Palladium - Cobalt-mediated double annulation Process: A new strategy to chiral and polysubstituted bis-cyclopentanoids on carbohydrate precursors

Article abstract of DOI:10.1021/jo951298s

The iodohydrins 2, 4, and 5 were prepared by the ring opening of benzyl 2-O-p-tosyl-3,4-anhydro-β-L-arabinopyranoside (1) or benzyl 2,3-anhydro-4-O-acetyl-α-D-ribopyranoside (3), respectively, using sodium acetate, sodium iodide, and acetic acid in acetone which on treatment with POCl₃ in pyridine yielded the unsaturated sugars 6 and 7. After deacetylation of 7 with MeOH/H₂O/Et₃N (3:2:1) and treatment of 8 with tosyl chloride/pyridine at 50°C 9 was obtained. The reaction of benzyl 2-O-p-tosyl-3,4-dideoxy-α-D-glycero-pent-3-enopyranoside (6) and benzyl 2,3,4-trideoxy-4-chloro-β-L-glycero-pent-2-enopyranoside (9) with the sodium enolate of dimethyl propargylmalonate in the presence of catalytic amounts of tetrakis(triphenylphosphine)palladium(0) afforded the branched-chain sugars 10 and 11. The isomer 10 was obtained as a minor product from 6 with retention of configuration around C-2, and the major isomer 11 as a result of allylic rearrangement in a ratio of 1:9. On the other hand, compound 9 afforded 10 as a major product and its regioisomer 11 as a minor product in a ratio of 8:2; formation of the above mentioned isomeric mixture involves cis and trans diastereomeric intermediates during the reaction. Treatment of these precursors with Co₂(CO)₈ in benzene followed by oxidative decomplexation with DMSO yielded in a stereoselective manner the polysubstituted bis-cyclopentanoids 12 and 13. The stereochemistry of 13 was assigned with the help of X-ray analysis. Attempts were made to prepare the tetracyclic systems 15 and 17 using 12 and 13 with 3-acetoxy-2-[(trimethylsilyl)methyl]-1-propene (14); however, the alkylation products 16 and 18 were obtained.

Full text of DOI:10.1021/jo951298s

3250
J . Org. Chem. 1996, 61, 3250 3255
P a lla d iu m Coba lt-Med ia ted Dou ble An n u la tion P r ocess: A New
Str a tegy to Ch ir a l a n d P olysu bstitu ted Bis-Cyclop en ta n oid s on
Ca r boh yd r a te P r ecu r sor s
Noshena Naz, Taleb H. Al-Tel, Yousef Al-Abed, and Wolfgang Voelter*
Abteilung fu¨r Physikalische Biochemie des Physiologisch-chemischen Instituts der Universita¨t Tu¨bingen,
Hoppe-Seyler-Strasse 4, D-72076 Tu¨bingen, Germany
Robert Ficker and Wolfgang Hiller
Anorganisch-chemisches Institut der Technischen Universita¨t Mu¨nchen, Lichtenbergstrasse 4, D-85747
Garching, Germany
Received J uly 19, 1995X
The iodohydrins 2, 4, and 5 were prepared by the ring opening of benzyl 2-O-p-tosyl-3,4-anhydro-
â-L-arabinopyranoside (1) or benzyl 2,3-anhydro-4-O-acetyl- -D-ribopyranoside (3), respectively,
using sodium acetate, sodium iodide, and acetic acid in acetone which on treatment with POCl3 in
pyridine yielded the unsaturated sugars 6 and 7. After deacetylation of 7 with MeOH/H2O/Et3N
(3:2:1) and treatment of 8 with tosyl chloride/pyridine at 50 °C 9 was obtained. The reaction of
benzyl 2-O-p-tosyl-3,4-dideoxy- -D-glycero-pent-3-enopyranoside (6) and benzyl 2,3,4-trideoxy-4-
chloro-â-L-glycero-pent-2-enopyranoside (9) with the sodium enolate of dimethyl propargylmalonate
in the presence of catalytic amounts of tetrakis(triphenylphosphine)palladium(0) afforded the
branched-chain sugars 10 and 11. The isomer 10 was obtained as a minor product from 6 with
retention of configuration around C-2, and the major isomer 11 as a result of allylic rearrangement
in a ratio of 1:9. On the other hand, compound 9 afforded 10 as a major product and its regioisomer
11 as a minor product in a ratio of 8:2; formation of the above mentioned isomeric mixture involves
cis and trans diastereomeric intermediates during the reaction. Treatment of these precursors
with Co2(CO)8 in benzene followed by oxidative decomplexation with DMSO yielded in a
stereoselective manner the polysubstituted bis-cyclopentanoids 12 and 13. The stereochemistry
of 13 was assigned with the help of X-ray analysis. Attempts were made to prepare the tetracyclic
systems 15 and 17 using 12 and 13 with 3-acetoxy-2-[(trimethylsilyl)methyl]-1-propene (14);
however, the alkylation products 16 and 18 were obtained.
In tr od u ction
systems.5 Of particular importance is the chemoselective
alkylation of an allylic function by Pd-catalyzed cyclo-
isomerization reactions6 or the cobalt-mediated cycliza-
tion (Pauson Khand reaction)7 of 1,6-enynes. This
heightened interest is based primarily upon the unusual
selectivity and reactivity associated with such reactions
which is not found in their classical organic reaction
counterparts.
Carbohydrates constitute an abundant and relatively
inexpensive source of chiral carbon compounds, and they
are readily available with a variety of functional, stere-
ochemical, and conformational features. Through chemi-
cal manipulation, these compounds can be transformed
into versatile synthetic intermediates, that bear func-
tional groups and chiral centers of a predetermined
nature and are amenable to elaboration into the struc-
tural framework of many natural products. In this
regard, studies in this laboratory have been engaged with
the development of new methods for the efficient and
economic synthesis of long-chain sugars,8a dihydro-8b and
tetrahydrofurans,8c,d and γ-lactones,8e derived from car-
Bis-cyclopentanoid rings of rich stereochemical func-
tionality are key intermediates for the synthesis of
pharmacologically interesting prostaglandin analogs1 and
are important substructural units of a wide variety of
natural products, particularly polyquinanes2 which were
shown to possess significant biological activities ranging
from simple antibiotic action to antitumor properties.3
Much work has been invested for accessing these syn-
thons.4 Of special importance are the syntheses de-
scribed by Fraser-Reid and co-workers,4d f taking advan-
tage of carbohydrate topology. In the last two decades,
increased attention has been devoted to the organome-
tallic-catalyzed functionalization and cyclization of enyne
X Abstract published in Advance ACS Abstracts, April 1, 1996.
(1) (a) Shibasaki, M.; Iseki, K.; Ikegami, S. Synth. Commun. 1980,
10 (7), 545 and references cited therein. (b) Magnus, P.; Becker, D. P.
J . Am. Chem. Soc. 1987, 109, 7495 and references cited therein. (c)
Whittel, B. J . R.; Moncada, S.; Whiting, T.; Vane, J . R. Prostaglandins
1980, 19, 605.
