Chemistry of 1-alkoxy-1-glycosyl radicals: Formation of β-mannopyranosides by radical decarboxylation and decarbonylation of manno-heptulosonic acid glycoside derivatives

Article abstract of DOI:10.1021/jo960799q

A method for the preparation of highly enriched β-mannopyranosides is described. A glycosyl donor 28 is prepared from tetraallyl mannonolactone by standard means and coupled to a number of primary carbohydrate alcohols, resulting in the isolation in excellent yields of axial disaccharides. Following exchange of the allyl groups for acetyl esters, the furan is oxidatively cleaved with catalytic RuO₂ and NaIO₄ and the resulting acid subjected to the Barton decarboxylation. Coupling of 28 to a secondary alcohol, methyl 2,3-isopropylidene-α-L-rhamnopyranoside, resulted in an apparent inversion of anomeric stereochemistry and isolation of an equatorial disaccharide.

Full text of DOI:10.1021/jo960799q

J . Org. Chem. 1996, 61, 6189-6198
6189
Ch em istr y of 1-Alk oxy-1-glycosyl Ra d ica ls: F or m a tion of
â-Ma n n op yr a n osid es by Ra d ica l Deca r boxyla tion a n d
Deca r bon yla tion of m a n n o-Hep tu loson ic Acid Glycosid e
Der iva tives
David Crich,* J ae-Taeg Hwang, and Hongwei Yuan
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
Received May 1, 1996X
A method for the preparation of highly enriched â-mannopyranosides is described. A glycosyl donor
28 is prepared from tetraallyl mannonolactone by standard means and coupled to a number of
primary carbohydrate alcohols, resulting in the isolation in excellent yields of axial disaccharides.
Following exchange of the allyl groups for acetyl esters, the furan is oxidatively cleaved with catalytic
RuO2 and NaIO4 and the resulting acid subjected to the Barton decarboxylation. Coupling of 28 to
a secondary alcohol, methyl 2,3-isopropylidene-R-L-rhamnopyranoside, resulted in an apparent
inversion of anomeric stereochemistry and isolation of an equatorial disaccharide.
Sch em e 1
In tr od u ction
The problems inherent in the chemical synthesis of the
â-mannopyranoside linkage continue to challenge and
inspire the synthetic organic chemist.1 In this laboratory
we have investigated a method involving radical ano-
meric inversion of the more readily available R-manno-
sides (Scheme 1),2 and a closely related protocol has been
described by the Curran group.3 Unfortunately, while
it was possible to demonstrate highly stereoselective
quenching4 of the sp3-hybridized,5 anomeric radicals in
the desired sense, the slow intramolecular hydrogen atom
abstraction step requires the use of unacceptably low
concentrations of stannane which in turn results in poor
chain propagation and, above room temperature, in a
competing fragmentation of the anomeric radical with
cleavage of the mannose C5-O5 bond.
Sch em e 2
for their radical decarboxylation to highly stereochemi-
cally enriched â-mannopyranosides.
Thus, we were prompted to explore alternative means
of generation of the 1-alkoxy-1-mannopyranosyl radical
and ultimately had recourse to the decarboxylation6 of
ulosonic acid glycosides which had served us well in the
preparation of 2-deoxy-â-glycosides from 3-deoxyulosonic
acid glycosides.7,8 This in turn raised the question of the
efficient synthesis of ulosonic acid glycosides, a well
appreciated problem in the field of ulosonic and sialic
acids.9 Herein, we describe the development of a method
for the synthesis of mannoulosonic acid glycosides and
Resu lts a n d Discu ssion
The formation of glycosidic linkages by coupling of
aglycons (B) to suitably protected ulosonic or sialic acid
glycosyl donors (A) is plagued by steric hindrance about
the anomeric center and instability of the incipient
oxacarbenium ion such that, in addition to the desired
glycoside (C), elimination to the (alkoxycarbonyl)glycal
(D) is a serious problem (Scheme 2). Indeed, this was
the main problem in our earlier synthesis of the C,D-
disaccharide of olivomycin A.7j
It was apparent therefore that the use of glycosyl
donors such as E, with the added steric congestion and
inductive destabilization of the incipient anomeric cation
over and above that already present in the 3-deoxy series
X Abstract published in Advance ACS Abstracts, August 15, 1996.
(1) (a) For a compilation of references to recent advances in this
area, see footnote 2b. (b) Stork, G.; La Clair, J . J . J . Am. Chem. Soc.
1996, 118, 247.
(2) (a) Crich, D.; Brunckova, J .; Yao, Q. Tetrahedron Lett. 1994, 35,
6619. (b) Crich, D.; Sun, S.; Brunckova, J . J . Org. Chem. 1996, 61,
605. (c) Dan, A.; Ito, Y.; Ogawa, T. J . Org. Chem. 1995, 60, 4680.
(3) Yamazaki, N.; Eichenberger, E. Curran, D. P. Tetrahedron Lett.
1994, 35, 6623.
(4) Axial quenching of 1-alkoxy-1-glycosyl radicals was initially
predictable in so far as it is effectively the microscopic reverse of
hydrogen atom abstraction from alkoxytetrahydropyrans by electro-
philic radicals wherein the axial hydrogen is abstracted up to eight
times as rapidly as the equatorial one: (a) Hayday, K.; McKelvey, R.
D. J . Org. Chem. 1976, 41, 2222. (b) Beckwith, A. L. J .; Easton, C. J .
J . Am. Chem. Soc. 1981, 103, 615. (c) Beckwith, A. L. J .; Brumby, S.
J . Chem. Soc., Perkin Trans. 2 1987, 1801.
(7) (a) Crich, D.; Ritchie, T. J . Tetrahedron 1988, 44, 2319. (b) Crich,
D.; Ritchie, T. J . J . Chem. Soc., Chem. Commun. 1988, 986. (c) Crich,
D.; Ritchie, T. J . J . Chem. Soc., Chem. Commun. 1988, 1461. (d) Crich,
D.; Ritchie, T. J . Carbohydr. Res. 1989, 190, c3. (e) Crich, D.; Ritchie,
T. J . J . Chem. Soc., Perkin Trans. 1 1990, 945. (f) Crich, D.; Lim, L. B.
L. Tetrahedron Lett. 1990, 31, 1897. (g) Crich, D.; Lim, L. B. L.
Tetrahedron Lett. 1991, 32, 2565. (h) Crich, D.; Lim, L. B. L. J . Chem.
Soc., Perkin Trans. 1 1991, 2205. (i) Crich, D.; Lim, L. B. L. J . Chem.
Soc., Perkin Trans. 1 1991, 2209. (j) Crich, D.; Hermann, F. Tetrahe-
dron Lett. 1993, 34, 3385.
(5) (a) Malatesta, V.; McKelvey, R. D.; Babcock, B. W.; Ingold, K.
U. J . Org. Chem., 1979, 44, 1872. (b) Malatesta, V. Ingold, K. U. J .
Am. Chem. Soc. 1981, 103, 609. (c) Gregory, A. R.; Malatesta, V. J .
Org. Chem. 1980, 45, 122.
(6) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron 1985,
41, 3901.
(8) Also see: (a) Kahne, D.; Yang, D.; Lim, J . J .; Miller, R.; Paguaga,
E. J . Am. Chem. Soc. 1988, 110, 8716. (b) Sugai, T.; Shen, G.-J .;
Ichikawa, Y.; Wong, C.-H. J . Am. Chem. Soc. 1993, 115, 413.
(9) (a) Okamoto, K.; Goto, T. Tetrahedron 1990, 46, 5835. (b)
DeNinno, M. P. Synthesis 1991, 583. (c) However, for recent advances,
see: Martichonok, V.; Whitesides, G. M. J . Org. Chem. 1996, 61, 1702.
S0022-3263(96)00799-2 CCC: $12.00 © 1996 American Chemical Society

6190 J . Org. Chem., Vol. 61, No. 18, 1996
Crich et al.
glycoside
Ta ble 1. Glycosyla tion Rea ction s
(F ), would not result in synthetically useful yields of
glycoside. We reasoned that the problem might be best
approached through use of a C-aryl, or heteroaryl,
glycosyl donor (G) in which the electron rich aryl group
would stabilize any anomeric cation and so promote
glycosylation, and subsequently be readily cleaved oxi-
datively to the acid (H) required for the stereodefining
radical decarboxylation step. The 2-furyl moiety was
selected for use as the latent carboxylic acid on the
grounds that (i) Danishefsky, as a corollary to his
synthesis of N-acetylneuraminic acid, had demonstrated
the ability of I to undergo trans-glycosylation reactions
in good yield;10 (ii) the Danishefsky group had subse-
quently cleanly oxidized the furan to the acid using the
Sharpless protocol;11 and (iii) Dondoni had described the
clean high yield addition of 2-furyllithium to tetraben-
zylglucopyranose, followed by ozonolytic cleavage,12 point-
ing the way to a rapid entry into G. The use of a
2-thiazolyl group as latent carboxylic acid, as advanced
by Dondoni,13 was eschewed because of the complex two
step cleavage it requires.
acceptor
equiv
entry donor
promoter solvent base (% yield)
1
2
3
4
5
6
7
8
9
4
4
MeOH (1.9) AgOTf
iPrOH (1.8) AgOTf
MeOH (1.1) AgOTf
MeOH (1.1) AgOTf
CH2Cl2 py
CH2Cl2 py
CH2Cl2 py
CH2Cl2 py
CH2Cl2 py
THF
CH2Cl2 py
CH2Cl2 py
5 (100)
6 (100)
16 (97)
32 (94)
35 (89)
15
28
28
28
28
28
28
29 (1.1)
30 (1.1)
31 (1.2)
31 (4)
AgOTf
AgOTF
AgOTf
AgOTf
AgOTf
DBMP 38 (86)
41 (10)
41 (65)
DBMP 41 (75)
31 (1.5)
THF
to form the derived O-acyl thiohydroxamate, followed by
addition of t-BuSH and white light photolysis. In this
manner the â-mannoside 11 was isolated in 75% yield.
Examination of the crude reaction, with the aid of an
authentic sample of the R-mannoside,18 revealed the
clean formation of the â-anomer (Table 2, entry 1).
Oxidative cleavage of the more hindered glycoside 6
proved to be somewhat less efficient than that of 5 such
that, even after 2 days at room temperature, 8 was
isolated in admixture (2:1) with a further compound of
closely similar polarity presumed to be the R-keto acid
9. This assignment was made on the grounds of mass
spectrometry of the mixture which, in addition to a peak
at m/z ) 321 representing [M - H]+• for 8, revealed a
further peak at m/z ) 349 corresponding to [8 + CO -
H]+, or [9 - H]+. 13C-NMR spectroscopy of the mixture,
with three carbonyl carbons at 169.3, 163.0, and 194.2
representing the two carboxyl carbons of 8 and 9 and the
carbonyl of the latter, respectively, also supported this
assignment.19 This recalcitrant mixture was subjected
to the decarboxylation procedure, resulting in the isola-
tion of 12 in 48% yield (Table 2, entry 2).
We began with a feasibility study in which 2,3,4,6-
tetra-O-methylmannopyranose (1)14 was conveniently
converted to the known 1,5-mannonolactone (2)15 by
oxidation with catalytic tetrapropylammonium perruth-
enate (TPAP)16 and N-methylmorpholine N-oxide (NMNO)
as stoichiometric oxidant in 93% yield. The same conver-
sion could also be affected by the Swern protocol17 in
excellent yield. Treatment of 2 with 2-furyllithium in
THF at -78 °C followed, after workup, by ethanethiol
and BF3‚OEt2 in CH2Cl2 from -78 to 0 °C provided the
glycosyl donor 4 in 83% overall yield for the two steps.
Purification of the intermediate 3 was not necessary for
the success of this operation. Treatment of 4 in CH2Cl2
with MeOH and 2-propanol in the presence of pyridine
as base and silver triflate as activator enabled the
isolation of the glycosides 5 and 6, respectively, both in
quantitative yield (Table 1, entries 1 and 2).
Oxidation of 5 according to the Sharpless protocol
provided the acid 7 in 77% yield. This was then subjected
to the Barton reductive decarboxylation protocol6 involv-
ing stirring with the heterocycle 10 and Et3N in CH2Cl2,
With the fundamental method established, attention
was turned to the use of a more apposite protecting group
than the methyl ether. The ideal blocking group for the
2,3,4,6-hydroxy groups of the mannopyranose framework
would meet several criteria aside from the usual consid-
erations of clean introduction and removal. Thus, it
should be compatible with the use of furyllithium and
with the use of oxidizing conditions for the cleavage of
(10) (a) Danishefsky, S. J .; Pearson, W. H.; Segmuller, B. E. J . Am.
Chem. Soc. 1985, 107, 1280. (b) DeNinno, M. P.; Danishefsky, S. J .;
Schulte, G. J . Am. Chem. Soc. 1988, 110, 3925. (c) Danishefsky, S. J .;
DeNinno, M. P.; Chen, S.-H. J . Am. Chem. Soc. 1988, 110, 3929.
