppm, and the cis stereochemistry of the two sub-
stituents of the tetrahydrofuran ring is in agreement with
the coupling constant J ) 7.6 Hz.
As previously stated, we expected to trap the bicyclic
σ-alkylpalladium intermediate resulting from the carbo-
palladation of the unsaturated carbohydrate 3a . Under
the cyclization conditions, addition of 1.2 equiv of sodium
tetraphenylborate resulted in the formation of a mixture
of the cyclized compound 14a (38%) and the unsaturated
carbohydrate 16 (20%) (Scheme 7). The latter arose from
the coupling of the first σ-vinylpalladium complex with
NaBPh4 via a transmetalation process. Increasing the
amount of NaBPh4 to 2 equiv gave only compound 16 in
43% yield. Substitution of sodium tetraphenylborate by
phenyltributylstannane without base resulted in the
formation of the same compound 16 in 40% yield.
(14) J effery, T. Tetrahedron Lett. 1993, 34, 1133.
(15) Bernocchi, E.; Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G.
Tetrahedron Lett. 1992, 33, 3073.
(16) (a) Hacksell, U.; Daves, G. D., J r. Organometallics 1983, 2, 772.
(b) Francis, J . W.; Henry, P. M. Organometallics 1992, 11, 2832. (c)
Saito, S.; Hara, T.; Takahashi, N.; Hirai, M.; Moriwake, T. Synlett 1992,
237. (d) Hosokawa, T.; Sagafuji, T.; Yamanaka, T.; Murahashi, S. I. J .
Organomet. Chem. 1994, 470, 253. (e) Ma, S.; Lu, X. J . Organomet.
Chem. 1993, 447, 305. (f) Kimura, M.; Harayama, H.; Tanaka, S.;
Tamaru, Y. J . Chem. Soc., Chem. Commun. 1994, 2531.
(17) (a) Duanet, J . P.; Cheng, C. H. Tetrahedron Lett. 1993, 34, 4019.
(b) Moinet, C.; Fiaud, J .-C. Tetrahedron Lett. 1995, 36, 2051.
(13) Chatterjee, S; Negishi, E.-I. J . Org. Chem. 1985, 50, 3406.

Synthesis of Enantiopure Bicyclic Compounds
J . Org. Chem., Vol. 62, No. 5, 1997 1345
ethylsilane. THF was distilled from sodium/benzophenone,
purged, and kept under a nitrogen atmosphere. Reactions
involving palladium complexes were carried out in a Schlenk
tube under a nitrogen atmosphere. 3,4,6-Tri-O-acetyl-D-glucal,
2,3-dibromopropene, PPh3, P(C6H4-2-Me)3, P(C6H4-4-OMe)3,
P(2-furyl)3, Ph2P(CH2)4PPh2, Ph2P(CH2)3PPh2, dppf, ClCH2-
CO2H, DEAD, Bu4NBr, Bu4NHSO4, TBDMSCl, Bu4NF‚3H2O,
DMAP, Pd(OAc)2, and Pd2(dba)3 were purchased from Aldrich
Chemical Co.
Sch em e 9
Benzyl(2-bromoprop-2-enyl)amine,19 tosyl(2-bromoprop-2-
enyl)amine,20 1,1-bis(methoxycarbonyl)-3-bromobut-3-ene,21 eth-
yl 4,6-di-O-acetyl-2,3-dideoxy-R-D-erythro-hex-2-enopyranoside
(1a ),8 tert-butyl 4,6-di-O-acetyl-2,3-dideoxy-R-D-erythro-hex-2-
enopyranoside (1b),8 p-tert-butylphenyl 4,6-di-O-acetyl-2,3-
dideoxy-R-D-erythro-hex-2-enopyranoside (1c),9 ethyl 4,6-di-O-
acetyl-2,3-dideoxy-â-D-erythro-hex-2-enopyranoside (7),11 and
4,6-di-O-acetyl-1,5-anhydro-2,3-dideoxy-D-erythro-hex-2-eni-
tol (11)12 were prepared by known procedures.
Sta n d a r d P r ep a r a tion of 6-O-(ter t-Bu tyld im eth ylsilyl)
Der iva tives 2a -c, 8, a n d 12. The corresponding diacetate
(8.66 mmol) was treated by 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
TBDMSCl (1.62 g, 10.77 mmol), 1.3 equiv of NEt3 (1.6 mL,
11.2 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.
as shown by Farina et al.,18 the first ligand binds less
tightly to the metal than the second one, promoting the
reaction process by readily dissociating from palladium-
(II) and so allowing an easy complexation of the oxygen
to the metal.
The next step, which is the â-dealkoxypalladation, may
or may not be concerted. While the results concerning
the cyclization of anomers 3 and 9 give no information
concerning the mechanism, the obtention of only the E
isomer 15 starting from 6 or 10 clearly indicates that this
last step is an ionic and not a concerted mechanism.