(2) (a) Paquette, L. A.; Doherty, A. M. Polyquinane Chemistry:
Reactivity and Structure; Concepts in Organic Chemistry; Sprin-
ger-Verlag: New York, 1987; Vol. 26, (b) Paquette, L. A. Topics Curr.
Chem. 1984, 119, 1.
(3) (a) Hartman, S.; Neeff, J .; Heer, U.; Mieke, D. FEBS Lett. 1978,
93, 339. (b) Keller-Schlerlein, W.; Lemke, J .; Nyfeler, R.; Zoehner, H.
Arch. Microbiol. 1972, 84, 301.
(4) (a) Clive, D. L. J .; Magnuson, S. R. Tetrahedron Lett. 1995, 36,
15. (b) Paquette, L. A.; Morwick, T. J . Am. Chem. Soc. 1995, 117, 1451.
(c) Rawal, V. H.; Dufour, C. J . Am. Chem. Soc. 1994, 116, 2613. (d)
Dickson, J . K., J r.; Fraser-Reid, B. J . Chem. Soc., Chem. Commun.
1990, 1440. (e) Dickson, J . K., J r.; Tsang, R.; Llera, J . M.; Fraser-Reid,
B. J . Org. Chem. Soc. 1989, 54, 5350, 5357. (f) Tsang, R.; Fraser-Reid,
B. J . Am. Chem. Soc. 1986, 108, 2116.
(5) (a) Heumann, A.; Reglier, M. Tetrahedron 1995, 51, 975 and
references cited therein. (b) Schore, N. E. Chem. Rev. 1988, 1081.
(6) Trost, B. M. Acc. Chem. Res. 1990, 23, 34.
(7) (a) Smit, W. A.; Caple, R.; Smoliakova, I. P. Chem. Rev. 1994,
94, 2359. (b) Rowley, E. G.; Schore, N. E. J . Org. Chem. 1992, 57, 6853.
(c) Schore, N. E.; Knudsen, M. J . J . Org. Chem. 1987, 52, 569.
(8) (a) Al-Tel, T. H.; Voelter, W. Tetrahedron Lett. 1995, 36, 523.
(b) Al-Tel, T. H.; Al-Abed, Y.; Voelter, W. J . Chem. Soc., Chem.
Commun. 1994, 1735. (c) Al-Tel, T. H.; Voelter, W. J . Chem. Soc.,
Chem. Commun. 1995, 239. (d) Al-Tel, T. H.; Al-Abed, Y.; Shekhani,
M. S.; Voelter, W. Tetrahedron Lett. 1993, 34, 7717. (e) Al-Abed, Y.;
Al-Tel, T. H.; Voelter, W. Tetrahedron 1993, 49, 9295.
S0022-3263(95)01298-9 CCC: $12.00 © 1996 American Chemical Society

Palladium Cobalt-Mediated Double Annulation Process
J . Org. Chem., Vol. 61, No. 10, 1996 3251
Sch em e 2
F igu r e 1. Polysubstituted bis-cyclopentanoids on carbohy-
drate precursors, synthons to differently configurated triquinane
and prostacyclin skeletons.
Sch em e 1
coupling of 3.6 Hz. In contrast, ring opening of 3 gave
two products (4 and 5) in a ratio of 8:2 in 96% combined
yield resulting from the nucleophilic attack at C-3 and
4
1
C-2. The adoption of C1 and C4 conformations for the
iodohydrins 4 and 5, respectively, is concluded from the
1
coupling constants between H-1 and H-2 in their H NMR
spectra. The iodohydrin 4 shows an equatorial axial
relationship between H-1 and H-2 with a coupling of 3.6
Hz and a diaxial relationship between H-2/3 and H-3/4
(J 2,3
10.4 Hz, J 3,4
10.8 Hz). On the other hand in
iodohydrin 5, a diaxial relationship between H-1/2 and
H-2/3 with large couplings (J 1,2 7.7 Hz, J 2,3 9.7 Hz)
and a small axial equatorial coupling between H-3/4 (J 3,4
3.4 Hz) confirms adoption of the 1C4 conformation. For
formation of the olefinic sugars 6 and 7, the MsCl/
pyridine and TsCl/pyridine methods12 were employed, but
no satisfactory results were obtained. However, if the
iodohydrin 2 and the mixture of 4 and 5 were treated
with POCl3 in pyridine at 40 °C,11 the unsaturated
sugars 6 and 7 were isolated in 70% and 55% yield,
respectively. After deacetylation of 7 with a mixture of
MeOH/H2O/Et3N (3:2:1),13 the allyl alcohol 8 was ob-
tained in quantitative yield. On treatment with tosyl
chloride/pyridine at 50 °C this gave the 4-chloro com-
pound 9 rather than the tosyl derivative, since the
chloride ions formed during the reaction displace the
highly reactive allylic sulfonate group in situ13 (Scheme
2).
bohydrate templates. Recently, we have communicated
preliminary results of a study9 disclosing the potential
applicability of palladium cobalt organometallic annu-
lation of carbohydrates. The present paper describes full
details of our work that includes additional results
elaborated on our chiral templates that can be further
manipulated to different configured triquinanes and
prostacyclin skeleta outlined in Figure 1. An advantage
of our approach is that the stereochemical features of our
synthons could be established unequivocally by subtle
changes in the location and the stereochemistry of the
allylic function in 6 and 9 and also by taking advantage
of the conformational preference of the product as a result
of the anomeric effect. The retrosynthetic analysis of our
approach to the bis-cyclopentanoid systems shows the
inherent simplicity of this strategy (Scheme 1).
Design for th e Syn th esis of Lon g-Ch a in Su ga r s
Usin g a P d (0) Ca ta lyst. In searching for a mild and
chemoselective approach to C C bond formation by the
substitution of a vinylic C H bond, we turned to the use
17
of a palladation reaction for the activation step14
and
Resu lts a n d Discu ssion
subsequent treatment with a nucleophile for the substi-
tution step.16a,17,18 Thus, alkylation of the olefinic sugars
6 and 9 involves the treatment of 6 with the sodium
enolate of dimethyl propargylmalonate in refluxing THF
in the presence of tetrakis(triphenylphosphine)palladium-
Syn th esis of Un sa tu r a ted Su ga r s. The starting
sugars 6 and 9, needed for the present study, were
prepared from easily accessible benzyl 2-O-p-tosyl-3,4-
anhydro-â-L-arabinopyranoside (1) and benzyl 2,3-anhy-
dro-4-O-acetyl- -D-ribopyranoside (3), respectively.10,11
The first step proceeds via epoxide ring opening of 1 and
3. When 1 was refluxed with sodium acetate, sodium
iodide and acetic acid in acetone for 4 5 h,11 the iodohy-
(12) Lemieux, R. U.; Fraga, E.; Watanabe, K. A. Can. J . Chem. 1968,
46, 61.
(13) Lichtenthaler, F. W.; Klingler, F. D.; J arglis, P. Carbohydr. Res.
1984, 132, C1.
(14) (a) Huttel, R. Synthesis 1972, 225. (b) Trost, B. M. Tetrahedron
1977, 33, 2615.
(15) (a) Huttel, R.; Diett, H.; Christ, H. Chem. Ber. 1964, 97, 2037.
