A new route to exo-glycals using the Ramberg-Baecklund rearrangement

Article abstract of DOI:10.1002/1099-0690(200204)2002:7<1305::AID-EJOC1305>3.0.CO;2-0

A new route to exo-glycals 4 is described in which glycosyl sulfones 3 are subjected to the Meyers variant of the Ramberg-Baecklund rearrangement. The conversion of sulfones derived from glucose, galactose, mannose, cellobiose, and ribose into di-, tri-, and tetra-substituted alkenes is reported. Preliminary mechanistic studies of this process are also described. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200204)2002:7<1305::AID-EJOC1305>3.0.CO;2-0

FULL PAPER
A New Route to exo-Glycals Using the Ramberg؊Bäcklund Rearrangement
Frank K. Griffin,[a] Duncan E. Paterson,[a] Paul V. Murphy,[a] and Richard J. K. Taylor*[a]
Dedicated to Professor Jean-Franc¸ois Normant on the occasion of his 65th birthday
Keywords: Carbohydrates / Sulfones / Rearrangements / Enol ethers
A new route to exo-glycals 4 is described in which glycosyl ported. Preliminary mechanistic studies of this process are
sulfones 3 are subjected to the Meyers variant of the
Ramberg−Bäcklund rearrangement. The conversion of sul-
fones derived from glucose, galactose, mannose, cellobiose,
also described.
(
Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
and ribose into di-, tri-, and tetra-substituted alkenes is re- 2002)
Introduction
sulted in their routine application as glycosyl donors in O-
glycoside synthesis.[11] The use of thioglycoside derivatives
as precursors to glycosyl anions has also been extensively
investigated, and is among the many approaches described
in a recent review on this subject.[12] Due to the long-
standing interest in sulfone and RambergϪBäcklund chem-
istry within our own research group,[13] we also recognised
the potential of such compounds: we envisaged a thioglyco-
side S,S-dioxide (glycosyl sulfone) being subjected to a
RambergϪBäcklund rearrangement to introduce an exo-
CϪC double bond at the anomeric position (Scheme 1).
Initial studies established that this was indeed a feasible
transformation, the scope of which appeared considerable
with regard to both the saccharide and aglycon portions.[14]
Shortly after we disclosed our own results, similar findings
were reported by Belica and Franck.[15] In the following sec-
tions the synthesis of a variety of glycosyl sulfones and their
conversion into exo-glycals are described.
The discovery of the fundamental roles played by oligo-
saccharides, and their lipid and protein conjugates, at a mo-
lecular level has stimulated the enormous growth in carbo-
hydrate research over the last three decades.[1] Crucial to
the expansion of knowledge in this area has been the contri-
bution of synthetic chemists in providing practical quanti-
ties of pure, naturally occurring carbohydrates and, perhaps
more significantly, chemically modified mono- and oligo-
saccharides. Particularly useful in this context are exo-gly-
cals (formally 2,5- or 2,6-anhydro-1-deoxy-hex- or -hept-1-
enitols) which are not only valuable in biological investi-
gations per se,[2] but are also important synthetic interme-
diates owing to the scope of the enol ether functional group
for further elaboration.[3] Herein we present a novel syn-
thetic route to exo-glycals employing the RambergϪ
Bäcklund rearrangement[4,5] as the key step.
The methods for exo-glycal synthesis may be divided into
two main categories: those in which the carbon skeleton is
constructed first and then subjected to an elimination reac-
tion,[6] and those in which unsaturation is incorporated dur-
ing CϪC bond formation such as in the olefination of sugar
lactones using the Tebbe[7] or Petasis[8] reagent, or Wittig
chemistry.[9] In a novel route recently reported by Toth and
´
Somsak,[10] 2,5- and 2,6-anhydroaldose tosylhydrazones are
´
transformed, in a BamfordϪStevens reaction, into glycosyl-
methyl carbenes, which then undergo a spontaneous 1,2-
hydrogen shift to give exo-methylenic sugar derivatives.
Scheme 1. Generic representation of the transformation of glycosyl
sulfones into exo-glycals via a RambergϪBäcklund rearrangement.
The ease of preparation and the chemical stability of al- PG ϭ protecting group
kyl and aryl thioglycosides, combined with their ready ac-
Results and Discussion
tivation to the corresponding sulfonium species, has re-
[a]
Synthesis of Glycosyl Sulfones
Department of Chemistry, University of York,
Heslington, York, YO10 5DD, UK
Fax: (internat.) ϩ44-1904/432-543
E-mail: rjkt1@york.ac.uk
Thioglycosides may be conveniently prepared from a
variety of common glycosyl donors, for example from the
Eur. J. Org. Chem. 2002, 1305Ϫ1322
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0407Ϫ1305 $ 17.50ϩ.50/0
1305

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
FULL PAPER
reaction of glycosyl esters with mercaptans in the presence
of a Lewis acid such as SnCl4,[16] by nucleophilic substitu-
tion of glycosyl halides[17] by thiolates or xanthate salts[18]
or from hemiacetals using disulfides, and a trialkylphos-
phane in a Mitsunobu-like process.[19,20] Our initial studies,
which were designed to explore the scope of the aglycon
in our methodology, were conducted on benzyl-protected
glucose derivatives (Scheme 2, a, and Table 1). Commen-
cing with tetra-O-benzyl--glucose (1), thioglycosylation
with a variety of thiols was accomplished using a modifica-
tion of Suzaki’s zinc triflate-mediated procedure[21] to pre-
pare S-glycosides 2b؊h as mixtures of α- and β-anomers,
which were separated and characterised individually. For
the preparation of the methyl thioglycosides 2aα and 2aβ,
the method reported by Landry and co-workers[19] using
dimethyl disulfide was employed in order to avoid handling
the toxic and volatile (b.p. 6 °C) methanethiol. We then ex-
tended the range of substrates in our study to include other
monosaccharides. The thioglycosides 2i and 2j were pre-
pared from peracetylated galactose (4) and mannose (5),
respectively, by boron trifluoride-mediated thioglycosyl-
ation, followed by deacetylation and benzylation (Scheme 2,
Table 1. Summary of the thioglycosides and glycosyl sulfones syn-
thesised according to Scheme 2; Cy ϭ cyclohexyl; Adam ϭ ad-
amant-2-yl
Entry
Saccharide
Aglycon
Yield
2 (α/β)
3
a
b
c
d
e
f
g
h
i
-Glucose
-Glucose
-Glucose
-Glucose
-Glucose
-Glucose
-Glucose
-Glucose
-Galactose
-Mannose
Cellobiose
-Ribose
Me
Et
Pr
Bzl
iPr
Cy
CHPh2
Adam[a]
Bzl
71 (3:1)
47 (3:1)
82 (3:1)
85 (2:1)
53 (4:1)
68 (3:1)
76 (4:1)
Ϫ
42[b] (1:5)
41[c] (α only)
19[d] (β only)
45
82
80
83
87
87
85
73
69
84
93
95
86
j
k
l
Bzl
Bzl
Et
[a]
In this example adamant-2-yl 2,3,4-tri-O-benzyl-6-O-tert-butyl-
dimethylsilyl-1-thio-α--glucopyranoside was used. [b] Overall yield
from 4. [c] Overall yield from 5. [d] Overall yield from cellobiose oc-
taacetate.
b and c). Thiocellobioside 2k was prepared from the corres- by reaction with Oxone in aqueous acetone to give the
ponding acetyl-protected glycosyl bromide according to the corresponding sulfones 3. For the more sterically de-
method of Durette and Shen,[22] and thioriboside 2l was manding benzhydryl sulfide 2g, peroxyacetic acid was re-
prepared from 2,3,5-tri-O-benzyl--ribofuranose[23] (6) by quired to obtain a satisfactory yield of the sulfone, and for
using Suzaki’s method (Scheme 2, d and e).[21] Sulfur the adamantyl derivative 2h,[24] meta-chloroperoxybenzoic
oxidation of these derivatives was achieved in most cases acid (mCPBA) was used as the oxidant.
Scheme 2. (i) R ϶ Me, Me3SiCl, Zn(OTf)2, RSH, MeCN, 40 °C; R ϭ Me, MeSSMe, BF3·OEt2, MeCN; (ii) BzlSH, BF3·OEt2, DCM;
(iii) MeONa, MeOH; (iv) NaH, BzlBr, DMF; (v) R ϶ CHPh2, Adam, Oxone, acetone, H2O, reflux; R ϭ CHPh2, H2O2, AcOH; R ϭ
Adam, mCPBA, NaHPO4, DCM. Adam ϭ adamant-2-yl, Bzl ϭ benzyl; DCM ϭ dichloromethane; mCPBA ϭ meta-chloroperoxyben-
zoic acid
1306
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
FULL PAPER
Ramberg؊Bäcklund Rearrangement of Glycosyl Sulfones
the olefin product is influenced by the configuration of the
starting sulfone. Thus a higher proportion of the (Z)-alkene
was obtained from the α-anomer 3dα than from the β-an-
omer 3dβ, perhaps reflecting the relative ease of formation
of the (pro-Z) and (pro-E) episulfones in these cases.
Exposure of glycosyl sulfones 3a؊l to the tandem halo-
genation-RambergϪBäcklund conditions developed by
Meyers[25] (KOH, CCl4, aq. tBuOH, 60 °C) or Chan[26]
(alumina-supported KOH, CBr2F2, tBuOH), in which α-
sulfonyl halogenation occurs in situ, yielded exo-glycals in
all cases, as shown in Scheme 3 and Table 2. When the re-
arrangement of 3a was carried out using Chan’s conditions,
the exo-methylenic sugar 4a was accompanied by 15Ϫ32%
of vinyl bromide 4m (R1 ϭ Br, R2 ϭ H), probably as a
result of gem-dibromination of the starting material fol-
lowed by RambergϪBäcklund rearrangement. No vinyl
halide was detected when Meyers’ Method was employed.
The tri-substituted olefinic products 4b؊d and 4c؊k were
As well as being useful intermediates, exo-glycals are of
interest in their own right as tools for the study of glycosid-
ase action[2] and, as such, must be accessible in their fully
deprotected form. The hydrogenolytic conditions required
for the cleavage of the benzyl ethers in products 4a؊l would
also undoubtedly effect the reduction of the enol ether
moiety, and hence a different protection strategy was exam-
ined (Scheme 4).
Acid-catalysed thioglycosylation of α--glucose penta-
obtained in good to excellent yield using Chan’s procedure, acetate, followed by oxidation, gave the known β-S-glycos-
with the (Z)-isomer predominating in most cases. Stereo- ide dioxide 8.[28] Zemplen deacetylation and subsequent re-
´
chemical assignment was based on the trend that the vinylic protection using tert-butyldimethylsilyl triflate/2,6-lutidine
1
protons of (Z)-exo-glycals resonate at lower field in the H furnished the tetra-O-silylated sulfone 9 in excellent yield.
NMR spectrum than those in the corresponding (E)-iso- Pleasingly,
this
material
readily
underwent
mers.[27] The more sterically hindered tetra-substituted al- RambergϪBäcklund rearrangement upon application of
kenes 4e؊h could only be formed under the more forcing the Chan conditions to give a 69% yield of enol ether 10 as
Meyers conditions, and although the yields in these cases a 89:11 (Z)/(E) isomeric mixture. Smooth desilylation was
are significantly lower, the availability of fully substituted then accomplished using tetra-n-butylammonium fluoride
alkenes using this methodology, particularly the con- (TBAF) producing the desired tetraol 11, which was con-
strained adamantylidene derivative 4h, is noteworthy. As ex- verted into its crystalline tetraacetate derivative 12 {mp
pected from a stereospecific process, the stereochemistry of 112Ϫ113 °C. [α]2D0 ϭ ϩ109.8 (c ϭ 1.0, CHCl3)} for charac-
Scheme 3. The scope of the RambergϪBäcklund rearrangement of glycosyl sulfones
Eur. J. Org. Chem. 2002, 1305Ϫ1322
1307

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
Table 2. Summary of RambergϪBäcklund rearrangements of glycosyl sulfones 3 to give exo-glycals 4
FULL PAPER
Sulfone
Saccharide
R1
H
R2
H
α/β
Conditions
Yield of 4
(Z)/(E)
3a
-Glucose
3:1
3:1
4:1
4:1
4:1
(i)
(ii)
(i)
(i)
(i)
(ii)
(i)
(i)
(ii)
(ii)
(i)
(ii)
(i)
(i)
(i)
(i)
54[a]
72
75
71
83
56
62[b]
61
51
32
57
20
83
94
80
58
Ϫ
Ϫ
3b
3c
3d
-Glucose
-Glucose
-Glucose
Me
Et
Ph
H
H
H
80:20
92:8
88:12
88:12
94:6
79:21
Ϫ
Ϫ
Ϫ
Ϫ
62:38
(Z) only
87:13
50:50
3dα
3dβ
3e
3f
3g
3h
3i
3j
3k
3l
-Glucose
-Glucose
-Glucose
-Glucose
-Glucose
-Glucose
-Galactose
-Mannose
Cellobiose
-Ribose
Ph
Ph
Me
H
H
α only
β only
3:1
4:1
4:1
α only
1:6
α only
β only
β only
Me
cyclohexyl
Ph
Ph
adamantyl
Ph
Ph
Ph
Me
H
H
H
H
[a]
When the reaction was carried out at 5 °C, vinyl bromide 4m (R1 ϭ Br, R2 ϭ H) was obtained in 15% yield along with 54% of 4a;
the yield of 4m could be increased to 32% (with 57% 4a) when the reaction was conducted at room temp. [b] 97% based on recovered 3dα.
Scheme 4. (i) BzlSH, SnCl4, DCM, Ϫ30 °C to room temp., 68%, then crystallisation of β-anomer; (ii) Oxone, THF, MeOH, H2O;
(iii) MeONa, MeOH; (iv) TBDMSOTf, 2,6-lutidine, DCM; (v) KOH/Al2O3, CBr2F2, tBuOH, DCM, 5 °C to room temp., 69%; (vi) TBAF,
THF; (vii) Ac2O, DMAP, DCM, 64% over 2 steps. TBDMSOTf ϭ tert-butyldimethylsilyl trifluoromethanesulfonate; TBAF ϭ tetra-n-
butylammonium fluoride; DMAP ϭ 4-dimethylaminopyridine
terisation purposes. NMR spectroscopy of the exo-glycal which of the two possible regioisomeric α-halosulfones was
12 confirmed the presence of the exo-methine moiety {δH being formed during the in situ halogenation step of the
(CDCl3) ϭ 5.76, s; δC (CDCl3) ϭ 111.4} and the observa- reaction? Scheme 5 shows the two alternative pathways,
tion of mutual NOEs between the vinylic proton (1-H) and either (or both) of which could be in operation. Although
the allylic proton (3-H) suggests a (Z)-configuration about the formation of vinyl bromide 4m from the reaction of
the double bond. Although this assignment cannot be made methyl sulfone 3a suggests that bromination occurs at the
unequivocally in the absence of the other geometric isomer αЈ-position in this substrate at least, no direct evidence in
on which to conduct the complementary NOE experiments, support of the precise mechanism could be found. [When
the observed chemical shift for 1-H is very close (∆δ ϭ 0.03) referring to 1-thioglycosides and their S,S-dioxide derivat-
to that observed for the major isomer of benzylated ana- ives, C1 of the saccharide shall be denoted as the α-sulfonyl
logue 4d, which is believed to be (Z) on the basis of its position and the corresponding site on the aglycon as αЈ.]
resonance at higher field than the minor co-product. Addi-
tional evidence is presented by the results of hydroboration
reactions involving 4d which are discussed in the following
paper.[3]
However, on examination of the RambergϪBäcklund re-
arrangement of sulfone 3dα using Chan’s protocol we found
that, by reducing the base stoichiometry from ca.
7.5 g·mmolϪ1 substrate to ca. 0.5 g·mmolϪ1 and shortening
the reaction time from 20 h to 2 h, the intermediate αЈ-bro-
mosulfone 13 could be isolated from the reaction mixture
in 36% yield along with exo-glycal 4d (18%) and unchanged
starting material 3dα (32%) (Scheme 6, a).
Mechanistic Studies
As these rearrangements were all carried out using one-
pot procedures, one aspect of the chemistry was unclear:
1308
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
FULL PAPER
Figure 1. ORTEP representation of bromosulfone 13a
Scheme 5. Alternative pathways for the tandem halogenation-
RambergϪBäcklund rearrangement of glycosyl sulfones involving
regioisomeric halosulfones
Scheme 6. Isolation of αЈ-bromosulfones from the tandem bromin-
ation-RambergϪBäcklund rearrangements of 3dα and 3dβ;
(i) 0.5 g·mmolϪ1 KOH/Al2O3, CBr2F2, tBuOH, DCM, 5 °C
Scheme 7. (i) 7.5 g·mmolϪ1 KOH/Al2O3, tBuOH, DCM, 5 °C; see
1H NMR spectroscopy revealed the halogenated material
to be an equimolar mixture of the diastereoisomeric αЈ-bro-
mosulfones 13a and 13b, which were separated by further
column chromatography and characterised individually.
Conclusive evidence came when one of the diastereoisomers
was crystallised and X-ray diffraction provided unambigu-
ous confirmation that bromination had indeed occurred at
the exocyclic position, as shown in Figure 1. A similar pro-
cedure was followed for the β-glycosyl sulfone 3dβ
(Scheme 6, b) and here also a separable pair of diastereo-
isomeric bromides (14a and 14b) was isolated, which dis-
played spectroscopic characteristics in full accordance with
their assigned structures.
Table 3 for yields
Table 3. RambergϪBäcklund rearrangements of isolated glycosyl
αЈ-bromosulfones
Substrate
Yield of 9d
(Z)/(E) ratio
13a
13b
14a
14b
89%
87%
81%
72%
89:11
89:11
45:55
45:55
In order to provide further evidence for the involvement and gave the expected exo-glycal 4d as the sole product and
of these species in the tandem halogenation- in high yield (Scheme 7 and Table 3).