Effectively, in the case of a concerted process involving
a syn (or eventually an anti) â-dealkoxypalladation, the
two anomers 6 and 10 would afford two different stere-
oisomers. Thus, we propose for this transformation an
ionic intermediate such as A in the cyclization of 3 and
9 and B in the case of 6 and 10, leading to the formation
of the unsaturated compounds 14a and 15, respectively,
by the elimination of the palladium species (Schemes 8
and 9). The dissociation of the aglycon or of the carbo-
hydrate moiety is facilitated by the coordination of the
oxygen atom to the palladium. However, more work is
needed to fully understand this reaction mechanism.
E t h yl 6-O-(ter t-b u t yld im et h ylsilyl)-2,3-d id eoxy-r-D-
er yth r o-h ex-2-en op yr a n osid e (2a ): yield 80%; oil; Rf 0.54
(petroleum ether/ethyl acetate 5/1); [R]20 +22.1 (c 1.0, CH2-
D
1
Cl2); H NMR (200 MHz) δ 5.95 (brd, 1H, J ) 10.2 Hz), 5.75
(brdd, 1H, J ) 2.3, 10.2 Hz), 4.96 (brs, 1H), 4.18 (ddd, 1H, J
) 1.8, 3.8, 8.1 Hz), 3.95-3.69 (m, 4H), 3.54 (dq, 1H, J ) 9.6,
7.1 Hz), 2.72 (d, 1H, J ) 3.8 Hz), 1.14 (t, 3H, J ) 7.1 Hz), 0.89
(s, 9H), 0.09 (s, 6H); 13C NMR (50 MHz) δ 132.95, 125.94, 93.88,
70.59, 66.28, 64.91, 63.79, 25.81, 18.21, 15.26, -5.34, -5.30.
Anal. Calcd for C14H28O4Si: C, 58.29; H, 9.78. Found: C,
58.11; H, 9.84.
Con clu sion
We have shown that various alkyl 4-O-bromoalkenyl-
R-∆2-glycopyranosides and their N- and C-analogues
undergo an unexpected palladium-mediated Heck-type
cyclization under J effery’s conditions. However, while
the erythro structures afforded bicyclic glycals, threo
derivatives led to the formation of a tetrahydrofuranic
structure, indicating the crucial role of the configuration
at C-4. On the other hand, the R or â configuration at
the anomeric center has no influence on this cyclization
process. In the presence of formiate as the hydride
source, the bicyclic σ-alkylpalladium intermediate could
be trapped to give a bicyclic 2-deoxyglucal.
Thus, we have demonstrated the efficiency and general
scope of a new Heck-type cyclization reaction, leading to
bicyclic carbohydrate-derivatized compounds that could
be used as potential precursors for the synthesis of
polycyclic natural products.
E t h yl 6-O-(ter t-b u t yld im et h ylsilyl)-2,3-d id eoxy-â-D-
er yth r o-h ex-2-en op yr a n osid e (8): yield 68%; oil; Rf 0.55
(petroleum ether/ethyl acetate 5/1); [R]20 +42.7 (c 1.05, CH2-
D
1
Cl2); H NMR (200 MHz) δ 6.10 (ddd, 1H, J ) 1.6, 2.9, 10.3
Hz), 5.90 (ddd, 1H, J ) 1.5, 1.7, 10.3 Hz), 5.05 (brs, 1H), 4.04-
3.99 (m, 1H), 3.94 (dq, 1H, J ) 9.7, 7.1 Hz), 3.89-3.78 (m,
3H), 3.53 (dq, 1H, J ) 9.7, 7.1 Hz), 2.81 (d, 1H, J ) 4.0 Hz),
1.21 (t, 1H, J ) 7.1 Hz), 0.92 (s, 9H), 0.08 (s, 6H); 13C NMR
(50 MHz) δ 132.87, 128.12, 96.59, 77.70, 66.10, 65.10, 63.45,
25.77, 18.13, 15.17, -5.53, -5.59. Anal. Calcd for C14H28O4-
Si: C, 58.29; H, 9.78. Found: C, 58.32; H, 9.71.
6-O-(ter t-Bu tyld im eth ylsilyl)-1,5-a n h yd r o-2,3-d id eoxy-
D-er yth r o-h ex-2-en itol (12): yield 77%; oil; Rf 0.23 (petroleum
ether/ethyl acetate 2/1); [R]20 -29.3 (c 1.0, CH2Cl2); 1H NMR
D
(200 MHz) δ 5.83 (brd, 1H, J ) 11.3 Hz), 5.75 (brd, 1H, J )
11.3 Hz), 4.23 (ddd, 1H, J ) 2.6, 2.7, 7.9 Hz), 4.15 (brs, 2H),
3.95 (dd, 1H, J ) 5.1, 9.8 Hz), 3.75 (dd, 1H, J ) 7.8, 9.8 Hz),
3.42 (ddd, 1H, J ) 5.1, 7.8, 7.9 Hz), 3.10 (d, 1H, J ) 2.6 Hz),
0.87 (s, 9H), 0.08 (s, 6H); 13C NMR (50 MHz) δ 128.74, 127.77,
77.74, 67.52, 66.34, 65.91, 26.56, 18.94, -5.31, -5.26. Anal.