(11) Carlsen, P. H. J .; Katsuki, T.; Martin, V. S.; Sharpless, K. B.
J . Org. Chem. 1981, 46, 3986.
(12) Dondoni, A.; Marra, A.; Scherrmann, M.-C. Tetrahedron Lett.
1993, 34, 7323.
(13) Dondoni, A.; Marra, A.; Merino, P. J . Am. Chem. Soc. 1994,
116, 3324.
(14) Drew, H. D. K.; Goodyear, E. H.; Haworth, W. N. J . Chem. Soc.
1927, 1237
(15) Haworth, W. N.; Hirst, E. L.; Smith, J . A. B. J . Chem. Soc. 1930,
2659
(16) Ley, S. V.; Norman, J .; Griffith, W. P.; Marsden, S. P. Synthesis
1994, 639.
(18) [R]23 +47.4° (c 1); 1H-NMR δ 3.35 (s, 3H), 3.39 (s, 3H), 3.45 (s,
D
3H), 3.42-3.45 (m, 4H), 3.50 (s, 3H), 3.51-3.55 (m, 2H), 3.57 (m, 3H),
4.78 (d, J ) 1.7 Hz, 1H); 13C NMR δ 54.8, 57.5, 58.8, 59.1, 60.5, 71.0,
71.6, 76.3, 76.9, 81.0, 97.8. Bott, H. G.; Haworth, W. N.; Hirst, E. L. J .
Chem. Soc. 1930, 2653 ([R]20 +57°, CHCl3).
D
(19) For previous examples of the oxidation of substituted furans
to 1,2-dicarbonyl compounds, see: (a) White, H. M.; Colomb, H. O.;
Bailey, P. S. J . Org. Chem. 1965, 30, 481. (b) Bailey, P. S.; White, H.
M.; Colomb, H. O. J . Org. Chem. 1965, 30, 487.
(17) Mancuso, A. J .; Huang, S.-L.; Swern, D. J . Org. Chem. 1978,
43, 2480.

Chemistry of 1-Alkoxy-1-glycosyl Radicals
J . Org. Chem., Vol. 61, No. 18, 1996 6191
Ta ble 2. F u r a n Clea va ge a n d Deca r boxyla tion
dithioacetal 21. Evidently, the pyranose 19 is strained
and rapidly opens to 20, which then resists closure.24
mannoside
(% yield)
entry furan
acid (% yield)
7 (74)
methoda
â:R
1
2
3
4
5
6
7
8
5
6
A
A
A
A
B
B
B
C
11 (75)
12 (48)
46 (80)
47 (35)
47 (56)
48 (67)
49 (0)
>25:1
>25:1
>10:1
>25:1
>25:1
>25:1
8 + 9 (2:1, 90)
33
36
36
39
42
6
34 (∼100)
37 (∼100)
37 (∼100)
40 (∼100)
43 + 44 (4:1, 100)
8 + 9 (2:1, 90)
12 (68)
>25:1
a
A ) Barton decarboxylation with 10; B ) Barton decarboxy-
lation with 45; C ) decarbonylation of thiol ester.
the furan ring. On the basis of the premise that the furan
ring could be oxidatively degraded selectively in the
presence of benzyl ethers, we initially investigated this
common carbohydrate protecting group. Tetra-O-ben-
zylmannonolactone (13) smoothly furnished the adduct
14 as a mixture of anomers essentially quantitatively,
and this was converted immediately to the anomerically
pure glycosyl donor 15 in 94% yield by treatment with
ethanethiol and BF3‚OEt2. The coupling of 15 with 1.1
equiv of MeOH in CH2Cl2 was instantaneous with silver
triflate as activator and pyridine as acid scavenger,
enabling the isolation of the glycoside 16 in 97% yield as
a single anomer. Attempted oxidation of 16 with cata-
lytic RuO2 and sodium, potassium, or tetrabutylammo-
nium periodate in biphasic mixtures of acetontrile, CCl4,
and water over a range a pH values unfortunately all
resulted in failure owing to the competing oxidation of
the the benzyl ethers and the liberation of benzoic acid.
Various other approaches to the degradation of the furan
ring were also unsatisfactory. Oxidation with mCPBA20
resulted in cleavage of the glycosidic bond, and treatment
with bromine in water21 led to the isolation of 17,
suggesting that attack on the intermediate arenium ion
was sterically hindered. Carefully controlled ozonolysis
experiments suggested that the furan C4′-C5′ was
readily and rapidly attacked, but that of the more
hindered C2′-C3′ bond could not compete with oxidation
of the benzyl ether functions. Singlet oxygenation22 of
16 also resulted in failure with the recovery of substrate,
presumably for steric reasons. This series of experi-
ments, apart from ruling out the use of benzyl ethers,
served to reveal the somewhat sterically hindered nature
of the furan 2′-3′ bond in this type of system. The
obvious use of acetonide protecting groups was thwarted
when reaction of furyllithium with 2,3:4,6-diisopropy-
lidene-1,5-mannonolactone23 (18) resulted in the isolation
of the furyl ketone 20 rather than of the anticipated
pyranose form (19), as signaled by the presence of signals
δ 185.5 and 1655 cm-1, in the 13C-NMR and IR spectra,
respectively, indicative of a furyl ketone and of the clear
presence of an hydroxy group (IR). Treatment of 20 with
ethanethiol and BF3‚OEt2 or ZnCl2 did not lead to the
ethyl thioglycoside analogous to 4 or 15 but rather the
In light of the above, we were constrained to adopt a
strategy in which an initial set of 2,3,4,6-blocking groups
were exchanged for acetates prior to oxidative cleavage
of the furan ring. The allyl ether hydroxy protecting
group was selected for this purpose.25 On a large scale,
tetra-O-allylmannopyranose 22 was best prepared by
Fischer glycosylation of d-mannose with methoxyethanol
to give the glycoside 23, followed by perallylation with
NaH and allyl bromide in DMF to give 24 in essentially
quantitative yield for the two steps. Treatment of 24
with TiCl4 in dichloromethane gave 97% of the chloride
25, which could then be readily hydrolyzed to 22.
Subsequent Swern oxidation (92%) gave lactone 26,
allowing for an overall yield of 85% from d-mannose.
Attempted direct oxidation of 25 to 26 by the Kornblum
protocol26 (DMSO, AgBF4) was unsuccessful. In passing
we note the very clean conversion of 24 to the glycosyl
chloride 25 with TiCl4 and suggest that methoxyethyl
glycosides might generally function as a substantially
more economical variant of the 2-(trimethylsilyl)ethyl
glycosides.27 Treatment of 26 with furyllithium cleanly
gave 27, devoid of any open chain tautomer, and subse-
quent reaction with ethanethiol and BF3‚OEt2 gave the
glycosyl donor 28 as a single anomer, and in 92% yield
for the two steps.
Glycosidation of 28 with 1.1 equiv of MeOH in CH2Cl2
in the presence of pyridine and silver triflate gave 94%
of the glycoside 32 (Table 1, entry 4). Reaction of 28 with
(24) Interestingly, this strain is mainly due to the 4,6-, rather than
the 2,3-acetonide, as subsequent experiments with 4,6-O-isopropy-
lidene-2,3-di-O-[[2-(trimethylsilyl)ethoxy]methyl]mannonolactone gave
exactly analogous results.
(25) Reviews: (a) Greene, T. W.; Wuts, P. G. M. Protective Groups
in Organic Synthesis; 2nd ed.; Wiley, New York, 1991. (b) Kocienski,
P. J . Protecting Groups; Georg Thieme Verlag: Stuttgart, 1994.
(26) Ganem, B.; Boeckman, R. K. Tetrahedron Lett. 1974, 917.
(27) (a) Lipshutz, B. H.; Pegram, J . J .; Morey, M. C. Tetrahedron
Lett. 1981, 22, 4603. (b) J ansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg,
J .; Magnusson, G. J . Org. Chem. 1988, 53, 5629. (c) J annson, K.;
Magnusson, G. Tetrahedron 1990, 46, 59. (d) Pozsgay, V. Tetrahedron
Lett. 1993, 34, 7175.
(20) (a) Williams, P. D.; LeGoff, E. J . Org. Chem. 1981, 46, 4143.
(21) (a) J urczak, J .; Pikul, S. Tetrahedron Lett. 1985, 26, 3039. (b)
Fitzpatrick, J . E.; Milner, D. J .; White, P. Synth. Commun. 1982, 12,
489.
(22) (a) Tsai, T. Y. R.; Wiesner, K. Can. J . Chem. 1982, 60, 2161.
(b) Atwal, K. S.; Sahoo, S. P.; Tsai, T. Y. R.; Wiesner, K. Heterocycles
1982, 19, 641. (c) Reveiw: Feringa, B. L. Rec. Trav. Chim. Pays-Bas
1987, 106, 469.
(23) Bandzouzi, A.; Lakhrissi, M.; Chapleur, Y. J . Chem. Soc., Perkin
Trans. 1 1992, 147.

6192 J . Org. Chem., Vol. 61, No. 18, 1996
Crich et al.
1.1 equiv of 1,2:3,4-di-O-isopropylidenegalactose (29)28 in
CH2Cl2 in the presence of silver triflate and pyridine as
acid scavenger resulted in the isolation of the glycoside
35 in 89% yield (Table 1, entry 5). A comparable protocol
with methyl 2,3,4-tri-O-acetylglucopyranose (30)29 using
2,6-di-tert-butyl-4-methylpyridine (DBMP) as base in
THF as solvent gave 86% of 38 (Table 1, entry 6). With
1.2 equiv of the more hindered rhamnose-derived second-
ary alcohol 3130 using pyridine as base in CH2Cl2, a
disappointing yield of only 10% of glycoside 41 was
obtained (Table 1, entry 7). This yield could be substan-
tially improved by use of 4 equiv of 31 (Table 1, entry 8),
but a more satisfactory protocol involved switching to the
more polar solvent THF and use of non-nucleophilic
DBMP as the acid scavenger; a 75% yield of 41 could be
obtained with only a 50% excess of 31 (Table 1, entry 9).
unsuccessful or ambiguous due to insufficient spectral
resolution. However, it was clear from the close similari-
ties in the 1H-NMR spectra and molecular rotations that,
with the exception of 41, all compounds had both the
same conformation of the mannose ring and anomeric
configuration. A subsequent NOE (vide infra) served to
confirm this assignment. The spectroscopic character-
istics (1H-, 13C-NMR) of 41 indicate that it is clearly
different from the other glycosides in terms of either
anomeric configuration or conformation of the mannopy-
ranosyl ring or both. Subsequent studies soon revealed
its chemistry to be equally different.
Efficient replacement of the allyl protecting groups by
acetate esters in the presence of the acid labile glycosidic
linkages was the next problem to be addressed. For the
methyl glycoside 32 this was achieved by isomerization
to the enol ethers either with Wilkinson’s catalyst
[(Ph3P)3RhCl] in refluxing 90% aqueous ethanol31,32 or,
preferably, with an iridium(I) [(Ph2MeP)2(COD)Ir+PF6
]
-
complex developed by Felkin33 which affected the conver-
sion in THF at room temperature. Without purification,
the enol ethers were cleaved with catalytic OsO4 and
NMNO,34 and the resulting tetraol was acetylated in the
usual manner to give 33. With Wilkinson’s catalyst the
conversion was achieved in 72% overall yield, as opposed
to 77% with the iridium catalyst. We note that, although
this protecting group exchange is necessarily a three-step
process, it was achieved cleanly and in high yield without
isolation and purification of any of the various intermedi-
ates.35 Double irradiation of the methyl protons in 33
resulted in a strong enhancement of the now well-
resolved resonance attributed to H-5, confirming its
assignment and, by extrapolation, those of 4, 7, 8, 15,
16, 28, 32, 35, and 38 as R-glycosides. Application of the
same three-step protecting group exchange to 35 provided
36 in 65 and 75% overall yields with Wilkinson’s and the
iridium catalyst, respectively. Likewise, the allyl groups
of 38 were converted to the esters of 39 in 71% overall
yield using the Felkin complex as isomerizing catalyst.
Application of the same protocol to 41 was problematic.