RambergϪBäcklund process, the individual bromosulfones
Although the yields and (Z)/(E) ratios of the alkene va-
13a, 13b, 14a, and 14b were treated with KOH/Al2O3 sus- ried between the two anomers, the product mixtures ob-
pended in tBuOH, in the absence of any brominating agent, tained were unaffected by the configuration of the bromine-
Eur. J. Org. Chem. 2002, 1305Ϫ1322
1309

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
Apart from its wide applicability, the most surprising fea-
FULL PAPER
bearing carbon, as shown in Table 3. This observation was
initially surprising because episulfone formation and de- ture of this methodology is the fact that, despite the prob-
composition are both stereospecific processes. Closer exam- able formation of anomeric α-sulfonyl carbanion interme-
ination by TLC, however, revealed that both diastereomeric diates, we did not observe any direct evidence of β-elimina-
pairs of bromosulfones suffer rapid epimerisation of the tion of the 2-alkoxy group to give 1,2-glycals, a process
benzylic centre before any product is formed, and hence, for which has severely hampered C-1 anionic approaches to C-
each anomer, the rearrangements commence from the same glycosylation. [Although no 1,2-glycals were isolated, β-
equilibrium mixture of epimers. The stereoselectivity of the elimination cannot be excluded as a contributory factor to-
RambergϪBäcklund rearrangements of these substrates wards the low yielding transformations leading to exo-gly-
must, therefore, be derived solely from the anomeric config- cals 4f and 4h. In these examples the rate of episulfone
uration. However, the fact that starting material was reco- formation may be sufficiently retarded that 1,2-glycal
vered from the rearrangement of α-anomer 3dα with its C1 formation becomes a competing process.] Indeed a number
stereochemistry intact, suggests that inversion of this centre of tactics, the most notable of which are described in Som-
[12]
´
is not a factor in the selectivity.
sak’s review, have been implemented in C-glycoside syn-
It is also surprising to note that in neither case are the thesis in order to overcome unwanted β-elimination of the
(Z)- and (E)-alkenes formed in the same ratio as in the tan- C2-substituent from glycosyl anions. Conceptually, these
dem halogenation-RambergϪBäcklund rearrangement se- either involve the introduction of a group of poor nucleofu-
quence. While the α-anomer still exhibits a high stereo- gality at the 2-position, as demonstrated by the glycosyl di-
selectivity in favour of the (Z)-alkene, the relative propor- anion method,[29] or a reduction of the anionic character of
tion of the (E)-isomer is increased by a factor of two. Even the sugar nucleophile, most notably by the reductive sama-
more unexpected is the fact that an essentially equimolar riation of glycosyl pyridyl sulfones in the absence of
mixture of (E)- and (Z)-olefins was obtained from the reac- HMPA[30a,30b] and in the presence of catalytic amounts of
tion of the β-anomer, whereas before the product was signi- NiI2.[30c] In our RambergϪBäcklund process we believe
ficantly enriched in the (Z)-isomer. One possible explana- that, although the substrates bear a moderately good leav-
tion for the differing selectivities between the stepwise and ing group[31] (benzyloxy or tert-butyldimethylsilyloxy), the
tandem processes is that during the latter, αЈ-bromination glycosyl anion intermediate is intercepted intramolecularly
may occur concurrently with deprotonation of the anomeric by a γ-elimination process (episulfone formation) before β-
centre and, assuming that episulfone formation then occurs elimination can occur.
more rapidly than epimerisation of the bromine-bearing
It is likely that the formation of 1,2-glycal 18 in these
carbon, any diastereoselectivity in the initial bromination systems would follow an E1cb mechanism since the sub-
step will be preserved and conveyed to the alkene product. strates bear a relatively acidic α-sulfonyl hydrogen and a
As already mentioned (vide supra) epimerisation of the moderate leaving group. 1,2-Eliminations of HX from six-
benzylic centres of isolated bromides 13 and 14 occurs at a membered rings usually proceed from a conformation in
faster rate than 1,3-elimination to form the episulfone inter- which the CϪH bond (or the derived nonbonding pair) and
mediate and, hence, some selectivity may be lost during the the nucleofuge are anti-periplanar, although Skrydstrup et
stepwise process.
al.[30a] have recently proposed that intermediate glycosyl sa-
Scheme 8. Conformational requirements for 1,3- and 1,2-elimination from glycosyl αЈ-bromosulfones leading to exo-glycals and 1,2-
glycals respectively
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Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
FULL PAPER
Organic extracts were dried over anhydrous sodium sulfate and col-
umn chromatography was carried out using 33Ϫ64 (60 A) silica gel
marium(III) species, generated from the reduction of glyco-
syl pyridyl sulfones in the absence of HMPA, undergo an
unprecedented syn-elimination to give 1,2-glycals. However,
Scheme 8 illustrates that for either syn- or anti-elimination
to occur, the predominant 4C1 conformation of the glucose-
derived molecules studied would be required to undergo a
conformational change. In this rationale we assume that C1
deprotonation of the αЈ-bromosulfones 13 and 14 takes
˚
(ICN). Melting points (m.p.) were determined with an Electro-
thermal IA9100 digital melting point apparatus and are uncorrec-
ted. Specific rotations were measured on a Jasco DIP-370 digital
polarimeter and are expressed in units of 10Ϫ2 deg·cmϪ2·gϪ1. Mass
spectrometry was carried out on a Fisons Analytical Autospec in-
strument using either chemical ionisation (CI) or fast atom bom-
bardment (FAB) techniques; all high resolution mass spectral de-
terminations are within 5 ppm of the calculated value. Elemental
4
place while in the C1 arrangement and that inversion of
the α-sulfonyl carbanion does not occur. The latter assump- analyses were performed by Chemical Analytical Services Unit,
University of Newcastle, UK using a Carlo Erba 1106 elemental
analyser. NMR spectra were recorded on a Jeol EX270 spectro-
tion is supported by the isolation of the α-thioglycoside di-
oxide 3dα from tandem halogenation RambergϪBäckund
rearrangements with its anomeric configuration intact
(Scheme 6, a).
1
meter, operating at H and 13C frequencies of 270 and 67.9 MHz,
respectively.
The trans relationship between HϪC(1) and BzlOϪC(2)
of 14 requires that, before 1,2-elimination can proceed, the
derived carbanion must adopt the boat (or twist boat) con-
formation represented by 17 in which the n-C1ϪC2ϪOBzl
dihedral angle approaches 180°. In attaining this geometry,
the pyranose ring must pass through the half-chair 15, and
it is at this point that the process may be halted by the
intervention of a competing process. The planarisation of
the O5ϪC1ϪC2 portion of the heterocycle coincides with
Methyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-
Methyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-
D
-glucopyranoside (2aα) and
-glucopyranoside[32] (2aβ):
D
To a suspension of the lactol 1, (3.00 g, 5.55 mmol) in dry MeCN
˚
(30 mL) over activated 4 A molecular sieves was added dimethyl
disulfide (1.2 mL, 13.3 mmol), followed by tri-n-butylphosphane
(3.36 mL, 13.5 mmol) and then boron trifluoride diethyl etherate
(2.88 mL, 23.4 mmol) and the resulting solution was heated to 60
°C and stirred overnight. After cooling, the solvent was removed
under reduced pressure and the residue was redissolved in DCM
the conformation which leads to the episulfone-forming (100 mL), washed with satd. aq. NaHCO3 (50 mL) then with water
(30 mL), dried, and purified by flash column chromatography (light
petroleum ether/EtOAc, 9:1Ǟ4:1) to afford the title compounds as
a colourless oil (1.50 g, 71%, 2aα/2aβ, 3:1). For characterisation
purposes, the anomers were separated by further column chroma-
tography (DCM/light petroleum ether, 1:1Ǟ4:1Ǟ1:0) to give first
2aα which was recrystallised from MeOH to give fine needles, Rf ϭ
0.34 (DCM); m.p. 57Ϫ58 °C. [α]2D0 ϭ ϩ106.7 (c ϭ 1.0, CHCl3);
ν˜max/cmϪ1: 3030, 2917, 1496, 1453, 1363, 1208, 1074; δH (270 MHz,
CDCl3): 2.05 (s, 3 H, SCH3), 3.59Ϫ3.64 (m, 1 H, 2-H), 3.64, 3.76
(ABX, J6A,6B ϭ 10.7, J6A,5 ϭ 1.7, J6B,5 ϭ 3.9 Hz, 2 H, 6-HA, 6-
HB), 3.85Ϫ3.92 (m, 2 H, 3-H, 4-H), 4.10Ϫ4.16 (ddd, J5,4 ϭ 9.6,
J5,6B ϭ 3.9, J5,6A ϭ 1.7 Hz, 1 H, 5-H), 4.47, 4.61 (AB, J ϭ 12.1
Hz, 2 H, CH2Ph), 4.46, 4.83 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.64,
4.74 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.76, 4.95 (AB, J ϭ 10.9 Hz,
2 H, CH2Ph), 5.32 (d, J1,2 ϭ 4.5 Hz, 1 H, 1-H), 7.12Ϫ7.15 (m, 2
H, 2 ϫ arom. H), 7.24Ϫ7.40 (m, 18 H, 18 ϫ arom. H); δC
(67.9 MHz, CDCl3): 12.4 (SCH3), 68.6, (C6), 72.3, 73.4, 75.0, 75.7
(4 ϫ CH2Ph), 70.3, 77.2, 79.6, 82.5, 84.4 (C1, C2, C3, C4, C5),
127.6, 127.7, 127.9, 128.0 (ϫ 2), 128.4 (ϫ 2) (arom. CH), 137.8,
137.9, 138.3, 138.7 (subst. arom. C); m/z (CI): 588 (20%, [M ϩ
NH4]ϩ), 392 (100%). Further elution gave 2aβ which was recrys-
tallised from MeOH to afford fine needles, Rf ϭ 0.24 (DCM); m.p.
69Ϫ70.5 °C, ref.[32] 64Ϫ66 °C. [α]2D0 ϭ ϩ9.7 (c ϭ 1.0, CHCl3), ref.[32]
transition state, and hence 1,3-elimination predominates. In
13 the HϪC(1) and BzlOϪC(2) bonds are cis and hence a
syn-elimination process may be possible from half-chair 16.
However, since episulfone formation also competes in deter-
mining the fate of this species, and considering the relative
leaving group capabilities of bromide and benzyloxy, 1,3-
elimination is likely to be preferred over 1,2-elimination.
Further experiments to probe the mechanism of this process
are currently in progress and the results will be reported in
due course.
Conclusion
In summary, we have shown that readily available glyco-
syl sulfones can be converted into exo-glycals in a tandem
halogenation-RambergϪBäcklund rearrangement. 1,1-Di-,
tri-, and tetra-substituted alkene products derived from glu-
cose, galactose, mannose, cellobiose, and ribose have been
prepared in this way. It is believed that the αЈ-halosulfonyl
intermediates formed in situ during this process preferen-
tially undergo 1,3-elimination to give spiroepisulfones as ϩ9.4 (c ϭ 0.79, CHCl3).
opposed to 1,2-elimination. The elaboration of these exo-
glycals is described in the accompanying paper.[3]
General Procedure for the Preparation of Thioglycosides 2b؊g and
2l From Lactols 1 and 6: Trimethylsilyl chloride (2.6 mmol) was
added to a suspension containing the lactol (2 mmol), zinc(II) tri-
flate (0.2 mmol), and thiol (1.3 mmol) in anhydrous MeCN
(10 mL) at 20 °C, after which the mixture rapidly became homogen-
eous. The solution was then heated to 40 °C and stirred for 3Ϫ4 h.
The solvent was removed in vacuo and the residue was purified by
Experimental Section
General Remarks: Dichloromethane (DCM) was distilled from cal-
cium hydride immediately prior to use. Light petroleum ether refers
to the fraction boiling in the range 40Ϫ60 °C and was redistilled flash chromatography (gradient elution with light petroleum ether/
before use. Alumina-supported potassium hydroxide (KOH/Al2O3)
EtOAc, 9:1Ǟ3:1) to afford the thioglycoside as a mixture of α- and
was prepared according to Chan’s procedure.[26] Reactions were β-anomers. Further column chromatography (elution with DCM/
monitored by TLC on silica gel 60 F254 (Merck) with detection by light petroleum ether, 4:1) followed by crystallisation, where pos-
charring with 10% sulfuric acid in methanol followed by heating.
sible, gave pure samples of each anomer for characterisation.
Eur. J. Org. Chem. 2002, 1305Ϫ1322
1311

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
FULL PAPER
Ethyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-
D
-glucopyranoside[33] (2bα): Hz, 1 H, 5-H), 4.43, 4.61 (AB, J ϭ 12.1 Hz, 2 H, CH2Ph), 4.46,
From 0.282 g of 1. Yield: 0.103 g, 34%; fine needles (MeOH); Rf ϭ 4.83 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.69 (A2, 2 H, CH2Ph), 4.76,
0.25 (DCM); m.p. 90Ϫ91 °C, ref.[33] 91 °C. [α]2D0 ϭ ϩ111.8 (c ϭ 4.96 (AB, J ϭ 10.7 Hz, 2 H, CH2Ph), 5.42 (d, J1,2 ϭ 4.6 Hz, 1 H,
1.0, CHCl3), ref.[33] ϩ108 (CHCl3).
Ethyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-
From 0.282 g of 1. Yield: 0.40 g, 13%; fine needles (MeOH); Rf ϭ
0.17 (DCM); m.p. 94Ϫ94.5 °C, ref.[33] 94 °C. [α]2D0 ϭ ϩ3.4 (c ϭ 1.0,
CHCl3), ref.[34] ϩ2.7 (c ϭ 1.6, CHCl3).
1-H), 7.11Ϫ7.37 (m, 20 H, 5 ϫ Ph); δC (67.9 MHz, CDCl3): 23.5,
23.7 [(CH3)2CHS], 33.9 [(CH3)2CHS], 68.5 (C6), 72.4, 73.35, 75.0,
75.65 (4 ϫ CH2Ph), 70.4, 77.5, 79.5, 82.5, 82.6 (C1ϪC5), 127.5,
127.6, 127.6, 127.7, 127.8, 128.0, 128.1, 128.3, 128.35 (arom. CH),
137.9 (ϫ 2), 138.3, 138.7 (subst. arom. C); m/z (CI): 616 (4%, [M
ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ).
D
-glucopyranoside[33,34] (2bβ):
Propyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-D
-glucopyranoside[35] (2cα):
From 1.03 g of 1. Yield: 0.70 g, 61%; colourless oil; Rf ϭ 0.36 (light
petroleum ether/EtOAc, 4:1). [α]2D0 ϭ ϩ110.0 (c ϭ 1.0, CHCl3),
ref.[35] ϩ84.1 (c ϭ 1.0, CHCl3).
Isopropyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-D-glucopyranoside (2eβ):
From 1.64 g of 1. Yield: 0.29 g, 11%; needles (MeOH); Rf ϭ 0.36
(light petroleum ether/EtOAc, 4:1); m.p. 86Ϫ87 °C. [α]2D0 ϭ ϩ4.6
(c ϭ 1.0, CHCl3); νmax/cmϪ1: 3006, 2868, 1497, 1454, 1360, 1210,
˜
Propyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-D-glucopyranoside (2cβ):
1154, 1065; δH (270 MHz, CDCl3): 1.34, 1.37 [6 H, 2 ϫ d, J ϭ
6.8 Hz, CH(CH3)2], 3.48 [br. hept., J ϭ 6.8 Hz, 1 H, CH(CH3)2],
3.40Ϫ3.49 (m, 2 H, 4-H, 5-H), 3.58 (t, J ϭ 8.7 Hz, 1 H, 3-H),
3.64Ϫ3.77 (m, 3 H, 2-H, 6-HA, 6-HB), 4.51Ϫ4.62 (m, 4 H, 1-H, 3
ϫ benzylic H), 4.72, 4.93 (AB, J ϭ 10.7 Hz, 2 H, CH2Ph), 4.82 (d,
J ϭ 10.9 Hz, 1 H, benzylic H), 4.84, 4.93 (AB, J ϭ 10.9 Hz, 2 H,
CH2Ph), 7.15Ϫ7.38 (m, 20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3):
23.96, 24.00 [(CH3)2CHS], 35.5 [(CH3)2CHS], 69.2 (C6), 73.3, 75.0,
75.5, 75.7 (4 ϫ CH2Ph), 78.0, 79.0, 82.0, 84.6, 86.7 (C1ϪC5), 127.5,
127.6 (ϫ 2), 127.7, 127.9, 128.1, 128.25, 128.35 (arom. CH), 138.0
(ϫ 2), 138.2, 138.5 (subst. arom. C); m/z (CI): 616 (4%, [M ϩ
NH4]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ NH4]ϩ 616.3092.
C37H42O5S·NH4 requires 616.3097.
From 1.03 g of 1. Yield: 0.24 g, 21%; needles (MeOH); Rf ϭ 0.36
(light petroleum ether/EtOAc, 4:1); m.p. 86.5Ϫ87 °C. [α]2D0 ϭ ϩ2.3
(c ϭ 1.0, CHCl3); νmax/cmϪ1: 3066, 3000, 1496, 1454, 1361, 1314,
˜
1243, 1147, 1094; δH (270 MHz, CDCl3): 1.00 (t, J ϭ 7.3 Hz, 3 H,
SCH2CH2CH3), 1.69 (sext., J ϭ 7.3 Hz, 2 H, SCH2CH2CH3), 2.67,
2.76 (ABX2, J ϭ 12.6, 7.3 Hz, 2 H, SCH2CH2CH3), 3.41Ϫ3.48 (m,
2 H, 2-H, 5-H), 3.57Ϫ3.77 (m, 4 H, 3-H, 4-H, 6-HA, 6-HB), 4.44
(d, J ϭ 9.7 Hz, 1 H, 1-H), 4.54, 4.61 (AB, J ϭ 12.1 Hz, 2 H,
CH2Ph), 4.57, 4.82 (AB, J ϭ 10.7 Hz, 2 H, CH2Ph), 4.74, 4.93
(AB, J ϭ 10.2 Hz, 2 H, CH2Ph), 4.84, 4.93 (AB, J ϭ 10.9 Hz, 2
H, CH2Ph), 7.16Ϫ7.39 (m, 20 H, 5 ϫ Ph); δC (67.9 MHz, CDCl3):
13.5
(SCH2CH2CH3),
23.25
(SCH2CH2CH3),
32.9
(SCH2CH2CH3), 69.1 (C6), 73.35, 75.0, 75.4, 75.7 (4 ϫ CH2Ph),
77.9, 79.0, 81.8, 85.2, 86.6 (C1ϪC5), 127.5, 127.6, 127.7, 127.8,
127.9, 128.1, 128.3 (ϫ 2) (arom. CH), 137.9, 138.0, 138.2, 138.4
(subst. arom. C); m/z (CI): 616 (100%, [M ϩ NH4]ϩ); found [M ϩ
NH4]ϩ 616.3100. C37H42O5S·NH4 requires 616.3097.
Cyclohexyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-D-glucopyranoside (2fα):
From 1.16 g of 1. Yield: 0.70 g, 51%; needles (MeOH); Rf ϭ 0.38
(light petroleum ether/EtOAc, 4:1); m.p. 89Ϫ90 °C. [α]2D0 ϭ ϩ115.3
(c ϭ 1.0, CHCl3); νmax/cmϪ1: 3006, 2933, 2856, 1454, 1207, 1072;
˜
δH (270 MHz, CDCl3): 1.25Ϫ1.57, 1.65Ϫ1.80, 1.89Ϫ2.01 [m, 10 H,
SCH(CH2)5], 2.70Ϫ2.79 [m, 1 H, SCH(CH2)5], 3.60Ϫ3.66 (m, 2 H,
4-H, 6-HA), 3.77 (dd, J6B,6A ϭ 10.6, J6B,5 ϭ 3.6 Hz, 1 H, 6-HB),
3.82Ϫ3.88 (m, 2 H, 2-H, 3-H), 4.25 (ddd, J5,4 ϭ 9.9, J5,6B ϭ 3.6,
Benzyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-D-glucopyranoside (2dα):
From 0.610 g of 1. Yield: 0.28 g, 38%; fine needles (MeOH); Rf ϭ
0.46 (DCM); m.p. 82.5Ϫ83.5 °C. [α]2D0 ϭ ϩ161.6 (c ϭ 1.0, CHCl3);
νmax/cmϪ1: 3030, 2914, 1497, 1453, 1363, 1074; δH (270 MHz,
˜
J5,6A ϭ 7 Hz, 1 H, 5-H), 4.43, 4.61 (AB, J ϭ 12.1 Hz, 2 H, CH2Ph),
CDCl3): 3.51Ϫ3.88 (m, 7 H, 2-H, 3-H, 4-H, 6-HA, 6-HB, SCH2Ph),
4.16Ϫ4.19 (m, 1 H, 5-H), 4.40, 4.49 (AB, J ϭ 11.6 Hz, 2 H,
CH2Ph), 4.46, 4.61 (AB, J ϭ 12.1 Hz, 2 H, CH2Ph), 4.46, 4.82
(AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.75, 4.93 (AB, J ϭ 10.9 Hz, 2
H, CH2Ph), 5.22 (d, J1,2 ϭ 5.3 Hz, 1 H, 1-H), 7.12Ϫ7.36 (m, 25
H, 5 ϫ Ph); δC (67.9 MHz, CDCl3): 33.3 (SCH2Ph), 68.4 (C6),
71.7, 73.4, 75.0, 75.6 (4 ϫ CH2Ph), 70.7, 77.4, 78.9, 82.1, 82.7 (C1,
C2, C3, C4, C5), 126.9, 127.5, 127.6 (ϫ 2), 127.7, 127.8 (ϫ 2),
127.9, 128.3 (ϫ 2), 128.6, 128.8, 129.1 (arom. CH), 137.5, 137.8,
138.0, 138.2, 138.6 (subst. arom. C); m/z (CI): 664 (40%, [M ϩ
NH4]ϩ), 108 (100%), 91(75%, [C7H7]ϩ); found C 76.20, H 6.50, S
5.12. C41H42O5S requires C, 76.13, H 6.55, S 4.96%.
4.45, 4.83 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.69 (A2, 2 H, CH2Ph),
4.75, 4.96 (AB, J ϭ 10.7 Hz, 2 H, CH2Ph), 5.44 (d, J1,2 ϭ 4.8 Hz,
1 H, 1-H), 7.11Ϫ7.40 (20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 25.7
(ϫ 2), 25.9, 33.6, 34.0 (5 ϫ cyclohexyl CH2), 42.5 (SCH on cyclo-
hexyl), 68.5 (C6), 72.3, 73.3, 75.0, 75.6 (4 ϫ CH2Ph), 70.3, 77.5,
79.5, 82.4, 82.6 (C1ϪC5), 127.5, 127.6, 127.7, 127.8, 128.0, 128.1,
128.25, 128.3 (arom. CH), 137.9 (d), 138.3, 138.7 (subst. arom. C);
m/z (CI): 656 (100%, [M ϩ NH4]ϩ); found [M ϩ NH4]ϩ 656.3418.
C40H46O5S·NH4 requires 656.3418.
Cyclohexyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-
From 1.16 g of 1. Yield: 0.23 g, 17%; fine needles (MeOH); Rf ϭ
0.38 (light petroleum ether/EtOAc, 4:1); m.p. 90.5Ϫ91.5 °C. [α]2D0
D-glucopyranoside (2fβ):
ϭ
Benzyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-D-glucopyranoside (2dβ):
ϩ4.3 (c ϭ 1.0, CHCl3); νmax/cmϪ1: 3006, 2933, 2856, 1454, 1207,
1072; δH (270 MHz, CDCl3): 1.21Ϫ1.63 (m, 6 H, 4 ϫ 3Ј-H, 2 ϫ
4Ј-H), 1.76 (br. s, 2 H, 2 ϫ 2Ј-H), 2.05 (br. d, J ϭ 13.3 Hz, 2 H, 2
ϫ 2Ј-H), 2.99 [tt, J ϭ 10.2, 3.6 Hz, 1 H, SO2CH(CH2)5], 3.42 (t,
J ϭ 8.7 Hz, 1 H, 4-H), 3.40Ϫ3.49 (m, 1 H, 5-H), 3.57 (t, J ϭ 8.7
˜
From 0.610 g of 1. Yield: 0.09 g, 13%; fine needles (MeOH); Rf ϭ
0.38 (DCM); m.p. 65Ϫ67 °C, ref.[18] 75.5Ϫ76 °C. [α]2D0 ϭ Ϫ42.2
(c ϭ 1.0, CHCl3), ref.[18] Ϫ40.2 (CHCl3); found C 75.93, H 6.50, S
4.97. C41H42O5S requires C, 76.13, H 6.55, S 4.96%.
Isopropyl
(2eα): From 1.64 g of of 1. Yield: 0.77 g, 42%; needles (MeOH);
Rf ϭ 0.36 (light petroleum ether/EtOAc, 4:1); m.p. 87Ϫ88 °C. CH2Ph), 4.82 (d, J ϭ 10.9 Hz, 1 H, benzylic H), 4.83, 4.92 (AB,
2,3,4,6-Tetra-O-benzyl-1-thio-α-
D
-glucopyranoside[36] Hz, 1 H, 3-H), 3.65Ϫ3.77 (m, 3 H, 2-H, 6-HA, 6-HB), 4.51Ϫ4.62
(m, 4 H, 1-H, 3 ϫ benzylic H), 4.72, 4.94 (AB, J ϭ 10.2 Hz, 2 H,
[α]2D0 ϭ ϩ102.2 (c ϭ 1.0, CHCl3), ref.[36] ϩ90.4 (c ϭ 1.0, CHCl3);
J ϭ 10.9 Hz, 2 H, CH2Ph), 7.16Ϫ7.39 (m, 20 H, 4 ϫ Ph); δC
(67.9 MHz, CDCl3): 25.7, 25.9, 26.1, 34.05, 34.2 (5 ϫ cyclohexyl
νmax/cmϪ1: 3005, 2867, 1497, 1454, 1364, 1152, 1073; δH (270 MHz,
˜
CDCl3): 1.28, 1.31 [2 ϫ d, J ϭ 6.8 Hz, 6 H, SCH(CH3)2], 2.97 CH2), 43.8 (SCH on cyclohexyl), 69.3 (C6), 73.3, 75.0, 75.5, 75.7
[hept., J ϭ 6.8 Hz, 1 H, SCH(CH3)2], 3.59Ϫ3.68 (m, 2 H, 4-H, 6- (4 ϫ CH2Ph), 78.0, 79.0, 82.0, 84.4, 86.7 (C1ϪC5), 127.5, 127.6,
HA), 3.77 (dd, J6B,6A ϭ 10.8, J6B,5 ϭ 3.6 Hz, 1 H, 6-HB), 3.82Ϫ3.88 127.75, 127.9, 128.3, 128.4 (arom. CH), 138.0 (ϫ 2), 138.2, 138.5
(m, 2 H, 2-H, 3-H), 4.22 (ddd, J5,4 ϭ 8, J5,6B ϭ 3.6, J5,6A ϭ 2.0
(subst. arom. C); m/z (CI): 656 (100%, [M ϩ NH4]ϩ).
1312
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
Benzhydryl 2,3,4,6-Tetra-O-benzyl-1-thio-α-
-glucopyranoside EtSH]ϩ), 295 (85%); found [M
FULL PAPER
D
ϩ
NH4]ϩ 482.2363.
(2gα): From 3.03 g of 1. Yield: 2.52 g, 62%; colourless oil; Rf ϭ
C28H32O4S·NH4 requires 482.2365.
0.41 (light petroleum ether/EtOAc, 4:1). [α]2D0 ϭ ϩ162.3 (c ϭ 2.0,
CHCl3); νmax/cmϪ1: 3005, 2869, 1496, 1453 1363, 1154, 1073; δH
Adamant-2-yl 2,3,4-Tri-O-benzyl-6-O-tert-butyldimethylsilyl-1-thio-
α- -glucopyranoside (2h): A solution of 2-adamantyl 6-O-tert-bu-
˜
D
(270 MHz, CDCl3): 3.55Ϫ3.62, 3.70, 3.77 (m, 4 H, 2-H, 4-H, 6HA,
6-HB), 3.89 (t, J ϭ 9.2 Hz, 1 H, 3-H), 4.32 (br. d, J ϭ 9.9 Hz, 1
H, 5-H), 4.39Ϫ4.54 (m, 4 H, 4 ϫ benzylic H), 4.62 (d, J ϭ 11.9
Hz, 1 H, benzylic H), 4.74, 4.94 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph),
4.83 (d, J ϭ 10.7 Hz, 1 H, benzylic H), 5.12 (d, J1,2 ϭ 5.6 Hz, 1
H, 1-H), 5.18 (s, 1 H, SCHPh2), 7.13Ϫ7.54 (m, 30 H, 6 ϫ Ph); δC
(67.9 MHz, CDCl3): 51.1 (SCHPh2), 68.7 (C6), 71.8, 73.4, 75.0,
75.7 (4 ϫ CH2Ph), 71.0, 77.5, 78.9, 82.6, 82.8 (C1ϪC5), 127.0,
127.3, 127.6 (ϫ 2), 127.75, 127.85, 127.9, 128.0, 128.1, 128.3, 128.4,
128.5, 128.7 (arom. CH), 137.6, 137.9, 138.2, 138.6, 141.1, 141.3
(subst. arom. C); m/z (CI): 740 (30%, [M ϩ NH4]ϩ), 574 (60%,
[M Ϫ CH(Ph)2]ϩ); found [M ϩ NH4]ϩ 740.3411. C47H46O5S·NH4
requires 740.3410.
tyldimethylsilyl-1-thio-α--glucoside[24] (0.92 g, 2.07 mmol) in
DMF (10 mL) was added to a slurry of sodium hydride (0.34 g,
60% w/w in mineral oil, 8.5 mmol) in DMF (5 mL) at 0 °C. After
stirring at 0 °C for a further 10 minutes, the reaction was allowed
to warm to room temp. over 1 h, after which it was recooled to 5
°C and benzyl bromide (1.00 mL, 8.42 mmol) added. The reaction
mixture was maintained at 5 °C for 1 h and then allowed to warm
to room temp. and was stirred overnight. After quenching with
MeOH, the mixture was partitioned between water (50 mL) and
toluene (50 mL). The organic layer was washed with water (5 ϫ
20 mL), brine (20 mL), dried, and concentrated. The crude product
was then purified by column chromatography (light petroleum
ether/EtOAc, 19:1Ǟ9:1) to afford 2h as a colourless oil (1.39 g,
94%); Rf ϭ 0.41 (light petroleum ether/EtOAc, 4:1). [α]2D0 ϭ ϩ116.6
Benzhydryl
2,3,4,6-Tetra-O-benzyl-1-thio-β-D-glucopyranoside
(c ϭ 1.0, CHCl3); νmax/cmϪ1: 3030, 2856, 1496, 1454, 1072; δH
˜
(2gβ): From 3.03 g of 1. Yield: 0.56 g, 14%; Colourless oil; Rf ϭ
0.41 (light petroleum ether/EtOAc, 4:1). [α]2D0 ϭ Ϫ23.3 (c ϭ 0.9,
(270 MHz, CDCl3): 0.03, 0.04 [2 ϫ s, 6 H, Si(CH3)2], 0.88 [s, 9 H,
SiC(CH3)3], 1.50Ϫ1.63, 1.70Ϫ2.02 (m, 10 H, 5 ϫ adamantyl CH2),
2.05Ϫ2.30 (m, 4 H, 4 ϫ adamantyl CH), 3.14 (br. s, 1 H, SCH of
adamantyl), 3.49 (dd, J4,5 ϭ 9.9, J4,3 ϭ 8.3 Hz, 1 H, 4-H),
3.72Ϫ3.79 (m, 3 H, 2-H, 6-HA, 6-HB), 3.88 (t, J ϭ 9.1 Hz, 1 H, 3-
H), 4.13 (ddd, J5,4 ϭ 9.9, J5,6 ϭ 3.9, 2.7 Hz, 1 H, 5-H), 4.55 (A2,
2 H, CH2Ph), 4.67, 4.89 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 4.77,
4.97 (AB, J ϭ 10.7 Hz, 2 H, CH2Ph), 5.31 (d, J1,2 ϭ 5.3 Hz, 1 H,
1-H), 7.22Ϫ7.41 (m, 15 H, 3 ϫ Ph); δC (67.9 MHz, CDCl3): Ϫ5.4,
Ϫ5.2 [(CH3)2Si], 18.4 [(CH3)3CSi], 26.0 [(CH3)3CSi], 27.3, 27.6,
33.0, 34.2 (4 ϫ adamantyl CH), 32.3, 32.5, 37.7, 38.7, 38.8 (5 ϫ
adamantyl CH2), 51.9 (SCH of adamantyl), 62.65 (C6), 72.1, 74.3,
75.0 (3 ϫ CH2Ph), 72.5, 77.7, 80.1, 82.7, 83.6 (C1ϪC5), 127.4,
127.6, 127.8, 127.9 (ϫ 2), 128.0, 128.1, 128.2, 128.4, 128.5, 128.8,
129.0 (arom. CH), 138.05, 138.35, 138.8 (subst. arom. C); m/z
(FAB): 737 (10%, [M ϩ Na]ϩ); found [M ϩ Na]ϩ 737.3679.
C43H58O5SSi·Na requires 737.3672.
CHCl3); νmax/cmϪ1: 3005, 2868, 1496, 1453 1360, 1124, 1067; δH
˜
(270 MHz, CDCl3): 3.18 (br. d, J ϭ 8.7 Hz, 1 H, 5-H), 3.51Ϫ3.77
(m, 4 H, 2-H, 4-H, 6-HA, 6-HB), 4.06Ϫ4.09 (m, 1 H, 3-H),
4.51Ϫ4.89 (m, 9 H, 1-H, 4 ϫ CH2Ph), 5.58 (s, 1 H, SCHPh2),
7.13Ϫ7.47 (m, 30 H, 6 ϫ Ph); δC (67.9 MHz, CDCl3): 52.2
(Ph2CHS), 68.6 (C6), 73.3, 74.9, 75.3, 75.7 (4 ϫ CH2Ph), 77.9, 78.8,
81.7, 83.65, 86.6 (C1ϪC5), 126.5, 127.1, 127.3, 127.5, 127.6, 127.7,
127.8, 127.8, 128.0, 128.15, 128.3, 128.4, 128.5, 128.7 (arom. CH),
138.0 (ϫ 2), 138.2, 138.4, 140.6, 140.9 (subst. arom. C); m/z (CI):
740 (2%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found C 78.16, H
6.45, S 4.17. C47H46O5S requires C, 78.09, H 6.41, S 4.43%.
Ethyl 2,3,5-tri-O-benzyl-α-D-ribofuranoside (2lα): From 2.65 g of 6.
Yield: 0.42 g, 14%; pale yellow oil; Rf ϭ 0.37 (light petroleum ether/
EtOAc, 4:1). [α]2D0 ϭ ϩ90.7 (c ϭ 1.3, CHCl3); νmax/cmϪ1: 3030,
˜
2924, 1496, 1453, 1362, 1263, 1208, 1104, 1027; δH (270 MHz,
CDCl3): 1.31 (t, J ϭ 7.5 Hz, 3 H, SCH2CH3), 2.79 (q, J ϭ 7.5 Hz,
2 H, SCH2CH3), 3.55 (dd, J ϭ 4, J ϭ 11 Hz, 1 H), 3.60 (dd, J ϭ
4, J ϭ 11 Hz, 1 H), 3.93 (t, J ϭ 6 Hz, 1 H) and 4.10 (t, J ϭ 5 Hz,
1 H, 2-H, 3-H, 5-HA, 5-HB), 4.29Ϫ4.33 (m, 1 H, 4-H), 4.41Ϫ4.78
(m, 6 H, 3 ϫ CH2Ph), 5.49 (d, J ϭ 5 Hz, 1 H, 1-H), 7.22Ϫ7.41
(m, 15 H, 3 ϫ Ph); δC (67.9 MHz, CDCl3): 14.9 (SCH2CH3), 25.0
(SCH2CH3), 69.1 (C5), 72.1, 72.4, 73.0 (3 ϫ CH2Ph), 76.8, 78.15,
80.2, 87.7 (C1ϪC4), 127.5, 127.6, 127.8, 128.0, 128.2 (arom. CH),
137.8, 137.9, 138.0 (subst. arom. C); m/z (CI): 482 (20%, [M ϩ
NH4]ϩ), 420 (50%, [M Ϫ EtSH]ϩ), 290 (100%); found [M ϩ NH4]ϩ
482.2362. C28H32O4S·NH4 requires 482.2365.
Benzyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-
and Benzyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-
D
-galactopyranoside (2iα)
D
-galactopyranoside
(2iβ): Boron trifluoride diethyl etherate (3.40 mL, 26.8 mmol) was
added to a solution of -galactose pentaacetate (4) (3.83 g,
9.8 mmol) and benzyl mercaptan (1.5 mL, 12.8 mmol) in DCM
(25 mL) at room temp. The reaction mixture was stirred for 20 h
after which it was poured into water and extracted with DCM (2
ϫ 50 mL). The combined organic parts were washed with water (2
ϫ 50 mL), dried, and concentrated in vacuo. The residue was puri-
fied by column chromatography (light petroleum ether/EtOAc,
4:1Ǟ1:1) to give benzyl 2,3,4,6-tetra-O-acetyl-1-thio--galactopyr-
´
Ethyl 2,3,5-Tri-O-benzyl-β-
D-ribofuranoside (2lβ): From 2.65 g of 6.
anoside as a colourless oil (2.77 g, 62%). Zemplen deacetylation
Yield: 1.32 g, 45%; pale yellow oil; Rf ϭ 0.34 (light petroleum ether/
followed by O-benzylation under standard conditions (NaH, BzlBr,
DMF) and purification by column chromatography (light petro-
EtOAc, 4:1). [α]2D0 ϭ Ϫ24.6 (c ϭ 3.3, CHCl3); ν˜max/cmϪ1: 3030,
2925, 1496, 1453, 1361, 1263, 1207, 1121, 1096; δH (270 MHz, leum ether/EtOAc, 19:1Ǟ9:1) afforded 2iα as a colourless oil
CDCl3): 1.23 (t, J ϭ 7.5 Hz, 3 H, SCH2CH3), 2.60, 2.69 (ABX3, (0.62 g, 10% from 4); Rf ϭ 0.27 (light petroleum ether/EtOAc, 4:1).
J ϭ 12.0, 7.5 Hz, 2 H, SCH2CH3), 3.52Ϫ3.62 (m, 2 H, 5-HA, 5-
HB), 3.87 (t, J ϭ 4.4 Hz, 1 H, 2-H), 4.00 (t, J ϭ 5.3 Hz, 1 H, 3-
[α]2D0 ϭ ϩ148.2 (c ϭ 0.9, CHCl3); ν˜max/cmϪ1: 3029, 2865, 1496,
1454, 1100, 1070; δH (270 MHz, CDCl3): 3.45Ϫ3.55 (m, 2 H, 6-
H), 4.28 (dt, J ϭ 5.1 Hz, 1 H, 4.6, 4-H), 4.49, 4.57 (AB, J ϭ 11.9 HA, 6-HB), 3.63, 3.72 (AB, J ϭ 13.8 Hz, 2 H, SCH2Ph), 3.76Ϫ3.80
Hz, 2 H, CH2Ph), 4.50, 4.57 (AB, J ϭ 12.1 Hz, 2 H, CH2Ph), 4.60, (m, 1 H, 3-H), 3.92 (br. d, J ϭ 2.7 Hz, 1 H, 4-H), 4.21 (dd, J2,3
4.67 (AB, J ϭ 11.9 Hz, 2 H, CH2Ph), 5.24 (d, J1,2 ϭ 3.9 Hz, 1 H, 9.9, J2,1 ϭ 5.6 Hz, 1 H, 2-H), 4.31 (br. t, J ϭ 6.8 Hz, 1 H, 5-H),
ϭ
1-H), 7.26Ϫ7.37 (m, 15 H, 3 ϫ Ph); δC (67.9 MHz, CDCl3): 15.0 4.41, 4.46 (AB, J ϭ 11.9 Hz, 2 H, CH2Ph), 4.48 (A2, 2 H, CH2Ph),
(SCH2CH3), 24.9 (CH3CH2S), 70.8 (C5), 79.3 (ϫ 2), 73.3 (3 ϫ 4.56, 4.92 (AB, J ϭ 11.4 Hz, 2 H, CH2Ph), 4.68, 4.81 (AB, J ϭ
CH2Ph), 78.1, 80.7, 81.6, 85.8 (C1ϪC4), 127.5, 127.6, 127.8, 128.0 11.9 Hz, 2 H, CH2Ph), 5.26 (d, J1,2 ϭ 5.6 Hz, 1 H, 1-H), 7.18Ϫ7.33
(ϫ 2), 128.3 (ϫ 2), 128.4 (arom. CH), 137.6, 137.7, 138.15 (subst.
(m, 25 H, 5 ϫ Ph); δC (67.9 MHz, CDCl3): 32.9 (SCH2Ph), 69.1
arom. C); m/z (CI): 482 (100%, [M ϩ NH4]ϩ), 420 (70%, [M Ϫ (C6), 71.9, 73.4, 74.7 (4 ϫ CH2Ph), 69.9, 74.95, 75.8, 79.7, 82.1
Eur. J. Org. Chem. 2002, 1305Ϫ1322
1313

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
(C1ϪC5), 126.5, 126.8, 127.4, 127.5, 127.5, 127.6, 127.7, 127.9, rous DMSO (10 mL) was slowly added a solution of the de-
FULL PAPER
128.0, 128.1, 128.2, 128.3 (ϫ 2) 128.95, 129.1 (arom. CH), 138.0,
138.1, 138.4, 138.7 (subst. arom. C); m/z (CI): 664 (85%, [M ϩ
acetylated thioglycoside (0.174 g) in DMSO (20 mL) and the mix-
ture was stirred for 1 h. Benzyl bromide (0.67 mL, 5.63 mmol) was
NH4]ϩ), 108 (100%); found [M
ϩ
NH4]ϩ 664.3100. added with a syringe and the reaction was stirred overnight. After
C41H42O5S·NH4 requires 664.3097. Ϫ Further elution gave 2iβ as quenching excess NaH with methanol (10 mL) the reaction mixture
a colourless oil (3.65 g, 58% from 3); Rf ϭ 0.24 (light petroleum
was partitioned between DCM (50 mL) and water (30 mL) and the
aqueous phase was further extracted with EtOAc (2 ϫ 20 mL). The
ether/EtOAc, 4:1). [α]2D0 ϭ Ϫ34.9 (c ϭ 3.1, CHCl3); νmax/cmϪ1
:
˜
3028, 2866, 1495, 1455, 1098, 1070, 1027; δH (270 MHz, CDCl3): organic parts were washed with water (20 mL), brine (30 mL),
3.45Ϫ3.55 and 3.58Ϫ3.63 (2 ϫ m, 4 H, 6-HA, 6-HB, SCH2Ph), dried, and concentrated in vacuo to give a pale yellow solid. The
3.81Ϫ3.98 (m, 4 H, 2-H, 3-H, 4-H, 5-H), 4.26 (d, J1,2 ϭ 9.7 Hz, 1 crude product was then purified by column chromatography (elu-
H, 1-H), 4.24, 4.49 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.24, 4.49 tion with light petroleum ether/EtOAc, 3:1) and recrystallised to
(AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.61, 4.94 (AB, J ϭ 11.6 Hz, 2 give the 2k as fine needles (0.212 g, 49%); Rf ϭ 0.35 (light petro-
H, CH2Ph), 4.68 (A2, 2 H, CH2Ph), 4.70, 4.76 (AB, J ϭ 10.2 Hz,
leum ether/EtOAc, 3:1); m.p. 125Ϫ127 °C. [α]2D0 ϭ Ϫ15.2 (c ϭ 1.0,
2 H, CH2Ph), 7.20Ϫ7.33 (m, 25 H, 5 ϫ Ph); δC (67.9 MHz, CDCl3): CHCl3); ν˜max/cmϪ1: 3029, 2907, 1496, 1454, 1362, 1216, 1122, 1069,
34.0 (SCH2Ph), 68.8 (C6), 72.7, 73.5, 74.5, 75.55 (4 ϫ CH2Ph), 1049, 1029; δH (270 MHz, CDCl3): 3.18Ϫ4.05 (m, 14 H, 2-H, 3-
73.7, 77.2, 78.25, 83.6, 84.0 (C1ϪC5), 126.9, 127.5, 127.6 (ϫ 2),
H, 4-H, 5-H, 6-HA, 6-HB, 2Ј-H, 3Ј-H, 4Ј-H, 5Ј-H, 6Ј-HA, 6Ј-HB,
127.8, 127.85, 128.1, 128.15, 128.2, 128.3, 128.4, 129.1 (arom. CH), SCH2Ph), 4.25 (d, J1,2 ϭ 9.5 Hz, 1 H, 1-H), 4.39Ϫ4.91 (m, 14 H,
137.8, 138.0, 138.2, 138.3, 138.6 (subst. arom. C); m/z (CI): 664
1Ј-H, 13 ϫ benzylic H), 5.09 (d, J ϭ 11.4 Hz, 1 H, benzylic H),
(100%, [M
ϩ
NH4]ϩ); found [M
ϩ
NH4]ϩ 664.3096. 7.15Ϫ7.37 (m, 40 H, 8 ϫ Ph); δC (67.9 MHz, CDCl3): 34.2
(SCH2Ph), 68.2, 68.9 (C6, C6Ј), 73.2, 73.3, 74.8, 75.1, 75.2, 75.4,
C41H42O5S·NH4 requires 664.3097.
