1-Benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride: A potent combination of shelf-stable reagents for the low-temperature conversion of thioglycosides to glycosyl triflates and for the formation of diverse glycosidic linkages

Article abstract of DOI:10.1021/ja0111481

The combination of 1-benzenesulfinyl piperidine (BSP) and trifluoromethanesulfonic anhydride (Tf₂O) forms a new, powerful, metal-free thiophile that can readily activate both armed and disarmed thioglycosides, via glycosyl triflates, in a matte

Full text of DOI:10.1021/ja0111481

J. Am. Chem. Soc. 2001, 123, 9015-9020
9015
1
-Benzenesulfinyl Piperidine/Trifluoromethanesulfonic Anhydride: A
Potent Combination of Shelf-Stable Reagents for the
Low-Temperature Conversion of Thioglycosides to Glycosyl Triflates
and for the Formation of Diverse Glycosidic Linkages
David Crich* and Mark Smith
Contribution from the Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
ReceiVed May 8, 2001
Abstract: The combination of 1-benzenesulfinyl piperidine (BSP) and trifluoromethanesulfonic anhydride (Tf2O)
forms a new, powerful, metal-free thiophile that can readily activate both armed and disarmed thioglycosides,
via glycosyl triflates, in a matter of minutes at -60 °C in dichloromethane, in the presence of 2,4,6-tri-tert-
butylpyrimidine (TTBP). The glycosyl triflates are rapidly and cleanly converted to glycosides, upon treatment
with alcohols, in good yield and selectivity.
1
0,11
Introduction
and N-iodosuccinimide-triflic acid (NIS/TfOH).
Kahne’s
1
2
sulfoxide glycosylation method and related methods using
glycosyl sulfimides are distinct from the mainstream insofar
as they require prior oxidation of the thioglycoside but, in doing
so, permit the formation of highly reactive glycosylating species
at low temperature. The need for ever more active yet milder
activating species is continually driving the field forward with
the current focus centered on iodine itself and on interhalogen
compounds. One striking feature of the above methods, with
is the lack of detailed
mechanistic information and, in particular, of the precise nature
of the actual glycosylating species.
Since their first reported use in the synthesis of a disaccha-
13
1
ride, thioglycosides have been among the most enduring and
widely used of glycosyl donors. Their lasting popularity stems
from a combination of relative ease of synthesis, stability,
compatibility with numerous protection and deprotection steps,
and orthogonality of activation with several other glycosyl
donors. In short, they are readily prepared, easily handled, and
14
1
5
2
,3
16,17
very versatile. Testaments to the current applicability of
thioglycosides in synthesis include Oscarson’s recent synthesis
the exception of the sulfoxide method,
4
of sucrose, while their central nature in the field and projected
longevity is nowhere better displayed than in Ley and Wong’s
independent choice of this class of donors for their donor
reactivity scales and programmed automated one-pot oligosac-
charide syntheses.5 The very stability that renders thioglyco-
sides attractive, however, reduces their activity in glycosylation
reactions. This has resulted in the continued development of a
range of activating agents and conditions beginning with the
original mercury and silver salt based methods, with their
obvious environmental and toxicological drawbacks, and now
encompassing a broad spectrum of nonmetallic thiophiles of
varying stability and activity. Systems currently in broad
common use include dimethyl(methylthio)sulfonium triflate
Our contribution to the field stems from the discovery that
benzenesulfenyl triflate is an extremely powerful thiophile that
converts thioglycosides to glycosyl triflates in a matter of
minutes at -78 °C and, thereby, enables the formation of
extremely hindered glycosidic linkages that were previously the
,6
1
8,19
hallmark of the sulfoxide method.
Our work with benzene-
sulfenyl triflate differs from its previous application to the
2
0
activation of glycosyl xanthates and from the relatively
widespread use of methylsulfenyl triflate (MeSOTf)8
,21,22
in the
mode of operation, requiring premixing of the thioglycoside and
(
10) Veenenman, G. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31,
275-278.
(11) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron Lett.
990, 31, 4313-4316.
12) Kahne, D.; Walker, S.; Cheng, Y.; Engen, D. V. J. Am. Chem. Soc.
7
8
(
DMTST), methylsulfenyl triflate (MeSOTf), benzeneselenyl
1
1
9
10
triflate (PhSeOTf), iodonium dicollidine perchlorate (IDCP),
(
989, 111, 6881-6882.
(13) Cassel, S.; Plessis, I.; Wessel, H. P.; Rollin, P. Tetrahedron Lett.