We suspected that a minor, comigrating, sulfur-based
impurity carried over from the glycosylation was at the
root of this problem, and indeed, when a highly purified
sample was obtained by repeated preparative TLC, the
isomerization was fast and clean. However, on a pre-
parative scale, the isomerization could be readily achieved
with t-BuO-K+ in DMSO.36 Subsequent treatment with
OsO4/NMNO followed by acetylation provided 42 in 65%
overall yield. Inspection of the coupling constants around
4
the mannosyl ring of 42 revealed it to be a C1 chair, as
were 33, 36, and 39, but the slightly downfield shift of
the H-2 and H-4 signals with respect to those in 33, 36,
and 39 and the comparatively upfield shift of the H-3
resonance suggested that it differs in anomeric configu-
ration. In addition, NOESY spectroscopy revealed cross
With the exception of 4, both thioglycosides (15, and
28) and each of the glycosides (7, 8, 16, 32, 35, 38, and
41) were obtained as anomerically pure compounds, and
with the single exception of 41, each is assigned the axial
configuration shown. This assignment is based on the
assumption that each is formed by preferential axial
attack of the alcohol or thiol on a delocalized, cation-like
precursor. Numerous attempts at the observation of
nuclear Overhauser effects between H-3/5 of the man-
nosyl fragment and the coupled alcohol were either
(31) (a) Corey, E. J .; Suggs, J . W. J . Org. Chem. 1973, 38, 3224. (b)
Gent, P. A.; Gigg, R. J . Chem. Soc., Chem. Commun. 1974, 277.
(32) For recent improvements with
a (Ph3P)3RhCl/BuLi couple,
see: Boons, G.-J .; Burton, A.; Isles, S. J . Chem. Soc., Chem. Commun.
1996, 141.
(33) (a) Baudry, D.; Ephritikhine, M.; Felkin, H. J . Chem. Soc.,
Chem. Commun. 1978, 694. (b) Oltvoort, J . J .; van Boeckel, C. A. A.;
de Konig, J . H.; van Boom, J . H. Synthesis 1981, 305.
(34) For an earlier example of this process see: Lamberth, C.;
Bednarski, M. D. Tetrahedron Lett. 1991, 32, 7369.
(28) Raymon, D. A. L.; Schroeder, E. F. J . Am. Chem. Soc. 1948,
70, 2785.
(29) Whistler, R. L.; Doner, L. W.; Kosik, M. Methods in Carbohy-
drate Chemistry; Whistler, R. L., BeMiller, J . N., Eds.; Academic
Press: New York, 1972; Vol. 6, p 411.
(30) (a) Levene, P. A.; Muskat, I. E. J . Biol. Chem. 1934, 105, 431.
(b) Bebault, G. M.; Dutton, G. G. S. Can. J . Chem. 1972, 50, 3373.
(35) Attempted application of this exchange process to the glycosyl
donor 28 failed, probably due to poisoning of the catalysts by the thiol
ether moiety: Yin, H.; Franck. R. W.; Cheng, S.-L.; Quigley, G. J .;
Todaro, L. J . Org. Chem. 1992, 57, 644.
(36) Gigg, R.; Warren, C. D. J . Chem. Soc., C 1968, 1903.

Chemistry of 1-Alkoxy-1-glycosyl Radicals
J . Org. Chem., Vol. 61, No. 18, 1996 6193
peaks between H-3 of the mannose ring and H-3 and H-5
of the furan moiety. Glycoside 42 and its immediate
precursor 41 are therefore â-glycosides. This reversal of
glycosylation stereochemistry with the more bulky sec-
ondary alcohol 31 can presumably be rationalized by
preferential attack along the less hindered equatorial
direction in the coupling with the cation derived from 28.
inseparable mixture of the two thiol esters 51 and 52 in
70% overall yield. This mixture of thiol esters was then
heated to reflux in benzene and treated with Bu3SnH and
AIBN as initiator resulting, by a process involving aryl
radical generation, cyclization and expulsion of the acyl
radical, decarbonylation, and axial quenching, in the
isolation of the â-mannoside 12 in 68% yield (Table 2,
entry 8). Furan 42 was oxidized with catalytic RuO2 and
NaIO4 in acetonitrile/CCl4/water for 24 h at reflux when
the acid 43 was isolated free of 44 but only in 79% yield.
Clearly, the more forcing conditions enabled complete
conversion of the furan to the acid but resulted in parallel
degradation of the carbohydrate. Nevertheless, 43 was
converted to the corresponding acyl chloride and then,
with 50, to the thiol ester 53, which was isolated in 27%
overall yield from 42. Treatment of 53 with Bu3SnH and
AIBN in benzene at reflux, or alternatively with UV
photolysis at room temperature, resulted in a complex
reaction mixture containing at least four closely migrat-
ing disaccharides, none of which could be positively
identified as 49.
Oxidative cleavage of 33, 36, and 39 was routinely
achieved with KIO4 and catalytic RuO2 in a two-phase
system of water, acetonitrile, and CCl4 buffered with K2-
CO3 and gave the corresponding acids 34, 37, and 40,
respectively, in essentially quantitative yield (Table 2,
entries 3-6). No advantage was gained by purification
of these polar compounds and as such they were used in
the subsequent step after a simple extractive workup.
Stirring 34 with 10 and Et3N in CH2Cl2 at room tem-
perature followed by addition of t-BuSH and white light
photolysis resulted in a very clean reaction mixture
comprised of the â-mannoside 46 and its R-anomer in a
ratio of at least 10:1. No significant improvement in ratio
was achieved by conducting the photolysis at 0 °C. Brief
purification by filtration on silica gel yielded 80% of
anomerically pure 46 (Table 2, entry 3), whose physical
characteristics (mp, [R]D) were in excellent accord with
the literature values.37 Application of the same decar-
boxylation protocol to acid 37 gave a disappointing yield
of only 35% of the â-mannoside 47 (Table 2, entry 4).
There was however no evidence for formation of the
corresponding R-anomer in the crude 1H-NMR spectrum,
and therefore, we reasoned that the low yield was a
function of increased steric hindrance about the carboxy-
lic acid. We therefore converted 37 to the corresponding
acyl chloride and allowed it to react at room temperature
with sodium omadine (45) before addition of t-BuSH and
exposure to the ambient laboratory light. In this manner
we obtained an improved 56% yield of the â-mannoside
47 (Table 2, entry 5). Again it was noteworthy that no
evidence for formation of the R-mannoside was found on
inspection of the crude photolyzate. Application of the
same protocol to 40 furnished the â-mannoside 48, free
of R-anomer, in 67% yield (Table 2, entry 6).
In conclusion, a method has been developed for the
preparation of mannosides with excellent â:R ratios in
which the anomeric configuration is determined by a
diastereoselective radical reaction. The method functions
well for primary but is not satisfactory for secondary
glycosyl acceptors, when complications arise in the
coupling and radical steps.
Oxidation of the furan 42, similar to that of 6 (Table
2, entry 2), was slow, and although complete consumption
of the substrate could be achieved, a pure sample of the
desired acid 43 could not be obtained (Table 2, entry 7).
As in the oxidation of 6, 43 was always contaminated by
a closely related product assigned the structure 44 on
the basis of an additional resonance in the 13C-NMR
spectrum at δ 192.4 ppm. Unfortunately, attempted
decarboxylation of this mixture, via the derived acyl
chlorides, proved fruitless (Table 2, entry 7), with no
Exp er im en ta l Section
Gen er a l. For general experimental detail, see footnote 2b.
2,3,4,6-Tetr a-O-m eth yl-D-m an n on o-1,5-lacton e (2). TPAP
(0.3 g, 5 mol %) was added to a solution of tetra-O-methylm-
annose14 (3.87 g, 16.4 mmol), NMNO (2.98 g, 24.7 mmol), and
activated molecular sieves in CH2Cl2 (30 mL) at 0 °C and then
warmed up to room temperature. After stirring overnight, the
reaction mixture was filtered through a short silica gel pad
with ethyl acetate and concentrated under reduced pressure
to give a colorless syrup which was purified by silica gel column
chromatography (3:1 ether:hexanes) to give the lactone 215
(3.73 g, 97%): 1H NMR δ 3.40 (3H, s), 3.46 (3H, s), 3.49-3.53
(4H, m), 3.58 (3H, s), 3.70 (2H, m), 3.82 (1H, m), 4.06 (1H, d,
J )2.74 Hz), 4.15 (1H, m); 13C NMR δ 57.5, 58.6, 59.1, 59.4,
1
evidence in the crude H-NMR for the formation of the
â-mannoside 49 or, indeed, of its R-anomer. It was
unclear, on the small scale employed, whether it was the
formation of the acid chloride, the formation of the O-acyl
thiohydroxamate, or the radical decarboxylation step that
lay at the root of the problem. We therefore resolved to
employ an alternative method for generation of the
anomeric radical which would allow, unlike the Barton
protocol, isolation of the intermediate derivative. To this
end thiol 5038 was condensed with the acyl chlorides
derived from the mixture of 8 and 9, resulting in an
71.7, 77.0, 77.5, 78.1, 78.8, 168.8; IR ν (melt) 1775 cm-1
.
S-E t h yl 1-Deoxy-1-(2-fu r yl)-2,3,4,6-t et r a -O-m et h yl-1-
th io-r-D-m a n n op yr a n osid e (4). A solution of furan (1.1 mL,
15.0 mmol) in THF (10 mL) was treated with n-BuLi (4.5 mL,
2.0 M in pentane, 9.0 mmol) at -78 °C and the reaction
mixture allowed to warm up to room temperature. After
stirring for 2 h, the 2-lithiofuran solution was transferred by
a cannula to a solution of the lactone (1.76 g, 7.5 mmol) in
THF (25 mL) at -78 °C. The reaction mixture was stirred at
this temperature for 2 h, warmed up to room temperature,
and quenched with 10% NH4Cl solution. The aqueous layer
was extracted with ether (3 × 20 mL). The combined organic
phase was washed with saturated sodium bicarbonate solution
(37) (a) Dale, J . K.; J . Am. Chem. Soc. 1924, 46, 1046. (b) Bonner,
W. A. J . Am. Chem. Soc. 1958, 80, 3372.
(38) Crich, D.; Yao, Q. J . Org. Chem. 1996, 61, 3566.

6194 J . Org. Chem., Vol. 61, No. 18, 1996
Crich et al.
and brine, dried (Na2SO4), and then concentrated under
reduced pressure to give the hemiketal as an brown oil.
Ethanethiol (2.3 mL, 31 mmoL) was added to a solution of
hemiketal in CH2Cl2 (25 mL). The reaction mixture was cooled
to -78 °C and BF3‚OEt2 (1.10 mL, 8.9 mmol) was added
dropwise to the reaction mixture followed by warming up to 0
°C. After 20 min, the reaction was quenched with saturated
sodium bicarbonate solution. The aqueous phase was ex-
tracted with CH2Cl2 (2 × 20 mL), and the combined organic
layer was washed with brine, dried (Na2SO4), and concentrated
to give a brown oil as a 6.5:1 mixture of isomers. Purification
by column chromatography (silica gel, 2:1 hexanes:ether) gave
61.2, 71.1, 72.9, 75.5, 77.8, 82.2, 100.3, 168.7; IR ν (melt) 1783,
3443 (br) cm-1
. This crude acid (110 mg, 0.38 mmol) was
dissolved in dry CH2Cl2 (10 mL) followed by the addition of
Et3N (78 mL, 0.56 mmol), and the reaction mixture treated
with 10 (93 mg, 0.56 mmol) in the dark for 4 h. t-BuSH (0.4
mL, 3.74 mmol) was added and the reaction mixture photo-
lyzed with a white tungsten light at 8 °C for 1 h. The reaction
mixture was diluted with CH2Cl2 (20 mL) and washed with
10% aqueous ammonium chloride and saturated aqueous
sodium bicarbonate. The organic phase was dried (Na2SO4)
and concentrated. The methyl â-mannoside 11 (70 mg, 75%)
was isolated by column chromatography (silica gel, 2:1
hexanes:ether): [R]23D -65.8° (c 1.0) (lit.40 [R]20D -87° , CHCl3);
1H NMR δ 3.15 (1H, dd, J ) 8.7, 3.1 Hz), 3.22-3.32 (2H, m),
3.37 (3H, s), 3.46 (3H, s), 3.49 (6H, s), 3.53-3.59 (4H, m), 3.63-
3.68 (2H, m), 4.26 (1H, s); 13C NMR 57.0, 57.3, 59.2, 60.6, 61.5,
71.8, 75.5, 76.6, 76.6, 83.9, 102.2.
Isop r op yl 2,3,4,6-Tet r a -O-m et h yl-â-D-m a n n op yr a n o-
sid e (12). Furan 6 (0.389 g, 1.13 mmol) was oxidized by
catalytic amount of RuO2 and NaIO4 (3.56 g, 16.6 mmol) in
CCl4 (14 mL), acetonitrile (14mL), and water (21 mL) for 2
days as described for the formation of 11 above to give a
mixture of the ulosonic acid 8 and the pyruvic acid 9 essentially
quantatively: 1H NMR (8 and 9, indistinguishable) δ 1.13 (6H,
m), 3.38 (3H, s), 3.43 (4H, s), 3.48 (3H, s), 3.49 (4H, m), 3.55-
3.70 (3H, m), 3.80-3.90 (2H, m), 7.70 (1H, br). 8: 13C NMR δ
23.0, 23.6, 57.9, 59.0, 60.7, 61.2, 69.4, 71.2, 73.0, 75.6, 78.3,
82.1, 100.6, 169.3; HRMS (M - H)+• 321.1549, found 321.1547.