75.6 (CH2Ph), 75.0, 76.5, 78.0, 79.1, 81.0, 82.8, 83.3, 84.8, 84.9,
Benzyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-D-mannopyranoside (2jα):
(C1, C2, C3, C4, C5, C2Ј, C3Ј, C4Ј, C5Ј), 102.4 (C1Ј), 127.0, 127.2,
127.3, 127.5, 127.6, 127.7, 127.8, 127.9, 128.1, 128.2, 128.4 (ϫ 2),
129.1 (arom. CH), 137.8, 138.1, 138.2 (ϫ 2), 138.4, 138.6, 139.2
(subst. arom. C); m/z (FAB): 1101.5 (100%, [M ϩ Na]ϩ), 181
(40%); found [M ϩ Na]ϩ 1101.4585. C68H70O10S·Na requires
1101.4587; found C 75.67, H 6.44. C68H70O10S requires C, 75.67,
H 6.54%.
Boron trifluoride diethyl etherate (2.4 mL, 18.9 mmol) was added
to a solution of -mannose pentaacetate (2) (2.09 g, 5.4 mmol) and
benzylmercaptan (0.8 mL, 6.8 mmol) in DCM (20 mL) at room
temp. The reaction solution was stirred for 14 h, after which the
solution was poured into water and extracted with DCM (2 ϫ
50 mL). The combined organic extracts was washed with water (2
ϫ 50 mL), dried, and concentrated. Purification by column chro-
matography (light petroleum ether/EtOAc, 4:1Ǟ1:1) followed by
recrystallisation from ethanol afforded benzyl 2,3,4,6-tetra-O-
acetyl-1-thio-α--mannoside[37] as fine needles (1.90 g, 78%); m.p.
General Procedure for the Oxidation of Thioglycosides to Glycosyl
Sulfones: A solution of Oxone (9 mmol) in water (25 mL) was
added to a solution of the thioglycoside (2 mmol) in acetone
(25 mL) and the mixture was stirred at reflux for 3 h. After cooling,
the acetone was evaporated under reduced pressure and water
(30 mL) added to the residue, which was then extracted with ether
(3 ϫ 50 mL), dried, and purified by flash chromatography (elution
with light petroleum ether/EtOAc, 3:1).
138Ϫ139 °C, ref.[37] 137Ϫ138.5 °C. Zemplen deacetylation followed
´
by O-benzylation under standard conditions (NaH, DMF then
BzlBr) and purification by column chromatography (light petro-
leum ether/EtOAc, 19:1Ǟ9:1) afforded 2jα as a colourless oil (41%
from 5); Rf ϭ 0.38 (light petroleum ether/EtOAc, 4:1). [α]2D0
ϭ
ϩ106.4 (c ϭ 2.2, CHCl3); νmax/cmϪ1: 3029, 2907, 1496, 1453, 1365,
1208, 1099, 1027; δH (270 MHz, CDCl3): 3.64 (dd, J6A,6B ϭ 10.8,
J6A,5 ϭ 1.7 Hz, 1 H, 6-HA), 3.67, 3.77 (AB, J ϭ 13.3 Hz, 2 H,
SCH2Ph), 3.72 (dd, J2,3 ϭ 3.2, J2,1 ϭ 1.2 Hz, 1 H, 2-H), 3.77Ϫ3.84
(m, 3 H, 3-H, 5-H, 6-HB), 4.03 (t, J ϭ 9.0 Hz, 1 H, 4-H), 4.12
(ddd, J5,4 ϭ 9.0, J5,6B ϭ 3.2, J5,6A ϭ 1.7 Hz, 1 H, 5-H), 4.45Ϫ4.88
(m, 8 H, 4 ϫ CH2Ph), 5.28 (d, J1,2 ϭ 1.2 Hz, 1 H, 1-H), 7.13Ϫ7.37
(m, 25 H, 5 ϫ Ph); δC (67.9 MHz, CDCl3): 34.6 (SCH2Ph), 69.0
(C6), 71.6, 71.8, 73.2, 75.05 (4 ϫ CH2Ph), 72.2, 74.9, 75.65, 80.3,
80.65 (C2ϪC5), 127.0, 127.4, 127.5, 127.5, 127.7, 127.8, 128.2,
128.25, 128.4, 129.0 (arom. CH), 137.7, 137.8, 138.1, 138.3, 138.4
(subst. arom. C); m/z (CI): 664 (100%, [M ϩ NH4]ϩ); found [M ϩ
NH4]ϩ 664.3097. C41H42O5S·NH4 requires 664.3097.
˜
Methyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-D-glucopyrano-
side (3aα): From 1.46 g of 2aα. Yield: 1.26 g; 82%; Rf ϭ 0.56 (light
petroleum ether/EtOAc, 1:1); m.p. 77Ϫ78 °C. [α]2D0 ϭ ϩ65.9 (c ϭ
1.0, CHCl3); νmax/cmϪ1: 3030, 2867, 1497, 1454, 1302 (SO2), 1210,
˜
1147 (SO2), 1099; δH (270 MHz, CDCl3): 2.94 (s, 3 H, SO2CH3),
3.59 (dd, J4,5 ϭ 9.9, J4,3 ϭ 7.5 Hz, 1 H, 4-H), 3.62, 3.72, (ABX,
J6A,6B ϭ 10.9, J6A,5Ј ϭ 4.9, J6B,5 ϭ 2.2 Hz, 2 H, 6-HA, 6-HB), 4.12
(dd, J2,3 ϭ 8.2, J2,1 ϭ 5.8 Hz, 1 H, 2-H), 4.34Ϫ7.39 (m, 2 H, 3-H,
5-H), 4.46, 4.74 (AB, J ϭ 11.2 Hz, 2 H, CH2Ph), 4.47, 4.55 (AB,
J ϭ 11.9 Hz, 2 H, CH2Ph), 4.72, 4.83 (AB, J ϭ 11.4 Hz, 2 H,
CH2Ph), 4.72, 4.86 (AB, J ϭ 11.2 Hz, 2 H, CH2Ph), 4.88 (d, J1,2 ϭ
5.8 Hz, 1 H, 1-H), 7.13Ϫ7.17 (m, 2 H, 2 ϫ arom. H), 7.24Ϫ7.40
(m, 18 H, 18 ϫ arom. H); δC (67.9 MHz, CDCl3): 40.2 (SO2CH3),
68.7 (C6), 73.5, 74.0, 74.2, 74.9 (4 ϫ CH2Ph), 75.3, 76.6, 77.5, 79.8
(C2, C3, C4, C5), 89.0 (C1), 127.7, 127.8, 128.0, 128.2, 128.4 (ϫ
2), 128.5 (arom. CH), 137.0, 137.7, 137.9, 138.1 (subst. arom. C);
m/z (CI): 620 (100%, [M ϩ NH4]ϩ), 391 (40%); found C 69.75, H
6.33, S 5.48. C35H38O7S requires C, 69.74, H 6.35, S 5.32%.
Benzyl 2,3,6-Tri-O-benzyl-4-O-(2Ј,3Ј,4Ј,6Ј-tetra-O-benzyl-β-
glucopyranosyl)-1-thio-β- -glucopyranoside (2k): solution of
benzyl 2,3,6-tri-O-acetyl-4-O-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β--gluco-
pyranosyl)-1-thio-β--glucopyranoside,[38] synthesised according to
the method of Durette and Shen,[22] (0.300 g, 0.40 mmol) in MeOH
(15 mL) was added a methanolic solution of sodium methoxide
D-
D
A
Methyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyrano-
(25% w/w, 0.65 mL, 2.84 mmol) and the mixture was stirred for side (3aβ): From 0.66 g of 2aβ. Yield: 0.59 g; 84%; Rf ϭ 0.56 (light
20 h. Amberlyst 15 ion-exchange resin was then added until the pH petroleum ether/EtOAc, 1:1); m.p. 107Ϫ110 °C. [α]2D0 ϭ ϩ33.8 (c ϭ
of the solution became neutral, the resin was removed by filtration,
1.0, CHCl3); δH (270 MHz, CDCl3): 2.95 (s, 3 H, SO2CH3),
the filtrate was evaporated in vacuo, triturated with DCM, and 3.58Ϫ3.83 (m, 5 H, 2-H, 4-H, 5-H, 6-HA, 6-HB), 4.07 (t, J ϭ 9.0
dried thoroughly under high vacuum to give a colourless oil Hz, 1 H, 3-H) 4.36 (d, J1,2 ϭ 9.0 Hz, 1 H, 1-H), 4.54 (A2, 2 H,
(0.174 g) which was used without further purification. To a suspen-
sion of NaH (60% dispersion in oil, 0.168 g, 4.20 mmol) in anhyd-
CH2Ph), 4.57, 4.81 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.78, 4.97
(AB, J ϭ 9.9 Hz, 2 H, CH2Ph), 4.88, 4.95 (AB, J ϭ 10.9 Hz, 2 H,
1314
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
CH2Ph), 7.15Ϫ7.18 (m, 2 H, 2 ϫ arom. H), 7.25Ϫ7.37 (m, 18 H, (67.9 MHz,
FULL PAPER
CDCl3):
13.2
(SO2CH2CH2CH3),
15.15
18 ϫ arom. H); δC (67.9 MHz, CDCl3): 39.0 (SO2CH3), 68.6 (C6), (SO2CH2CH2CH3), 53.8 (SO2CH2CH2CH3), 68.7 (C6), 73.4, 74.0,
73.4, 75.2, 75.4, 75.9 (4 ϫ CH2Ph), 76.5, 77.1, 79.8, 86.0 (C2, C3, 74.35, 75.1 (4 ϫ CH2Ph), 75.3, 76.7, 77.9, 80.2, 87.45 (C1ϪC5),
C4, C5), 90.6 (C1), 127.6, 127.6, 127.8, 128.0 (ϫ 2), 128.4, 128.5, 127.7, 127.8, 128.0, 128.1, 128.4, 128.5 (ϫ 2) (arom. CH), 137.1,
128.6 (arom. CH), 137.3, 137.5, 137.8, 138.1 (subst. arom. C); m/z 137.7, 138.0, 138.2 (subst. arom. C); m/z (CI): 648 (100%, [M ϩ
(CI): 620 (100%, [M ϩ NH4]ϩ), 391 (25%); found C 69.60, H 6.38, NH4]ϩ); found [M ϩ NH4]ϩ 648.2999. C37H42O7S·NH4 requires
S 5.41. C35H38O7S requires C, 69.74, H 6.35, S 5.32%.
648.2995.
Ethyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α- -glucopyranoside
D
Propyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside
(3bα): From 0.425 g of 2bα. Yield: 0.360 g; 80%; needles (MeOH);
Rf ϭ 0.16 (light petroleum ether/EtOAc, 3:1); m.p. 93.5Ϫ94 °C.
[α]2D0 ϭ ϩ69.2 (c ϭ 1.0, CHCl3); ν˜max/cmϪ1: 3031, 2922, 1496, 1453,
1363, 1209, 1074, 1154 (SO2), 1075, 1029; δH (270 MHz, CDCl3):
1.35 (t, J ϭ 7.5 Hz, 3 H, SO2CH2CH3), 3.02, 3.18 (ABX3, J ϭ
13.8, 7.5 Hz, 2 H, SO2CH2CH3), 3.58 (dd, J4,5 ϭ 10.0, J4,3 ϭ 7.8
Hz, 1 H, 4-H), 3.62, 3.71 (ABX, J6A,6B ϭ 10.9, J6A,5 ϭ 4.5, J6B,5 ϭ
2.2 Hz, 2 H, 6-HA, 6-HB), 4.10 (dd, J2,3 ϭ 8.6, J2,1 ϭ 5.8 Hz, 1 H,
2-H), 4.36 (ddd, J5,4 ϭ 10.0, J5,6A ϭ 4.5, J5,6B ϭ 2.2 Hz, 1 H, 5-
H), 4.43 (appt. t, J3,4 ϭ 7.8, J3,2 ϭ 8.6 Hz, 1 H, 3-H), 4.46, 4.55
(AB, J ϭ 12.1 Hz, 2 H, CH2Ph), 4.47, 4.76 (AB, J ϭ 11.2 Hz, 2
H, CH2Ph), 4.71, 4.89 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.74, 4.85
(AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.92 (d, J1,2 ϭ 5.8 Hz, 1 H, 1-H),
7.13Ϫ7.17 (m, 2 H, 2 ϫ arom. H), 7.23Ϫ7.35 (m, 16 H, 16 ϫ arom.
H), 7.37Ϫ7.41 (m, 2 H, 2 ϫ arom. H); δC (67.9 MHz, CDCl3): 6.0
(SO2CH2CH3), 46.6 (SO2CH2CH3), 68.6, (C6), 73.4, 74.0, 74.4,
75.3 (4 ϫ CH2Ph), 75.2, 76.6, 77.8, 80.2, 86.9 (C1, C2, C3, C4,
C5), 127.6, 127.7, 127.9, 128.1, 128.3, 128.4, 128.5 (arom. CH),
137.1, 137.6, 137.9, 138.2 (subst. arom. C); m/z (CI): 634 (100%,
[M ϩ NH4]ϩ), 108 (35%), 91 (75%, [C7H7]ϩ).
(3cβ): From 0.96 g of 2cβ. Yield: 0.73 g; 72%; colourless oil; Rf ϭ
0.32 (light petroleum ether/EtOAc, 1:1). [α]2D0 ϭ ϩ26.8 (c ϭ 1.0,
CHCl3); νmax/cmϪ1: 3088, 3065, 3041, 3006, 2870, 2933, 2877, 1355,
˜
1318, 1141, 1139 (SO2); δH (270 MHz, CDCl3): 1.00 (t, J ϭ 7.3 Hz,
3
H, SO2CH2CH2CH3), 1.77Ϫ1.96 (symm. m,
2
H,
SO2CH2CH2CH3), 3.01, 3.11 (ABXY, J ϭ 13.8, 9.7, 6.1 Hz, 2 H,
SO2CH2CH2CH3), 3.50Ϫ3.72 (m, 4 H, 3-H, 4-H, 6-HA, 6-HB), 3.79
(br. t, J ϭ 8.7 Hz, 1 H, 5-H), 4.10 (t, J ϭ 9.2 Hz, 1 H, 2-H), 4.36
(d, J1,2 ϭ 9.2 Hz, 1 H, 1-H), 4.53 (A2, 2 H, CH2Ph), 4.57, 4.81
(AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.77, 4.99 (AB, J ϭ 9.9 Hz, 2 H,
CH2Ph), 4.87, 4.95 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 7.15Ϫ7.39 (m,
20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 13.2 (SO2CH2CH2CH3);
15.2 (SO2CH2CH2CH3), 52.85 (SO2CH2CH2CH3), 68.6 (C6), 73.3,
75.1, 75.4, 75.85 (4 ϫ CH2Ph), 77.2 (ϫ 2), 79.7, 86.1, 89.35
(C1ϪC5), 127.6 (ϫ 2), 127.75, 127.9, 128.0 (ϫ 2), 128.35, 128.4,
128.5, 128.6 (arom. CH), 137.4, 137.5, 137.8, 138.1 (subst. arom.
C); m/z (CI): 648 (100%, [M ϩ NH4]ϩ); found [M ϩ NH4]ϩ
648.3000. C37H42O7S·NH4 requires 648.2995.
Benzyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-D-glucopyranoside
(3dα): From 1.54 g of of 2dα. Yield: 1.41 g; 87%; fine needles
(MeOH); Rf ϭ 0.20 (light petroleum ether/EtOAc, 3:1); m.p.
125Ϫ126.5 °C. [α]2D0 ϭ ϩ105.9 (c ϭ 1.0, CHCl3); ν˜max/cmϪ1: 3031,
2867, 1496, 1454, 1364, 1318 (SO2), 1099; δH (270 MHz, CDCl3):
Ethyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside
(3bβ): From 0.411 g of 2bβ. Yield: 0.380 g; 88%; fine needles
(MeOH); Rf ϭ 0.16 (light petroleum ether/EtOAc, 4:1); m.p. 93Ϫ94
°C. [α]2D0 ϭ ϩ43.5 (c ϭ 0.3, CHCl3); ν˜max/cmϪ1: 3041, 2938, 1363,
1317 (SO2), 1145 (SO2), 1097, 1073; δH (270 MHz, CDCl3): 1.38 (t,
J ϭ 7.5 Hz, 3 H, SO2CH2CH3), 3.07, 3.17 (ABX3, J ϭ 14.1, 7.5
Hz, 2 H, SO2CH2CH3), 3.55Ϫ3.72 (m, 4 H, 4-H, 5-H, 6-HA, 6-
HB), 3.79 (t, J ϭ 9.0 Hz, 1 H, 3-H), 4.11 (t, J ϭ 9.2 Hz, 1 H, 2-
H), 4.39 (d, J1,2 ϭ 9.2 Hz, 1 H, 1-H), 4.53 (A2, 2 H, CH2Ph), 4.56,
4.81 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.78, 4.00 (AB, J ϭ 9.7 Hz,
2 H, CH2Ph), 4.87, 4.95 (AB, J ϭ 11.2 Hz, 2 H, CH2Ph), 7.15Ϫ7.18
(m, 2 H, 2 ϫ arom. H), 7.23Ϫ7.39 (m, 18 H, 18 ϫ arom. H); δC
(67.9 MHz, CDCl3): 6.1 (SO2CH2CH3), 45.7 (SO2CH2CH3), 68.6,
(C6), 73.3, 75.1, 75.4, 75.9 (4 ϫ CH2Ph), 77.2 (ϫ 2), 79.8, 86.1,
88.9 (C1, C2, C3, C4, C5), 127.6, 127.7 (ϫ 2), 127.9 (ϫ 2), 128.0,
128.2, 128.3, 128.4, 128.5, 128.6, (arom. CH), 137.4, 137.6, 137.8,
138.1 (subst. arom. C); m/z (CI): 634 (100%, [M ϩ NH4]ϩ), 108
(45%), 91 (73%, [C7H7]ϩ); found C 70.03, H 6.42, S 5.14.
C36H40O7S requires C, 70.11, H 6.54, S 5.20%.
3.51 (dd, J ϭ 9.9, 8.2 Hz, 1 H, 4-H), 3.60, 3.72 (ABX, J6A,6B
ϭ
10.5, J6A,5 ϭ 5.3, J6B,5 ϭ 1.9 Hz, 2 H, 6-HA, 6-HB), 4.04 (dd, J2,3 ϭ
8.7, J2,1 ϭ 6.1 Hz, 1 H, 2-H), 4.11, (d, J ϭ 13.8 Hz, 1 H, SO2CH-
AHBPh), 4.43Ϫ4.64 (m, 7 H, SO2CHAHBPh, 2 ϫ CH2Ph, 3-H, 5-
H), 4.72Ϫ4.90 (m, 5 H, 2 ϫ CH2Ph, 1-H), 7.15Ϫ7.43 (m, 25 H, 5
ϫ Ph); δC (67.9 MHz, CDCl3): 58.2 (CH2Ph), 68.8 (C6), 73.4, 73.8,
74.5, 75.3 (4 ϫ CH2Ph), 75.1, 76.7, 77.9, 80.5, 85.7 (C1, C2, C3,
C4, C5), 127.7, 127.8, 128.0 (ϫ 2), 128.1, 128.3, 128.4, 128.6, 128.7,
131.0 (arom. CH), 137.1, 137.6, 137.9, 138.2 (subst. arom. C); m/z
(CI): 696 (45%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found C 72.47,
H 6.17, S 4.91. C41H42O7S requires C, 72.54, H 6.24, S 4.72%.
Benzyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside
(3dβ): From 1.00 g of 2dβ. Yield: 0.74 g; 70%; colourless oil; Rf ϭ
0.20 (light petroleum ether/EtOAc, 3:1). [α]2D0 ϭ ϩ0.3 (c ϭ 1.0,
CHCl3); νmax/cmϪ1: 3031, 2867, 1496, 1454, 1364, 1318 (SO2),
˜
1099; δH (270 MHz, CDCl3): 3.49Ϫ3.56 (m, 2 H, 2 ϫ CH),
3.62Ϫ3.77 (m, 3 H, 5-H, 6-HA, 6-HB), 4.04Ϫ7.16 (m, 3 H, CH,
SO2CH2Ph), 4.53, 4.80 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.54Ϫ7.59
(m, 3 H, CH, CH2Ph), 4.71, 4.97 (AB, J ϭ 9.7 Hz, 2 H, CH2Ph),
4.80, 4.91 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 7.14Ϫ7.36 (m, 23 H,
23 ϫ arom. H), 7.46Ϫ7.49 (m, 2 H, 2 ϫ arom. H); δC (67.9 MHz,
CDCl3): 57.1 (SO2CH2Ph), 68.9 (C6), 73.4, 75.1, 75.4, 75.8 (4 ϫ
CH2Ph), 76.8, 77.0, 79.4, 85.9, 86.5 (C1, C2, C3, C4, C5), 127.4,
127.5, 127.7, 127.8, 127.9, 128.0, 128.3, 128.4, 128.6, 128.8, 128.9,
131.1 (arom. CH), 137.2, 137.5, 137.7, 138.0 (subst. arom. C); m/z
(CI): 696 (45%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ).
Propyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-D-glucopyranoside
(3cα): From 0.99 g of 2cα. Yield: 0.87 g; 83%; needles (MeOH);
Rf ϭ 0.36 (light petroleum ether/EtOAc, 1:1); m.p. 97.5Ϫ98.0 °C.
[α]2D0 ϭ ϩ73.1 (c ϭ 1.0, CHCl3); νmax/cmϪ1: 3088, 2870, 1360, 1314,
˜
1146, 1135 (SO2), 1028; δH (270 MHz, CDCl3): 0.96 (t, J ϭ 7.3 Hz,
3
H, SO2CH2CH2CH3), 1.84 (sext., J ϭ 7.3 Hz, 2 H,
SO2CH2CH2CH3), 2.97, 3.12 (ABX2, J ϭ 13.8, 7.3 Hz, 2 H,
SO2CH2CH2CH3), 3.57 (dd, J4,5 ϭ 9.8, J4,3 ϭ 8.0 Hz, 1 H, 4-H),
3.61, 3.71 (ABX, J6A,6B ϭ 10.7, J6B,5 ϭ 1.5, J6A,5 ϭ 4.9 Hz, 2 H,
6-HA, 6-HB), 4.10 (dd, J2,3 ϭ 8.5, J2,1 ϭ 6.1 Hz, 1 H, 2-H), 4.37
(ddd, J5,4 ϭ 9.8, J5,6A ϭ 4.9, J5,6B ϭ 1.5 Hz, 1 H, 5-H), 4.43 (t,
J ϭ 8.1 Hz, 1 H, 3-H), 4.46, 4.55, (AB, J ϭ 12.1 Hz, 2 H, CH2Ph), Isopropyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-
D-glucopyrano-
4.47, 4.77 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 4.72, 4.89 (AB, J ϭ side (3eα): From 1.096 g of 2eα. Yield: 1.12 g; 97%; fine needles
11.4 Hz, 2 H, CH2Ph), 4.75, 4.84 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), (MeOH); Rf ϭ 0.45 (light petroleum ether/EtOAc, 1:1); m.p.
4.88 (d, J1,2 ϭ 6.1 Hz, 1 H, 1-H), 7.14Ϫ7.41 (20 H, 4 ϫ Ph); δC 105Ϫ106 °C. [α]2D0 ϭ ϩ81.2 (c ϭ 1.0, CHCl3); ν˜max/cmϪ1: 3006,
Eur. J. Org. Chem. 2002, 1305Ϫ1322
1315

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
FULL PAPER
2871, 1497, 1454, 1364, 1314 (SO2), 1207, 1143, 1095; δH
1359, 1301 (SO2), 1096, 1072; δH (270 MHz, CDCl3): 1.03Ϫ1.32,
(270 MHz, CDCl3): 1.32, 1.35 [2 ϫ d, J ϭ 7.0 Hz, 6 H, 1.51Ϫ1.68 (m, 6 H, 4 ϫ 3Ј-H, 2 ϫ 4Ј-H), 1.76 (br. d, J ϭ 12.8 Hz,
SO2CH(CH3)2], 3.44 [hept., J ϭ 7.0 Hz, 1 H, SO2CH(CH3)2], 3.58 1 H, 2Ј-H), 1.94 (br. t, J ϭ 12.8 Hz, 2 H, 2 ϫ 2Ј-H), 2.20 (br. d, J ϭ
(dd, J4,5 ϭ 9.9, J4,3 ϭ 8.5 Hz, 1 H, 4-H), 3.62, 3.70 (ABX, J6A,6B ϭ 12.8 Hz, 1 H, 2Ј-H), 3.26 [tt, J ϭ 12.1, 3.4 Hz, 1 H, SO2CH(CH2)5],
10.8, J6B,5 ϭ 2.2, J6A,5 ϭ 4.4 Hz, 2 H, 6-HA, 6-HB), 4.09 (dd, J2,3 ϭ 3.53Ϫ3.61 (m, 3 H, 3-H, 4-H, 6-HA), 3.67 (d, J6B,6A ϭ 10.2 Hz, 1
9.2, J2,1 ϭ 6.3 Hz, 1 H, 2-H), 4.38 (ddd, J5,4 ϭ 9.9, J5,6A ϭ 4.4,
H, 6-HB), 3.79 (br. t, J ϭ 9.5 Hz, 1 H, 5-H), 4.15 (t, J ϭ 9.2 Hz,
J5,6B ϭ 2.2 Hz, 1 H, 5-H), 4.45, 4.55 (AB, J ϭ 12.1 Hz, 2 H, 1 H, 2-H), 4.45 (d, 1 H, J1,2 ϭ 9.5 Hz, 1 H, 1-H), 4.51 (A2, 2 H,
CH2Ph), 4.48, 4.81 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 4.52 (t, J ϭ CH2Ph), 4.56, 4.81 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 4.77, 5.02
9.0 Hz, 1 H, 3-H), 4.71, 4.89 (AB, J ϭ 11.4 Hz, 2 H, CH2Ph), 4.77, (AB, J ϭ 10.0 Hz, 2 H, CH2Ph), 4.87, 4.96 (AB, J ϭ 10.9 Hz, 2
4.93 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 5.06 (d, J ϭ 6.3 Hz, 1 H, 1-
H), 7.14Ϫ7.44 (m, 20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 13.3, 22.6, 24.8, 25.0, 25.1, 25.75 (5 ϫ cyclohexyl CH2), 58.9 (SO2CH of
16.3 [(CH3)2CHSO2], 51.7 [(CH3)2CHSO2], 68.6 (C6), 73.4, 74.0, cyclohexyl), 68.8 (C6), 73.35, 75.1, 75.4, 75.9 (4 ϫ CH2Ph), 77.15
H, CH2Ph), 7.16Ϫ7.40 (m, 20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3):
74.6, 75.5 (4 ϫ CH2Ph), 75.3, 76.7, 78.3, 80.7, 84.85 (C1ϪC5), (ϫ 2), 79.75, 86.2, 87.2 (C1ϪC5), 127.6, 127.7, 127.8, 127.9, 128.0,
127.6, 127.7, 127.8, 128.1, 128.3, 128.4 (ϫ 2), 128.5 (arom. CH), 128.1, 128.4, 128.5, 128.7 (arom. CH), 137.5, 137.6, 137.8, 138.15
137.3, 137.7, 138.1, 138.4 (subst. arom. C); m/z (CI): 616 (40%,
(subst. arom. C); m/z (CI): 688 (100%, [M ϩ NH4]ϩ); found C
[M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ NH4]ϩ 648.3001. 71.67, H 6.86, S 4.69. C40H46O7S requires C, 71.62, H 6.91, S
C37H42O7S·NH4 requires 648.2995.
4.78%.
Isopropyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-
D
-glucopyrano-
Benzhydryl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-D-glucopyr-
side (3eβ): From 0.98 g of 2cβ. Yield: 0.90 g; 87%; amorphous solid; anoside (3gα): From 0.55 g of 2gα. Yield: 0.052 g; 9%; colourless
Rf ϭ 0.45 (light petroleum ether/EtOAc, 1:1). [α]2D0 ϭ ϩ25.4 (c ϭ oil; Rf ϭ 0.37 (light petroleum ether/EtOAc, 1:1). [α]2D0 ϭ ϩ112.3
1.0, CHCl3); νmax/cmϪ1: 3006, 2874, 1497, 1454, 1361, 1328 (SO2),
(c ϭ 0.8, CHCl3); νmax/cmϪ1: 3005, 2868, 1496, 1453 1360, 1124,
˜
˜
1310, 1210, 1145, 1097; δH (270 MHz, CDCl3): 1.33, 1.41 [2 ϫ d, 1067; δH (270 MHz, CDCl3): 3.07Ϫ3.13 (m, 1 H, 5-H), 3.52Ϫ3.63,
J ϭ 7.0 Hz, 6 H, CH(CH3)2], 3.48 [hept., J ϭ 7.0 Hz, 1 H, 4.03Ϫ4.14 (m, 6 H, 1-H, 2-H, 3-H, 4-H, 6-HA, 6-HB), 4.52, 4.90
CH(CH3)2], 3.54Ϫ3.62 (m, 3 H, 3-H, 4-H, 6-HA), 3.69 (d, J6B,6A ϭ (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 4.59 (A2, 2 H, CH2Ph), 4.70, 4.99
10.5 Hz, 1 H, 6-HB), 3.80 (br. t, J ϭ 8.7 Hz, 1 H, 5-H), 4.15 (t, (AB, J ϭ 9.7 Hz, 2 H, CH2Ph), 4.80 (A2, 2 H, CH2Ph), 5.76 (s, 1
J ϭ 9.0 Hz, 1 H, 2-H), 4.47Ϫ4.52 (m, 3 H, 1-H, CH2Ph), 4.55, H, CHPh2), 7.12Ϫ7.15, 7.21Ϫ7.44 (m, 28 H, 28 ϫ arom. CH),
4.81 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 4.77, 5.13 (AB, J ϭ 9.9 Hz, 7.63Ϫ7.66 (m, 2 H, 2 ϫ arom. CH); δC (67.9 MHz, CDCl3): 68.4
2 H, CH2Ph), 4.87, 4.96 (AB, J ϭ 11.1 Hz, 2 H, CH2Ph), 7.15Ϫ7.40 (C6), 73.3, 75.05, 75.5, 75.8 (4 ϫ CH2Ph), 69.9 (SO2CHPh2), 77.0,
(m, 20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 13.1, 16.1 [CH(CH3)2], 77.1, 79.2, 86.0, 87.2, (C1ϪC5), 127.5, 127.7, 127.9, 128.1, 128.2,
51.0 [CH(CH3)2], 68.7 (C6), 73.25, 75.1, 75.4, 75.9 (4 ϫ CH2Ph), 128.35, 128.414 128.5, 128.65, 128.7, 128.8, 129.9, 130.1,
77.2 (ϫ 2), 79.8, 86.15, 87.5 (C1ϪC5), 127.6, 127.7, 127.9, 127.9,
130.5.130.8 (arom. CH), 132.7, 137.2, 137.6, 137.8, 138.1 (subst.
128.0, 128.35, 128.45, 128.7 (arom. CH), 137.4, 137.55, 137.8, 138.1 arom. C); m/z (FAB): 777 (80%, [M ϩ Na]ϩ), 439 (100%); found
(subst. arom. C); m/z (CI): 616 (4%, [M ϩ NH4]ϩ), 91 (100%,
[C7H7]ϩ); found C 70.75, H 6.78, S 4.87. C37H42O7S requires C,
70.45, H 6.71, S 5.08%.
[M ϩ Na]ϩ 777.2868. C47H46O7S·Na requires 777.2862.
Benzyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α- -galactopyrano-
D
side (3iα): From 1.85 g of 2iα. Yield: 1.24 g; 64%; needles (MeOH);
Cyclohexyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-
D
-glucopyr-
Rf ϭ 0.34 (light petroleum ether/EtOAc, 4:1); m.p. 115Ϫ116 °C.
anoside (3fα): From 1.40 g of 2fα. Yield: 1.33 g; 90%; fine needles [α]2D0 ϭ ϩ112.2 (c ϭ 0.9, CHCl3); νmax/cmϪ1: 3007, 2874, 1496,
˜
(MeOH); Rf ϭ 0.42 (light petroleum ether/EtOAc, 1:1); m.p. 1455, 1332 (SO2), 1209, 1150 (SO2), 1108; δH (270 MHz, CDCl3):
115Ϫ116 °C. [α]2D0 ϭ ϩ79.6 (c ϭ 1.0, CHCl3); νmax/cmϪ1: 3011,
3.46Ϫ3.59 (m, 3 H, 3-H, 6-HA, 6-HB), 3.74 (dd, J2,3 ϭ 9.0, J2,1
2938, 1454, 1302 (SO2), 1216, 1143 (SO2), 1096; δH (270 MHz, 5.8 Hz, 1 H, 2-H), 3.83 (br. d, J4,3 ϭ 2.4 Hz, 1 H, 4-H), 4.13Ϫ4.16
CDCl3): 1.02Ϫ1.25, 1.47Ϫ1.64 (m, 6 H, 4 ϫ 3Ј-H, 2 ϫ 4Ј-H), 1.77 (m, 2 H, SO2CH2Ph), 4.41Ϫ4.78 (m, 8 H, 1-H, 5-H, 6 ϫ benzylic
ϭ
˜
(br. d, J ϭ 10.7 Hz, 1 H, 2Ј-H), 1.86 (br. d, J ϭ 10.7 Hz, 1 H, 2Ј- H), 4.90 (d, J ϭ 9.7 Hz, 1 H, benzylic H), 4.98 (d, J ϭ 11.6 Hz, 1
H), 1.94 (br. d, J ϭ 12.6 Hz, 2 H, 2 ϫ 2Ј-H), 3.21 [tt, J ϭ 12.1, H, benzylic H), 7.23Ϫ7.46 (m, 25 H, 5 ϫ Ph); δC (67.9 MHz,
3.2 Hz, 1 H, SO2CH(CH2)5], 3.54 (dd, J4,5 ϭ 9.9, J4,3 ϭ 8.5 Hz, 1
CDCl3): 56.8 (SO2CH2Ph), 69.2 (C6), 73.1, 73.3, 74.5, 75.6 (4 ϫ
H, 4-H), 3.60, 3.71 (ABX, J6A,6B ϭ 10.5, J6A,5 ϭ 5.1, J6B,5 ϭ 2.0 CH2Ph), 73.65 (ϫ 2), 78.4, 83.4, 88.05 (C1ϪC5); 127.5, 127.6,
Hz, 2 H, 6-HA, 6-HB), 4.08 (dd, J2,3 ϭ 9.2, J2,1 ϭ 6.3 Hz, 1 H, 2- 127.7, 127.9, 128.2, 128.3, 128.5, 128.7, 128.8, 131.6 (arom. CH),
H), 4.40 (ddd, J5,4 ϭ 9.9, J5,6A ϭ 5.1, J5,6B ϭ 2.0 Hz, 1 H, 5-H), 137.55, 137.6, 137.9, 138.2 (subst. arom. C); m/z (CI): 696 (5%, [M
4.44, 4.55 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.44, 4.81 (AB, J ϭ ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found C 72.52, H 6.16, S 4.57.
11.1 Hz, 2 H, CH2Ph), 4.53 (t, J ϭ 9.0 Hz, 1 H, 3-H), 4.71, 4.93 C41H42O5S requires C, 72.54, H 6.24, S 4.72%.
(AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.77, 4.87 (AB, J ϭ 10.6 Hz, 2
Benzyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyrano-
H, CH2Ph), 5.02 (d, J1,2 ϭ 6.3 Hz, 1 H, 1-H), 7.15Ϫ7.39 (m, 20
H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 22.75, 24.8, 25.0, 25.1, 25.9 (5
ϫ cyclohexyl CH2), 59.7 (SO2CH of cyclohexyl), 68.8 (C6), 73.4,
74.0, 74.5, 75.45 (4 ϫ CH2Ph), 75.2, 76.9, 78.4, 80.75, 84.6
(C1ϪC5), 127.6 (ϫ 2), 127.75, 127.8, 128.0, 128.3, 128.35, 128.4,
128.5 (arom. CH), 137.3, 137.7, 138.1, 138.4 (subst. arom. C); m/z
(CI): 688 (8%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ
NH4]ϩ 688.3288. C40H46O7S·NH4 requires 688.3308.
side (3iβ): From 0.67 g of 2jβ. Yield: 0.58 g; 82%; colourless oil;
Rf ϭ 0.34 (light petroleum ether/EtOAc, 1:1). [α]2D0 ϭ ϩ1.9 (c ϭ
0.9, CHCl3); ν˜max/cmϪ1: 3031, 2872, 1496, 1454, 1318 (SO2), 1126,
1101; δH (270 MHz, CDCl3): 3.37, 3.73 (ABX, J6A,6B ϭ 10.2,
J6A,5 ϭ 3.6, J6B,5Ј Hz ϭ 8.0 Hz, 2 H, 6-HA, 6-HA), 3.94 (br. s, 1
H, 4-H), 4.08 (d, J ϭ 13.6 Hz, 1 H, SO2CHAHBPh), 4.38Ϫ4.39,
4.55Ϫ4.79, 4.78Ϫ4.87 (m, 13 H, 1-H, 2-H, 3-H, 5-H, 4 ϫ CH2Ph,
SO2CHAHBPh), 7.15Ϫ7.49 (m, 25 H, 5 ϫ Ph); δC (67.9 MHz,
CDCl3): 57.9 (SO2CH2Ph), 69.0 (C6), 73.4, 73.7, 73.8, 74.2 (4 ϫ
Cyclohexyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyr-
anoside (3fβ): From 0.48 g of 2fβ. Yield: 0.43 g; 85%; fine needles CH2Ph), 74.1, 75.0, 75.1, 77.5, 85.25 (4 ϫ CH2Ph), 127.6, 127.8,
(MeOH); Rf ϭ 0.42 (light petroleum ether/EtOAc, 1:1); m.p. 92Ϫ93 127.9, 128.0, 128.2, 128.3, 128.4, 128.4, 128.6, 128.7, 129.0, 129.3,
°C. [α]2D0 ϭ ϩ18.4 (c ϭ 1.7, CHCl3); ν˜max/cmϪ1: 3009, 2860, 1453,
131.1 (arom. CH), 137.5, 137.7, 137.9, 138.3 (subst. arom. C); m/z
1316
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
FULL PAPER
(CI): 696 (15%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found C 72.52,
H 6.16, S 4.57. C41H42O7S requires C, 72.54, H 6.24, S 4.72%.
Hz, 2 H, CH2Ph), 4.72, 4.85 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.72,
4.88 (AB, J ϭ 11.4 Hz, 2 H, CH2Ph), 4.96 (d, 1 H, J1,2 ϭ 5.8 Hz,
1-H), 7.24Ϫ7.44 (m, 15 H, 3 ϫ Ph); δC (67.9 MHz, CDCl3): Ϫ5.3,
Ϫ5.1 [(CH3)2Si], 18.45 [(CH3)3CSi), 25.9 [(CH3)3CSi], 26.7, 27.4,
27.5, 28.65 (4 ϫ adamantyl CH), 31.6, 32.1, 37.1, 38.9, 39.1 (5 ϫ
adamantyl CH2), 62.2 (C6), 64.5 (SO2CH of adamantyl), 73.9,
74.3, 75.0 (3 ϫ CH2Ph), 76.4, 77.2, 78.3, 80.3, 86.0 (C1ϪC5), 127.6,
127.7, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6 (arom.
CH), 137.5, 138.3, 138.35 (subst. arom. C); m/z (CI): 769 (30%, [M
ϩ Na]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ Na]ϩ 769.3573.
C43H58O7SSi·Na requires 769.3570.