Calcd for C12H24O3Si: C, 58.97; H, 9.83. Found: C, 59.43; H,
9.96.
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 0.25
mm silica gel plates (60 F-254, Merck). Compounds were
visualized under UV light (254 nm) or by spraying with a H2-
SO4 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 tetram-
Gen er a l P r oced u r e for In ver sion of Con figu r a tion a t
C-4. To the 4-hydroxyl erythro compound 2a or 8 (1.18 g, 4.09
mmol) in 40 mL of toluol was added 2.14 g (8.18 mmol) of PPh3
(19) Mori, M.; Chiba, K.; Okita, M.; Kayo, I.; Ban, Y. Tetrahedron
1985, 41, 375.
(20) Bussas, R.; Kresze, G. Liebigs Ann. Chem. 1980, 629.
(21) Grigg, R.; Stevenson, P.; Worakun, T. Tetrahedron 1988, 44,
2033.
(18) Farina, V.; Krishnan, B. J . Am. Chem. Soc. 1991, 113, 9585.

1346 J . Org. Chem., Vol. 62, No. 5, 1997
Nguefack et al.
and 0.77 g (8.18 mmol) of ClCH2CO2H. The solution was
stirred for 15 min at 0 °C, and 1.30 mL (8.18 mmol) of DEAD
was injected. After the solution was stirred for 30 min at 0
°C and 24 h at room temperature, OPPh3 was separated and
the resulting solution was concentrated under vacuum. The
resulting ester was directly treated with a catalytic amount
of sodium methoxide in methanol (60 mL). After evaporation
of the solvent and addition of 50 mL of CH2Cl2, the organic
layer was washed with 0.1 M aqueous NH4Cl and saturated
aqueous NaCl. After drying, the solvent was removed under
reduced pressure and the residue was purified by column
chromatography on silica gel with petroleum ether/ethyl
acetate as eluent to afford the corresponding 4-hydroxyl threo
compound.
Gen er a l P r oced u r e for O-Alk yla tion . To the 4-hydroxyl
compound (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 quenched with 10 mL of H2O and
extracted with 3 × 15 mL of Et2O. After drying, the solvent
was removed under reduced pressure and the crude product
was purified by column chromatography on silica gel with
petroleum ether/ethyl acetate as the eluent to afford the
O-alkylated compound.
4-O-(2′-Br om op r op -2′-en yl)-6-O-(ter t-bu tyld im eth ylsi-
lyl)-1,5-a n h yd r o-2,3-d id eoxy-D-er yth r o-h ex-2-en itol (13):
yield 80%; oil; Rf 0.42 (petroleum ether/ethyl acetate 5/1); [R]20
D
1
+57.3 (c 1.0, CH2Cl2); H NMR (200 MHz) δ 6.25 (brd, 1H, J
) 1.5 Hz), 5.93 (brd, 1H, J ) 10.3 Hz), 5.87 (brd, 1H, J ) 10.3
Hz), 5.58 (dd, 1H, J ) 0.8, 1.5 Hz), 4.30-4.13 (m, 4H), 4.11
(brdd, 1H, J ) 2.5, 7.7 Hz), 3.92 (dd, 1H, J ) 2.7, 11.3 Hz),
3.85 (dd, 1H, J ) 4.8, 11.3 Hz), 3.45 (ddd, 1H, J ) 2.7, 4.8, 7.7
Hz), 0.91 (s, 9H), 0.08 (s, 6H); 13C NMR (50 MHz) δ 130.29,
129.51, 125.93, 118.93, 78.03, 73.81, 71.13, 65.94, 63.88, 26.71,
19.16, -4.68, -4.79. Anal. Calcd for C15H27O3BrSi: C, 49.58;
H, 7.47. Found: C, 49.14; H, 7.48.
Eth yl 4-O-(2′-Br om opr op-2′-en yl)-2,3-dideoxy-r-D-er yth -
r o-h ex-2-en op yr a n osid e (3d ). The silyl derivative 3a (1.1
g, 2.71 mmol) in 20 mL of THF was treated with 871 mg (2.71
mmol) of Bu4NF‚3H2O. The solution was stirred at room
temperature for 1.5 h and then concentrated under vacuum.