9: 13C NMR δ 23.3, 23.6, 58.2, 59.4, 60.8, 61.1, 69.4, 70.6, 73.9,
75.3, 79.5, 82.2, 101.8, 163.0, 194.2; HRMS (M - H)+• 349.1498,
found 349.1490. As described for 11, this mixture was
subjected to decarboxylation with 10 and t-BuSH with white
light photolysis at 8 °C for 1hr to give 12 (50%, 43 mg)
4 (2.164 g, 83%) and an unidentified isomer (0.21 g). 4: [R]23
D
1
+22.5° (c 1.0); H NMR δ 0.98 (3H, t, J ) 7.5 Hz), 2.09-2.28
(2H, m), 3.13 (3H, s), 3.39 (3H, s), 3.41-3.50 (7H, m), 3.60 (1H,
dd, J ) 11.0, 2.0 Hz), 3.70 (1H, dd, J ) 11.1, 5.6 Hz), 3.78
(1H, dd, J ) 9.5, 3.0 Hz), 3.96 (1H, d, J ) 3.1 Hz), 4.10 (1H,
ddd, J ) 10.0, 5.6, 2.0 Hz), 6.33 (1H, dd, J ) 3.3, 1.8 Hz), 6.45
(1H, dd, J ) 3.2, 1.0), 7.36 (1H, m); 13C NMR δ 14.2, 22.3,
57.8, 59.2, 60.5, 61.0, 71.7, 73.0, 76.4, 80.1, 82.7, 89.2, 108.8,
110.5, 141.0, 151.9. Anal. Calcd for C16H26O6S: C, 55.47; H,
7.56. Found: C, 55.20; H, 7.51. Isomer:39 [R]23D +77.4° (c 1.0);
1H NMR δ 1.1(3H, t, J ) 3.8 Hz), 2.33 (2H, q, J ) 7.3Hz),
3.16-3.23 (4H, m), 3.3 (1H, d, J ) 9.4 Hz), 3.38 (3H, s), 3.35-
3.70 (10H, m), 6.31 (1H, m), 6.52 (1H, dd, J ) 3.2, 0.6 Hz), 7.4
(1H, d, J ) 0.7 Hz); 13C-NMR δ 13.6, 21.2, 59.3, 60.3, 60.8,
60.9, 71.3, 72.4, 79.5, 85.0, 86.7, 88.6, 109.4, 110.2, 142.5, 153.6.
Meth yl 1-(2-Fu r yl)-2,3,4,6-tetr a-O-m eth yl-r-D-m an n opy-
r a n osid e (5). To a stirred mixture of 4 (1.01 g, 2.92 mmol),
MeOH (0.22 mL, 5.43 mmol), pyridine (0.36 mL, 4.38 mmol),
and activated molecular sieves (500 mg) in CH2Cl2 (10 mL)
was added silver triflate (0.91 g, 3.50 mmol), and the reaction
mixture was stirred for 2 h at room temperature in the dark.
The mixture was then filtered through a short pad of silica
gel (1:1 hexanes:ethyl acetate with 1% Et3N). The solvent was
evaporated to give 5 in quantative yield: [R]23D +24.1° (c 1.0);
1H NMR δ 3.01 (3H, s), 3.08 (3H, s), 3.39-4.52 (4H, m), 3.52
(3H, s), 3.53 (3H, s), 3.58 (1H, m), 3.67 (2H, m), 3.72 (1H, dd,
J ) 9.4, 3.2 Hz), 3.84 (1H, d, J ) 3.2 Hz), 6.37(1H, dd, J ) 3.3,
1.8Hz), 6.56 (1H, dd, J ) 3.3, 0.6Hz), 7.40 (1H, m); 13C NMR δ
49.1, 57.8, 59.3, 60.6, 60.8, 71.8, 72.6, 76.1, 78.9, 82.2, 89.2,
110.4, 110.5, 141.9, 150.3. Anal. Calcd for C15H24O7: C, 56.95;
H, 7.65. Found: C, 56.85; H, 7.62.
following isolation by column chromatography (silica gel, 2:1
1
hexanes:ether): [R]23 -103° (c 1.0); H NMR δ1.12 (3H, d, J
D
) 6.0 Hz), 1.22 (3H, d, J ) 6.2 Hz), 3.15 (1H, dd, J ) 8.4, 3.1
Hz), 3.20-3.31 (2H, m), 3.36 (3H, s), 3.46 (3H, s), 3.48 (3H, s),
13
3.5-3.7 (6H, m), 3.98 (1H, sept.J ) 5.8 Hz), 4.43 (1H, s);
-
CNMR δ 21.4, 23.4, 57.2, 59.2, 60.6, 61.6, 70.8, 72.0, 75.5, 76.5,
77.4, 84.0, 99.1. Anal. Calcd for C13H26O6: C, 56.10; H, 9.41.
Found: C, 56.24; H, 9.20.
S-E t h yl 2,3,4,6-Tet r a -O-b en zyl-1-d eoxy-1-(2-fu r yl)-1-
th io-r-D-m a n n op yr a n osid e (15). Gen er a l P r oced u r e for
t h e P r ep a r a t ion of Th ioglycosid es. A solution of furan
(0.82 mL, 0.77 g, 11 mmol) in THF (20 mL) at -78 °C was
treated with n-BuLi (4.13 mL, 2.0 M solution in pentane, 8.3
mmol). The reaction mixture was allowed to warm up to room
temperature and stirred for 2 h. This 2-lithiofuran solution
was then transferred by a cannula to a solution of 1341 (4.0393
g, 7.50 mmol) in THF (40 mL) at -78 °C. The reaction mixture
was stirred at this temperature for 2 h. Water (100 mL) was
poured in and the mixture warmed to room temperature.
Extraction with CH2Cl2, drying with Na2SO4, and concentra-
tion in vacuo gave the hemiketal 14 as an oil which was
subjected to the next reaction immediately. Ethanethiol (2.8
mL, 2.3 g, 38 mmol) was added to the solution of the hemiketal
14 in dry CH2Cl2 (50 mL). The solution was cooled to 0 °C
and treated with BF3‚OEt2 (1.1 mL, 1.3 g, 8.9 mmol) for 5 min
before quenching with saturated aqueous NaHCO3. The
organic phase was separated and further washed with satu-
rated aqueous NaHCO3 twice. Drying (Na2SO4) and evapora-
tion of the solvent under vacuum yielded the thioglycoside 15
as a clear oil. The oil was purified by silica gel column
chromatography (6:1 hexanes:ether with 1% Et3N) to give 4.58
Isop r op yl 1-(2-F u r yl)-2,3,4,6-tetr a -O-m eth yl-r-D-m a n -
n op yr a n osid e (6). Reaction of 4 (0.95 g, 2.74 mmol), isopro-
pyl alcohol (0.38 mL, 4.93 mmol), pyridine (0.34 mL, 4.11
mmol), silver triflate (0.854 g, 3.29 mmol), and activated
molecular sieves in CH2Cl2 essentially as described for 5 gave
6 quantatively in the form of a colorless syrup: [R]23 +26.1°
D
1
(c 1.0); H NMR δ 0.72 (3H, d, J ) 6.1 Hz), 1.15 (3H, d, J )
6.2 Hz), 3.14 (3H, s), 3.40-3.50 (4H, m), 3.54 (3H, s), 3.55 (3H,
s), 3.67 (2H, m), 3.72-3.82 (3H, m), 3.90 (1H, d, J ) 3.0 Hz),
6.37 (1H, dd, J ) 3.3, 1.8 Hz), 6.56 (1H, dd, J ) 3.3, 0.7 Hz),
7.38 (1H, m); 13C NMR δ 22.7, 23.6, 57.8, 59.3, 60.7, 60.8, 65.6,
72.0, 72.8, 76.4, 79.1, 82.2, 99.0, 109.8, 110.8, 141.1, 151.7.
Anal. Calcd for C17H28O7: C, 59.29; H, 8.19. Found: C, 59.32;
H, 8.24.
Met h yl 2,3,4,6-Tet r a -O-m et h yl-â-D-m a n n op yr a n osid e
(11). RuO2 (4 mg, 5 mol %) was added to a biphasic solution
of NaIO4 (1.74 g, 8.01 mmol) in CCl4 (10 mL), acetonitrile (5
mL), and water (15 mL), and after the mixture was stirred
for 20 min, 5 (0.173 g, 0.55 mmol) in acetonitrile (5 mL) was
added to the reaction mixture. The resulting yellow-green
mixture was stirred strongly for 2 days at room temperature
and then diluted with ethyl acetate. The aqueous phase was
extracted with ethyl acetate (5 × 20 mL), and the combined
organic phases were filtered through a pad of Celite, activated
carbon, and sodium sulfate. The filtrate was concentrated to
give the ulosonic acid 7 (124mg, 77%) as a pale blackish
syrup: 1H NMR δ 3.25 (3H, s), 3.42 (3H, s), 3.46-3.50 (4H,
m), 3.51 (3H, s), 3.52-3.55 (5H, m), 3.66 (2H, m), 3.85 (1H, d,
J ) 2.6 Hz), 7.60 (1H, br); 13C NMR δ 50.9, 58.0, 59.0, 60.6,
g (94%) pure thioglycoside 15: [R]23 +13.3° (c 1.39) 1H NMR
D
δ 1.05 (3H, t, J ) 7.5 Hz), 2.23 (1H, m), 2.33 (1H, m), 3.82
(1H, dd, J ) 11.5, 1.7 Hz), 3.93 (1H, dd, J ) 11.5, 5.5 Hz),
4.05 (1H, app t, J ) 9.8 Hz), 4.24 (1H, d, J ) 11.3 Hz), 4.27-
4.37 (3H, m), 4.51 (1H, d, J ) 11.3 Hz), 4.59 (1H, d, J ) 11.9
Hz), 4.61 (1H, d, J ) 10.9 Hz), 4.71 (2H, app s), 4.75 (1H, d, J
(40) Bott, H. G.; Haworth, W. N.; Hirst, E. L. J . Chem. Soc. 1930,
2653.
(39) Owing to insufficient spectral resolution, it is unclear whether
this isomer differs from 4 in anomeric configuration or is the result of
a manno- to gluco-isomerization.
(41) (a) Lewis, M. D.; Cha, J .; Kishi, Y. J . Am. Chem. Soc. 1982,
104, 4976. (b) Lopez, R.; Fernandez-Mayoralas, A. J . Org. Chem. 1994,
59, 737.

Chemistry of 1-Alkoxy-1-glycosyl Radicals
J . Org. Chem., Vol. 61, No. 18, 1996 6195
) 11.9 Hz), 4.92 (1H, d, J ) 10.9 Hz), 6.41 (1H, dd, J ) 3.2,
1.8 Hz), 6.52 (1H, dd, J ) 3.2, 0.9 Hz), 7.08-7.10 (2H, m),
7.19-7.39 (18H, m), 7.41 (1H, dd, J ) 1.8, 0.9 Hz); 13C NMR
δ 14.4, 22.5, 69.4, 72.2, 73.3, 73.8, 74.7, 74.9, 75.1, 78.9, 81.3,
89.6, 109.1, 110.6, 127.2, 127.3, 127.5, 127.6, 127.7 (2C), 127.8,
127.9, 128.0, 128.2, 128.3, 128.4, 138.3, 138.4, 138.5, 138.7,
141.1, 152.3. Anal. Calcd for C40H42O6S: C, 73.82; H, 6.50.
Found: C, 73.90; H, 6.60.
Anal. Calcd for C18H27ClO5: C, 60.25; H, 7.58. Found: C,
59.97; H, 7.68.