Benzyl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-α-D-mannopyrano-
side (3jα): From 1.05 g of 2jα. Yield: 1.02 g; 93%; colourless oil;
Rf ϭ 0.53 (light petroleum ether/EtOAc, 1:1). [α]2D0 ϭ ϩ66.3 (c ϭ
2.3, CHCl3); νmax/cmϪ1: 3031, 2867, 1496, 1454, 1366, 1314 (SO2),
˜
1110 (SO2), 1027; δH (270 MHz, CDCl3): 3.65Ϫ3.66 (m, 2 H, 6-
HA, 6-HB), 3.88 (t, J ϭ 8.2 Hz, 1 H, 4-H), 4.14 (dd, J2,1 ϭ 7.5,
J2,3 ϭ 3.2 Hz, 1 H, 2-H), 4.37Ϫ4.62 (m, 11 H, 3-H, 5-H, 9 ϫ
benzylic H), 4.75 (d, J ϭ 9.9 Hz, 1 H, benzylic H), 4.75 (d, J1,2
7.5 Hz, 1 H, 1-H), 7.13Ϫ7.39 (m, 25 H, 5 ϫ Ph); δC (67.9 MHz,
CDCl3): 56.6 (SO2CH2Ph), 69.3 (C6), 72.6, 73.0, 73.15, 74.2 (4 ϫ Ethyl S,S-Dioxo-2,3,5-tri-O-benzyl-β-
CH2Ph), 70.8, 73.85, 75.95, 79.0, 86.9 (5 ϫ CH), 126.8, 127.3, 0.62 g of 2lβ. Yield: 0.57 g; 86%; colourless oil; Rf ϭ 0.56 (light
127.4, 127.6, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3, 128.6, 128.8,
petroleum ether/EtOAc, 1:1). [α]2D0 ϭ ϩ39.9 (c ϭ 1.0, CHCl3); ν˜max
130.8, 130.9 (arom. CH), 137.1, 137.9, 137.95, 138.0 (subst. arom. cmϪ1: 3030, 2923, 1497, 1454, 1363, 1312 (SO2), 1136 (SO2), 1085,
ϭ
D
-ribofuranoside (3lβ): From
/
C); m/z (CI): 696 (30%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found 1040; δH (270 MHz, CDCl3): 1.34 (t,
J
ϭ
7.5 Hz,
3
2
H,
H,
ϭ
C 72.41, H 6.15, S 4.73. C41H42O7S requires C, 72.54, H 6.24, S
4.74%.
SO2CH2CH3), 2.97, 3.08 (ABX3, J ϭ 14.7, 7.5 Hz,
SO2CH2CH3), 3.58, 3.67 (ABX, J5A,5B ϭ 10.9, J5A,4 ϭ 6.6, J5B,4
2.9 Hz, 2 H, 5-HA, 5-HB), 4.00 (dd, J3,2 ϭ 8.3, J3,4 ϭ 5.1 Hz, 1 H,
3-H), 4.38 (d, J ϭ 11.4 Hz, 1 H, benzylic H), 4.42Ϫ4.58 (m, 6 H,
2-H, 4-H, 4 ϫ benzylic H), 4.70 (d, J ϭ 11.9 Hz, 1 H, benzylic H),
4.93 (d, J1,2 ϭ 1.5 Hz, 1 H, 1-H), 7.22Ϫ7.41 (m, 15 H, 3 ϫ Ph);
δC (67.9 MHz, CDCl3): 6.15 (SO2CH2CH3), 44.0 (SO2CH2CH3),
70.3 (C5), 72.3, 72.6, 73.2 (3 ϫ CH2Ph), 75.1, 78.35, 82.7, 93.7
(C1ϪC4), 127.6, 128.0, 128.15, 128.3, 128.4, 128.5 (arom. CH),
136.6, 137.1, 137.8 (subst. arom. C); m/z (CI): 514 (100%, [M ϩ
NH4]ϩ); found C 67.42, H 6.59, S 6.52. C28H32O6S requires C,
67.72, H 6.49, S 6.46%.
Benzhydryl S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyr-
anoside (3gβ): Hydrogen peroxide solution (1.2 mL, 35% in water,
12 mmol) was added slowly to a solution of 2gβ (1.19 g, 1.65 mmol)
in acetic acid (15 mL) at 0 °C. The reaction solution was then al-
lowed to warm to room temp. and was stirred overnight. The solv-
ent was removed in vacuo and the residue redissolved in DCM,
washed with water (3 ϫ 50 mL), dried, and concentrated. The
crude product was purified by column chromatography (light pet-
roleum ether/EtOAc, 4:1Ǟ1:1) to give 3gβ as a colourless oil
(0.91 g, 73%); Rf ϭ 0.37 (light petroleum ether/EtOAc, 1:1). [α]2D0
ϩ26.4 (c ϭ 1.7, CHCl3); ν˜max/cmϪ1: 3005, 2868, 1496, 1453 1360, Benzyl
1124, 1067; δH (270 MHz, CDCl3): 3.28 (ddd, J5,4 ϭ 9.8, J5,6A benzyl-β-
6.0 Hz, J5,6B ϭ 2.4, 1 H, 5-H), 3.45 (d, J ϭ 9.7 Hz, 1 H, 1-H), 3.50 solution of the thioglycoside 2k (0.196 g, 0.182 mmol) in DCM
(t, J ϭ 9.7 Hz, 1 H, 4-H), 3.63 (t, J ϭ 9.7 Hz, 1 H, 3-H), 3.68Ϫ3.79 (7 mL) was added Na2HPO4 (0.129 g, 0.91 mmol) followed by
ϭ
S,S-Dioxo-2,3,6-tri-O-benzyl-4-O-(2Ј,3Ј,4Ј,6Ј-tetra-O-
-glucopyranosyl)-1-thio-β- -glucopyranoside (3k): To a
ϭ
D
D
(m, 2 H, 6-HA, 6-HB), 4.05 (t, J ϭ 9.5 Hz, 1 H, 2-H), 4.52, 4.79 mCPBA (0.094 g, 0.54 mmol) and the reaction mixture was stirred
(AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.62 (A2, 2 H, CH2Ph), 4.81, 4.92 overnight. The solution was then diluted with DCM (20 mL),
(AB, J ϭ 10.4 Hz, 2 H, CH2Ph), 4.86 (A2, 2 H, CH2Ph), 5.71 (s, 1
washed with aq. Na2S2O3 (1 , 10 mL), aq. NaOH (1 , 10 mL),
H, CHPh2), 7.13Ϫ7.45, 7.57Ϫ7.60 (m, 30 H, 6 ϫ Ph); δC brine (30 mL), and dried. The crude product obtained on evapora-
(67.9 MHz, CDCl3): 67.1 (SO2CHPh2), 69.2 (C6), 73.4, 75.6, 76.4 tion of the solvent was chromatographed on silica (elution with
(ϫ 2) (4 ϫ CH2Ph), 76.6, 77.7, 79.8, 86.5, 87.4 (C1ϪC5), 127.5,
light petroleum ether/EtOAc, 3:1) to give the 3k as a colourless
foam (0.190 g, 95%), Rf ϭ 0.25 (light petroleum ether/EtOAc, 3:1).
127.6, 127.8, 128.0, 128.1, 128.4, 128.6, 128.7, 129.0, 129.1, 129.5
(arom. CH), 133.9, 135.3, 137.85, 137.95, 138.1, 138.1 (subst. arom. [α]2D0 ϭ ϩ7.9 (c ϭ 1.5, CHCl3); νmax/cmϪ1: 3031, 2909, 1496, 1401,
˜
C); m/z (FAB): 777 (80%, [M ϩ Na]ϩ), 439 (100%).
1361, 1334, 1314 (SO2), 1214, 1149, 1121 (SO2), 1071, 1029; δH
(270 MHz, CDCl3): 3.30Ϫ3.41 (m, 3 H, 5-H, 5Ј-H, 4-H), 3.50Ϫ3.68
(m, 5 H, 3-H, 6-HA, 6-HB, 2Ј-H, 4Ј-H), 3.76 (d, J6Ј,5Ј ϭ 3.4 Hz, 6Ј-
Adamant-2-yl S,S-Dioxo-2,3,4-tri-O-benzyl-6-O-tert-butyldimethyl-
silyl-1-thio-α-D-glucopyranoside (3h): 3-Chloroperoxybenzoic acid
HA, 6Ј-HB, 2 H), 3.94 (t, J ϭ 9.2 Hz, 1 H, 3Ј-H), 4.03 (t, J2,1
ϭ
(1.16 g, 57Ϫ86% purity, 3.83Ϫ5.78 mmol) was added portionwise
to a stirred solution of 2h (0.663 g, 0.93 mmol) in DCM (20 mL)
containing Na2HPO4 (0.66 g, 4.65 mmol) at 0 °C. The reaction
mixture was then stirred at room temp. for 2.5 h after which time
it was diluted with ether (50 mL) and aq. Na2S2O3 (0.1 , 20 mL)
and stirred for a further 0.5 h. The organic layer was separated
and washed with aq. NaOH (1.0 , 20 mL), water (50 mL), brine
(50 mL), dried, and concentrated. The crude product was purified
by column chromatography (light petroleum ether/EtOAc,
9:1Ǟ2:1) to afford 3hα as a colourless syrup (0.481 g, 69%); Rf ϭ
0.37 (light petroleum ether/EtOAc, 2:1). [α]2D0 ϭ ϩ70.9 (c ϭ 0.6,
9.2 Hz, 1 H, 2-H), 4.14 (d, J1,2 ϭ 9.2 Hz, 1 H, 1-H), 4.14 (d, J ϭ
13.6 Hz, 1 H, SO2CHAHBPh), 4.37 (A2, 2 H, CH2Ph), 4.42Ϫ4.56
(m, 5 H, SO2CHAHBPh, 2 ϫ CH2Ph), 4.67Ϫ4.92 (m, 8 H, 1Ј-H, 7
ϫ benzylic H), 5.09 (d, J ϭ 11.4 Hz, 1 H, benzylic H), 7.14Ϫ7.43
(m, 40 H, 8 ϫ Ph); δC (67.9 MHz, CDCl3): 57.0 (SO2CH2Ph), 68.0,
68.8 (C6, C6Ј), 73.2 (ϫ 2), 74.9, 75.1, 75.2, 75.3, 75.7 (CH2Ph),
75.0, 76.0, 76.2, 77.9, 79.6, 82.7, 84.0, 84.9, 87.1 (C1, C2, C3, C4,
C5, C2Ј, C3Ј, C4Ј, C5Ј), 102.7 (C1Ј), 127.3, 127.4 (ϫ 2), 127.5,
127.6, 127.7, 127.8, 128.1, 128.2, 128.3 (ϫ 2), 128.4, 128.7 (ϫ 2),
131.1 (arom. CH), 137.4, 137.8, 138.1, 138.3, 138.4, 138.8 (ϫ 2),
139.2 (subst. arom. C); m/z (FAB): 1133.4 (100%, [M ϩ Na]ϩ), 871
(20%); found [M ϩ Na]ϩ 1133.4487. C68H70O12S·Na requires
1133.4486.
CHCl3); νmax/cmϪ1: 3011, 2862, 1453, 1363, 1301 (SO2), 1096,
˜
1073; δH (270 MHz, CDCl3): 0.03, 0.04 [2 ϫ s, 6 H, Si(CH3)2], 0.88
[s, 9 H, SiC(CH3)3], 1.55Ϫ1.77, 1.84Ϫ1.96 (m, 10 H, 5 ϫ adam-
antyl CH2), 2.35Ϫ2.65 (m, 4 H, 4 ϫ adamantyl CH), 3.48 (br. s, 1 General Procedures for the Ramberg؊Bäcklund Rearrangement of
H, SO2CH of adamantyl), 3.62 (dd, J4,5 ϭ 9.8, J4,3 ϭ 7.8 Hz, 1 H, Glycosyl Sulfones. (i) Chan’s Method: A solution of the glycosyl
4-H), 3.78Ϫ3.85 (m, 2 H, 6-HA, 6-HB), 4.08 (dd, J2,3 ϭ 8.3, J2,1
ϭ
sulfone (0.3 mmol) in DCM (1 mL) was added to a vigorously
5.8 Hz, 1 H, 2-H), 4.21 (dt, J5,4 ϭ 9.8, J5,6A ϭ J5,6B ϭ 2.6 Hz, 1 stirred suspension of KOH/Al2O3 (25% w/w, 3 g) in tBuOH/DCM
H, 5-H), 4.46 (t, J ϭ 8.0 Hz, 1 H, 3-H), 4.62, 4.79 (AB, J ϭ 11.1
Eur. J. Org. Chem. 2002, 1305Ϫ1322
(10:1 mL) in a sealed flask, cooled to 5 °C, and CBr2F2 (10 mmol)
1317

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
added dropwise over a period of 2 min. The mixture was allowed 68.8 (C9), 73.2, 73.4, 74.4, 74.5 (4 ϫ CH2Ph), 77.7, 78.4, 79.3, 85.3
FULL PAPER
to warm to room temp. and was then stirred overnight or until the
starting material had been consumed. The reaction mixture was
then diluted with DCM (20 mL) in order to precipitate potassium
tert-butoxide, filtered through Celite , and the filtrate evaporated
under reduced pressure. The crude product was purified by flash
chromatography (elution with light petroleum ether/EtOAc, 4:1,
with 1% Et3N) to afford the exo-glycal.
(C5ϪC8), 112.6 (C3), 127.3, 127.4, 127.5, 127.6, 127.7, 127.7,
127.8, 127.9, 128.05, 128.3 (ϫ 2), 128.4 (arom. CH), 138.0, 138.1,
138.2, 138.4 (subst. arom. C), 147.45 (C4); m/z (CI): 582 (20%, [M
ϩ
NH4]ϩ), 457 (100%); found [M
C37H40O5·NH4 requires 582.3219.
ϩ
NH4]ϩ 582.3211.
(Z,E)-2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-1-phenyl-D-
gluco-hept-1-enitol (4d). Chan’s Method: From 0.104 g of 3d (α/β ϭ
4:1). Yield: 0.078 g; 83% (Z/E ϭ 88:12); colourless oil; Rf ϭ 0.30
(ii) Meyers Method: Powdered potassium hydroxide (3 g,
53.5 mmol) was added to a stirred mixture of tBuOH (6 mL) and
water (1.5 mL) at 60 °C. After the base had dissolved, a solution
of the glycosyl sulfone (0.3 mmol), in CCl4 (6 mL) was added, and
the biphasic mixture was stirred at 60 °C for 1 h. After cooling to
room temp., the lower aqueous layer was removed and the organic
phase was washed with brine, dried, and the solvent removed in
vacuo. Purification by column chromatography (elution with light
petroleum ether/EtOAc, 4:1 with 1% Et3N) afforded the exo-glycal.
(light petroleum ether/EtOAc, 3:1); νmax/cmϪ1: 3030, 2866, 1669
˜
(CϭC), 1495, 1453, 1088; δH (270 MHz, CDCl3): (Z)-isomer,
3.76Ϫ3.91 (m, 4 H, 4-H, 5-H, 7-HA, 7-HB), 4.04 (br. d, J3,4 ϭ 4.6
Hz, 1 H, 3-H), 4.11 (ddd, J6,5 ϭ 9.7, J6,7A ϭ 4.2, J6,7B ϭ 1.9 Hz,
1 H, 6-H), 4.56, 4.77 (AB, J ϭ 11.4 Hz, 2 H, CH2Ph), 4.59, 4.66
(AB, J ϭ 12.1 Hz, 2 H, CH2Ph), 4.62, 4.79 (AB, J ϭ 11.6 Hz, 2
H, CH2Ph), 4.66, 4.79 (AB, J ϭ 11.4 Hz, 2 H, CH2Ph), 5.73 (s, 1
H, 1-H), 7.16Ϫ7.40 (m, 23 H, 23 ϫ arom. H), 7.67Ϫ7.71 (m, 2 H,
2 ϫ arom. H); (E)-isomer (selected data) 6.48 (s, 1 H, 1-H); δC
(67.9 MHz, CDCl3): (Z)-isomer, 69.1 (C7), 71.7, 73.5 (ϫ 2), 74.0
(4 ϫ CH2Ph), 76.9, 77.8, 79.2, 84.5 (C3, C4, C5, C6), 109.5 (C1),
126.3, 127.6, 127.7, 127.8 (ϫ 2), 127.9 (ϫ 2), 128.1, 128.3, 128.4,
128.5, 128.7 (arom. CH), 135.1, 137.9, 138.1, 138.2 (subst. arom.
C); m/z (CI): 630 (70%, [M ϩ NH4]ϩ), 612 (20%, [M ϩ H]ϩ), 505
(85%), 415 (25%), 399 (35%), 91 (100%, [C7H7]ϩ). Meyers’ Method:
From 0.125 g 3d (α/β ϭ 4:1) was obtained 0.063 g 4d; 56%
(Z/E ϭ 88:12).
2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-
tol[7b,8] (4a) and (Z,E)-2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-bromo-
1-deoxy- -gluco-hept-1-enitol (4m). Chan’s Method: From 0.108 g
D-gluco-hept-1-eni-
D
of 3a (α/β ϭ 3:1). Yield: 0.54 g of 4a; 54%; fine needles (hexane);
Rf ϭ 0.31 (light petroleum ether/EtOAc, 4:1); m.p. 66.5Ϫ67 °C,
ref.[8] 65Ϫ68 °C. [α]2D0 ϭ ϩ62.3 (c ϭ 1.0, DCM), ref.[8] ϩ58.4 (c ϭ
1.0, DCM) and 0.017 g of 4m; 15%; colourless oil; Rf ϭ 0.61 (light
petroleum ether/EtOAc, 4:1); δH (270 MHz, CDCl3): (Z)-isomer:
3.59Ϫ3.78 (m, 3 H, 5-H, 7-HA, 7-HB), 3.88 (d, J3,4 ϭ 5.3 Hz, 1 H,
3-H), 3.97 (br. d, J6,5 ϭ 9.7 Hz, 1 H, 6-H), 4.34Ϫ4.68 (m, 9 H, 4
ϫ CH2Ph, 4-H), 5.46 (s, 1 H, 1-H), 7.07Ϫ7.32 (m, 20 H, 4 ϫ Ph);
(E)-isomer (selected data): 3.82 (td, J ϭ 4.9, 1.7 Hz, 1 H, 6-H),
4.77Ϫ4.81 (m, 1 H, benzylic H), 5.86 (s, 1 H, 1-H), 7.15Ϫ7.39 (m,
20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): (Z)-isomer: 68.3 (C7), 70.3,
73.4, 73.5, 74.0 (CH2Ph), 77.2, 77.8, 83.75, 86.7 (C3, C4, C5, C6),
127.5, 127.75, 127.8, 127.95, 128.2, 128.3, 128.4, 128.5 (arom. CH),
137.3, 137.4, 137.8, 137.9, 138.2 (subst. arom. C), 151.05 (C2);
m/z (CI): 582 (1%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ
NH4]ϩ 632.2012. C35H35BrO5·NH4 requires 632.2012. Meyers’
Method: From 0.100 g of 3a (α/β ϭ 3:1). Yield: 0.64 g 4a; 72%.
3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-2-methyl-D-gluco-
octit-2-enitol (4e). Meyers’ Method: From 0.132 g of 3e (α/β ϭ 3:1).
Yield: 0.061 g; 51%; colourless oil; Rf ϭ 0.56 (light petroleum ether/
EtOAc, 4:1); νmax/cmϪ1: 3030, 2958, 1662 (CϭC), 1488, 1453, 1361,
˜
1090, 1072; δH (270 MHz, CDCl3): 1.60 (s, 3 H, CH3), 1.76 (s, 3
H, CH3), 3.66 (dd, J6,7 ϭ 9.9, J6,5 ϭ 5.3 Hz, 1 H, 6-H), 3.72Ϫ3.75
(m, 2 H, 8-HA, 8-HB), 3.91 (dd, J5,4 ϭ 8.1, J5,6 ϭ 5.3 Hz, 1 H, 5-
H), 4.30 (ddd, J7,6 ϭ 9.9, J7,8A ϭ 4.1 Hz, J7,8B ϭ 2.4, 1 H, 7-H),
4.37 (d, J ϭ 12.4 Hz, 1 H, benzylic H), 4.42 (d, J ϭ 2.2 Hz, 1 H,
4-H), 4.49Ϫ4.68 (m, 7 H, 7 ϫ benzylic H), 7.19Ϫ7.37 (m, 20 H, 4
ϫ Ph); δC (67.9 MHz, CDCl3): 17.7, 18.9 [(CH3)2CϭC], 69.5 (C8),
70.15, 72.2, 73.5, 73.8 (4 ϫ CH2Ph), 72.8, 74.7, 78.5, 83.25
(C4ϪC7), 114.25 (C2), 127.25, 127.4, 127.8, 128.0, 128.25, 128.4,
128.7, 128.75, 128.9, 129.0, 129.2, 129.4, 129.7, 129.8 (arom. CH),
138.4, 138.8, 138.9, 139.1 (subst. arom. C), 140.4 (C3); m/z (CI):
582 (1%, [M ϩ NH4]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ NH4]ϩ
582.3217. C37H40O5·NH4 requires 582.3219.
(Z,E)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-D-gluco-oc-
tit-2-enitol (4b). Chan’s Method: From 0.205 g of 3b (α/β ϭ 4:1).