(b) Lupin, M. S.; Powell, J .; Shaw, B. L. J . Chem. Soc. A 1966, 1687.
(c) Ketley, A. D.; Braatz, J . J . Chem. Soc., Chem. Commun. 1968, 169.
(d) Volger, H. C. Recl. Trav. Chim. Pays-Bas 1969, 88, 225.
(16) (a) Trost, B. M.; Fullerton, T. J . J . Am. Chem. Soc. 1973, 95,
292. (b) Trost, B. M.; Strege, P. E. Tetrahedron Lett. 1974, 2603. (c)
Trost, B. M.; Strege, P. E.; Weber, L.; Fullerton, T. J .; Dietsche, T. J .
J . Am. Chem. Soc. 1978, 100, 3407.
4
drin 2 was obtained as a single product adopting the C1
conformation. The 1H NMR spectrum shows two diaxial
relationships between H-2/3 and H-3/4 with coupling
constants J 2,3
9.4 Hz and J 3,4
10.5 Hz and one
equatorial axial relationship between H-1/2 with a small
(9) Naz, N.; Al-Tel, T. H.; Al-Abed, Y.; Voelter, W. Tetrahedron Lett.
1994, 35, 8581.
(10) Kowollik, W. Ph. D. Thesis, University of Tu¨bingen, 1987.
(11) Paulsen, H.; Koebernick, W. Chem. Ber. 1977, 110, 2127.
(17) (a) Tsuji, J .; Takahashi, H.; Morikawa, M. Tetrahedron Lett.
1965, 4387. (b) Tsuji, J . Bull. Chem. Soc. J pn. 1973, 46, 1896.

3252 J . Org. Chem., Vol. 61, No. 10, 1996
Naz et al.
Sch em e 3
Sch em e 5
Sch em e 4
ated by octacarbonyldicobalt. This increasingly popular
organometallic process has been the subject of numerous
studies and investigations by a number of groups.22 Our
own interests have focused on the observed stereoselec-
tivity with respect to both, allylic and propargylic sub-
stituents. Here we report its application to the construc-
tion of bicyclic systems on sugar templates. On the basis
of mechanistic hypothesis it can be reasonably predicted
that the substrates 10 and 11 on treatment with octac-
arbonyldicobalt will form the hexacarbonyldicobalt com-
plexes (10a and 11a ) by coordination of the acetylenic
function followed by oxidative addition of the cyclic double
bond which upon carbonylative insertion and oxidative
decomplexation results in the bicyclopentanoid systems.23
Therefore, the propargyl derivatives 10 and 11, after
reaction with Co2(CO)8 in benzene at rt, were converted
quantitatively into the corresponding hexacarbonyldico-
balt complexes 10a and 11a as red oils which upon
heating to 50 °C with DMSO24 afforded the tricyclic
products 12 and 13 in 75% and 77% yield, respectively
(0) and triphenylphosphine,19 leading to a mixture of the
regioisomers 10 and 11 in a ratio of 1:9 in 92% combined
yield (Scheme 3). When a similar palladium-catalyzed
alkylation was performed with 7, there was very little
conversion; but interestingly, if 9 was treated with the
sodium enolate of dimethyl propargylmalonate at 0 °C
under these conditions the same mixture of the branched-
chain sugars 10 and 11 was obtained in a ratio of 8:2 in
79% combined yield (Scheme 3). The regiochemical
results observed for 10 and 11 can be understood by
considering the mechanism of allylic alkylation5a,20 ac-
cording to Scheme 4, in which the cis and trans diaster-
eomeric intermediates (palladium π-allyl complexes) are
formed from the olefin in an activation step and then
during the substitution step a new carbon carbon bond
can be formed at C(a) or C(b) either with retention of the
olefin at its original position or with allyl rearrangement
(overall inversion), resulting in the formation of the
diastereomeric mixture (III and IV). The ratio of 10 and
11 from 6 or 9 indicates that, upon establishment of an
equilibrium, the amount of the isomer IV exceeds that
of the isomer III. Compounds 10 and 11 show charac-
teristic chemical shifts and coupling constants for the
olefinic proton that resonate in the δ 6.0 5.7 region
having long vinylic couplings, J 3,4 10.2 Hz and J 2,3
10.5 Hz, respectively. The anomeric proton in 10 pro-
duced a triplet at δ 4.78 with a coupling constant of 2.6
1
(Scheme 5). The H NMR spectra show vinylic signals
at δ 5.95 and 5.94 for 12 and 13, respectively, and
deshielded signals (δ 3.27 and 2.9) for the ring-fusion
proton (H-4 in 12 and H-2 in 13) adjacent to the keto
1
function. The H NMR spectra also give evidence that
the carbonylative acetylenic insertion takes place from
the same side as the propargylic moiety25 (12: J 1,2 3.4,
J 2,3 7.1, J 3,4 7.6 Hz; 13: J 1,2 7.9, J 2,3 7.3, J 3,4
6.6 Hz). The absolute stereochemistry of the cis-fused
cyclopentanoids was unambiguously assigned with the
help of X-ray analysis for compound 13. The X-ray
structure analysis of compound 13 revealed no significant
differences in the refinement between the model (R
values R1 0.0307, wR2 0.0797, Flack parameter 0.05
with an esd of 0.77) and its inverse (R1 0.0322, wR2
0.081, Flack parameter 1.3 with an esd of 0.8). The first
model above, however, is in agreement with the synthesis
from known components. A graphic representation of the
1
Hz, while the H NMR spectrum of 11 shows a doublet
for the anomeric proton at δ 4.86 with a very weak allylic
coupling of J 1,2 0.9 Hz. Additional features of interest
(21) (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. J .
Chem. Soc., Chem. Commun. 1971, 36. (b) Khand, I. U.; Knox, G. R.;
Pauson, P. L.; Watts, W. E. J . Chem. Soc., Perkin Trans. 1 1973, 975.
(c) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman,
M. I. J . Chem. Soc., Perkin Trans. 1 1973, 977.
(22) For reviews on the Pauson Khand reaction, see (a) Pauson, P.
L.; Khand, I. U. Ann. N.Y. Acad. Sci. 1977, 295, 2. (b) Pauson, P. L.
Tetrahedron 1985, 41, 5855. (c) Pauson, P. L. In Organometallics in
Organic Synthesis; de Meijere, A.; tom Dieck, H., Eds., Springer-
Verlag: Berlin, 1987; p 234. (d) Schore, N. E. Org. React. 1991, 40, 1.
(e) Schore, N. E. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 5, p 1037.
(23) (a) Magnus, P.; Exon, C.; Albaugh-Robertson, P. Tetrahedron
1985, 41, 5861. (b) Magnus, P.; Principe, L. M.; Slater, M. J . J . Org.
Chem. 1987, 52, 1483.
(24) Chung, Y. K.; Lee, B. Y.; J eong, N.; Hudecek, M.; Pauson, P. L.
Organometallics 1993, 12, 220.
in 10 and 11 are small long-range couplings (J
2.7 Hz)
from the alkyne protons to the propargylic methylene
protons.
Coba lt-Med ia ted Cyclop en ta n n u la tion P r ocess.