(
1) Ferrier, R. J.; Hay, R. W.; Vethaviyasar, N. Carbohydr. Res. 1973,
7, 55-61.
2) Oscarson, S. In Carbohydrates in Chemistry and Biology; Ernst, B.,
Hart, G. W., Sina y¨ , P., Eds.; Wiley-VCH: Weinheim, 2000; Vol. 1, pp
2
1998, 39, 8097-8100.
(
(14) Kartha, K. P. R.; Aloui, M.; Field, R. A. Tetrahedron Lett. 1996,
37, 5175-5178.
9
3-116.
(15) Ercegovic, T.; Meijer, A.; Magnusson, G.; Ellervik, U. Org. Lett.
2001, 3, 913-915.
(
3) Garegg, P. J. AdV. Carbohydr. Chem. Biochem. 1997, 52, 179-266.
(4) Oscarson, S.; Schgelmeble, F. W. J. Am. Chem. Soc. 2000, 122,
(16) Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217-11223.
(17) Gildersleeve, J.; Pascal, R. A.; Kahne, D. J. Am. Chem. Soc. 1998,
120, 5961-5969.
8
869-8872.
5) Douglas, N. L.; Ley, S. V.; Lucking, U.; Warriner, S. L. J. Chem.
Soc., Perkin Trans. 1 1998, 51-65.
6) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong,
(
(18) Crich, D.; Sun, S. J. Am. Chem. Soc. 1998, 120, 435-436.
(19) Crich, D.; Sun, S. Tetrahedron 1998, 54, 8321-8348.
(20) Martichonok, V.; Whitesides, G. M. J. Org. Chem. 1996, 61, 1702-
1706.
(
C.-H. J. Am. Chem. Soc. 1999, 121, 734-753.
(7) Fugedi, P.; Garegg, P. J. Carbohydr. Res. 1986, 149, C9-C12.
(8) Dasgupta, F.; Garegg, P. J. Carbohydr. Res. 1988, 177, C13-C17.
(9) Ito, Y.; Ogawa, T. Tetrahedron Lett. 1988, 29, 1061-1064.
(21) Birberg, W.; Lonn, H. Tetrahedron Lett. 1991, 32, 7453-7456.
(22) Dasgupta, F.; Garegg, P. J. Carbohydr. Res. 1990, 202, 225-238.
1
0.1021/ja0111481 CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/21/2001

9016 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Crich and Smith
Scheme 1
Scheme 3
triflate in the 19F NMR spectrum which contained only two
resonances (δ 4.26 and -3.07) corresponding to unreacted triflic
2
6
anhydride and the triflate anion. At higher temperatures
2
6
Scheme 2
decomposition set in.
A further low-temperature NMR experiment, however, re-
vealed that the combination of 1 and Tf2O and DTBMP or TTBP
converted a thiomannoside 6 to the mannosyl triflate 7 (Scheme
3
). We reasoned that the reaction of 1 and triflic anhydride is
an equilibrium that favors the starting materials over the salt 5.
We further reasoned (i) that salt 5 does not proceed to give
benzenesulfenyl triflate (Scheme 2) and (ii) that salt 5 was a
potent thiophile in its own respect, capable of converting
thioglycosides to glycosyl triflates which, in turn, pulls the initial
equilibrium in the forward direction.
Based on this reasoning we investigated two further thiosul-
finates 8 and 9 with a view to displacing the equilibrium in the
forward direction and, so, of providing a more potent reagent.
the sulfenyl triflate.18,19 This enables formation of the extremely
reactive glycosyl triflate and in doing so provides valuable
mechanistic insight of the type that is necessarily lacking from
methods involving activation of the donor in the presence of
the activator.