The residue was dissolved in 20 mL of Et2O and the solution
washed with 3 × 30 mL of a saturated aqueous solution of
NaCl and dried. After removal of the solvent under reduced
pressure, the residue was purified by column chromatography
on silica gel with petroleum ether/ethyl acetate 1/1 as the
eluent to give 0.67 g (85%) of 3d as an oil: Rf 0.25; [R]20D +58.7
1
(c 0.5, CH2Cl2); H NMR (200 MHz) δ 6.07 (brd, 1H, J ) 10.3
Hz), 5.93 (brd, 1H, J ) 1.6 Hz), 5.79 (ddd, 1H, J ) 2.2, 2.3,
10.3 Hz), 5.63 (d, 1H, J ) 1.6 Hz), 5.01 (brs, 1H), 4.24 (brd,
1H, J ) 14.2 Hz), 4.16 (brd, 1H, J ) 14.2 Hz), 4.09 (brd, 1H,
J ) 9.1 Hz), 3.95-3.75 (m, 4H), 3.54 (dq, 1H, J ) 9.6, 7.1 Hz),
1.90 (t, 1H, J ) 5.8 Hz), 1.24 (t, 3H, J ) 7.1 Hz); 13C NMR (50
MHz) δ 129.13, 129.90, 127.02, 118.38, 94.18, 72.96, 70.42,
69.51, 64.01, 62.09, 15.25. Anal. Calcd for C11H17O4Br: C,
45.06; H, 5.84. Found: C, 44.80; H, 5.94.
E t h yl
4-O-(2′-b r om op r op -2′-en yl)-6-O-(ter t-b u 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 e (3a ): yield 73%; oil; Rf 0.46 (petroleum ether/ethyl acetate
1
10/1); [R]20 +39.2 (c 1.1, CH2Cl2); H NMR (200 MHz) δ 5.95
D
(brd, 1H, J ) 10.3 Hz), 5.85 (dd, 1H, J ) 1.5, 2.9 Hz), 5.71
(ddd, 1H, J ) 2.2, 2.3, 10.3 Hz), 5.51 (dd, 1H, J ) 0.9, 1.5 Hz),
4.89 (brs, 1H), 4.13 (brd, 1H, J ) 13.9 Hz), 4.06 (brd, 1H, J )
13.9 Hz), 3.85-3.65 (m, 5H), 3.44 (dq, 1H, J ) 9.7, 7.0 Hz),
1.14 (t, 3H, J ) 7.0 Hz), 0.82 (s, 9H), 0.08 (s, 6H); 13C NMR
(50 MHz) δ 129.38, 130.22, 127.43, 117.91, 94.10, 72.96, 70.74,
70.47, 63.86, 62.95, 26.03, 18.47, 15.37, -5.09, -5.23.
Gen er a l P r oced u r e for N- a n d C-Alk yla tion . To a
solution of 2.0 g (6.94 mmol) of 2a in 60 mL of CH2Cl2 at room
temperature was added 170 mg (1.4 mmol) of DMAP, 2.8 mL
(34.7 mmol) of pyridine, and 2.7 mL (34.7 mmol) of methyl
chloroformate. The mixture was stirred for 24 h at room
temperature. After addition of 60 mL of a water solution of
CuSO4.5 H2O, the solution was extracted with 4 × 50 mL of
Et2O. The organic layer was dried, the solvent was removed
under reduced pressure, and the product was purified by
column chromatography on silica gel with petroleum ether/
ethyl acetate 3/1 as the eluent to give 1.8 g (75%) of the
carbonate 2d . To a solution of this carbonate 2d (500 mg, 1.44
mmol) in 10 mL of dry THF was added 838 mg (2.89 mmol) of
TsNHCH2CBrdCH2, 659 mg (2.89 mmol) of BnNHCH2-
CBrdCH2, or 726 mg (2.89 mmol) of (MeO2C)2CHCH2-
CBrdCH2 and the catalytic system obtained by reacting
Pd2(dba)3 (33 mg, 0.036 mmol) and dppb (31 mg, 0.072 mmol)
in 10 mL of THF. 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 that was
purified by column chromatography on silica gel using petro-
leum ether/ethyl acetate as the eluent.
E t h yl 6-O-(ter t-b u t yld im et h ylsilyl)-4-[N-t osyl-N-(2′-
br om opr op-2′-en yl)am in o]-2,3,4-tr ideoxy-r-D-er yth r o-h ex-
2-en op yr a n osid e (4a ): yield 87%; oil; Rf 0.45 (petroleum
ether/ethyl acetate 5/1); [R]20D +65.4 (c 0.75, CH2Cl2); 1H NMR
(300 MHz) δ 7.73 (d, 2H, J ) 8.1 Hz), 7.32 (d, 2H, J ) 8.1 Hz),
5.99 (ddd, 1H, J ) 1.5, 1.7, 1.7 Hz), 5.85 (ddd, 1H, J ) 2.7,
2.7, 10.2 Hz), 5.63 (dd, 1H, J ) 2.1, 2.5 Hz), 5.14 (brdd, 1H, J
) 1.8, 10.2 Hz), 4.91 (d, 1H, J ) 3.0 Hz), 4.36 (ddd, 1H, J )
1.8, 3.0, 9.7 Hz), 4.21 (brd, 1H, J ) 17.1 Hz), 3.94 (ddd, 1H, J
) 1.9, 6.5, 9.7 Hz), 3.86 (dd, 1H, J ) 1.9, 11.3 Hz), 3.81 (dq,
1H, J ) 9.7, 7.1 Hz), 3.76 (brd, 1H, J ) 17.1 Hz), 3.60 (dd, 1H,
J ) 6.5, 11.3 Hz), 3.48 (dq, 1H, J ) 9.7, 7.1 Hz), 2.44 (s, 3H),
1.19 (t, 3H, J ) 7.1 Hz), 0.88 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H);
13C NMR (75 MHz) δ 144.10, 137.08, 131.12, 127.45, 129.73,
129.98, 126.44, 119.60, 93.67, 86.45, 68.71, 63.69, 63.18, 53.48,
26.07, 21.73, 18.51, 15.30, -5.03, -5.16. Anal. Calcd for
C24H38O5BrSiSN: C, 51.41; H, 6.81; N, 2.49. Found: C, 51.65;
H, 6.73; N, 2.79.