The Pauson-Khand reaction21 is a convenient synthetic
route to bicyclic systems derived from 1,6-enynes, medi-
(18) (a) Trost, B. M.; Dietsche, T. J .; Fullerton, T. J . J . Org. Chem.
1974, 39, 737. (b) Trost, B. M.; Weber, L. J . Org. Chem. 1975, 40, 3617.
(c) Trost, B. M.; Dietsche, T. J .; Fullerton, T. J . J . Am. Chem. Soc.
1975, 97, 1611. (d) Trost, B. M.; Weber, L.; Strege, P. E.; Fullerton, T.
J .; Dietsche, T. J . J . Am. Chem. Soc. 1978, 100, 3416, 3426.
(19) Trost, B. M.; Lautens, M.; Chan, C. J ebaratnam, D. J .; Mueller,
T. J . Am. Chem. Soc. 1991, 113, 636.
(20) (a) Trost, B. M. Acc. Chem. Res. 1980, 13, 385. (b) Trost, B. M.;
Verhoeven, T. R. J . Am. Chem. Soc. 1980, 102, 4730.
(25) (a) Marco-Contelles, J . Tetrahedron Lett. 1994, 35, 5059. (b)
Magnus, P.; Principe, L. M. Tetrahedron Lett. 1985, 26, 4851.

Palladium Cobalt-Mediated Double Annulation Process
J . Org. Chem., Vol. 61, No. 10, 1996 3253
Sch em e 6
F igu r e 2. Perspective plot of compound 13 along with the
atomic numbering scheme. Double bonds are shown in black
with filled lines.
results were obtained with compound 13. Variations in
solvents (e.g. THF, toluene, dichloromethane),33 catalysts
(tetrakis(triphenylphosphine)palladium(0) and diben-
zylideneacetone palladium(0) chloroform complex)34 and
ligands (triethyl phosphite, triphenyl phosphine)34 and
use of a catalytic amount of n-BuLi35 gave almost the
same results. Also, the reactions with 2-(chloromethyl)-
3-(trimethylsilyl)propene36 and TiCl4 in CH2Cl2 did not
lead to the expected tetracyclic systems 15 and 17.
Probably, alkylation products 16 and 18, involving eno-
late formation, compete with the cycloaddition products
15 and 17, or electron-transfer processes (e.g., oxidation
of the Pd catalyst) in these cases disrupt the cycloaddi-
tion.37,33,28
molecule is shown in Figure 2. The six-membered ring
(O1, C1, C2, C3, C4, C5) with the calculated parameters
of pucker Q 0.524 A , Θ 38.0° and Φ 318.7° has a
1
conformation midway between chair C4 (Θ 0) and half-
1
chair H6 (Θ 50 8, Φ 330°). The endocyclic torsion
angles in the sequence O1 to C5 are 55.4, 25.1, 16.1,
32.3, 57.4, and 73.6. There are no zero angles, but the
small angle of 16.1 corresponds to that expected to be
zero for the half-chair conformation 1H6. The substitu-
ents O2, C10, C8, and C6 are in axial, bisectional, axial,
and equatorial positions, respectively. The five-mem-
bered cyclopentenone ring (C2, C3, C8, C9, C10) exhibits
an envelope conformation with the atom C2 being 36 pm
outside the plane. The five-membered ring formed by
the atoms C3, C4, C6, C7 and C8 is in a half-chair
conformation confirmed by the calculated puckering
parameter Φ 201.5°.
Although the cyclopentation was not successful with
the above mentioned reagents and conditions, there are
a number of other reagents and methods reported in the
27,29a,38
literature26
which can be employed for cyclopen-
Im p lem en ta tion of th e P d -Ca ta lyzed Cycloa d d i-
tion P r otocol. The following studies establish the
feasibility of fusing a cyclopentane ring laterally to the
bicyclic enone systems 12 and 13.26 During the past
decade a large number of methods have been developed27
for cyclopentane annulations. One of the more direct
methods for this task is the palladium(II)-mediated [3
2] cycloaddition of 3-acetoxy-2-[(trimethyllsilyl)methyl]-
tannulation on our bis-cyclopentanoid systems.
Su m m a r y
In summary, the palladium-catalyzed functionalization
of the tosylate 6 and chloride 9 has proved to be a useful
method for the preparation of the unsaturated branched-
chain sugars 10 and 11. These enyne precursors were
successfully used for the regio- and stereoselective syn-
theses of bis-cyclopentanoids on sugar templates by the
intramolecular Pauson Khand cycloaddition reaction.
The development of further useful conversions to natural
products based upon these synthons is the object of
ongoing studies in our laboratories.
31
1-propene (14)28 to enone systems. B. M. Trost et al.29
have explored the cycloaddition of 14 according to eq 1
Exp er im en ta l Section
as a general route for methylenecyclopentane formation.
However, when 12 was treated with 14 in the presence
of palladium(II) acetate and triisopropyl phosphite in
refluxing THF,32 unexpectedly the alkylation product
1628,33 was obtained instead of 15 in 30% yield with 60%
recovery of the starting material (Scheme 6). Similar
Gen er a l Met h od s a n d Ma t er ia ls. All crystallographic
investigations were performed on an automated four-circle
single crystal diffractometer CAD4-T (ENRAF-NONIUS, Delft,
NL) with graphite-monochromated Mo K radiation at low
temperatures 211 K. The compound 13 crystallizes in the
orthorhombic space group P212121 with the lattice parameters
a
879.5(1), b
1005.6(1), and c
2124.0(1) pm, V
1.8785(3) nm3, and Z 4. Calculations were performed with
the programs CADSHEL,39 SIR92,40 SHEXL-93,41 SHELXTL-
PLUS,42 and PLATON-95.43 The authors have deposited all
(26) (a) Exon, C.; Magnus, P. J . Am. Chem. Soc. 1983, 105, 2477.
(b) Piers, E.; Karunaratne, V. J . Chem. Soc., Chem. Commun. 1984,
959. (c) Trost, B. M. Chem. Soc. Rev. 1982, 141.
(27) Ramaiah, M. Synthesis 1983, 529.
(28) Trost, B. M.; Chan, D. M. T. J . Am. Chem. Soc. 1983, 105, 2315.
(29) (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1. (b)
J ones, M. D.; Kemmitt, R. D. W. J . Chem. Soc., Chem. Commun. 1986,
1201.
(30) For related work see (a) Shimizu, I.; Ohashi, Y.; Tsuji, J .
Tetrahedron Lett. 1984, 25, 5183. (b) Shimizu, I.; Ohashi, Y.; Tsuji, J .
Tetrahedron Lett. 1985, 26, 3825.
(34) Trost, B. M.; King, S. A.; Schmidt, T. J . Am. Chem. Soc. 1989,
111, 5902.
(35) Trost, B. M.; Nanninga, T. N. J . Am. Chem. Soc. 1985, 107,
1293.
(36) Knapp, S.; O’Connor, U.; Mobilio, D. Tetrahedron Lett. 1980,
21, 4557.
(31) For 1,3-diyl reactions, see: Little, R. D. Chem. Rev. 1986, 86,
875.
(32) Trost, B. M.; Renaut, P. J . Am. Chem. Soc. 1982, 104, 6668.