The main drawback with benzenesulfenyl triflate is its
instability and the need to prepare it in situ from benzenesulfenyl
20,23
chloride and silver triflate,
neither of which are ideal, with
the former being both obnoxious and itself unstable and the
latter light and water sensitive. For this reason a primary goal
of our laboratory for several years has been the development
of an alternative and more practical synthesis of benzenesulfenyl
triflate or of an equivalent thereof capable of converting
thioglycosides to glycosyl triflates at low temperature. Our first
success was the combination of S-aryl arenethiosulfinates and
trifluoromethanesulfonic anhydride which, while demonstrably
not producing benzenesulfenyl triflate, did bring about glyco-
Ultimately, 8 was selected for development and was successfully
employed, in conjunction with triflic anhydride, in a number
24,25
sylation with armed
thioglycosides rapidly and in high yield
26
of glycosylation reactions. Although it represented a significant
step in the right direction, the MPBT/Tf2O combination suffered
several shortcomings. First, unlike benzenesulfenyl triflate itself,
it did not activate disarmed thioglycosides. Second, to achieve
high conversion of the thioglycoside several equivalents of the
reagent and triflic anhydride were required. Finally, isolation
of the coupled product was sometimes tedious owing to the
formation of several undetermined byproducts. We reasoned that
a more potent reagent would result if the key equilibrium could
be tipped further in favor of the thiophilic salt or, indeed, by
encouraging fragmentation of the initial salt to benzenesulfenyl
triflate. On this basis we have now prepared and investigated
two sulfinate esters (10, 11) and a sulfinamide (12) and find
the latter to be an ideal reagent for the activation of both armed
and disarmed thioglycosides.
at -60 °C.2 We now report our continued work in this direction
that has resulted in the development of an S-aryl sulfinamide
as a shelf-stable reagent capable, when used in only minimal
excess and in conjunction with trifluoromethanesulfonic anhy-
6
2
4,25
dride, of converting thioglycosides, armed and disarmed,
to glycosyl triflates and so to glycosidic bonds cleanly and in
high yield.
Results and Discussion
Our initial investigation of the thiosulfinates was based on
earlier work from the Oae group in which it was established
that thiosulfinate 1 reacts with trifluoroacetic anhydride at -20
°
C to give a complex mixture of products, thought to contain
the sulfenyl carboxylate 2 and sulfinyl carboxylate 3, and
resulting ultimately in the formation of diphenyl disulfide (4)
The two sulfinate esters (10, 11) were prepared in the hope
that the adducts would undergo fragmentation to benzenesulfenyl
triflate, and acetone and triflic acid, or formaldehyde and
TMSOTf, respectively. In reality neither represented any
improvement over MPBT, with low-temperature NMR experi-
ments showing incomplete conversion of the sulfinate in the
presence of Tf2O alone and the need for several equivalents of
Tf2O to bring about complete activation of the standard
thioglycoside (Table 1). Clearly, a more nucleophilic sulfinate
was required and we therefore turned to the sulfinamides and,
in particular, 12. This substance was very readily prepared and
isolated on a multigram scale. It is white, crystalline, readily
dried, and appears to be completely shelf-stable under ambient
laboratory conditions. Moreover, as demonstrated by the
standard low-temperature NMR experiments, it reacts fully with
triflic anhydride and converts the standard thioglycoside to the
(
Scheme 1).27
We reasoned that the more reactive Tf2O would react rapidly
with 1 at lower temperatures to provide an initial salt (5), which
would further react with the formation of two molecules of
1
benzenesulfenyl triflate (Scheme 2). Low-temperature H and
1
9
F NMR spectra, however, revealed that this was not the case.
Indeed conversion of the thiosulfinate 1 at -60 °C was low
and there was no evidence for the formation of benzenesulfenyl
(
(
23) Effenberger, F.; Russ, W. Chem. Ber. 1982, 115, 3719-3736.
24) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J.
Am. Chem. Soc. 1988, 110, 5583-5584.
(
25) Andrews, C. W.; Rodebaugh, R.; Fraser-Reid, B. J. Org. Chem.
1
996, 61, 5280-5289.
(
26) Crich, D.; Smith, M. Org. Lett. 2000, 4067-4069.
(27) Morishita, T.; Furukawa, N.; Oae, S. Tetrahedron 1981, 37, 3115-
3
120.

1-Benzenesulfinyl Piperidine/Trifluoromethanesulfonic Anhydride
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 9017
Table 1. The Quantity of Tf
Thioglycoside 6 to Its Corresponding Triflate 7
2
O Required to Fully Activate the
Scheme 4
entry
coupling reagent
Tf
2
O (mol equiv)
1
2
3
4
5
6
1
8
9
10
11
12
2
1.5
1.5
3
2
1
Scheme 5
glycosyl triflate16,19 in a matter of minutes at -60 °C more or
less stoichiometrically (Table 1).