2,3,4,6-Tetr a -O-a llyl-D-m a n n on o-1,5-la cton e (26). The
mannosyl chloride 25 (34.33 g, 95.7 mmol) was dissolved in
200 mL of THF and treated with 200 mL of 2 M aqueous HCl
at room temperature for 30 h. The solution was poured into
400 mL of saturated aqueous sodium bicarbonate and ex-
tracted with ether (4 × 200 mL). The ether layers were dried
(Na2SO4) and concentrated in vacuo, affording tetraallylman-
nose 22 (31.53 g, 97%) as a slightly yellow oil which was mainly
the R-anomer and subjected to the following reaction without
further purification. R-Anomer: 1H NMR δ 3.15 (1H, br),
3.53-3.80 (5H, m), 3.90-4.20 (8H, m), 4.35 (1H, ddt, J ) 12.7,
5.8, 1.5 Hz), 5.10-5.37 (9H, m), 5.83-6.02 (4H, m); 13C NMR
δ 69.7, 70.9, 71.0, 72.1, 72.2, 73.8, 74.8, 75.2, 79.1, 92.8, 116.49,
116.54, 117.3, 117.4, 134.5, 134.86, 134.94, 135.0. To a stirred
solution of oxalyl chloride (8.89 mL, 12.9 g, 102 mmol) in CH2-
Cl2 (250 mL) cooled at -78 °C was added a solution of DMSO
(14.5 mL, 15.9 g, 204 mmol) in CH2Cl2 (30 mL). After 2 min
of stirring, 22 (31.53 g, 92.62 mmol) in 80 mL of CH2Cl2 was
added within 5 min. The resulting reaction mixture was
stirred at this low temperature for 15 min before Et3N (64.5
mL, 46.9 g, 463 mmol) was added. After stirring for another
5 min, the mixture was allowed to warm up to room temper-
ature and quenched with water (400 mL). The organic layer
was separated and the aqueous layer was washed with CH2-
Cl2 (2 × 150 mL). The combined organic layers were dried
(Na2SO4) and concentrated under vacuum. The crude product
was purified by column chromatography (silica gel, 3:1 hex-
Meth yl 2,3,4,6-Tetr a -O-ben zyl-1-(2-fu r yl)-r-D-m a n n opy-
r a n osid e (16). Sta n d a r d P r oced u r e for th e Glycosyla -
tion Rea ction s. To a well stirred mixture of 15 (263.2 mg,
0.404 mmol), MeOH (24.6 µL, 19.5 mg, 0.607 mmol), pyridine
(49.1 µL, 48.0 mg, 0.607 mmol), and activated 4 A molecular
sieves (∼150 mg) in CH2Cl2 (8 mL) was added silver triflate
(114.3 mg, 0.445 mmol), and the reaction mixture stirred for
15 min at room temperature in the dark. The mixture was
then filtered through a short pad of silica gel (4:1 hexanes:
ether with 1% Et3N). The solvent was removed under reduced
pressure to yield the crude methyl mannoside 16 as an oil.
The pure product (243.3 mg, 97%) was obtained by flash
column chromatography (silica gel, 4:1 hexanes:ether with 1%
Et3N) as an oil: [R]23 +11.3° (c 1.76); 1H NMR δ 3.06 (3H, s),
D
3.80-3.93 (3H, m), 4.02 (1H, app t, J ) 9.7 Hz), 4.18-4.26
(3H, m), 4.46 (1H, d, J ) 11.5 Hz), 4.60 (1H, d, J ) 11.7 Hz),
4.62-4.70 (3H, m), 4.76 (1H, d, J ) 12.0 Hz), 4.93 (1H, d, J )
10.8 Hz), 6.43 (1H, dd, J ) 3.2, 1.8 Hz), 6.61 (1H, dd, J ) 3.2,
0.9 Hz), 7.05-7.10 (2H, m), 7.19-7.39 (18H, m), 7.41 (1H, dd,
J ) 1.8, 0.9 Hz); 13C NMR δ 49.3, 69.5, 72.1, 73.4 (2C), 74.2,
74.6, 75.1, 77.0, 81.2, 99.6, 110.5, 110.8, 127.2, 127.4, 127.48
(2C), 127.54, 127.7, 127.9, 127.98, 128.01, 128.29 (2C), 128.33,
138.4, 138.5, 138.6, 138.7, 141.9, 150.8. Anal. Calcd for
C39H40O7: C, 75.46; H, 6.50. Found: C, 75.30; H, 6.51.
anes:ethyl acetate) to give the lactone (28.85 g, 92%) as a pale
1
yellow oil: [R]23 +41.4° (c 1.82); H NMR δ 3.67 (1H, app s),
D
3.69 (1H, app s), 3.73 (1H, dd, J ) 7.0, 1.7 Hz), 4.06-4.35 (10H,
m), 4.47 (1H, ddt, J ) 12.9, 5.0, 1.6 Hz), 5.14-5.38 (8H, m),
5.80-6.01 (4H, m); 13C NMR δ 69.3, 70.8, 71.8, 71.9, 72.4, 75.1,
75.6, 76.9, 78.5, 117.35, 117.45, 117.9, 118.2, 133.5, 133.9,
134.2, 134.3, 169.2. Anal. Calcd for C18H26O6: C, 63.89; H,
7.74. Found: C, 63.52; H, 7.63.
2,3,4,6-Tetr a -O-a llyl-D-m a n n op yr a n osyl Ch lor id e (25).
A mixture of D-mannose (18.02 g, 0.100 mol), 2-methoxyethanol
(80 mL, 1.0 mol), benzene (20 mL), and p-toluenesulfonic acid
monohydrate (190 mg, 1.0 mmol) was heated to 110-120 °C
under a Dean-Stark water separator for 5 h. The solution
was cooled to room temperature and Et3N (2 mL) was added.
The solvent was removed under reduced pressure at 65 °C,
giving 2-methoxyethyl mannopyranoside 23 as a syrup. The
syrup was dissolved in 500 mL of DMF, followed by the
addition of allyl bromide (51.9 mL, 72.6 g, 600 mmol). To this
solution cooled to 0 °C was added sodium hydride (24.00 g,
60% in mineral oil, 600 mmol) portionwise over 1 h, and the
resulting mixture was stirred overnight. The reaction mixture
was poured into ice water (1 L) and extracted with ether (5 ×
400 mL). The organic phase was dried (Na2SO4) and concen-
trated in vacuo. The so-obtained oil was taken up in petroleum
ether (500 mL) and washed with acetonitrile (4 × 200 mL).
The combined acetonitrile solution was concentrated under
reduced pressure to afford the title compound 24 (38.13 g, 96%)
as a pale yellow oil, which was shown by NMR to be a mixture
of two anomers containing a very small amount of the
â-isomer. This oil was used without further purification.
R-Anomer: 1H NMR δ 3.37 (3H, s), 3.49-3.83 (10H, m), 3.98-
4.20 (7H, m), 4.35 (1H, ddt, J ) 12.3, 5.8, 1.4 Hz), 4.86 (1H, d,
J ) 1.8 Hz), 5.09-5.35 (8H, m), 5.82-6.01 (4H, m); 13C NMR
δ 58.8, 66.2, 69.1, 70.9, 71.3, 71.4, 71.6, 72.1, 73.7, 74.5, 74.7,
79.3, 97.9, 116.2, 116.3, 116.5, 117.1, 134.7, 134.8, 134.9 (2C).
To a solution of 24 (38.13 g, 95.7 mmol) in CH2Cl2 (500 mL)
at 0 °C was added cautiously a solution of TiCl4 in CH2Cl2 (115
mL, 1.0 M solution, 115 mmol) over 15 min. TLC showed that
the reaction was essentially over after the addition. After 30
min of further stirring at 0 °C the reaction was quenched with
saturated aqueous sodium bicarbonate, and the mixture was
filtered through Celite. The organic layer was separated, and
the aqueous layer was further extracted twice with CH2Cl2.
The combined organic solution was dried (Na2SO4) and the
solvent evaporated under vacuum to yield 25 (34.33 g, 100%)
as an oil which was somewhat unstable and immediately
subjected to the subsequent reaction: 1H NMR δ 3.58-3.85
(4H, m), 3.85-4.20 (9H, m), 4.29 (1H, ddt, J ) 12.4, 5.6, 1.5
Hz), 5.05-5.35 (8H, m), 5.75-5.95 (4H, m), 6.03 (1H, d, J )
1.6 Hz); 13C NMR δ 68.1, 71.3, 72.1, 72.2, 73.8, 73.9, 74.3, 77.5
(2C), 91.6, 116.5, 117.0 (2C), 118.0, 134.3, 134.5 (2C), 134.7.
S-Eth yl 2,3,4,6-Tetr a -O-a llyl-1-d eoxy-1-(2-fu r yl)-1-th io-
r-D-m a n n op yr a n osid e (28). A solution of furan (1.33 mL,
1.24 g, 18.2 mmol) in THF (30 mL) at -78 °C was treated with
n-BuLi (6.4 mL, 2.0 M solution in pentane, 12.8 mmol). The
reaction mixture was allowed to warm up to room temperature
and stirred for 2 h. This 2-lithiofuran solution was then
transferred by a cannula to a solution of 26 (4.1112 g, 12.15
mmol) in THF (50 mL) at -78 °C. The reaction mixture was
stirred at this temperature for 2 h. Water (100 mL) was
poured in and the mixture warmed to room temperature.
Extraction with CH2Cl2, drying with Na2SO4, and concentra-
tion in vacuo gave the hemiketal 27 as an oil. This oil was
taken up in dry CH2Cl2 (80 mL), and ethanethiol (4.5 mL, 3.8
g, 61 mmol) was added. The solution was cooled to 0 °C and
treated with BF3‚OEt2 (1.6 mL, 1.8 g, 13 mmol) for 5 min before
being quenched with saturated aqueous NaHCO3. The organic
phase was separated and washed additionally with saturated
aqueous NaHCO3 twice. Drying (Na2SO4) and evaporation of
the solvent under vacuum yielded the thioglycoside as a brown
oil. The oil was purified by column chromatography (silica gel,
8:1 hexanes:ethyl acetate with 1% Et3N), giving 5.021 g (92%)
of pure thioglycoside 28: [R]23D +17.9° (c 0.95) 1H NMR δ 1.02
(3H, t, J ) 7.5 Hz), 2.16 (1H, m), 2.27 (1H, m), 3.67-3.82 (5H,
m), 3.98-4.24 (8H, m), 4.35 (1H, ddt, J ) 12.3, 5.7, 1.5 Hz),
4.98-5.37 (8H, m), 5.57 (1H, m), 5.83-6.02 (3H, m), 6.35 (1H,
dd, J ) 3.2, 1.8 Hz), 6.46 (1H, dd, J ) 3.2, 0.8 Hz), 7.39 (1H,
dd, J ) 1.7, 0.9 Hz); 13C NMR δ 14.3, 22.3, 69.4, 71.1, 72.2,
73.5, 73.7, 73.9, 74.9, 78.2, 80.4, 89.6, 109.0, 110.5, 116.4, 116.5,
116.8, 116.9, 134.7, 134.98, 135.04 (2C), 140.9, 152.1. Anal.
Calcd for C24H34O6S: C, 63.97; H, 7.61. Found: C, 64.06; H,
7.70.
Meth yl 2,3,4,6-Tetr a -O-a llyl-1-(2-fu r yl)-r-D-m a n n op y-
r a n osid e (32). To a well stirred mixture of 28 (484.7 mg,
1.076 mmol), methanol (65.4 µL, 51.7 mg, 1.61 mmol), pyridine
(131 µL, 128 mg, 1.61 mmol), and activated 4 A molecular
sieves (∼300 mg) in dichloromethane was added silver triflate
(304.1 mg, 1.18 mmol), and the reaction mixture was stirred
for 15 min at room temperature in the dark. The mixture was
then filtered through a short pad of silica gel (6:1 hexanes:

6196 J . Org. Chem., Vol. 61, No. 18, 1996
Crich et al.
ethyl acetate with 1% Et3N). The solvent was removed under
vacuum, yielding the crude methyl mannoside as an oil. The
pure product (425 mg, 94%) was obtained by flash column
chromatography (silica gel, 6:1 hexanes:ethyl acetate with 1%
app s), 5.00 (2H, m), 5.10-5.25 (4H, m), 5.31 (2H, m), 5.60
(1H, m), 5.88-6.03 (3H, m), 6.34 (1H, dd, J ) 3.2, 1.8 Hz),
6.55 (1H, dd, J ) 3.3, 0.9 Hz), 7.35 (1H, dd, J ) 1.8 Hz, 0.9
Hz); 13C NMR δ 17.4, 26.3, 27.7, 54.7, 64.7, 68.8, 71.2, 72.4,
73.4, 73.7, 73.9, 74.5, 75.8, 76.0, 77.1, 77.6, 80.4, 97.8, 100.7,
108.5, 110.6, 111.4, 115.7, 116.1, 116.2, 116.3, 135.1, 135.36,
135.44, 135.6, 140.9, 150.4. Anal. Calcd for C32H46O11: C,
63.35; H, 7.64. Found: C, 62.97; H, 7.47.
Et3N) as an oil: [R]23 +23.4° (c 3.45); 1H NMR δ 3.02 (3H, s),
D
3.65-3.78 (6H, m), 3.91 (1H, m), 3.96 (1H, d, J ) 3.1 Hz),
4.06-4.23 (5H, m), 4.37 (1H, ddt, J ) 12.3, 5.7, 1.4 Hz), 5.03
(2H, m), 5.10-5.36 (6H, m), 5.51 (1H, m), 5.85-6.02 (3H, m),
6.38 (1H, dd, J ) 3.3, 1.8 Hz), 6.54 (1H, dd, J ) 3.3, 0.9 Hz),
7.41 (1H, dd, J ) 1.8, 0.9 Hz); 13C NMR δ 49.2, 69.5, 71.0,
72.3, 73.0, 73.3, 73.9, 74.5, 76.4, 80.2, 99.5, 110.4, 110.6, 116.5
(3C), 116.9, 134.9, 135.0, 135.1 (2C), 141.7, 150.5. Anal. Calcd
for C23H32O7: C, 65.70; H, 7.67. Found: C, 65.25; H, 7.61.