E t h yl
4-O-(2′-b r om op r op -2′-en yl)-6-O-(ter t-b u t yld i-
m e t h ylsilyl)-2,3-d id e oxy-r-D -t h r eo-h e x-2-e n op yr a n o-
sid e (6): yield 65%; oil; Rf 0.46 (petroleum ether/ethyl acetate
10/1); [R]20D -105.9 (c 1.1, CH2Cl2); 1H NMR (200 MHz) δ 6.17
(dd, 1H, J ) 4.6, 10.1 Hz), 6.02 (dd, 1H, J ) 2.9, 10.1 Hz),
5.94 (dd, 1H, J ) 1.5, 3.0 Hz), 5.60 (brd, 1H, J ) 1.5 Hz), 5.06
(d, 1H, J ) 2.9 Hz), 4.26 (brd, 1H, J ) 14.2 Hz), 4.17 (brd, 1H,
J ) 14.2 Hz), 4.09 (ddd, 1H, J ) 2.4, 6.6, 6.6 Hz), 3.97-3.75
(m, 4H), 3.55 (dq, 1H, J ) 9.7, 7.1 Hz), 1.24 (t, 3H, J ) 7.1
Hz), 0.89 (s, 9H), 0.09 (s, 6H); 13C NMR (50 MHz) δ 129.81,
130.34, 126.63, 117.50, 93.84, 73.17, 71.10, 67.57, 63.56, 62.19,
25.89, 18.25, 15.30, -5.34, -5.60. Anal. Calcd for C17H31O4-
BrSi: C, 50.11; H, 7.66. Found: C, 50.23; H, 7.69.
E t h yl
4-O-(2′-b r om op r op -2′-en yl)-6-O-(ter t-b u t yld i-
m et h ylsilyl)-2,3-d id eoxy-â-D-er yth r o-h ex-2-en op yr a n o-
sid e (9): yield 72%; oil; Rf 0.46 (petroleum ether/ethyl acetate
1
10/1); [R]20 +26.9 (c 0.8, CH2Cl2); H NMR (200 MHz) δ 6.06
D
(ddd, 1H, J ) 1.5, 3.4, 10.3 Hz), 5.94 (brd, 1H, J ) 1.6 Hz),
5.87 (ddd, 1H, J ) 1.5, 1.5, 10.3 Hz), 5.62 (brs, 1H), 5.08 (dd,
1H, J ) 1.5, 3.4 Hz), 4.26 (d, 1H, J ) 13.9 Hz), 4.16 (d, 1H, J
) 13.9 Hz), 4.85-3.98 (m, 1H), 3.91 (dq, 1H, J ) 9.6, 7.1 Hz),
3.85-3.76 (m, 3H), 3.55 (dq, 1H, J ) 9.6, 7.1 Hz), 1.22 (t, 3H,
J ) 7.1 Hz), 0.90 (s, 9H), 0.08 (s, 6H); 13C NMR (50 MHz) δ
129.57, 129.40, 127.63, 117.90, 95.02, 76.55, 73.04, 69.32,
63.30, 62.97, 25.90, 18.31, 15.25, -5.27, -5.31. Anal. Calcd
for C17H31O4BrSi: C, 50.11; H, 7.66. Found: C, 50.06; H, 8.11.