Yield: 0.138 g of 4b; 75% (Z/E ϭ 80:20); colourless oil; Rf ϭ 0.58
(light petroleum ether/EtOAc, 4:1); ν˜max/cmϪ1: 3030, 2958, 1662
(CϭC), 1488, 1453, 1361, 1090, 1072; δH (270 MHz, CDCl3): 1.68
(dd, J ϭ 6.8, 1.5 Hz, 3 H, CH3CHϭ), 3.64Ϫ3.83 (m, 5 H, 4-H, 5-
H, 6-H, 8-HA, 8-HB), 3.89Ϫ3.94 (m, 1 H, 7-H), 4.50Ϫ4.87 (m, 8
H, 4 ϫ CH2Ph), 5.02 (qd, J ϭ 6.0, 1.2 Hz, 1 H, 2-H, Z isomer),
7.14Ϫ7.37 (m, 20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 9.7 (CH3),
68.9 (C8), 72.4, 73.4, 74.2, 74.4 (4 ϫ CH2Ph), 77.8, 77.9, 79.2, 85.1
(C4ϪC7), 104.9 (C2), 127.3, 127.5, 127.6 (ϫ 2), 127.7, 127.8, 127.9,
128.1, 128.3 (ϫ 2), 128.4 (ϫ 2), 128.5 (arom. CH), 138.0, 138.1,
138.3, 138.3 (subst. arom. C), 148.4 (C3); m/z (CI): 582 (1%, [M ϩ
NH4]ϩ), 91 (100%, [C7H7]ϩ); found [M ϩ NH4]ϩ 582.3217.
C36H38O5·NH4 requires 582.3219.
2,3,4,6-Tetra-O-benzyl-
yers’ Method: From 0.174 g of 3f (α/β ϭ 4:1). Yield: 0.051 g; 32%;
colourless oil; Rf ϭ 0.52 (light petroleum ether/EtOAc, 4:1); ν˜max
cmϪ1
3030, 3009, 2960, 2936, 1665, 1492, 1451, 1361; δH
D-glucopyranosylidene cyclohexane (4f). Me-
/
:
(270 MHz, CDCl3): 1.35Ϫ1.55 (br. s, 6 H, 2 ϫ 3Ј-H, 2 ϫ 4Ј-H, 2
ϫ 5Ј-H), 1.91Ϫ2.04 (2 H, 2Ј-Hax, 6Ј-Hax), 2.20Ϫ2.38 (2 H, 2Ј-Heq,
6Ј-Heq), 3.59 (dd, J4,5 ϭ 9.9, J4,3 ϭ 5.6 Hz, 1 H, 4-H), 3.55Ϫ3.66
(m, 2 H, 6-HA, 6-HB), 3.84 (dd, J3,4 ϭ 5.6, J3,2 ϭ 2.2 Hz, 1 H, 3-
H), 4.21 (dt, J5,4 ϭ 9.9, J5,6 ϭ 2.9 Hz, 1 H, 5-H), 4.29 (d, J ϭ 12.1
(Z,E)-4,8-Anhydro-5,6,7,9-tetra-O-benzyl-1,2,3-trideoxy-
D-gluco- Hz, 1 H, benzylic H), 4.37 (d, J2,3 ϭ 2.2 Hz, 1 H, 2-H), 4.42Ϫ4.62
non-3-entitol (4c). Chan’s Method: From 0.201 g of 3c (α/β ϭ 4:1). (m, 7 H, 7 ϫ benzylic H), 7.12Ϫ7.28 (m, 20 H, 4 ϫ Ph); δC
Yield: 0.135 g; 75% (Z/E ϭ 92:8); colourless oil; Rf ϭ 0.59 (light
(67.9 MHz, CDCl3): 26.7, 26.8, 27.4, 28.4, 28.9 (CϭC(CH2)5], 68.9,
69.7, 71.7, 73.1, 73.3 (C6, 4 ϫ CH2Ph), 72.0, 74.4, 77.9, 82.9
(C2ϪC5), 122.6 (CϭC(CH2)5], 127.3 127.5, 127.7, 127.8, 127.9,
petroleum ether/EtOAc, 4:1); νmax/cmϪ1: 3006, 2964, 1603 (CϭC),
˜
1497, 1458, 1362, 1272, 1089; δH (270 MHz, CDCl3): 0.90 (t, J ϭ
7.5 Hz, 3 H, CH2CH3), 2.05Ϫ2.14 (m, 2 H, CH2CH3), 3.57Ϫ3.74 128.2, 128.3, 128.4 (arom. CH), 137.2 (C1), 138.0, 138.4, 138.5,
(m, 5 H) 3.84 (d, J ϭ 7.5 Hz, 1 H, 8-H), 4.41Ϫ4.85 (m, 8 H, 4 ϫ 138.6 (subst. arom. C): m/z (CI): 622 (3%, [M ϩ NH4]ϩ), 90 (100%,
CH2Ph), 4.92 (br. t, J ϭ 7.5 Hz, 1 H, 3-H, Z-isomer), 7.06Ϫ7.26 [C7H7]ϩ); found [M ϩ NH4]ϩ 605.3267. C40H44O5·NH4 requires
(m, 20 H, 4 ϫ Ph); δC (67.9 MHz, CDCl3): 14.5 (C1), 17.7 (C2), 605.3267.
1318
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
FULL PAPER
2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-1,1-diphenyl-
hept-1-enitol (4g). Chan’s Method: From 0.160 g of 3g (α/β ϭ 4:1). (C7, 4 ϫ CH2Ph), 74.3, 75.0, 79.7, 81.8 (C3ϪC6), 114.9 (C1),
Yield: 0.061 g; 57%; colourless oil; Rf ϭ 0.57 (light petroleum ether/ 127.1, 127.5, 127.6, 127.8, 127.9, 128.15, 128.3, 128.9 (arom. CH),
D
-gluco-
25 H, 5 ϫ Ph); δC (67.9 MHz, CDCl3): 69.2, 69.8, 71.4, 73.3, 75.1
EtOAc, 4:1); νmax/cmϪ1: 3066, 2871, 1454, 1365, 1313, 1108, 1083, 134.45, 138.06, 138.12, 138.34, 138.38 (subst. arom. C), 148.45
1027; δH (270 MHz, CDCl3): 3.79Ϫ3.90 (m, 4 H, 4-H, 5-H, 7-HA, (C2); m/z (CI): 630 (35%, M ϩ [NH4]ϩ), 108 (100%); found C
7-HB), 4.20, 4.62 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.26, 4.34 (AB, 80.01, H 6.61. C41H40O5 requires C, 80.37, H 6.58%.
J ϭ 11.6 Hz, 2 H, CH2Ph), 4.40 (br. s, 1 H, 3-H), 4.45, 4.51 (AB,
˜
(Z,E)-1-Phenyl-2,6-anhydro-3,4,7-tri-O-benzyl-5-O-(2Ј,3Ј,4Ј,6Ј-
J ϭ 12.4 Hz, 2 H, CH2Ph), 4.58, 4.66 (AB, J ϭ 11.4 Hz, 2 H,
tetra-O-benzyl-β-D-glucopyranosyl)-1-deoxy-D-gluco-hept-1-enitol
CH2Ph), 4.60Ϫ4.66 (m, 1 H, 6-H), 7.08Ϫ7.33, 7.44Ϫ7.48 (m, 30
H, 6 ϫ Ph); δC (67.9 MHz, CDCl3): 69.3, 69.6, 70.9, 73.05, 73.4
(C7, 4 ϫ CH2Ph), 72.7, 74.4, 78.3, 83.0 (C3ϪC6), 122.5 (C1),
126.1, 126.7, 127.2, 127.2, 127.4, 127.5, 127.8, 127.85, 127.9, 128.1,
128.2, 128.25, 128.35, 130.0, 130.2, 131.4 (arom. CH), 137.6, 138.0,
138.3, 138.7, 139.1, 140.5 (subst. arom. C), 144.95 (C2); m/z (CI):
706 (25%, [M ϩ NH4]ϩ), 108 (100%); found [M ϩ NH4]ϩ 706.3539.
C47H44O5·NH4 requires 706.3532.
(4k). Chan’s Method: From 0.086 g of 3k. Yield: 0.064 g; 80% (Z/
E ϭ 87:13); white solid; Rf ϭ 0.39 (light petroleum ether/EtOAc,
3:1); νmax/cmϪ1: 3029, 2909, 1660 (CϭC), 1600 (CϭC), 1496, 1454,
˜
1210, 1181, 1150, 1071, 1028; δH (270 MHz, CDCl3): 3.31Ϫ3.37
(m, 1 H), 3.44 (t, J ϭ 9.0 Hz, 1 H), 3.55Ϫ3.73 (m, 6 H), 3.81 (br.
s, 2 H), 3.96Ϫ4.02 (m, 2 H,), 4.14 (dd, J ϭ 9.9 Hz, 1 H), 4.34Ϫ4.94
(m, 20 H), 5.51 (s, 1 H, 1-H, Z-isomer), 6.43 (s, 1 H, 1-H, E-iso-
mer), 7.14Ϫ7.34 (m, 50 H, 50 ϫ arom. H), 7.66Ϫ7.69 (m, 2 H, 2
ϫ arom. H); δC (67.9 MHz, CDCl3): 68.6, 68.7 (C7, C6Ј), 70.4,
72.3, 73.2, 73.3, 74.9 (ϫ 2), 75.6, (CH2Ph), 74.8, 75.6, 77.7, 77.9,
78.6, 81.8, 82.4, 84.8 (C3, C4, C5, C6, C2Ј, C3Ј, C4Ј, C5Ј), 103.6
(C1Ј), 109.2 (C1), 126.1, 126.9, 127.3, 127.5 (ϫ 2), 127.6, 127.7,
127.8 (ϫ 2), 128.1, 128.2, 128.2, 128.3 (ϫ 2), 128.6 (arom. CH),
129.0, 135.4, 137.9, 138.1, 138.2, 138.3, 138.5, 138.7 (subst. arom.
C), 148.1 (C2); m/z (FAB): 1068 (95%, [M ϩ Na]ϩ), 181 (100%);
found [M ϩ Na]ϩ 1067.4707. C68H68O10·Na requires 1067.4710.
2-(2,3,4-Tri-O-benzyl-6-O-tert-butyldimethylsilyl-α-D-glucopyra-
nosylidene)-adamantane (4h). Meyers’ Method: From 0.156 g of 3h.
Yield: 0.029 g; 20%; colourless oil; Rf ϭ 0.67 (light petroleum ether/
EtOAc, 4:1); ν˜max/cmϪ1: 3032, 2925, 1676 (CϭC), 1454, 1363, 1193,
1096, 1085; δH (270 MHz, CDCl3): 0.098, 0.103 (2 ϫ s, 6 H, 2 ϫ
CH3Si), 0.92 [s, 9 H, (CH3)3CSi], 1.69Ϫ2.05 (m, 12 H, 5 ϫ CH2, 2
ϫ CH, adamantyl), 2.52Ϫ2.58 (br. s, 1 H, allylic CH, adamantyl),
3.35Ϫ3.43 (br. s, 1 H, allylic CH, adamantyl), 3.73 (dd, J4,5 ϭ 9.9,
J4,3 ϭ 6.0 Hz, 1 H, 4-H), 3.91Ϫ3.93 (m, 2 H, 6-HA, 6-HB), 3.95
(dd, J3,4 ϭ 6.0, J3,2 ϭ 1.9 Hz, 1 H, 3-H), 4.14Ϫ4.19 (m, 1 H, 5-H),
4.39, 4.69 (AB, J ϭ 12.1 Hz, 2 H, CH2Ph), 4.44 (d, J2,3 ϭ 1.9 Hz,
1 H, 2-H), 4.54, 4.62 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph), 4.67, 4.76
(AB, J ϭ 11.4 Hz, 2 H, CH2Ph), 7.28Ϫ7.37 (m, 15 H, 3 ϫ Ph); δC
(67.9 MHz, CDCl3): Ϫ5.4, Ϫ5.3 [(CH3)2Si], 18.3 [(CH3)3CSi], 25.9
[(CH3)3CSi], 28.2, 28.35, 29.2, 31.9 (4 ϫ adamantyl CH), 37.1, 38.4,
38.8, 39.5, 39.75 (5 ϫ adamantyl CH2), 62.2 (C6), 68.9, 71.6, 73.5
(3 ϫ CH2Ph), 72.2, 75.0, 77.8, 83.9 (C2ϪC5), 127.4, 127.6, 127.9,
128.2, 128.3, 128.3 (arom. CH), 129.8 (OϪCϭC), 134.2 (C1),
138.15, 138.6, 138.75 (subst. arom. C); m/z (FAB): 703 (100%, [M
ϩ Na]ϩ); found [M ϩ Na]ϩ 769.3573. C43H56O5Si·Na requires
769.3570.
(Z,E)-3,6-Anhydro-4,5,7-tri-O-benzyl-1,2-dideoxy-D-ribo-hept-2-
enitol (4l). Chan’s Method: From 0.152 g of 3l. Yield: 0.138 g; 75%
(Z/E ϭ 50:50); colourless oil; Rf ϭ 0.54 (light petroleum ether/
EtOAc, 4:1); νmax/cmϪ1: 3032, 2925, 2853, 1676 (CϭC), 1496, 1454,
˜
1363, 1259, 1193, 1085; δH (270 MHz, CDCl3): 1.63, 1.67 (2 ϫ d,
J ϭ 8 Hz, 6 H, 2 ϫ CH3CHϭ), 3.46Ϫ3.61 (m, 2 H), 3.73 (d, J ϭ
8 Hz, 2 H), 3.91Ϫ4.00 (m, 2 H), 4.09 (d, J ϭ 4 Hz, 1 H), 4.33Ϫ4.88
(m, 16 H), 5.06 (q, J ϭ 7 Hz, 1 H, 2-H, E-isomer) 7.19Ϫ7.38 (m,
30 H, 3 ϫ Ph); δC (67.9 MHz, CDCl3): 9.9, 12.4 (2 ϫ CH3), 68.8,
69.0, 69.35, 70.1, 71.8, 72.2, 73.2, 73.25 (2 ϫ C7, 6 ϫ CH2Ph),
71.4, 74.7, 76.9, 77.65, 79.8, 81.0 [2 ϫ (C3ϪC5)], 97.5, 98.3 (2 ϫ
C2), 127.5 (ϫ 2), 127.6, 127.75, 127.8, 127.9 (ϫ 2), 128.2, 128.3
(arom. CH), 137.4, 137.5, 138.0 (ϫ 2), 138.1, 138.3 (subst. arom.
Na]ϩ 453.2057.
(Z,E)-2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-1-phenyl-D-
C), 152.2, 153.0 (2
ϫ C3); found [M ϩ
galacto-hept-1-enitol (4i). Chan’s Method: From 0.280 g of 3i (α/β ϭ
1:6). Yield: 0.210 g; 83% (Z/E ϭ 62:38); colourless oil; Rf ϭ 0.46
(light petroleum ether/EtOAc, 4:1); ν˜max/cmϪ1: 3029, 2868, 1660
(CϭC), 1496, 1454, 1364, 1312, 1108, 1096; δH (270 MHz, CDCl3):
3.58Ϫ3.92, 4.01Ϫ4.15 (m, 6 H, 3-H, 4-H, 5-H, 6-H, 7-HA, 7-HB),
4.38Ϫ4.49 (m, 2 H, CH2Ph), 4.62 (d, J ϭ 11.6 Hz, 1 H, benzylic
H), 4.69Ϫ4.82 (m, 4 H, 2 ϫ CH2Ph), 4.92 (d, J ϭ 11.6 Hz, 1 H,
benzylic H), 5.97 (s, 1 H, 1-H), 7.13Ϫ7.39, 7.67Ϫ7.70 (m, 25 H, 5
ϫ Ph); δC (67.9 MHz, CDCl3): 69.2 (C7), 72.9, 73.2, 73.5, 74.0 (4
ϫ CH2Ph), 74.2, 77.3, 78.2, 81.4 (C3ϪC6), 110.8 (C1), 126.4, 127.0,
127.4, 127.5, 127.5, 127.6, 127.8, 127.9 (ϫ 2), 128.1, 128.2, 128.3,
128.35, 128.8, 129.3, 129.6 (arom. CH), 135.0, 137.8, 138.0, 138.2,
138.4 (subst. arom. C), 150.1 (C2); m/z (CI): 630 (30%, M ϩ
[NH4]ϩ), 108 (100%); found [M ϩ NH4]ϩ 630.3218. C41H40O5·NH4
requires 630.3219.
C28H30O4·Na requires 453.2066.
Benzyl 2,3,4,6-Tetra-O-acetyl-1-thio-β-
D
-glucopyranoside[39] (7β):
Tin(IV) chloride (0.99 mL, 8.45 mmol) was added to a solution
containing α--glucose pentaacetate (3.00 g, 7.69 mmol) and
benzyl mercaptan (1.80 mL, 15.37 mmol) in dry DCM (150 mL) at
Ϫ30 °C and the resulting mixture was allowed to warm to room
temp. and was stirred overnight. The reaction was quenched with
brine (30 mL), extracted with DCM (2 ϫ 50 mL), the organic parts
washed with satd. aq. NaHCO3 (30 mL), then with brine (30 mL),
and dried. The solvent was evaporated in vacuo and purified by
flash chromatography (light petroleum ether/EtOAc, 3:1Ǟ1:1) to
yield first an equimolar mixture of 7α and 7β as a colourless oil
(2.39 g, 68%). Recrystallisation of the product mixture from ether
gave pure 7β as colourless needles (0.933 g, 27%), Rf ϭ 0.45 (light
petroleum ether/EtOAc, 1:1); m.p. 101.5Ϫ103 °C, ref.[39] 103Ϫ104
°C. [α]2D0 ϭ Ϫ95.4 (c ϭ 1.0, CHCl3), ref.[39] Ϫ84.4 (c ϭ 1.1, CHCl3).
(Z)-2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-1-phenyl-D-manno-
hept-1-enitol (4j). Chan’s Method: From 0.200 g of 3jα. Yield:
0.17 g; 94%; colourless oil; Rf ϭ 0.50 (light petroleum ether/EtOAc,
Benzyl
S,S-Dioxo-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyrano-
4:1); νmax/cmϪ1: 3031, 2871, 1454, 1365, 1109, 1084, 1027; δH side[28] (8): Oxone (1.61 g, 2.62 mmol) was added to a solution of
(270 MHz, CDCl3): 3.72Ϫ3.91 (m, 4 H, 4-H, 6-H, 7-HA, 7-HB), the thioglycoside 7β (0.20 g, 0.44 mmol) in a mixture of THF,
˜
4.11 (d, J ϭ 3.0 Hz, 1 H, 3-H) and 4.22 (t, J ϭ 9.0 Hz, 1 H, 5-H),
4.48 (d, J ϭ 12.5 Hz, 1 H, benzylic H), 4.55Ϫ4.72 (m, 5 H, 5 ϫ overnight at room temp. The bulk of the organic solvents was evap-
benzylic H), 4.80 (d, J ϭ 13.0 Hz, 1 H, benzylic H) and 4.99 (d, orated under reduced pressure and brine (50 mL) added to the res-
J ϭ 10.0 Hz, 1 H, benzylic H), 5.57 (s, 1 H, 1-H), 7.18Ϫ7.70 (m, idue which was then extracted with EtOAc (3 ϫ 50 mL), washed
MeOH, and water (18:6:6 mL) at 5 °C and the mixture was stirred
Eur. J. Org. Chem. 2002, 1305Ϫ1322
1319

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
FULL PAPER
with water, dried, and concentrated in vacuo to give a white solid. SiC(CH3)3], 25.7 (ϫ 2), 25.8, (ϫ 2) [4 ϫ SiC(CH3)3], 62.3 (C7),
Recrystallisation from MeOH furnished pure 8 as colourless 72.6, 74.8, 77.2, 77.6 (C3, C4, C5, C6), 106.4 (C1), 125.2, 127.8 (ϫ
needles (0.155 g, 72%), Rf ϭ 0.32 (light petroleum ether/EtOAc, 2), 128.3 (ϫ 2) (arom. CH), 136.5 (subst. arom. C), 151.6 (C2);
1:1); m.p. 198Ϫ200 °C, ref.[28] 199 °C. [α]2D0 ϭ Ϫ46.9 (c ϭ 1.0,
CHCl3), ref.[28] Ϫ44.6 (c ϭ 2, CHCl3).
m/z (FAB): 731.5 (40%, [M ϩ Na]ϩ), 445 (20%), 176 (100%); found
[M ϩ Na]ϩ 731.4349. C37H72O5Si4·Na requires 731.4355.