On the basis of the NMR experiments, a protocol was
developed and optimized for glycosidic bond formation. This
simply involved cooling a 1:1 mixture of the thioglycoside and
BSP (12) to -60 °C in dichloromethane in the presence of the
hindered base 2,4,6-tri-tert-butylpyrimidine (TTBP),2 treatment
with 1.1 equiv of triflic anhydride, and, after 5 min, addition of
the acceptor alcohol, warming to room temperature, and work
up. A series of disaccharides, selected to illustrate the wide range
of coupling types possible, were prepared in this manner with
the results presented in Table 2. Highlights include â-selective
8
1
8,19
mannosylations (Entries 1-3),
R-selective glucosylations
29
Scheme 6
(
Entries 6 and 7), â-selective galactosylation with nonpartici-
1
2
pating groups through the use of propionitrile as solvent and
the nitrile effect (Entry 10),30 as well as such relatively standard
linkages such as â-glucosides, â-galactosides, â-aminogluco-
sides, and â-xylosides (Entries 4, 5, 8, 9, 11, and 12) achieved
through neighboring group participation, as well as similarly
directed R-rhamnosides (Entries 13). With respect to neighboring
group participation it is noteworthy that the perbenzoylated
glucosyl and xylosyl donors 23 and 38, as well as the
peracetylated rhamnosyl donor 40, gave high yields of ortho
esters (Table 3) when the coupling was conducted under the
standard conditions in the presence of TTBP as base. The
saccharides from these donors (Table 2, entries 4, 5, 12, and
1
3) were obtained directly in high yield by the simple expedient
31
of omitting the base. In contrast the perbenzoylated galactosyl
donor 30 provided the glycosides directly even in the presence
of TTBP (Table 2, entries 8 and 9). TTBP is a very mild base
5
). As expected on the basis of our earlier work with 2,3-di-
29
O-benyl-4,6-O-benzylidene protected glucosyl donors, this
reaction was extremely R-selective. Although we have not
explored such possibilities at the present time, the probable
differential reactivity of thioglycosides and selenoglycosides to
the BSP/Tf2O reagent combination should open up the way to
one-pot oligosaccharide syntheses.
(
pKa 1.02 in 50% aqueous ethanol)32 and it is possible that its
triflate salt is sufficiently acidic to rearrange the kinetic
galactosyl ortho esters. This explanation of course assumes that
galactosyl ortho esters are somewhat more reactive than
comparable glucosyl ortho esters just as standard galactosyl
3
3
donors are more reactive than their glucosyl counterparts.
As a final demonstration of the power of the new reagent
combination, we turned to the double glycosylation of carbo-
hydrate diols. A first example (Scheme 6) included the coupling
of a 4,6-glucopyranosyl diol 47 to the phthalimide protected
glucosamine donor 36 and resulted in the isolation of the
trisaccharide 48 in 85% yield.
In general we have worked with phenyl thioglycosides as
donors but the example of Table 2, entry 3 shows that this was
a purely arbitrary choice with ethyl thioglycosides working
equally well. With a view to further broadening the scope of
our reaction we have also determined that a selenoglycoside
34,35
46, such as popularized by Pinto and co-workers,
is activated
A second example included the coupling of a mannopyranosyl
diol 50 to a highly R-selective mannosyl donor 4936 resulting
in the formation of the mannotriose 51 (Scheme 7). This
particular example constitutes a synthesis of a protected version
of the trisaccharide substrate of the mannose binding protein
by the standard BSP/TTBP/Tf2O reagent combination (Scheme
(
26.
28) Crich, D.; Smith, M.; Yao, Q.; Picione, J. Synthesis 2001, 323-
3
(
(
(
29) Crich, D.; Cai, W. J. Org. Chem. 1999, 64, 4926-4930.
30) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett 1990, 694-696.
31) Crich, D.; Dai, Z.; Gastaldi, S. J. Org. Chem. 1999, 64, 5224-
3
7
concanavalin A.
5
229.
As is evident from the examples of Table 2 and Schemes
(
32) van der Plas, H. C.; Koudijs, A. Recl. TraV. Chim. Pays Bas 1978,
5
-7 the BSP/Tf2O combination is considerably more powerful
9
7, 159-161.
than the original MPBT/Tf2O combination. It activates the full
range of armed and disarmed glycosyl donors and does so under
a standard set of conditions, except when ortho ester formation
(33) Miljkovic, M.; Yeagley, D.; Deslongchamps, P.; Dory, Y. L. J. Org.
Chem. 1997, 62, 7597-7604.
(
(
34) Mehta, S.; Pinto, B. M. J. Org. Chem. 1993, 58, 3269-3276.
35) Metha, S.; Pinto, B. M. In Modern Methods in Carbohydrate
Synthesis; Kahn, S. H., O’Neill, R. A., Eds.; Harwood Academic: Am-
sterdam, The Netherlands, 1996; pp 107-129.