E t h yl
4-O-(2′-b r om op r op -2′-en yl)-6-O-(ter t-b u t yld i-
m e t h ylsilyl)-2,3-d id e oxy-â-D -t h r eo-h e x-2-e n op yr a n o-
sid e (10): yield 76%; oil; Rf 0.46 (petroleum ether/ethyl acetate
10/1); [R]20D -63.2 (c 0.75, CH2Cl2); 1H NMR (200 MHz) δ 6.13
(ddd, 1H, J ) 1.3, 4.8, 10.1 Hz), 5.96 (brd, 1H, J ) 1.5 Hz),
5.92 (brd, 1H, J ) 10.1 Hz), 5.59 (brd, 1H, J ) 1.5 Hz), 5.08
(brd, 1H, J ) 1.3 Hz), 4.26 (brd, 1H, J ) 13.8 Hz), 4.19 (brd,
1H, J ) 13.8 Hz), 4.02-3.72 (m, 5H), 3.63 (dq, 1H, J ) 9.6,
7.1 Hz), 1.24 (t, 1H, J ) 7.1 Hz), 0.90 (s, 9H), 0.09 (s, 6H); 13
C
NMR (50 MHz) δ 129.89, 132.58, 127.66, 117.39, 97.53, 75.89,
73.09, 68.47, 63.77, 62.13, 25.91, 18.28, 15.27, -5.28, -5.34.
Anal. Calcd for C17H31O4BrSi: C, 50.11; H, 7.66. Found: C,
50.27; H, 7.60.
Eth yl 6-O-(ter t-bu tyldim eth ylsilyl)-4-[1′,1′-bis(m eth oxy-
car 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 (5): yield 80%; oil; Rf 0.46 (petroleum

Synthesis of Enantiopure Bicyclic Compounds
J . Org. Chem., Vol. 62, No. 5, 1997 1347
ether/ethyl acetate 5/1); [R]20 +50.5 (c 0.8, CH2Cl2); 1H NMR
5.9 Hz), 5.00-4.96 (m, 2H), 4.93 (dd, 1H, J ) 4.5, 5.9 Hz), 4.38
(brd, 1H, J ) 13.0 Hz), 4.29 (brd, 1H, J ) 13.0 Hz), 4.12 (dd,
1H, J ) 7.6, 8.7 Hz), 3.85 (dd, 1H, J ) 3.4, 11.9 Hz), 3.76 (dd,
1H, J ) 5.8, 11.9 Hz), 3.46 (ddd, 1H, J ) 3.4, 5.8, 8.7 Hz),
3.18-3.14 (m, 1H), 2.67 (brs, 1H); 13C NMR (75 MHz) δ 149.93,
142.87, 105.97, 99.94, 74.28, 73.67, 69.84, 61.96, 38.53.
(2R,3S,1′R) 2-[1′-Hyd r oxy-2′-[(ter t-bu tyld im eth ylsilyl)-
oxy]eth yl]-3-(E)-(2′-eth oxyeth en yl)-4-m eth ylen etetr a h y-
d r ofu r a n (15): yield 67%; oil; Rf 0.26 (petroleum ether/ethyl
acetate 10/1); [R]20D -30.9 (c 0.9, CH2Cl2); 1H NMR (300 MHz)
δ 6.34 (d, 1H, J ) 12.7 Hz), 4.93 (brd, 2H, J ) 2.2 Hz), 4.80
(dd, 1H, J ) 9.9, 12.7 Hz), 4.54 (ddd, 1H, J ) 1.9, 1.9, 13.0
Hz), 4.38 (brd, 1H, J ) 13.0 Hz), 3.93 (dd, 1H, J ) 3.8, 7.6
Hz), 3.85-3.59 (m, 5H), 3.26 (brdd, 1H, J ) 7.6, 9.9 Hz), 2.40
(d, 1H, J ) 3.8 Hz), 1.29 (t, 3H, J ) 7.0 Hz), 0.89 (s, 9H), 0.07
(s, 6H); 13C NMR (75 MHz) δ 152.41, 148.57, 103.84, 100.77,
81.29, 72.06, 71.45, 64.72, 64.33, 45.78, 25.89, 18.29, 14.66,
-5.36, -5.38. Anal. Calcd for C17H32O4Si: C, 62.15; H, 9.81.
Found: C, 62.56; H, 9.69.
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 3a (410 mg, 1.01
mmol) was allowed to react under the previously described
conditions for palladium(0)-catalyzed cyclization in the pres-
ence 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 on silica gel.
Eth yl 6-O-(ter t-bu tyld im eth ylsilyl)-4-O-(2′-p h en ylp r op -
2′-en yl)-2,3-dideoxy-r-D-er yth r o-h ex-2-en opyr an oside (16):
yield 40%; oil; Rf 0.36 (petroleum ether/ethyl acetate 10/1);
[R]20D +104.3 (c 1.2, CH2Cl2); 1H NMR (200 MHz) δ 7.60-7.30
(m, 5H), 6.04 (brd, 1H, J ) 10.2 Hz), 5.76 (ddd, 1H, J ) 2.2,
2.3, 10.2 Hz), 5.52 (d, 1H, J ) 1.1 Hz), 5.34 (d, 1H, J ) 1.1
Hz), 4.99 (s, 1H), 4.55 (d, 1H, J ) 12.6 Hz), 4.35 (d, 1H, J )
12.6 Hz), 4.01-3.45 (m, 6H), 1.23 (t, 3H, J ) 7.1 Hz), 0.91 (s,
9H), 0.08 (s, 3H), 0.06 (s, 3H). Anal. Calcd for C23H36O4Si:
C, 68.27; H, 8.96. Found: C, 67.82; H, 8.69.