(33) Trost, B. M.; Seoane, P.; Mignani, S.; Acemoglu, M. J . Am.
Chem. Soc. 1989, 111, 7487.
(37) Balavoine, G.; Eskenazi, C.; Guillemot, M. J . Chem. Soc., Chem.
Commun. 1979, 1109.
(38) (a) Magnus, P.; Quagllato, D. A. Organometallics 1982, 1, 1243.
(b) Crimmins, M. T.; Mascarella. W. J . Am. Chem. Soc. 1986, 108, 3435.
(c) Bal, S. A.; Marfat, A.; Helquist, P. J . Org. Chem. 1982, 47, 5045.

3254 J . Org. Chem., Vol. 61, No. 10, 1996
Naz et al.
crystallographic data for compound 13 with the Fachinforma-
tionszentrum Karlsruhe, D-76344 Eggenstein-Leopoldshafen.
These data can be obtained, on request, by quoting the names
of authors, journal, and the deposit number CSD-401655.
NMR spectra were obtained with the indicated solvents and
chemical shifts are given in ppm on the δ scale from internal
tetramethylsilane. All reactions were monitored by thin-layer
chromatography carried out on 0.25 mm silica gel plates (60
F-254, E. Merck, Darmstadt, Germany). Plates were visual-
ized under UV light (where appropriate), sprayed with an
orcinol/H2SO4 solution, and heated to develop. Preparative
thin-layer chromatography was performed on 0.5 × 20 × 20
silica gel plates (60 F-254, E. Merck). Column chromatography
was performed by using silica gel 60 (70 230 mesh ASTM,
Merck). THF was distilled from sodium benzophenone and
POCl3 from calcium hydride under nitrogen. The reagent
3-acetoxy-2-[(trimethyllsilyl)-methyl]-1-propene was prepared
according to the procedure given in reference 28. All other
reagents were used as received.
1 H, J
11.4 Hz), 4.56 (d, 1 H, J
7.7 Hz), 4.08 (dd, 1 H, J
13.1, 3.6 Hz), 3.86 (dd, 1 H,
13.1, 1.8 Hz), 2.67 (br s, 1
7.7, 9.7 Hz), 4.04 (dd, 1 H, J
9.7, 3.4 Hz), 3.56 (dd, 1 H, J
J
H), 2.07 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 170.7, 136.5,
128.4 128.0, 101.6, 73.1, 71.1, 69.3, 63.3, 33.1, 20.9; [ ]20
D
30.6° (c 1.0, CHCl3); MS (FD) m/ z 392.3 (M ). Anal. Calcd
for C14H17IO5 (392.19): C, 42.87; H, 4.37; I 32.36. Found: C,
42.29; H, 4.32; I, 32.34.
Ben zyl 2-O-p-Tosyl-3,4-d id eoxy- -D-glycer o-p en t-3-en o-
p yr a n osid e (6). Compound 2 (2.3 g, 6.2 mmol) was dissolved
in 20 mL of absolute pyridine and cooled at 40 °C. Freshly
distilled POCl3 (2 mL, 3.5 equiv, 21.6 mmol) was added
dropwise with stirring, and the mixture was further stirred
for 3 4 h at 0 °C. The reaction mixture was added to 300 mL
of ice water and stirred for 45 min. The hydrolyzed product
was extracted with dichloromethane, and the organic phase
was washed with saturated Na2S2O3 solution and water. The
residue was dried (Na2SO4) and filtered and solvent removed
by distillation under reduced pressure to give a syrup which
was purified by column chromatography using 60% petroleum
ether/CH2Cl2 to CH2Cl2 to give 1.12 g (70%) product. Oil; H
NMR (CDCl3, 250 MHz) δ 7.67 (br d, 2 H, J
7.21 (m, 5 H), 7.16 (br d, 1 H, J
10.5, 2.4 Hz), 5.54 (dm, 1 H, J
3.8, 2.5 Hz), 4.78 (d, 1 H, J
Hz), 4.40 (d, 1 H, J
Hz), 3.93 (dq, 1 H, J
Ben zyl 2-O-p -tosyl-4-iod o-4-d eoxy- -D-xylop yr a n osid e
(2). Benzyl 2-O-p-tosyl-3,4-anhydro-â-L-arabinopyranoside (1)
(3.24 g, 8.61 mmol) was dissolved in 130 mL of acetone and
sodium iodide (5.16 g, 4 equiv, 34.4 mmol), sodium acetate
(0.64 g, 0.9 equiv, 7.8 mmol), and 19.4 mL of acetic acid were
added, and the reaction mixture was refluxed for 4 5 h. After
cooling, the solvent was evaporated and acetic acid was
removed by adding toluene. The syrup was dissolved in
dichloromethane and washed with saturated Na2S2O3, satu-
rated NaHCO3 solution, and finally water. The residue was
dried (Na2SO4) and solvent removed by distillation under
reduced pressure to give a solid product which was recrystal-
lized from ethyl acetate and n-hexane to give 4.1 g (95%) of 2:
Mp 168 170 °C; 1H NMR (CDCl3, 250 MHz) δ 7.75 (br d, 2 H,
1
8.3 Hz), 7.30
7.9 Hz), 5.84 (dq, 1 H, J
10.5 Hz), 4.92 (br dd, 1 H, J
3.8 Hz), 4.65 (d, 1 H, J
12.1
14.6, 2.5
12.1 Hz), 4.12 (dq, 1 H, J
14.3, 2.6 Hz), 2.33 (s, 3 H); 13C NMR
(CDCl3, 63 MHz) δ 137.0, 130.2, 129.7 127.8, 121.1, 93.7, 72.1,
70.0, 60.3, 21.6, [ ]20
81.3° (c 4.0, CHCl3); MS (FD) m/ z
1). Anal. Calcd for C19H20O5S (360.43): C, 63.32;
D
361.1 (M
H, 5.60; S, 8.90. Found: C, 63.0; H, 5.64; S, 8.43.
Ben zyl 2,3-Dideoxy-4-O-acetyl- -D-glycer o-pen t-2-en opy-
r a n osid e (7). Using the procedure for 6, the mixture of 4 and
5 (5 g, 12.8 mmol) in 40 mL of absolute pyridine and POCl3
(4.1 mL, 3.5 equiv, 44.6 mmol) afforded a syrup which was
purified by column chromatography using n-hexane to 5% CH2-
Cl2/n-hexane to give 1.74 g (55%) of 7. Oil; H NMR (CDCl3,
250 MHz) δ 7.30 7.20 (m, 5 H), 5.87 (dt, 1 H, J
J
8.3 Hz), 7.32 (m, 5 H), 7.27 (br d, 2 H, J
8.4 Hz), 5.40
(d, 1 H, J
J
J
H, J
J
3.6 Hz), 4.70 (d, 1 H, J
12.0 Hz), 4.30 (dd, 1 H, J
9.4, 3.2 Hz), 3.98 (dd, 1 H, J
10.0, 4.7 Hz), 3.72 (t, 1 H, J
3.4 Hz), 2.43 (s, 3 H); 13C NMR (CDCl3, 63 MHz) δ 145.2,
12.0 Hz), 4.43 (d, 1 H,
9.2, 3.6 Hz), 4.13 (ddd, 1 H,
10.5, 5.2 Hz), 3.88 (dd, 1
1
10.0 Hz), 2.67 (d, 1 H,
10.4, 1.1
Hz), 5.80 (dt, 1 H, J
1 H), 4.75 (d, 1 H, J
10.3, 2.0 Hz), 5.25 (m, 1 H), 4.95 (br s,
11.8 Hz), 4.50 (d, 1 H, J
11.3, 6.1 Hz), 3.75 (dd, 1 H, J
137.1, 134.0, 129.9, 128.5 127.8, 96.4, 79.2, 71.6, 69.9, 64.0,
11.8 Hz),
11.0, 7.8
27.2, 21.7; [ ]20
34.1° (c 1.73, CHCl3); MS (FD) m/ z 504.7
3.84 (dd, 1 H, J
D
(M ). Anal. Calcd for C19H21IO6S (504.34): C, 45.25; H, 4.20;
I, 25.16; S, 6.36. Found: C, 44.77; H, 4.37; I, 24.61; S, 6.49.