(36) Crich, D.; Cai, W.; Dai, Z. J. Org. Chem. 2000, 65, 1291-1297.
(37) Naismith, J. H.; Field, R. A. J. Biol. Chem. 1996, 271, 972-976.

9018 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Crich and Smith
Table 2. Coupling Reactions of Thioglycosides Using 1-Benzenesulfinyl Piperidine (BSP)/Tf
2
O as Activatora
a
All reactions, unless stated, were conducted in dichloromethane at -60 °C. b Anomeric ratios of 1:>9 and >9:1 are conservative minima; in
all such cases the minor isomer was not detected in the NMR spectra of the reaction mixtures. c Reaction performed in propionitrile at -60 °C in
the presence of TTBP.

1-Benzenesulfinyl Piperidine/Trifluoromethanesulfonic Anhydride
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 9019
Table 3. Formation of Ortho Esters in the Presence of TTBP
pyridines. In addition it is considerably easier and more
2
8,40
economical to prepare on a large scale.
Nevertheless, its
more crystalline nature renders it somewhat insoluble in
dichloromethane at -78 °C, which explains the choice of -60
°
C as the reaction temperature for the new methodology. We
see no reason the 2,6-di-tert-butylated pyridines should not be
employed in this chemistry if the experimentalist prefers or if
lower temperatures are required.
Finally, it is appropriate to compare and contrast the BSP/
Tf2O method with Gin’s excellent dehydrative glycosylation.4
The two methods obviously have close parallels insofar as both
take readily accessible, stable glycosyl donors and couple them
to acceptors by means of a combination of triflic anhydride and
a nucleophilic sulfur IV reagent. Simple protected thioglycosides
and pyranoses are both readily synthesized in two steps from
the sugars themselves and there appears to be no substantial
difference between the two methods at the level of donor
preparation. The two methods diverge in the nature of the actual
glycosylating species with the present chemistry involving
intermediate glycosyl triflates, which have been conclusively
excluded in the case of the dehydrative method. It appears that
the two methods should be largely interchangeable with the BSP/
Tf2O definitely having the edge for the preparation of difficult
linkages such as the â-mannosides (Table 2, entries 1-3).
1,42
Scheme 7
Experimental Section
Preparation of 1-Benzenesulfinyl Piperidine 12. A solution of
PhSOCl (58.0 g, 0.365 mol) in diethyl ether (200 mL) was slowly added
to a cooled solution (5 °C) of piperidine (72 mL, 0.73 mol) in diethyl
ether (200 mL). The reaction mixture was stirred at room temperature
for 1 h, filtered, and then concentrated under reduced pressure. The
solid residue was triturated with hexanes to give the title product as a
4
3
white crystalline solid (53.4 g, 70%): mp 84-85 °C (lit. mp 83-84
1
°
2
2
C); H NMR δ 1.41-1.53 (6 H, m), 2.83-2.87 and 2.89-3.04 (each
H, m), 7.37-7.42 (3 H, m), 7.56-7.59 (2 H, m); 13C NMR δ 23.8,
6.1, 46.9, 126.1, 128.7, 130.6 and 143.3; MS (EI) m/z 210 (MH ).
+
General Experimental Protocol for the Preparation of Glycosides.
To a stirred solution containing the thioglycoside (0.185 mmol),
-benzenesulfinyl piperidine (BSP 12; 0.185 mmol), TTBP (0.370
mmol), and activated 3 Å powdered sieves in dichloromethane (5 mL),
at -60 °C under an argon atmosphere, was added Tf O (0.203 mmol).
1
2
After 5 min, a solution of the glycosyl acceptor (0.277 mmol) in
dichloromethane (2 mL) was added. The reaction mixture was stirred
for 2 min at -60 °C and then warmed to room temperature, filtered,
3
washed with saturated aqueous NaHCO , followed by brine, dried
is a problem and the base has to be omitted. In this matter it
differs from most other methods of thioglycoside activation,
(MgSO ), and concentrated under reduced pressure. The glycosides were
4
isolated by chromatography on silica gel.