1,2:3,4-Di-O-isop r op ylid en e-6-O-[2,3,4,6-tetr a -O-a llyl-1-
(2-fu r yl)-r-D-m a n n op yr a n osyl]-r-D-ga la ctop yr a n ose (35).
The thioglycoside 28 (949.9 mg, 2.108 mmol) and 29 (603.6
mg, 2.319 mmol) were azeotroped three times from toluene.
They were then diluted with anhydrous CH2Cl2 (15 mL). The
solution was then treated with pyridine (0.26 mL, 0.25 g, 3.2
mmol), 4 A molecular sieves, and silver triflate (595.8 mg,
2.319 mmol) for 30 min according to the above general
glycosylation protocol for the preparation of 32 to give the
disaccharide 35 in 89% (1.223 g) yield after column chroma-
tography (silica gel, 4.5:1 hexanes:ethyl acetate with 1%
Et3N): [R]23D -15.5° (c 1.00); 1H NMR δ 1.28 (3H, s), 1.32 (3H,
s), 1.35 (3H, s), 1.54 (3H, s), 3.32 (1H, dd, J ) 10.6, 4.8 Hz),
3.52 (1H, dd, J ) 10.6, 6.8 Hz), 3.68-3.90 (7H, m), 3.93 (1H,
dd, J ) 9.4, 3.0 Hz), 4.00 (1H, d, J ) 3.0 Hz), 4.03-4.21 (6H,
m), 4.25 (1H, dd, J ) 5.0, 2.4 Hz), 4.34 (1H, ddt, J ) 12.5, 5.6,
1.5 Hz), 4.53 (1H, dd, J ) 7.9, 2.4 Hz), 5.01 (2H, m), 5.10-
5.37 (6H, m), 5.47 (1H, d, J ) 5.0 Hz), 5.55 (1H, m), 5.86-
6.01 (3H, m), 6.35 (1H, dd, J ) 3.2, 1.8 Hz), 6.53 (1H, dd, J )
3.2, 0.8 Hz), 7.35 (1H, J ) 1.7, 0.8 Hz); 13C NMR δ 24.4, 25.0,
25.9, 26.1, 61.5, 67.1, 69.3, 70.6, 70.7, 71.2, 71.3, 72.2, 73.0,
73.4, 73.6, 74.5, 76.6, 80.0, 96.2, 99.5, 108.4, 109.1, 110.5 (2C),
116.2, 116.4, 116.5 (2C), 135.1, 135.3, 135.4 (2C), 141.5, 150.9.
Anal. Calcd for C34H48O12: C, 62.95; H, 7.46. Found: C, 62.97;
H, 7.49.
Meth yl 2,3,4,6-Tetr a -O-a cetyl-1-(2-fu r yl)-r-D-m a n n op y-
r a n osid e (33). Gen er a l P r otocol for P r otectin g Gr ou p
Exch a n ges. Meth od A. A solution of 32 (94.8 mg, 0.225
mmol) and DABCO (12.6 mg, 0.112 mmol) in 90% aqueous
ethanol (5 mL) was heated to about 50 °C, followed by the
addition of (Ph3P)3RhCl (21 mg, 0.023 mmol). The suspension
was gently refluxed for 6 h. Water (10 mL) was poured into
the reaction mixture, and the mixture was extracted with CH2-
Cl2 (3 × 10 mL). The combined organic solution was dried
1
(Na2SO4) and concentrated in vacuo. The H NMR spectrum
showed that all of the allyl protecting groups were converted
to 1-propenyl groups. The residue was taken up in 85%
aqueous acetone (5 mL) and was treated with NMNO (111 mg,
0.948 mmol) and a catalytic amount of OsO4 for 10 h. A black
residue was obtained after removal of the solvent under
vacuum which was directly taken up in CH2Cl2 (10 mL) and
treated with acetic anhydride (0.21 mL, 0.23 g, 2.2 mmol) and
DMAP (5.6 mg, 0.046 mmol) overnight. The reaction was
quenched with saturated aqueous NaHCO3 (15 mL). Extrac-
tion with CH2Cl2, drying with Na2SO4, and evaporation of the
solvent gave crude 33, which was purified by column chroma-
tography (silica gel, 2:1 hexanes:ethyl acetate with 1% Et3N).
The yield was 69.7 mg (72%): [R]23 +13.5° (c 1.35); 1H NMR
D
δ 1.88 (3H, s), 1.97 (3H, s), 2.06 (3H, s), 2.10 (3H, s), 3.09 (3H,
s), 3.99 (1H, ddd, J ) 10.1, 5.8, 2.8 Hz), 4.24 (1H, dd, J ) 12.1,
2.8 Hz), 4.34 (1H, dd, J ) 12.1, 5.8 Hz), 5.29 (1H, app t, J )
10.0 Hz), 5.53 (1H, dd, J ) 10.0, 3.4 Hz), 5.63 (1H, d, J ) 3.4
Hz), 6.34 (1H, dd, J ) 3.3, 1.8 Hz), 6.49 (1H, dd, J ) 3.3, 0.9
Hz), 7.38 (1H, dd, J ) 1.8, 0.9 Hz); 13C NMR δ 20.3, 20.6, 20.7
(2C), 49.7, 66.1, 69.5, 69.6, 70.1, 98.8, 110.0, 110.9, 143.0, 148.2,
169.2, 169.77, 169.84, 170.6. Anal. Calcd for C19H24O11: C,
53.27; H, 5.65. Found: C, 53.16; H, 5.80.
Meth yl 2,3,4-Tr i-O-a cetyl-6-O-[2,3,4,6-tetr a -O-a llyl-1-(2-
fu r yl)-r-D-m a n n op yr a n osyl]-r-D-glu cop yr a n osid e (38). A
mixture of 28 (1.091 g, 2.421 mmol), 30 (0.853 g, 2.663 mmol),
and DTBMP (0.597 g, 2.905 mmol) was dried by azeotropic
evaporation with toluene three times with a rotary evaporator.
This mixture was then dissolved in anhydrous THF (15 mL),
and crushed activated 4 A molecular sieves (∼0.4 g) were
added. Treatment with silver triflate (0.747 g, 2.905 mmol)
according to the standard glycosylation protocol described for
the preparation of 32 gave the disaccharide 38 in 86% (1.469
g) yield after column chromatography (neutral alumina, 3:1
Meth od
B for P r otectin g Gr ou p Exch a n ge. To a
solution of the mannoside 32 (424.9 mg, 1.010 mmol) and
DABCO (11.3 mg, 0.101 mmol) in dry THF (20 mL) was added
[(Ph2MeP)2(COD)IrPF6] (43 mg, 0.051 mmol), and the red
suspension was deoxygenated by bubbling with dry nitrogen
for 10 min. The catalyst was then activated with dry hydrogen
for 10 min while the red color disappeared. To effect the
isomerization, the solution was further degassed for 5 min and
stirred for 2 h at room temperature. Evaporation of the solvent
gave the tetra-1-propenyl-protected mannoside, which was
then treated by the same procedure as in method A with OsO4
(catalytic), NMNO (497 mg, 4.24 mmol), acetic anhydride (0.92
mL, 1.0 g, 9.8 mmol), and DMAP (25 mg, 0.20 mmol) to afford
the acetyl-protected mannoside 33 in a yield of 332 mg (77%).
1,2:3,4-Di-O-isop r op ylid en e-6-O-[2,3,4,6-tetr a -O-a cetyl-
1-(2-fu r yl)-r-D-m an n opyr an osyl]-r-D-galactopyr an ose (36).
Meth od A. Following the standard procedure for protecting
group exchanges described for the preparation of 33, disac-
charide 35 (265 mg, 0.408 mmol) was first treated with (Ph3P)3-
RhCl‚2H2O (78.5 mg, 0.082 mmol) and DABCO (22.8 mg, 0.203
mmol) in refluxing 90% ethanol (10 mL) and then with a small
crystal of OsO4 and NMNO (201 mg, 1.72 mmol) in 85%
aqueous acetone (10 mL), followed by acetylation with acetic
anhydride (0.37 mL, 0.40 g, 3.9 mmol) and DMAP (20 mg, 0.16
mmol) in CH2Cl2, to give the title compound 36 (174 mg) as a
colorless crystalline solid with an overall yield of 65% after
silica gel chromatography purification (2:1 hexanes:ethyl
acetate with 1% Et3N): mp 120-121 °C; [R]23D -23.2° (c 1.71);
1H NMR δ 1.27 (3H, s), 1.34 (3H, s), 1.36 (3H, s), 1.59 (3H, s),
1.87, (3H, s), 1.97 (3H, s), 2.07 (3H, s), 2.10 (3H, s), 3.38 (1H,
dd, J ) 10.5, 4.0 Hz), 3.54 (1H, dd, J ) 10.5, 7.0 Hz), 3.98
(1H, m), 4.14 (1H, dd, J ) 7.9, 1.7 Hz), 4.28 (4H, m), 4.57 (1H,
dd, J ) 7.9, 2.4 Hz), 5.30 (1H, app t, J ) 10.0 Hz), 5.48 (1H,
d, J ) 4.9 Hz), 5.53 (1H, dd, J ) 10.0, 3.4 Hz), 5.67 (1H, d, J
) 3.4 Hz), 6.32 (1H, dd, J ) 3.3, 1.7 Hz), 6.50 (1H, dd, J )
3.3, 0.9 Hz), (1H, dd, J ) 1.7, 0.9 Hz); 13C NMR δ 20.3, 20.6,
hexanes:ethyl acetate): [R]23 +95.1° (c 1.00); 1H NMR δ 1.92
D
(3H, s), 1.98 (3H, s), 2.06 (3H, s), 3.06 (1H, dd, J ) 11.1, 1.8
Hz), 3.38 (3H, s), 3.46 (1H, dd, J ) 11.1, 6.8), 3.65-3.89 (8H,
m), 3.97 (1H, d, J ) 3.0 Hz), 4.05-4.18 (5H, m), 4.33 (1H, ddt,
J ) 12.7, 5.6, 1.3 Hz), 4.83-4.91 (3H, m), 5.01 (2H, m), 5.10-
5.25 (6H, m), 5.40, (1H, app t, J ) 9.7 Hz), 5.52 (1H, m), 5.85-
5.98 (3H, m), 6.36 (1H, dd, J ) 3.2, 1.8 Hz), 6.52 (1H, dd, J )
3.2, 0.9 Hz), 7.35 (1H, dd, J ) 1.8 Hz, 0.9 Hz); 13C NMR δ
20.5, 20.6, 20.7, 55.1, 61.0, 67.9, 69.0, 69.3, 70.4, 70.8, 71.1,
72.2, 73.2, 73.4, 73.7, 74.2, 76.7, 79.9, 96.3, 99.4, 110.5, 110.7,
116.1, 116.4, 116.5, 116.8, 135.0, 135.07, 135.11, 135.2, 141.7,
150.4, 169.5, 170.1 (2C) Anal. Calcd for C35H48O15: C, 59.31;
H, 6.83. Found: C, 59.53; H, 6.93.
Meth yl 2,3-O-Isop r op ylid en e-4-O-[2,3,4,6-tetr a -O-a llyl-
1-(2-fu r yl)-â-D -m a n n op yr a n osyl]-r-L -r h a m n op yr a n o-
sid e (41). The donor 28 (449.0 mg, 0.996 mmol) and 31 (324.5
mg, 1.487 mmol) were dried by azeotropic evaporation with
toluene three times with a rotary evaporator. This mixture
was then dissolved in anhydrous THF (8 mL) and treated with
DTBMP (306.9 mg, 1.495 mmol), 4 A molecular sieves, and
silver triflate (307.2 mg, 1.196 mmol) according to the standard
glycosylation method for the preparation of 32 to give the 41
in 75% (452 mg) yield after column chromatography (silica gel,
7:1 hexanes:ethyl acetate with 1% Et3N): [R]23D -9.3° (c 1.08);
1H NMR δ 0.99 (3H, d, J ) 6.4 Hz), 1.27 (3H, s), 1.40 (3H, s),
3.15 (1H, dd, J ) 9.3, 6.7 Hz), 3.33 (3H, s), 3.55 (1H, m), 3.68-
4.25 (15H, m), 4.34 (1H, ddt, J ) 12.2, 5.9, 1.3, Hz), 4.71 (1H,

Chemistry of 1-Alkoxy-1-glycosyl Radicals
J . Org. Chem., Vol. 61, No. 18, 1996 6197
20.7 (2C), 24.1, 25.0, 25.8, 26.0, 62.4, 62.6, 65.9, 67.3, 69.4,
69.7, 70.2, 70.6 (2C), 71.2, 96.1, 98.3, 108.7, 109.1, 110.0, 110.7,
142.7, 148.6, 169.2, 169.7, 169.8, 170.6. Anal. Calcd for
C30H40O16: C, 54.88; H, 6.14. Found: C, 55.03; H, 6.24.