Ben zyl 3-Iod o-3-d eoxy-4-O-a cetyl- -D-xylop yr a n osid e
(4) a n d Ben zyl 2-iod o-2-d eoxy-4-O-a cetyl- -D-a r a bin op y-
r a n osid e (5). Using the procedure for 2, compound 3 (4 g,
15.13 mmol) in 163 mL of acetone, sodium iodide (9.07 g, 4
equiv, 60.5 mmol), sodium acetate (1.1 g, 0.9 equiv, 13.6 mmol),
and 13 mL of acetic acid afforded a mixture of the solid
products 4 and 5. A 3.8 g amount of 4 was recrystallized from
ether and n-hexane, and the rest of the mixture of 4 and 5
was separated by column chromatography using petroleum
ether to 5% ethyl acetate/petroleum ether to give 1 g (total in
81% yield) of 4 and 0.9 g (15%) of 5. Compound 4: Mp 87 89
°C; 1H NMR (CDCl3, 400 MHz) δ 7.25 7.16 (m, 5 H), 4.92 (ddd,
Hz), 2.0 (s, 3 H); 13C NMR (CDCl3, 63 MHz) δ 129.1, 128.5,
128.0, 127.8, 93.3, 70.0, 65.1, 60.1, 21.0; [ ]20
100.7° (c 1.20,
D
CHCl3); MS (FD) m/ z 248.6 (M ). Anal. Calcd for C14H16O4
(248.28): C, 67.73; H, 6.50. Found: C, 67.19; H, 6.69.
Ben zyl 2,3-Did eoxy- -D-glycer o-p en t-2-en op yr a n osid e
(8). Compound 7 (1.5 g, 6.04 mmol) in 18 mL of methanol/
water/triethylamine (3:2:1) was stirred at rt for 4 h. The
solvent was carefully evaporated at rt. The residue was
dissolved in dichloromethane, washed with water. The organic
phase was dried (Na2SO4), filtered and the solvent evaporated
to give 1.24 g product in quantitative yield. Oil; 1H NMR
(CDCl3, 250 MHz) δ 7.30 7.20 (m, 5 H), 5.92 (dt, 1 H, J
10.3, 1.2 Hz), 5.67 (dt, 1 H, J
1.2 Hz), 4.74 (d, 1 H, J
Hz), 4.15 (m, 1 H), 3.70 (dd, 1 H, J
1 H, J
MHz) δ 137.6, 133.3, 128.5, 128.1 127.4, 93.5, 70.0, 63.6, 63.1;
[ ]20
74.6° (c 0.73, CHCl3); MS (FD) m/ z 205.7 (M ).
10.3, 2.2 Hz), 4.92 (br t, 1 H,
11.7 Hz), 4.50 (d, 1 H, J
J
11.8
11.0, 5.5 Hz), 3.60 (dd,
1 H, J
10.5, 5.5 Hz), 4.70 (d, 1 H, J
3.6 Hz), 4.62 (d, 1 H,
11.0, 8.3 Hz), 2.3 (br s, 1 H); 13C NMR (CDCl3, 63
J
11.7 Hz), 4.38 (d, 1 H, J
11.6 Hz), 4.30 (t, 1 H, J
10.8
10.7,
Hz), 3.66 (ddd, 1 H, J
5.4 Hz), 3.39 (t, 1 H, J
10.4, 3.6 Hz), 3.54 (dd, 1 H, J
10.5 Hz), 2.24 (d, 1 H, J
9.7 Hz),
D
1.95 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 169.5, 136.5,
Anal. Calcd for C12H14O3 (206.24): C, 69.88; H, 6.84.
Found: C, 69.69; H, 6.80.
128.4 128.0, 96.4, 73.4, 71.7, 69.7, 60.1, 33.4, 20.8; [ ]20
D
100.2° (c 1.93, CHCl3); MS (FD) m/ z
392.3 (M ). Anal.
Ben zyl 2,3,4-Tr ideoxy-4-ch lor o-â-L-glycer o-pen t-2-en opy-
r a n osid e (9). Compound 8 (1.1 g, 5.34 mmol) was dissolved
in 10 mL of absolute pyridine, and p-toluenesulfonyl chloride
(1.53 g, 1.5 equiv, 8.0 mmol) was added portionwise. The
resulting mixture was stirred at 50 °C for 3 4 h and cooled to
rt, and ice water was added. The product was extracted with
dichloromethane and washed with a 2 N HCl solution, a
saturated NaHCO3 solution, and finally water. The residue
was dried (Na2SO4) and filtered and solvent removed by
distilation under reduced pressure. The rest of the pyridine
was evaporated by adding toluene which gave 1.12 g (94%) of
a crystalline product. Mp 75 78 °C; 1H NMR (CDCl3, 250
Calcd for C14H17IO5 (392.19): C, 42.87; H, 4.37; I, 32.36.
Found: C, 43.13; H, 4.38; I, 32.30. Compound 5: Mp 126
128 °C; 1H NMR (CDCl3, 400 MHz) δ 7.35 7.24 (m, 5 H), 5.50
(dd, 1 H, J
3.2, 2.0 Hz), 4.83 (d, 1 H, J
11.7 Hz), 4.58 (d,
(39) Kopf, J .; Ru¨bcke, H-Chr. Program CADSHEL, 1993. Version
3.1.
(40) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.;
Burla, M. C.; Polidori,G.; Camalli, M. J . Appl. Crystallogr. 1994, 27,
435.
(41) Sheldrick, G. M. Program SHELXL-93, University of Go¨ttingen.
(42) Program Package SHELXTL-PC, Release 5.0, 1995. Siemens
Industrial Automation, Inc., Madison, WI 53719.
(43) Spek, A. L. Program PLATON-95 for geometric calculations,
University of Utrecht, NL.