Eth yl 2,3,4-tr id eoxy-2′,3′,4′,5′-tetr a h yd 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 (17): yield 62%; oil; Rf 0.47 (petroleum ether/
ethyl acetate 10/1); [R]20D +197.7 (c 1.5, CH2Cl2); 1H NMR (200
MHz) δ 4.99 (dd, 2H, J ) 1.9, 4.0 Hz), 4.89 (dd, 1H, J ) 5.6,
6.9 Hz), 4.47 (ddd, 1H, J ) 1.8, 3.7, 13.2 Hz), 4.28 (brd, 1H, J
) 13.2 Hz), 3.98-3.65 (m, 5H), 3.46 (dq, 1H, J ) 9.6, 7.1 Hz),
2.80-2.67 (m, 1H), 2.02 (ddt, 1H, J ) 5.6, 5.6, 14.3 Hz), 1.72
(ddd, 1H, J ) 6.9, 11.1, 14.3 Hz), 1.19 (t, 3H, J ) 7.1 Hz), 0.91
(s, 9H), 0.08 (s, 6H); 13C NMR (50 MHz) δ 150.13, 104.88, 96.75,
77.01, 71.41, 70.87, 64.38, 62.58, 39.10, 31.43, 25.95, 18.43,
15.16, -5.26, -5.36. Anal. Calcd for C16H31O4Si: C, 60.91;
H, 9.90. Found: C, 60.47; H, 10.17.
D
(300 MHz) δ 5.94 (brd, 1H, J ) 10.5 Hz), 5.76 (ddd, 1H, J )
1.7, 1.7, 10.5 Hz), 5.68 (d, 1H, J ) 1.9 Hz), 5.55 (d, 1H, J )
1.9 Hz), 5.02 (brs, 1H), 4.20-4.13 (m, 1H), 3.77-3.65 (m, 3H),
3.69 (s, 3H), 3.67 (s, 3H), 3.44 (dq, 1H, J ) 9.8, 7.1 Hz), 3.24
(d, 1H, J ) 15.9 Hz), 3.15 (d, 1H, J ) 15.9 Hz), 3.76-2.79 (m,
1H), 1.50 (t, 3H, J ) 7.1 Hz), 0.89 (s, 9H), 0.08 (s, 3H), 0.07 (s,
3H); 13C NMR (50 MHz) δ 170.21, 169.47, 127.23, 129.86,
126.77, 122.03, 92.69, 72.66, 64.14, 63.33, 60.06, 52.74, 52.45,
43.47, 37.12, 25.83, 18.21, 15.30, -5.31, -5.40. Anal. Calcd
for C22H37O7BrSi: C, 50.66; H, 7.15. Found: C, 50.44; H, 7.14.
Sta n d a r d P a lla d iu m (0)-Med ia ted Cycliza tion P r oce-
d u r e. A solution of 1.01 mmol of the 2,3-unsaturated glycoside
3a -d , 4a , 5, 6, 9, 10, or 13 in CH3CN (15 mL) and H2O (3
mL) was heated in the presence of Pd(OAc)2 (11 mg, 0.05
mmol), PPh3 (26.5 mg, 0.10 mmol), Bu4NHSO4 (1.0 mmol), and
NEt3 (700 µl, 2.5 mmol) at 80 °C for 24 h. The progress of the
reaction was monitored by TLC. When the starting material
was no longer present, the reaction was quenched with 10 mL
of water, and the mixture was extracted with 3 × 30 mL of
Et2O. Evaporation of the solvent under reduced pressure gave
an oil that was purified by column chromatography on silica
gel to give the pure product.
1,2,3,4-Tet r a d eoxy-2′,3′,4′,5′-t et r a h yd r o-6-O-(ter t-b u -
tyldim eth ylsilyl)-4′-m eth ylen e-D-r ibo-h ex-1-en opyr an oso-
[4,3-b]fu r a n (14a ): yield 75%; oil; Rf 0.56 (petroleum ether/
ethyl acetate 10/1); [R]20D +145.5 (c 1.3, CH2Cl2); 1H NMR (200
MHz) δ 6.30 (dd, 1H, J ) 1.7, 6.0 Hz), 4.92 (ddd, 2H, J ) 2.6,
2.7, 2.7 Hz), 4.80 (dd, 1H, J ) 4.3, 6.0 Hz), 4.43 (brd, 1H, J )
13.8 Hz), 4.37 (brd, 1H, J ) 13.8 Hz), 4.10 (dd, 1H, J ) 7.4,
7.4 Hz), 3.85 (dd, 1H, J ) 3.5, 11.4 Hz), 3.75 (dd, 1H, J ) 5.1,
11.4 Hz), 3.50 (ddd, 1H, J ) 3.5, 5.1, 7.4 Hz), 3.10-3.00 (m,
1H), 0.90 (s, 9H), 0.09 (s, 6H); 13C NMR (50 MHz) δ 150.71,
143.16, 105.63, 99.67, 74.91, 70.70, 69.95, 62.45, 38.43, 25.96,
18.50, -5.29, -5.33.