Meth od B. Following Method B for the preparation of 33,
with [(Ph2MeP)2(COD)IrPF6] (22 mg, 0.025 mmol) as the
catalyst, the title compound 36 (252 mg) was obtained in 75%
yield from disaccharide 35 (331 mg, 0.510 mmol), a catalytic
amount of OsO4, NMNO (269 mg, 2.29 mmol), acetic anhydride
(0.48 mL, 0.52 g, 5.1 mmol), and DMAP (25 mg, 0.20 mmol).
Meth yl 2,3,4-Tr i-O-a cetyl-6-O-[2,3,4,6-tetr a -O-a cetyl-1-
(2-fu r yl)-r-D-m a n n op yr a n osyl]-r-D-glu cop yr a n osid e (39).
Meth od B. Following the standard procedure (Method B for
the preparation of 33), disaccharide 38 was treated with [(Ph2-
MeP)2(COD)IrPF6] in THF at room temperature followed by
OsO4 and NMNO in 85% aqueous acetone, and acetic anhy-
dride, DMAP, and pyridine in CH2Cl2. The crude product was
purified by column chromatography (neutral alumina, 3:2
hexanes:ethyl acetate). Recrystallization in ether and hexanes
The filtrate was concentrated under reduced pressure to yield
105.8 mg (∼100%) of 34 as a black residue which was not
further purified at this stage: 1H NMR δ 1.96 (3H, s), 2.05
(3H, s), 2.10 (3H, s), 2.11 (3H, s), 3.33 (3H, s), 3.96 (1H, ddd,
J ) 10.1, 5.8, 2.5 Hz), 4.22 (1H, dd, J ) 12.4, 2.5 Hz), 4.33
(1H, dd, J ) 12.4, 5.8 Hz), 5.26 (1H, app t, J ) 10.1 Hz), 5.37
(1H, dd, J ) 10.1, 3.3 Hz), 5.61 (1H, d, J ) 3.3 Hz), 7.05 (1H,
br); 13C NMR δ 20.5 (2C), 20.6, 20.7, 51.5, 62.2, 65.1, 69.1, 69.5,
70.6, 99.1, 166.3, 169.0, 169.6, 169.7, 171.0.
1,2:3,4-Di-O-isop r op ylid en e-6-O-(3,4,5,7-tetr a -O-a cetyl-
r-D-m a n n o-2-h ep tu lop yr a n osid on ic a cid )-r-D-ga la ctop y-
r a n ose (37). Disaccharide 36 (237.2 mg, 0.361 mmol) was
oxidized by a catalytic amount of RuO2 and KIO4 (697.9 mg,
3.03 mmol) in CCl4 (7 mL), CH3CN (7 mL), and water (10.5
mL) buffered at pH 7-8 with potassium carbonate according
to the standard protocol for the cleavage of the furan group.
The title ulosonic acid 37 (226 mg) was obtained in essentially
quantitative yield: 1H NMR δ 1.31 (3H, s), 1.33 (3H, s), 1.41
(3H, s), 1.57 (3H, s), 1.96 (3H, s), 2.07 (3H, s), 2.10 (3H, s),
2.11 (3H, s), 3.60-3.72 (2H, m), 4.03 (1H, m), 4.19 (1H, dd, J
) 7.9, 1.9 Hz), 4.22-4.37 (4H, m), 4.60 (1H, dd, J ) 7.9, 2.5
Hz), 5.28 (1H, app t, J ) 10.2 Hz), 5.36 (1H, dd, J ) 10.2, 3.2
Hz), 5.48 (1H, d, J ) 4.9 Hz), 5.62 (1H, d, J ) 3.2 Hz), 9.21
(1H, br); 13C NMR δ 14.1, 20.5, 20.7, 20.8, 24.2, 25.0, 25.8, 26.0,
60.4, 62.0, 64.9, 65.0, 67.4, 69.3, 69.7, 70.5, 70.6, 71.2, 96.1,
98.5, 109.0, 109.6, 166.2, 169.0, 169.6, 169.8, 171.1.
gave disaccharide 39 as colorless crystals in 71% yield: mp
1
174-176 °C; [R]23 +75.2°; H NMR δ 1.88 (3H, s), 1.92 (3H,
D
s), 1.96 (3H, s), 1.98 (3H, s), 2.06 (3H, s), 2.08 (3H, s), 2.12
(3H, s), 3.08 (1H, dd, J ) 10.6, 1.8 Hz), 3.45 (1H, dd, J ) 10.6,
8.5 Hz), 3.49 (3H, s), 3.94 (1H, m), 4.20-4.28 (3H, m), 4.75
(1H, dd, J ) 10.5, 9.2 Hz), 4.82 (1H, dd, J )10.2, 3.7 Hz), 4.95
(1H, d, J ) 3.7 Hz), 5.27 (1H, app t, J ) 9.9 Hz), 5.44 (1H, dd,
J ) 10.2, 9.3 Hz), 5.52 (1H, dd, J ) 10.1, 3.4 Hz), 5.63 (1H, d,
J ) 3.4 Hz), 6.33 (1H, dd, J ) 3.3, 1.8 Hz), 6.49 (1H, dd, J )
3.3, 0.9 Hz), 7.37 (1H, dd, J ) 1.8, 0.9 Hz); 13C NMR δ 20.3,
20.5, 20.6 (2C), 20.70 (2C), 20.75, 55.3, 62.0, 62.5, 65.9, 67.9,
69.3, 69.5, 69.7, 69.9, 70.0, 70.9, 96.1, 98.3, 110.2, 111.1, 143.0,
148.1, 169.1, 169.7, 169.8 (2C), 169.9, 170.2, 170.6. Anal.
Calcd for C31H40O19: C, 51.96; H, 5.63. Found: C, 51.90; H,
5.73.
Meth yl 2,3,4-Tr i-O-a cetyl-6-O-(3,4,5,7-tetr a -O-a cetyl-r-
D-m a n n o-2-h ep tu lop yr a n osid on ic a cid )-r-D-glu cop yr a -
n osid e (40). Ulosonic acid glycoside 40 was obtained in
essentially quantitative yield (163 mg) from 39 (168 mg, 0.235
mmol) according to the standard protocol: 1H NMR δ 1.96 (3H,
s), 2.00 (3H, s), 2.03 (3H, s), 2.06 (3H, s), 2.09 (3H, s), 2.10
(3H, s), 2.15 (3H, s), 3.47 (3H, s), 3.45-3.49 (1H, m, overlap
with the singlet at 3.47 ppm), 3.55 (1H, dd, J ) 9.9, 8.3 Hz),
4.03-4.13 (1H, m), 4.21-4.35 (3H, m), 4.82 (1H, dd, J ) 10.4,
9.2 Hz), 4.82 (1H, dd, J ) 10.2, 3.7 Hz), 4.96 (1H, d, J ) 3.6
Hz), 5.26 (1H, app t, J ) 9.9 Hz), 5.36 (1H, dd, J ) 10.2, 3.2
Meth yl 2,3-O-Isopr opyliden e-4-O-[2,3,4,6-tetr a-O-acetyl-
1-(2-fu r yl)-â-D -m a n n op yr a n osyl]-r-L -r h a m n op yr a n o-
sid e (42). To a solution of 41 (445 mg, 0.733 mmol) in 5 mL
of anhydrous DMSO was added t-BuO-K+ (0.400 g, 3.27
mmol). The reaction was heated to 85-90 °C for 1.5 h. After
cooling to room temperature, the black solution was poured
into 25 mL of water and extracted with ether (5 × 15 mL).
The combined ether solution was further washed with water
(4 × 10 mL). The organic solution was dried with Na2SO4 and
Hz), 5.49 (1H, app t, J ) 9.7 Hz), 5.61 (1H, d, J ) 3.2 Hz); 13
C
NMR δ 20.51 (2C), 20.59 (2C), 20.63, 20.66, 20.75, 55.4, 62.2,
63.2, 65.0, 67.6, 69.1, 69.2, 69.5, 69.8, 70.7, 70.8, 96.2, 98.1,
165.7, 169.1, 169.7 (2C), 170.0, 170.1, 170.3, 171.0.
Meth yl 2,3-O-Isopr opyliden e-4-O-(3,4,5,7-tetr a-O-acetyl-
r-D-m a n n o-2-h ep tu lop yr a n osid on ic a cid )-â-L-r h a m n op y-
r a n osid e (43) a n d th e Keto Acid 44. Oxidation of 42
according to the standard procedure using excess (three times)
of KIO4 and catalytic RuO2 gave an approximately 4:1 mixture
of title compound 43 and the keto acid 44 in essentially
quantitative yield after 2 weeks of stirring: 1H NMR δ 1.29
(3H, d, J ) 6.5 Hz), 1.33 (3H, s), 1.52 (3H, s), 1.98 (3H, s),
2.06 (3H, s), 2.09 (3H, s), 2.13 (3H, s), 3.37 (3H, s), 3.40 (1H,
dd, J ) 9.8, 6.7 Hz), 3.70 (1H, m), 4.03-4.27 (4H, m), 4.34
(1H, dd, J ) 12.0, 2.2 Hz), 4.84 (1H, app s), 5.28-5.38 (2H,
m), 5.59 (1H, d, J ) 2.2 Hz), 9.60 (1H, br); 13C NMR δ 17.3,
20.57 (2C), 20.65, 20.8, 26.4, 27.5, 54.8, 61.5, 63.7, 64.8, 69.3,
70.1, 71.2, 75.9, 76.7, 80.9, 97.4, 99.7, 109.6, 165.3, 168.8, 169.6,
169.9, 171.4. Keto acid 44 was characterized by the presence
of an additional resonance in the 13C-NMR spectrum at δ
192.4.
1
concentrated in vacuo to give 420 mg of a brown oil. The H
NMR of the oil indicated that all the allyl ether functions were
isomerized to the corresponding enol ethers. The oil was taken
up in 85% aqueous acetone (15 mL) and treated with OsO4
and NMNO (0.365 g, 3.12 mmol) and then with acetic
anhydride (0.65 mL, 0.70 g, 6.9 mmol), pyridine (0.56 mL, 0.55
g, 6.9 mmol), and DMAP (4.2 mg, 0.035 mmol) as described
above for the preparation of 33 to afford 0.257 g of title
compound 42 as a clear oil after column chromatography (silica
gel, 3:2 hexanes:ethyl acetate) purification: [R]23 -24.7° (c
D
1
0.75); H NMR δ 0.89 (3H, d, J ) 6.4 Hz), 1.32 (3H, s), 1.49
(3H, s), 1.86 (3H, s), 1.98 (3H, s), 2.05(3H, s), 2.08 (3H, s), 3.27
(1H, dd, J ) 9.9, 7.2 Hz), 3.30 (3H, s), 3.61 (1H, m), 4.06 (1H,
app d, J ) 5.6), 4.09-4.31 (3H, m), 4.38 (1H, dd, J ) 12.4, 3.2
Hz), 4.74 (1H, app s), 5.41 (1H, app t, J ) 9.9 Hz), 5.49 (1H,
dd, J ) 10.2, 3.1 Hz), 5.74 (1H, d, J ) 3.1 Hz), 6.33 (1H, dd, J
) 3.3, 1.8 Hz), 6.56 (1H, dd, J ) 3.3, 0.8 Hz), 7.33 (1H, dd, J
) 1.8, 0.8 Hz); 13C NMR δ 17.0, 20.4, 20.7, 20.78, 20.82, 26.5,
27.9, 54.7, 61.8, 64.1, 65.8, 69.8, 70.0, 70.3, 76.2, 77.18, 77.20,
97.5, 99.8, 109.0, 110.5, 111.9, 142.3, 148.2, 169.4, 169.7, 170.1,
170.8. Anal. Calcd for C28H38O15: C, 54.72; H, 6.23. Found:
C, 54.36; H, 6.58.
Met h yl 2,3,4,6-Tet r a -O-a cet yl-â-D-m a n n op yr a n osid e
(46). Deca r boxyla tion P r otocol A. The crude acid 34 (103
mg, 0.253 mmol) was dissolved in anhydrous CH2Cl2 (10 mL)
followed by the addition of Et3N (88 µL, 64 mg, 0.63 mmol).