MHz) δ 7.30 7.20 (m, 5 H), 6.50 (ddd, 1 H, J
11.1, 1.2 Hz),
5.85 (dd, 1 H, J
10.5, 3.1 Hz), 5.06 (dd, 1 H, J
3.0, 0.9
Hz), 4.74 (d, 1 H, J
11.7 Hz), 4.50 (d, 1 H, J
11.7 Hz), 4.30

Palladium Cobalt-Mediated Double Annulation Process
J . Org. Chem., Vol. 61, No. 10, 1996 3255
(dd, 1 H, J
12.7, 1.3 Hz); 13C NMR (CDCl3, 63 MHz) δ 137.2, 128.5, 128.2,
128.1 127.9, 92.2, 69.9, 63.7, 49.9; [ ]20
207.8° (c 0.86 ,
CHCl3); MS (FD) m/ z 224.2 (M ). Anal. Calcd for C12H13
12.5, 2.9 Hz), 4.23 (m, 1 H), 3.60 (dd, 1 H, J
Hz); 13C NMR (CDCl3, 100 MHz) δ 207.4, 183.7, 171.0, 168.9,
137.2, 128.4 127.7, 126.4, 97.0, 70.2, 65.7, 59.8, 53.3, 52.9,
51.3, 46.8, 37.6, 34.3; [ ]29
16.6° (c 1.46, CH2Cl2); MS (FD)
386.5 (M ). Anal. Calcd for C21H22O7 (386.40): C,
D
D
-
m/ z
ClO2 (224.68): C, 64.15; H, 5.83; Cl, 15.78. Found: C, 63.96;
H, 5.90; Cl, 14.37.
65.28; H, 5.74. Found: C, 65.33; H, 5.51.
Ben zyl 2,3,4-Tr id eoxy- -D-r ib op yr a n osid o[4,3,2-cd ]-
6,6-b is(m e t h oxyca r b on yl)b icyclo[3.3.0]oct a n -8-e n -10-
on e (13). Using the procedure to prepare 12, compound 11
(300 mg, 0.83 mmol) and Co2(CO)8 (315.17 mg, 1.1 equiv, 0.92
mmol) in 5 mL of absolute benzene and absolute DMSO (0.17
mL, 3 eq, 2.5 mmol) afforded 231 mg (77%) of the title
compound. Mp 102 104 °C; 1H NMR (CDCl3, 400 MHz) δ
P r op a n ed ioic Acid , [2-(Ben zyloxy)-2,3-d ih yd r o-6H-p y-
r a n -3-yl]-2-p r op yn yl-Dim eth yl Ester (10). Benzyl 2,3,4-
trideoxy-4-chloro-â-L-glycero-pent-2-enopyranoside (9) (1 g, 4.5
mmol), triphenylphosphine (29.3 mg, 2.5 mol %) and tetrakis-
(triphenylphosphine)palladium (129 mg, 2.5 mol %) were
dissolved in 10 mL of THF and stirred at 0 °C for 20 min under
argon. In another flask, to a suspension of NaH (178.6 mg,
60% dispersion, 1 equiv, 4.5 mmol) in 10 mL of THF, dimethyl
propargylmalonate (neat, 0.68 mL, 1 equiv, 4.5 mmol) was
added dropwise under argon at 0 °C and the reaction mixture
stirred for 20 min at the same temperature. The first solution
was added to the second one via a double-ended needle, and
the reaction mixture was stirred at 0 °C for 1 h. After
completion of the reaction (TLC analysis), the solvent was
evaporated, and the mixture of 10 and 11 was column
chromatographed, eluting first with 5% CH2Cl2/petroleum
ether followed by 40% CH2Cl2/petroleum ether to afford 1.07
7.15 7.0 (m, 5 H), 5.79 (d, 1 H, J
2.2 Hz), 4.90 (d, 1 H, J
12.6 Hz), 4.15 (d, 1 H, J 12.6 Hz),
20.3 Hz), 3.20
6.6
7.3 Hz); 13C
7.9 Hz), 4.34 (d, 1 H, J
3.59 (s, 3 H), 3.51 (s, 3 H), 3.38 (d, 1 H, J
3.13 (m, 2 H), 3.10 (t, 1 H, J
Hz), 2.93 (d, 1 H, J 20.2 Hz), 2.90 (t, 1 H, J
12.0 Hz), 3.0 (t, 1 H, J
NMR (CDCl3, 100 MHz) δ 206.8, 180.6, 171.3, 168.8, 137.2,
128.2 127.1, 127.0, 94.3, 69.4, 63.1, 53.5, 53.2, 52.9, 49.8, 46.2,
38.9, 34.1; [ ]29
160.2° (c 0.68, CH2Cl2); MS (FD) m/ z 387
D
(M ). Anal. Calcd for C21H22O7 (386.40): C, 65.28; H, 5.74.
Found: C, 64.94; H, 5.70.
Ben zyl 2,3,4-Tr id eoxyr ibop yr a n osid o[4,3,2-cd ]-10,10-
b is(m et h oxyca r b on yl)-7-(2-m et h yl-2-p r op en yl)b icyclo-
[3.3.0]octa n -7-en -6-on e (16). To a mixture of triisopropyl
phosphite (0.04 mL, 7 eq, 0.18 mmol) and Pd(OAc)2 (5.8 mg,
10 mol %) in 5 mL of THF were added 12 (100 mg, 0.26 mmol)
in 3 mL of THF and 3-acetoxy-2-[(trimethyllsilyl)methyl]-1-
propene (14; 142.72 mg, 3.4 equiv, 0.88 mmol), and the reaction
mixture was refluxed for 48 h. As soon as there was no further
conversion, the reaction was stopped by adding 5 mL of
n-hexane/ethyl acetate (8:2) and the mixture filtered through
Celite. The starting material and product were separated on
TLC plates using 10% ethyl acetate/dichloromethane to give
16 (30%) and recovered starting material (60%). Oil; 1H NMR
(CDCl3, 250 MHz) δ 7.30 7.25 (m, 5 H), 4.70 (br s, 1 H), 4.67
1
g (67%) of 10 and 0.19 g (12%) of 11. Compound 10: Oil; H
NMR (CDCl3, 400 MHz) δ 7.28 7.25 (m, 5 H), 6.06 (br dd, 1
H, J
d, 1 H, J
11.8 Hz), 4.10 (dd, 1 H, J
12.2 Hz), 3.69 (s, 3 H), 3.64 (s, 3 H), 2.88 (br t, 1 H, J
Hz), 2.84 (br d, 2 H, J 2.6 Hz), 1.97 (t, 1 H, J
2.7 Hz); 13
10.2, 5.5 Hz), 5.85 (dq, 1 H, J
10.2, 4.2 Hz), 4.78 (br
11.8 Hz), 4.44 (d, 1 H, J
2.6 Hz), 4.68 (d, 1 H, J
12.3, 4.2 Hz), 3.96 (d, 1 H, J
5.1
C
NMR (CDCl3, 100 MHz) δ 170.1, 169.5, 137.9, 129.6, 128.8,
128.6 127.3, 119.9, 92.4, 78.5, 71.8, 69.3, 58.7, 52.9, 52.8, 35.7,
23.2; [ ]20
50.1° (c 1.8, CHCl3); MS (FD) m/ z 358.1 (M ).
D
Anal. Calcd for C20H22O6 (358.39): C, 67.03; H, 6.19.
Found: C, 66.96; H, 6.34.