1,2,3,4-Tet r a d eoxy-2′,3′,4′,5′-t et r a h yd r o-6-O-(ter t-b u -
t yld im et h ylsilyl)-4′-m et h ylen e-1′-N-t osyl-D-r ibo-h ex-1-
en op yr a n oso)[4,3-b]p yr r ole (14b): yield 81%; oil; Rf 0.68
(petroleum ether/ethyl acetate 3/1); [R]20 +64.9 (c 1.1, CH2-
D
1
Cl2); H NMR (300 MHz) δ 7.72 (d, 2H, J ) 8.1 Hz), 7.32 (d,
2H, J ) 8.1 Hz), 6.42 (dd, 1H, J ) 1.5, 6.1 Hz), 5.03 (ddd, 1H,
J ) 2.0, 2.1, 2.1 Hz), 4.88 (ddd, 1H, J ) 2.0, 2.3, 2.3 Hz), 4.79
(dd, 1H, J ) 4.7, 6.1 Hz), 4.26 (dd, 1H, J ) 2.3, 11.8 Hz), 4.01
(brd, 1H, J ) 14.9 Hz), 3.90 (brd, 1H, J ) 14.9 Hz), 3.84 (dd,
1H, J ) 7.4, 11.8 Hz), 3.77 (dd, 1H, J ) 7.6, 9.8 Hz), 3.47 (ddd,
1H, J ) 2.3, 7.4, 9.8 Hz), 2.44 (s, 3H), 2.43-2.40 (m, 1H), 0.94
(s, 9H), 0.12 (s, 6H); 13C NMR (50 MHz) δ 144.67, 134.52,
129.59, 127.59, 147.69, 144.07, 109.41, 98.22, 75.59, 63.25,
56.52, 51.63, 38.59, 25.06, 21.59, 18.54, -5.03, -5.17.
1,2,3,4-Tet r a d eoxy-6-O-(ter t-b u t yld im et h ylsilyl)-1′,1′-
bis(m eth oxyca r bon yl)-4′-m eth ylen e-D-r ibo-h ex-1-en op y-
r a n oso)[4,3-b]cyclop en ta n e (14c): yield 80%; oil; Rf 0.70
Ack n ow led gm en t . Financial support from the
CNRS, the MESR, and MESRES for a fellowship (J .-
F.N.) is gratefully acknowledged.
(petroleum ether/ethyl acetate 5/1); [R]20 +101.2 (c 1.0, CH2-
D
Cl2); 1H NMR (300 MHz) δ 6.12 (dd, 1H, J ) 2.3, 6.3 Hz), 4.97
(brs, 2H), 4.55 (brdd, 1H, J ) 2.7, 6.3 Hz), 4.39 (ddd, 1H, J )
1.5, 6.1, 6.5 Hz), 3.79 (dd, 1H, J ) 6.5, 10.5 Hz), 3.72 (s, 3H),
3.70 (s, 3H), 3.65 (dd, 1H, J ) 6.1, 10.5 Hz), 3.45 (dddd, 1H, J
) 1.8, 2.3, 2.3, 16.9 Hz), 3.31 (brd, 1H, J ) 9.1 Hz), 3.14 (brd,
1H, J ) 9.1 Hz), 2.58 (ddd, 1H, J ) 2.3, 2.3, 16.9 Hz), 0.91 (s,
9H), 0.09 (s, 3H), 0.08 (s, 3H); 13C NMR (75 MHz) δ 172.12,
171.31, 150.36, 140.98, 107.52, 103.02, 73.23, 63.78, 59.99,
52.74, 52.82, 43.30, 40.40, 36.46, 25.88, 18.33, -5.27, -5.41.
1,2,3,4-Tetr a d eoxy-2′,3′,4′,5′-tetr a h yd r o-4′-m eth ylen e-
D-r ibo-h ex-1-en op yr a n oso)[4,3-b]fu r a n (14d ): yield 68%;
Su p p or tin g In for m a tion Ava ila ble: Full data for all new
compounds described in this paper, including 1H and 13C NMR
spectra, with complete peak assignments and copies of 1H and
13C NMR spectra for new compounds having microanalyses
that do not come within 0.4% for C and/or H calculated values
(34 pages). This material is contained in libraries on micro-
fiche, 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.
oil; Rf 0.37 (petroleum ether/ethyl acetate 5/1); [R]20 +205.3
D
1
(c 1.1, CH2Cl2); H NMR (300 MHz) δ 6.37 (dd, 1H, J ) 1.8,
J O961881O