The solution was treated with 10 (72 mg, 0.38 mmol) in the
dark for 4 h. t-BuSH (0.29 mL, 232 mg, 2.6 mmol) was injected
and the mixture was photolyzed with a tungsten light at 0 °C
for 1 h. The reaction mixture was diluted with 20 mL of CH2-
Cl2 and washed with 10% aqueous ammonium chloride and
saturated aqueous sodium bicarbonate. The organic solution
was dried (Na2SO4) and concentrated under reduced pressure
to give a mixture containing the â-mannoside and the 2-pyridyl
tert-butyl disulfide. Pure 46 (73 mg, 80%) was isolated by
column chromatography (silica gel, 2:1 hexanes:ethyl acetate)
and recrystallization from isopropyl alcohol: mp 158-159 °C
Meth yl 3,4,5,7-Tetr a -O-a cetyl-r-D-m a n n o-2-h ep tu lop y-
r a n osid on ic Acid (34). Typ ica l P r oced u r e for Oxid a tive
Clea va ge of F u r a n to Ca r boxylic Acid . KIO4 (505.1 mg,
2.20 mmol) was added to a biphasic solution of 33 (112.0 mg,
0.261 mmol) in CCl4 (4 mL), acetonitrile (4 mL), and water (6
mL). The pH of the aqueous layer was adjusted to 7-8 with
solid potassium carbonate. To this suspension was added
catalytic RuO2, and the resulting dark green mixture was
strongly stirred at room temperature overnight. The mixture
was diluted with a large amount of ethyl acetate, and the
separated organic layer was dried with Na2SO4 and filtered.
20
1
(lit.37 mp 161 °C); [R]23 -45.6° (c 0.63) (lit.37 [R]D -47°); H
D
NMR δ 1.99 (3H, s), 2.05 (3H, s), 2.10 (3H, s), 2.19 (3H, s),
3.53 (3H, s), 3.67 (1H, ddd, J ) 9.8, 5.3, 2.6 Hz), 4.16 (1H, dd,

6198 J . Org. Chem., Vol. 61, No. 18, 1996
Crich et al.
J ) 12.2, 2.6 Hz), 4.32 (1H, dd, J ) 12.2, 5.3 Hz), 4.56 (1H, d,
J ) 1.1 Hz), 5.05 (1H, dd, J ) 10.0, 3.3 Hz), 5.27 (1H, app t,
J ) 9.9 Hz), 5.48 (1H, dd, J ) 3.3, 0.9 Hz); 13C NMR δ 20.5,
20.6, 20.67, 20.74, 57.4, 62.4, 65.9, 68.5, 71.0, 72.3, 99.6, 169.5,
169.9, 170.3, 170.7.
mixture followed by addition of oxalyl chloride (99 µL, 1.15
mmol). After stirring for 2 h, the solvent was evaporated
under reduced pressure and the pale blackish mixture con-
taining the acid chlorides was dissolved in dry CH2Cl2 (10 mL).
DMAP (138 mg, 1.15 mmol) was added to reaction mixture
followed by the additon of 50 (329.6 mg, 1.15 mmol). After
stirring overnight, the reaction mixture was quenched with
saturated ammonium chloride solution, the aqueous phase was
extracted with ethyl acetate (3 × 10 mL), and the combined
organic phases were concentrated. The residue was purified
by column chromatography (silica gel, 2:1 hexanes:ethyl
acetate) to give a mixture (1:1.6 ratio) of the two thioesters
51 and 52 (388 mg, 70% based on 6). IR ν (melt) 1738, 1679
cm-1; 1H NMR (for 51 and 52, signals indistinguishable) δ 1.01
(3H, d, J ) 6.2 Hz), 1.11 (3H, d, J ) 6.2 Hz), 1.18 (8H, m),
3.34 (3H, s), 3.38 (3H, s), 3.45-3.55 (8H, m), 3.57-3.70 (3H,
m), 3.77-3.95 (2H, m), 6.82 (1H, dd, J )7.5, 1.7 Hz), 7.27 (1H,
td, J ) 7.8, 1.8 Hz), 7.34 (1H, dd, J ) 8.0, 1.6 Hz), 7.96 (1H,
dd, J ) 7.8, 1.4 Hz); 13C NMR (51) δ 23.4, 23.7, 27.6, 28.0,
38.4, 40.2, 57.9, 59.7, 60.6, 61.2, 67.3, 71.5, 74.2, 75.1, 78.6,
82.8, 94.7, 102.0, 127.8, 128.1, 128.8, 143.7, 146.6, 199.7; 13C
NMR (52) δ 23.2, 23.7, 27.8, 27.8, 38.0, 40.3, 58.2, 59.5, 60.6
(2C), 68.0, 71.2, 73.8, 75.8, 78.3, 82.5, 94.5, 101.1, 128.0, 128.4,
128.8, 143.6, 146.0, 191.0, 192.2. To a solution of this mixture
of thioesters (68 mg) in dry benzene (1.2 mL) was added AIBN
(3 mg) and Bu3SnH (47 mL, 0.18 mmol), and the reaction
mixture was refluxed for 2 h under argon. The solvent was
then evaporated and the residue purified by column chroma-
tography (silica gel, 2:1 hexanes:ethyl acetate with 1% Et3N)
to give 12 (22 mg, 68%) identical with the sample isolated
above.
1,2:3,4-Di-O-isop r op ylid en e-6-O-(2,3,4,6-tetr a -O-a cetyl-
â-D-m a n n op yr a n osyl)-r-D-ga la ctop yr a n ose (47). Deca r -
boxyla tion P r otocol B. Crude 37 (107 mg, 0.163 mmol) in
anhydrous benzene (8 mL) was treated with sodium hydride
(7.2 mg 60% in mineral oil, 0.18 mmol). After stirring for 30
min, a tiny drop of pyridine was added, followed by the
addition of oxalyl chloride (16 µL, 23 mg, 0.18 mmol). The
reaction mixture was stirred for 1 h and cannulated into a
suspension of anhydrous 45 (98 mg, 0.65 mmol, dried at 100
°C under vacuum for 5 h) and t-BuSH (0.28 mL, 224 mg, 2.5
mmol) in benzene (10 mL). The resulting reaction mixture
was stirred under ambient laboratory light for 15 h and then
filtered through a short pad of silica gel (2:1 hexanes:ethyl
acetate) to give a yellow oily residue after concentration under
reduced pressure. Purification by column chromatography
(silica gel, 2:1 hexanes:ethyl acetate with 1% Et3N) afforded
the title â-mannoside 47 (56 mg, 58%) as a clear oil: [R]23
D
1
-65.3° (c 0.58); H NMR δ 1.320 (3H, s), 1.324 (3H, s), 1.44
(3H, s), 1.51 (3H, s), 1.99 (3H, s), 2.04 (3H, s), 2.09 (3H, s),
2.17 (3H, s), 3.67 (1H, ddd, J ) 9.8, 5.3, 2.6 Hz), 3.77 (1H, dd,
J ) 12.7, 8.6 Hz), 3.96-4.02 (2H, m), 4.14 (1H, dd, J ) 12.3,
2.5 Hz), 4.19 (1H, dd, J ) 7.9, 1.5 Hz), 4.29 (1H, app d, J )
4.9, 2.5 Hz), 4.31 (1H, dd, J ) 12.3, 5.3 Hz), 4.58 (1H, dd, J )
7.9, 2.5 Hz), 4.87 (1H, d, J ) 1.0 Hz), 5.07 (1H, dd, J ) 10.0,
3.4 Hz), 5.25 (1H, app t, J ) 9.9 Hz), 5.49-5.51 (2H, m); 13C
NMR δ 20.6, 20.7, 20.81, 20.84, 24.3, 25.0, 25.9, 29.7, 62.5,
66.1, 68.2, 68.9, 69.1, 70.4, 70.7, 71.0, 71.3, 72.3, 96.2, 98.7,
108.8, 109.4, 169.7, 169.9, 170.2, 170.8. Anal. Calcd for
C26H38O15: C, 52.88; H, 6.49. Found: C, 53.05; H, 6.63.
Th iol Ester 53. Furan 42 (0.205 g, 0.334 mmol) was
oxidized by catalytic RuO2 and NaIO4 in CCl4, CH3CN, and
water essentially according to the standard protocol except
that the solution was heated under reflux for 24 h rather than
simply stirring at room temperature. In this manner the crude
acid 43 was isolated (156 mg, 76%), free of the keto acid 44.
This acid was converted to the corresponding acid chloride by
treatment with sodium hydride, oxalyl chloride, and DMF. The
acid chloride was then converted, by treatment with 50, to 53,
Meth yl 2,3,4-Tr i-O-a cetyl-6-O-(2,3,4,6-tetr a -O-a cetyl-â-
D-m a n n op yr a n osyl)-r-D-glu cop yr a n osid e (48). Following
decarboxylation protocol B, 40 (163 mg, 0.235 mmol) was
converted to the corresponding acyl chloride with sodium
hydride (10 mg, 60% in mineral oil, 0.26 mmol), oxalyl chloride
(23 µL, 33 mg, 0.26 mmol), and a tiny drop of DMF followed
by the treatment with sodium salt 45 and t-BuSH to give crude
â-linked disaccharide 48. Purification by column chromatog-
raphy (2:1 hexanes:ethyl acetate) and recrystallization (hex-
anes and ether) gave disaccharide 48 (102 mg, 67%) as an
1
as a pale yellow oil (80 mg, 27%); H NMR δ 1.15 (3H, d, J )
6.3 Hz), 1.29 (3H, s), 1.42 (3H, s), 1.50 (3H, s), 1.55 (3H, s),
1.93 (3H, s), 1.96 (3H, s), 2.01 (3H, s), 2.02 (3H, s), 3.32 (3H,
s), 3.45 (1H, m), 3.63 (1H, m), 3.70 (2H, dd, J ) 47.8, 13.4
Hz), 4.00-4.15 (4H, m), 4.37 (1H, dd, J ) 12.1, 3.5Hz), 4.78
(1H, s), 5.27 (1H, dd, J ) 10.2, 3.1 Hz), 5.36 (1H, t, J ) 10.1
Hz), 5.53 (1H, d, J ) 3.1 Hz), 6.84 (1H, td, J ) 7.8, 2.0 Hz),
7.22-7.35 (2H, m), 7.95 (1H, dd, J ) 7.8, 1.1 Hz); 13C NMR δ
17.5, 20.6, 20.7 (3C), 26.3, 27.8, 28.0, 28.2, 38.6, 39.9, 54.7,
61.3, 64.0, 65.5, 69.6, 70.4, 70.5, 76.1, 77.4, 78.7, 94.4, 97.4,
101.4, 109.2, 128.0, 128.3, 128.6, 143.2, 146.1, 168.8, 169.5,
169.8, 170.4, 196.4; IR ν (melt) 1684, 1754 cm-1. Anal. Calcd
for C35H47IO15S: C, 48.50; H, 5.47. Found: C, 48.68; H, 5.52.
amorphous solid: mp 125-126 °C (lit.42 mp 127-128 °C); [R]23
D
+35.7° (c 1.05) (lit.42 [R]23D +35°); 1H NMR δ 1.99 (3H, s), 2.00
(3H, s), 2.02 (3H, s), 2.04 (3H, s), 2.07 (3H, s), 2.10 (3H, s),2.17
(3H, s), 3.36 (3H, s), 3.56 (1H, dd, J ) 11.3, 8.2 Hz), 3.66 (1H,
ddd, J ) 9.8, 5.4, 2.4 Hz), 3.88-3.98 (2H, m), 4.30 (1H, dd, J
) 12.1, 2.3 Hz), 4.32 (1H, dd, J ) 12.2, 5.4 Hz), 4.70 (1H, d, J
) 0.9 Hz), 4.81-4.96 (3H, m) 5.05 (1H, dd, J ) 10.1, 3.3 Hz),
5.25 (1H, app t, J ) 9.9 Hz), 5.46 (1H, app t, J ) 9.7 Hz), 5.52
(1H, dd, J ) 3.3, 0.9 Hz); 13C NMR δ 20.5, 20.62, 20.65, 20.68,
20.7, 20.8 (2C), 55.1, 62.3, 65.8, 68.3, 68.5, 69.18, 69.24, 69.9,
70.8, 70.9, 72.4, 96.2, 99.3, 169.6, 169.85, 169.95 (2C), 170.1,
170.2, 170.7.
Ack n ow led gm en t. We are grateful to the NSF
(CHE 9222697) for support of this work. D.C. is a
Fellow of the A. P. Sloan Foundation.
Su p p or tin g In for m a tion Ava ila ble: 1H- and 13C-NMR
spectra of 7, 8 + 9, 34, 37, 40, 43 + 44, and 51 + 52 (14 pages).
This material is contained in libraries on microfiche, im-
mediately 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.
Isop r op yl 2,3,4,6-Tet r a -O-m et h yl-â-D-m a n n op yr a n o-
sid e (12) via th e Th ioester s 51 a n d 52. A mixture of
ulosonic and keto acids 8 and 9 (300 mg), prepared, as
described under 12 above, was taken up in dry benzene (3 mL)
and treated with sodium hydride (46 mg, 60% in mineral oil,
1.15 mmol). One drop of DMF was added to the reaction
(42) Wulff, G.; Wichelhaus, J . Chem. Ber. 1979, 112, 2847.
J O960799Q