P r op a n ed ioic Acid , [6-(Ben zyloxy)-3,6-d ih yd r o-2H-p y-
r a n -3-yl]-2-p r op yn yl-Dim eth yl Ester (11). Using the pro-
cedure to prepare 10, with benzyl 2-O-p-tosyl-3,4-dideoxy- -
D-glycero-pent-3-enopyranoside (6) (1 g, 1 equiv, 2.77 mmol),
triphenylphosphine (29.14 mg, 4 mol %) and tetrakis(tri-
phenylphosphine)palladium (128.4 mg, 4 mol %) in 10 mL of
THF, NaH (277 mg, 60% dispersion, 2.5 equiv, 7.0 mmol), and
dimethyl propargylmalonate (neat; 1.05 mL, 2.5 equiv, 7 mmol)
in 10 mL of THF, after refluxing for 1 h, 0.1 g (10%) of 10 and
0.68 g (69%) of 11 were collected. Compound 11: Oil; 1H NMR
(CDCl3, 400 MHz) δ 7.27 7.20 (m, 5 H), 6.0 (br dt, 1 H, J
(d, 1 H, J
1 H, J
11.8 Hz), 4.61 (br s, 1 H) 4.60 (br s, 1 H), 4.50 (d,
11.8 Hz), 3.75 (br t, 1 H, J
11.7 Hz), 3.72 (s, 3 H),
3.67 (s, 3 H), 3.45 (d, 1 H, J
dd, 1 H, J
19.4 Hz), 3.40 (m, 1 H), 3.28 (br
9.6, 7.6 Hz), 3.0 (d, 1 H, J
20.2 Hz), 2.97 (dd,
1 H, J
11.4, 9.6 Hz), 2.80 (br s, 2 H), 2.78 (dd, 1 H, J 6.8,
3.0 Hz), 1.58 (s, 3 H); 13C NMR (CDCl3, 63 MHz) δ 206.7, 170.7,
171.1, 169.1, 141.6, 137.2, 135.8, 128.5 127.8, 111.9, 96.9, 70.3,
63.3, 59.8, 53.4, 53.0, 50.5, 44.7, 37.6, 33.3, 31.8, 22.5; [ ]20
D
22.6° (c 1.13, CHCl3); MS (FD) m/ z 440.3 (M ). C25H28O7
(440.49).
10.5, 0.9 Hz), 5.73 (dt, 1 H, J
0.9 Hz), 4.65 (d, 1 H, J
Hz), 3.84 3.80 (m, 2 H), 3.65 (s, 3 H), 3.62 (s, 3 H), 3.24 (m,
10.4, 2.7 Hz), 4.86 (br d, 1 H,
Ben zyl 2,3,4-Tr id eoxy- -D-r ib op yr a n osid o[4,3,2-cd ]-
6,6-bis(m eth oxycar bon yl)-9-(2-m eth yl-2-pr open yl)bicyclo-
[3.3.0]octa n -8-en -10-on e (18). Using the procedure for 16,
triisopropyl phosphite (0.04 mL, 7 equiv, 0.18 mmol), Pd(OAc)2
(5.8 mg, 10 mol %) in 5 mL of THF, 13 (100 mg, 0.26 mmol) in
3 mL of THF, and 14 (142.72 mg, 3.4 equiv, 0.88 mmol) gave
18 (30%) and recovered starting material (60%). Oil; 1H NMR
J
12.0 Hz), 4.43 (d, 1 H, J 12.0
1 H), 2.82 (dd, 1 H, J
2.7 Hz), 2.0 (t, 1 H, J
17.5, 2.7 Hz), 2.76 (dd, 1 H, J
17.5,
2.7 Hz); 13C NMR (CDCl3, 100 MHz)
δ 169.4, 169.0, 136.1, 129.7, 128.4, 127.9 127.6, 127.4, 93.2,
78.4, 72.1, 69.4, 58.9, 52.8, 36.8, 22.5; [ ]20
54.7° (c 1.93,
D
CHCl3); MS (FD) m/ z 357.9 (M ). Anal. Calcd for C20H22O6
(358.39): C, 67.03; H, 6.19. Found: C, 67.10; H, 6.19.
(CDCl3, 400 MHz) δ 7.30 7.10 (m, 5 H), 5.10 (d, 1 H, J
Hz), 4.68 (br s, 1 H), 4.63 (br s, 1 H), 4.45 (d, 1 H, J
7.8
12.3
Ben zyl 2,3,4-Tr id eoxyr ibop yr a n osid o[4,3,2-cd ]-10,10-
bis(m eth oxyca r bon yl)bicyclo[3.3.0]octa n -7-en -6-on e (12).
Compound 10 (300 mg, 0.83 mmol) and Co2(CO)8 (315.2 mg,
1.1 equiv, 0.92 mmol) were dissolved in 5 mL of absolute
benzene and stirred at rt for 2 3 h. Then, absolute DMSO
(0.2 mL, 3 equiv, 2.5 mmol) was added, and the reaction
mixture was stirred at 50 °C for 24 h. After completion of the
reaction (TLC analysis), the solvent was evaporated and the
residue column chromatographed using 60% to 90% CH2Cl2/
n-hexane, affording 225 mg (75%) of an oil. 1H NMR (CDCl3,
Hz), 4.30 (d, 1 H, J
12.3 Hz), 3.70 (s, 3 H), 3.65 (s, 3 H), 3.46
(d, 1 H, J
20.4 Hz), 3.32 (ddd, 1 H, J 9.6, 6.6, 1.5 Hz),
3.22 (m, 2 H), 3.13 (t, 1 H, J
6.6 Hz), 3.09 (t, 1 H, J
7.6
Hz), 2.92 (d, 1 H, J
20.4 Hz), 2.80 (br t, 2 H, J
15.7 Hz),
1.50 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 206.3, 173.9, 171.4,
169.1, 141.5, 137.1, 136.1, 128.2 127.4, 112.2, 94.5, 69.5, 63.0,
53.6, 53.2, 52.8, 49.0, 44.4, 39.0, 33.3, 32.2, 22.2; [ ]20
101.6°
D
(c 1.06, CHCl3); MS (FD) m/ z 440.3 (M ). C25H28O7 (440.49).
Ack n ow led gm en t. The authors are grateful to the
Ministerium fu¨r Wissenschaft und Forschung Baden-
Wu¨rtemberg, Germany, for providing Ph.D. scholarship
to N.N. Financial support from Fonds der Chemischen
Industrie and Hewlett-Packard is greatly acknowledged.
400 MHz) δ 7.30 7.20 (m, 5 H), 5.60 (d, 1 H, J
1.5 Hz), 4.70
(d, 1 H, J 12.0 Hz), 4.60 (d, 1 H, J 3.4 Hz), 4.50 (d, 1 H,
J
11.9 Hz), 3.75 (dd, 1 H, J
11.8, 7.6 Hz), 3.72 (s, 3 H),
19.4 Hz), 3.48 (m, 1 H), 3.28 (br
10.1, 7.6 Hz), 3.14 (br dd, 1 H, J 19.4, 1.5 Hz),
3.68 (s, 3 H), 3.52 (d, 1 H, J
dd, 1 H, J
3.02 (dd, 1 H, J
11.7, 9.7 Hz), 2.78 (dd, 1 H, J
7.1, 3.5
J O951298S