indeed from most glycosylations methods, which, with few
Preparation of Methyl 2,4-Di-O-benzyl-3-O-(2,3-O-carbonyl-4,6-
O-benzylidene-r-D-mannopyranosyl)-6-O-(2,3-O-carbonyl-4,6-O-
benzylidene-r-D-mannopyranosyl)-r-D-mannoside (51). To a stirred
solution containing the thioglycoside 4936 (0.140 g, 0.36 mmol), BSP
exceptions,38 require alternative conditions for arming and
disarming protecting groups. Such generalized reaction condi-
tions should obviously facilitate use of the method by nonspe-
cialists and can only be of benefit in the eventual development
of fully automated oligosaccharide synthesizers.39 It is also
pertinent to draw attention to the much facilitated purification
with BSP glycosylations than with the original MPBT ones. In
effect, fewer byproducts are generated and, because less reagent
is required, separation of these is considerably easier. In this
chemistry we have employed 2,4,6-tri-tert-butylpyrimidine
1
2 (0.080 g, 0.38 mmol), TTBP (0.164 g, 0.66 mmol), and activated 3
Å powdered sieves in dichloromethane (5 mL), at -60 °C under an
argon atmosphere, was added Tf O (0.064 mL, 0.39 mmol). After 5
2
44
min, a solution of the glycosyl acceptor 50 (0.062 g, 0.165 mmol) in
dichloromethane (2 mL) was added. The reaction mixture was warmed
to room temperature, filtered, washed with saturated aqueous NaHCO3,
followed by brine, dried (MgSO
pressure. The residue was purified by chromatography on silica gel
ethyl acetate:hexanes (1:1)] to give the title product as a clear viscous
4
), and concentrated under reduced
[
(TTBP) as the hindered, nonnucleophilic base in preference to
the more common 2,6-di-tert-butylated pyridines. This is
(40) Anderson, A. G.; Stang, P. J. Organic Syntheses; Wiley: New York,
because TTBP is a white crystalline solid that is not hygroscopic
and not readily sublimed on drying under vacuum. As such it
possesses numerous advantages over the analogous hindered
1990; Collect. Vol. 7, pp 144-149.
28
(41) Garcia, B. A.; Poole, J. L.; Gin, D. Y. J. Am. Chem. Soc. 1997,
1
19, 7597-7598.
42) Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc. 2000, 122, 4269-
279.
(43) Maricich, T. J.; Angeletakis, C. N. J. Org. Chem. 1984, 49, 1931-
1934.
(44) Jiang, L.; Chan, T.-H. J. Org. Chem. 1998, 63, 6035-6038.
(
4
(
(
38) Yan, L.; Kahne, D. J. Am. Chem. Soc. 1996, 118, 9239-9248.
39) Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Science 2001, 291,
1
523-1527.

9020 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Crich and Smith
oil (0.10 g, 65%). [R]20
+11.7 (c 0.8); H NMR (C
1
D
) δ 3.13 (3 H,
129.8, 136.8, 136.9, 137.7, 137.8; HRMS calcd for C49
(MNa ): 949.2895. Found: 949.2950.
H
O
18Na
D
6
6
50
+
s), 3.37 and 3.44 (each 1 H, t, J ) 10.5 Hz), 3.52 (1 H, dd, J ) 8 and
0 Hz), 3.58-3.62 (2 H, m), 3.65-3.68 (2 H, m), 3.73-3.78 (2 H,
m), 3.87 (1 H, dt, J ) 5 and 10 Hz), 4.06 (1 H, d, J ) 7 Hz), 4.10 (1
H, dd, J ) 5 and 10 Hz), 4.17 (1 H, q, J 10 Hz), 4.20 (1 H, dd, J )
and 10 Hz), 4.25-4.28 (2 H, m), 4.33 (1 H, d, J ) 11.5 Hz), 4.39
and 4.43 (each 1 H, t, J ) 7.5 Hz), 4.50 (1 H, d, J ) 11.5 Hz), 4.63
1 H, d, J ) 11 Hz), 4.66 (1 H, d, J ) 1.5 Hz), 4.70 (1 H, d, J ) 11
Hz), 5.11 and 5.15 (each 1 H, s), 5.43 and 5.49 (each 1 H, s), 7.24-
.63 (20 H, m); C NMR δ 55.6, 60.0, 60.3, 66.9, 68.9, 69.0, 72.3,
3., 75.1, 75.4, 75.5, 75.8, 76.8, 77.6, 78.2, 78.6, 78.9, 79.1, 97.0, 98.2,
8.3, 102.3, 102.4, 126.5, 126.6, 128.4, 128.8, 128.9, 129.1, 129.2,
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Acknowledgment. We thank the NIH (GM 57335) for
support of this work.
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Supporting Information Available: Full experimental
(
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details, characterization data, and H NMR spectra for all new
compounds (PDF). This material is available free of charge via
the Internet at http://pubs.acs.org.
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