Benzyl S,S-Dioxo-1-thio-2,3,4,6-tetra-O-(tert-butyldimethylsilyl)-β-
(Z)-2,6-Anhydro-3,4,5,7-tetra-O-acetyl-1-deoxy-1-phenyl-D-gluco-
D
-glucopyranoside (9): A methanolic solution of sodium methoxide
hept-1-enitol (12): A THF solution of tetra-n-butylammonium flu-
oride (1 , 2.20 mL, 2.20 mmol) was slowly added to a solution of
(25% w/w, 0.02 mL, 0.1 mmol) was added to a solution of the sul-
fone 8 (0.50 g, 1.03 mmol) in MeOH (20 mL) and the mixture was the alkene 10 (0.19 g, 0.27 mmol) in THF (15 mL) at 5 °C and the
stirred for 2 h. Amberlyst 15 ion-exchange resin was then added
until the pH of the solution became neutral, the resin was removed
resultant yellow solution was stirred for 1 h at room temp. The
solution was then treated with Ac2O (0.20 mL, 2.1 mmol) and
by filtration and the filtrate evaporated in vacuo, triturated with DMAP (0.010 g, 0.08 mmol) and stirred for 2 h. The solvent was
DCM, and dried thoroughly under high vacuum to give a colour-
less oil which was used in the next step without further purification.
A suspension of the crude, deprotected sulfone (0.324 g) in DCM
removed in vacuo and the residue chromatographed on a short alu-
mina column (elution with light petroleum ether/EtOAc, 4:1) to
afford 12 as a white crystalline solid (0.065 g, 57% over two steps),
(3 mL) was treated with 2,6-lutidine (0.95 mL, 8.1 mmol) followed Rf ϭ 0.38 (light petroleum ether/EtOAc, 1:1); m.p. 112Ϫ113 °C.
by tert-butyldimethylsilyl trifluoromethanesulfonate (1.4 mL,
6.1 mmol) and the mixture was stirred for 6 h. The solvent was
evaporated under reduced pressure and the residue was partitioned
[α]2D0 ϭ ϩ109.8 (c ϭ 1.0, CHCl3); ν˜max/cmϪ1: 3025, 2930, 1755 (Cϭ
O), 1676 (CϭC), 1495, 1449, 1371, 1220, 1040; δH (270 MHz,
CDCl3): 2.07 (ϫ 2), 2.13, 2.18 (12 H, 4s, CH3CO), 4.12 (m, 1 H,
between ether (100 mL) and brine (75 mL). A further extraction 6-H), 4.27Ϫ4.39 (m, 2 H, 7-HA, 7-HB), 5.16Ϫ5.24 (m, 2 H, 4-H,
with ether (2 ϫ 50 mL), followed by washing with 5% aq. CuSO4 5-H), 5.53Ϫ5.56 (m, 1 H, 3-H), 5.76 (d, J1,3 ϭ 0.5 Hz, 1 H, 1-H),
(2 ϫ 30 mL), satd. aq. NaHCO3, then with brine (30 mL), drying, 7.20Ϫ7.35 (m, 3 H, 2 ϫ arom. H), 7.60Ϫ7.64 (m, 2 H, 2 ϫ arom.
and column chromatography on neutral alumina (light petroleum H); δC (67.9 MHz, CDCl3): 20.6, 20.7 (ϫ 2), 20.9 (CH3CO), 62.3
ether/EtOAc, 9:1) afforded 9 as a colourless oil (0.761 g, 96% over
(C7), 68.7, 70.2, 73.4, 75.1 (C3, C4, C5, C6), 111.4 (C1), 127.3,
128.3, 129.0 (arom. CH), 133.8 (subst. arom. C), 145.6 (C2), 169.0,
two steps), Rf ϭ 0.53 (light petroleum ether/EtOAc, 4:1). [α]2D0
ϭ
Ϫ32.3 (c ϭ 1.0, CHCl3); ν˜max/cmϪ1: 2928, 2858, 1472, 1463, 1361, 169.4, 169.8, 170.6 (CH3CO); m/z (CI): 438 (75%, [M ϩ NH4]ϩ),
1330 (SO2), 1259 (C-Si), 1152 (SO2), 1105; δH (270 MHz, CDCl3):
0.06 (ϫ 2), 0.07, 0.10, 0.12, 0.13 (ϫ 2), 0.17 [8 ϫ s, 24 H, 4 ϫ 420.1423. C21H24O9·NH4 requires 420.1420; found C 59.49, H 5.84.
378 (30%), 361 (27%), 301 (100%), 243 (30%); found [M ϩ NH4]ϩ
Si(CH3)2], 0.83, 0.88, 0.94, 0.95 [4 ϫ s, 36 H, 4 ϫ SiC(CH3)3],
3.66Ϫ3.71 (m, 1 H, 5-H), 3.75Ϫ3.87 (m, 4 H, 3-H, 4-H, 6-HA, 6-
HB), 4.14, 4.49 (AB, J ϭ 13.6 Hz, 2 H, SO2CH2Ph), 4.29 (br. d,
J2,1 ϭ 6.0 Hz, 1 H, 2-H), 4.38 (d, J1,2 ϭ 6.0 Hz, 1 H, 1-H),
7.36Ϫ7.39 (m, 3 H, 3 ϫ arom. H), 7.44Ϫ7.48 (m, 2 H, 2 ϫ arom.
H); δC (67.9 MHz, CDCl3): Ϫ5.3, Ϫ5.2, Ϫ5.1, Ϫ4.9, Ϫ4.4, Ϫ4.2,
Ϫ4.1, Ϫ3.0 [4 ϫ Si(CH3)2], 17.8 (ϫ 2), 18.0, 18.4 [4 ϫ SiC(CH3)3],
25.7, 25.8 (ϫ 2), 25.9, 26.0 [4 ϫ SiC(CH3)3], 56.4 (C6), 64.1
(SO2CH2Ph), 69.7, 70.2, 77.2, 82.8, 89.1 (C1, C2, C3, C4, C5),
128.0 (subst. arom. C) 128.6 (ϫ 2), 128.7), 131.0 (ϫ 2), (arom. CH);
m/z (FAB): 798 (40%, [M ϩ Na]ϩ), 487 (20%), 329 (50%); found
[M ϩ Na]ϩ 797.4126. C37H74O7SSi4·Na requires 797.4130.
C21H24O9 requires C, 59.99, H 5.75%.
(S)-(Phenylbromomethyl) S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-
α-
D-glucopyranoside (13a) and (R)-(Phenylbromomethyl) S,S-Dioxo-
2,3,4,6-tetra-O-benzyl-1-thio-α-
D-glucopyranoside (13b): A solution
of the sulfone 3dα (0.250 g, 0.39 mmol) in DCM (2 mL) was added
to a vigorously stirred suspension of KOH/Al2O3 (25% w/w, 0.5 g)
in tBuOH/DCM (8:2 mL) at 5 °C followed after 10 min by 3 ali-
quots of CBr2F2 (1 mL, 10.9 mmol each). The mixture was stirred
for 30 min before the addition of more KOH/Al2O3 (1.1 g in 3
portions) and CBr2F2 (5 mL, 43.8 mmol in 2 portions). After a
further 90 min the reaction was diluted with DCM, filtered through
Celite , and the filtrate concentrated in vacuo. Column chromato-
(Z,E)-2,6-Anhydro-1-deoxy-3,4,5,7-tetra-O-(tert-butyldimethyl- graphy of the residue (light petroleum ether/EtOAc, 5:1) gave three
silyl)-1-phenyl- -gluco-hept-1-enitol (10): To a solution of the sul- fractions. The first contained 4d as a colourless oil (0.039 g, 22%,
D
fone 9 (0.30 g, 0.39 mmol) in DCM (1 mL) was added tBuOH Z/E ϭ 94:6). The second fraction contained the α-bromosulfone
(5 mL) followed by KOH/Al2O3 (25% w/w, 4 g) and the mixture (0.080 g, 36%, 1:1 mixture of diastereomers) which was further
was cooled to 5 °C. The flask was sealed with a septum and 3
purified by column chromatography (elution with DCM/light pet-
aliquots of CBr2F2 (1 mL, 10.9 mmol each) were added over a
roleum ether 5:1) to give 13a as a colourless oil (0.040 g), Rf ϭ 0.41
period of 3 h. and the mixture was stirred overnight. Usual workup (DCM). [α]2D0 ϭ ϩ78.0 (c ϭ 1.8, CHCl3); ν˜max/cmϪ1: 3031, 2926,
gave the crude product which was purified by flash chromatography 1496, 1454, 1362, 1329 and 1147 (SO2), 1103; δH (270 MHz,
(elution with light petroleum ether/EtOAc, 9:1) to give 10 as a col-
ourless oil (0.190 g, 69%, Z/E ϭ 89:11), Rf ϭ 0.39 (light petroleum
CDCl3): 3.44 (dd, J4,5 ϭ 10.2, J4,3 ϭ 8.5 Hz, 1 H, 4-H), 3.53, 3.79
(ABX, J6A,6B ϭ 10.4, J6A,5 ϭ 6.8, J6B,5 ϭ 1.7 Hz, 2 H, 6-HA, 6-
ether, Al2O3). [α]2D0 ϭ ϩ36.9 (c ϭ 1.2, CHCl3); νmax/cmϪ1: 2929, HB), 4.15 (dd, J2,3 ϭ 9.0, J2,1 ϭ 6.3 Hz, 1 H, 2-H), 4.43 (t, J ϭ 8.5
2858, 1662 (CϭC), 1473, 1463, 1389, 1362, 1374, 1257 (C-Si), 1162, Hz, 1 H, 3-H), 4.48, 4.81 (AB, J ϭ 9.7 Hz, 2 H, CH2Ph), 4.50Ϫ4.60
˜
1101; δH (270 MHz, CDCl3): 0.10, 0.11, (ϫ 2), 0.12, (ϫ 3) 0.14,
0.15 [5 ϫ s, 24 H, 4 ϫ Si(CH3)2], 0.84, 0.90, 0.91, 0.92 [4 ϫ s, 36
(m, 3 H, 5-H, CH2Ph), 4.72, 4.94 (AB, J ϭ 11.6 Hz, 2 H, CH2Ph),
4.74, 4.87 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 5.62 (d, J1,2 ϭ 6.3 Hz,
H, 4 ϫ SiC(CH3)3], 3.79Ϫ3.85 (m, 2 H, 4-H, 7-HAЈ), 3.96 (br. d, 1 H, 1-H), 6.23 [s, 1 H, CH(Br)Ph], 7.16Ϫ7.37 (m, 23 H, 23 ϫ
J ϭ 9.2 Hz, 1 H, 5-H), 3.98 (dd, J7B,7A ϭ 11.4, J7B,6 ϭ 1.7 Hz, 1 arom. H), 7.42Ϫ7.44 (m, 2 H, 2 ϫ arom. H); δC (67.9 MHz,
4
H, 7-HB), 4.11 (dd, J3,4 ϭ 3.2, J3,1 ϭ 1 Hz, 1 H, 3-H), 4.25 (ddd, CDCl3): 58.7 [SO2CH(Br)Ph], 69.0 (C6), 73.5, 74.0, 74.7, 75.6 (4 ϫ
J6,5 ϭ 9.2, J6,7A ϭ 4.1, J6,7B ϭ 1.7 Hz, 1 H, 6-H), 5.21 (s, 1 H, 1- CH2Ph), 75.7, 76.8, 78.2, 80.8, 85.6 (C1, C2, C3, C4, C5), 127.7 (ϫ
H), 7.12 (tt, Jortho ϭ 7.3, Jmeta ϭ 1.2 Hz, 1 H, para-arom. H), 2), 127.8, 128.0, 128.4 (ϫ 2), 128.6, 129.3, 130.3, 130.7 (arom. CH),
7.24Ϫ7.29 (m, 2 H, 2 ϫ meta-arom. H), 7.63Ϫ7.67 (m, 2 H, 2 ϫ 137.1, 137.6, 137.8, 138.1 (subst. arom. C); m/z (FAB): 781 (25%,
ortho arom. H); δC (67.9 MHz, CDCl3): Ϫ5.4 (ϫ 2), Ϫ5.0, Ϫ4.9,
[M ϩ Na]ϩ), 779 (21%, [M ϩ Na]ϩ), 545 (20%), 439 (55%), 91
Ϫ4.6, Ϫ4.4, Ϫ3.9 (ϫ 2) [4 ϫ Si(CH3)2], 17.9 (ϫ 2), 18.0, 18.2 [4 ϫ (100%, [C7H7]ϩ); found [M ϩ Na]ϩ 779.1650. C41H41BrO7S·Na
1320
Eur. J. Org. Chem. 2002, 1305Ϫ1322

A New Route to exo-Glycals Using the RambergϪBäcklund Rearrangement
FULL PAPER
requires 779.1654. Ϫ Further elution gave 13b as a waxy solid 131.1 (arom. CH), 130.7 [subst. arom. C of CH(Br)Ph], 137.2,
(0.030 g), Rf ϭ 0.37 (DCM). [α]2D0 ϭ ϩ95.1 (c ϭ 0.7, CHCl3); δH
(270 MHz, CDCl3): 3.47 (dd, J4,5 ϭ 10.1, J4,3 ϭ 9.0 Hz, 1 H, 4-
H), 3.56, 3.73 (ABX, J6A,6B ϭ 10.8, J6A,5 ϭ 5.6, J6B,5 ϭ 1.7 Hz, 2
H, 6-HA, 6-HB), 3.97 (dd, J2,3 ϭ 9.3, J2,1 ϭ 6.6 Hz, 1 H, 2-H),
4.43Ϫ4.49 (m, 1 H, 5-H), 4.49 (t, J ϭ 8.7 Hz, 1 H, 3-H), 4.50, 4.80
(AB, J ϭ 11.2 Hz, 2 H, CH2Ph), 4.51Ϫ4.61 (m, 2 H, CH2Ph), 4.66,
4.77 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.79, 4.90 (AB, J ϭ 10.7 Hz,
2 H, CH2Ph), 4.96 (d, J1,2 ϭ 6.3 Hz, 1 H, 1-H), 6.09 [s, 1 H,
CH(Br)Ph], 7.14Ϫ7.18 (m, 2 H, 2 ϫ arom. H), 7.24Ϫ7.39 (m, 21
H, 21 ϫ arom. H), 7.56Ϫ7.60 (m, 2 H, 2 ϫ arom. H); δC
(67.9 MHz, CDCl3): 63.1 [SO2CH(Br)Ph], 68.7 (C6), 73.5, 74.5,
74.6, 75.6 (4 ϫ CH2Ph), 75.6, 76.8, 78.5, 80.9, 85.6 (C1, C2, C3,
C4, C5), 127.7 (ϫ 2), 127.9, 128.0, 128.2, 128.4 (ϫ 2), 128.5, 128.6,
130.3, 130.4, (arom. CH), 131.4 [subst. arom. C of CH(Br)Ph],
136.9, 137.5, 137.9, 138.2 (subst. arom. C); found [M ϩ NH4]ϩ
779.1650. C41H41BrO7S·NH4 requires 779.1654. The third fraction
contained recovered 3dα (0.064 g, 32%) which showed identical Rf,
1H NMR and mass spectroscopic data to that already described
for this compound.
137.6, 137.8, 138.1 (subst. arom. C); found [M ϩ Na]ϩ 779.1658.
C41H41BrO7S·Na requires 779.1654.
X-ray Crystallographic Study of 13a: C41H41BrO7S, Mw ϭ 757.73,
˚
T ϭ 293(2) K, Mo-Kα radiation, λ ϭ 0.71073 A, orthorhombic,
space group P212121, a ϭ 16.049(4), b ϭ 23.479(13), c ϭ 10.284(9)
3
Ϫ3
˚
˚
A; α ϭ β ϭ γ ϭ 90°; V ϭ 3875(4) A , Z ϭ 4, Dc ϭ 1.299 g·cm
,
F(000) ϭ 1576, crystal size 0.7 ϫ 0.4 ϫ 0.4 mm. MSC Rigaku
AFC6S four-circle diffractometer, 2.35 Ͻ θ Ͻ 25, 3855 collected
reflections, of which 3827 were unique and 1735 having F0 Ͼ 4σ(F0)
being regarded as observed. An empirical absorption correction
based on 10 azimuthal scans (Tmin ϭ 0.950, Tmax ϭ 1.000) was
applied to the data. The structure was solved by direct methods
using SHELXS-86[40] and refined by full-matrix least-squares on
F2 with SHELXL-97[41] No restraints or constraints were used. All
non-hydrogen atoms were refined anisotropically. All hydrogen
atoms were included in calculated positions using a riding model
with Csp2ϪH
ϭ
0.93 A, Csp3(CRH2)ϪH
ϭ
0.97 A,
˚
˚
3
˚
Csp (CHR2)ϪH ϭ 0.98 A. Isotropic U values for hydrogen atoms
were calculated as 1.2 multiplied by the equivalent isotropic dis-
placement parameter for the atom to which the hydrogen is at-
tached. Full-matrix least-squares refinement based on F2 gave R1 ϭ
0.1671, wR2 ϭ 0.1842 for all data and a goodness of fit, GooF ϭ
S ϭ 1.007 for 451 parameters. A weighting scheme with w ϭ 1/
[σ2(F02) ϩ (0.0873P)2 ϩ 02.7367P], where P ϭ [max(Iobs,0) ϩ 2F2c]/
3 was applied at the end of the refinement. The final absolute struc-
ture parameter[42] was 0.01(3), i.e. it is less than 1 s.u. from zero,
indicating the absolute configuration of the structure is correct.
The final Fourier difference synthesis showed the largest peak and
(Phenylbromomethyl) S,S-Dioxo-2,3,4,6-tetra-O-benzyl-1-thio-β-D-
glucopyranoside (14a and 14b): A solution of the sulfone 3dβ
(0.090 g, 0.133 mmol) in DCM (1 mL) was added to a vigorously
stirred suspension of KOH/Al2O3 (25% w/w, 0.5 g) in tBuOH/DCM
(6:2 mL) at 5 °C followed after 10 min by 3 aliquots of CBr2F2
(0.5 mL, 5.47 mmol each) at intervals of 10 min. The reaction mix-
ture was diluted with DCM, filtered through Celite , and the fil-
trate concentrated in vacuo. Column chromatography of the residue
(elution with light petroleum ether/EtOAc, 5:1) gave three main
fractions. The first contained 4d as a colourless oil (0.008 g, 10%,
Z/E ϭ 79:21). The second fraction contained 14 (0.050 g, 50%, 1:1
mixture of diastereomers) which was further purified by column
chromatography (DCM/light petroleum ether 5:1) to give the more
mobile diastereomer 14a as a colourless oil (0.042 g), Rf ϭ 0.44
hole to be 0.271 and Ϫ0.402 e·AϪ3. The following quantities are
˚
given in the information for the structure and were calculated as
follows: goodness of fit (GooF ϭ S) was calculated by using the
formula: {Σ[w(F02 Ϫ Fc2)2]/(n Ϫ p)}2, where p ϭ number of para-
meters, n ϭ number of data. R-Factors were calculated using the
formulae: R1 ϭ [Σ(||Fo| Ϫ |Fc||)1/2]/Σ|Fo|; wR2 ϭ [Σw(F02 Ϫ Fc2)2/
(DCM). [α]2D0 ϭ ϩ17.5 (c ϭ 1.8, CHCl3); νmax/cmϪ1: 3031, 2922,
˜
Σw(F02)2]1/2
.
1496, 1454, 1344 and 1154 (SO2), 1094; δH (270 MHz, CDCl3): 3.24
(ddd, J5,4 ϭ 9.5, J5,6A ϭ 6.1, J5,6B ϭ 1.9 Hz, 1 H, 5-H), 3.47 (appt.
t, J4,3 ϭ 8.7, J4,5 ϭ 9.5 Hz, 1 H, 4-H), 3.57 (t, J ϭ 8.7 Hz, 1 H, 3-
H), 3.59Ϫ3.63 (m, 1 H, 6-HA), 3.68 (dd, J6B,6A ϭ 10.7, J6B,5 ϭ 1.9
Hz, 1 H, 6-HB), 3.93 (d, J1,2 ϭ 9.5 Hz, 1 H, 1-H), 4.10 (appt. t,
J2,3 ϭ 8.7, J2,1 ϭ 9.5 Hz, 1 H, 2-H), 4.51, 4.77 (AB, J ϭ 10.9 Hz,
2 H, CH2Ph), 4.53, 4.62 (AB, J ϭ 11.9 Hz, 2 H, CH2Ph), 4.71,
4.97 (AB, J ϭ 9.5 Hz, 2 H, CH2Ph), 4.77, 4.89 (AB, J ϭ 11.2 Hz,
2 H, CH2Ph), 6.07 [s, 1 H, CH(Br)Ph], 7.11Ϫ7.14 (m, 2 H, 2 ϫ
arom. H), 7.21Ϫ7.41 (m, 21 H, 21 ϫ arom. H), 7.61Ϫ7.65 (m, 2
H, 2 ϫ arom. H); δC (67.9 MHz, CDCl3): 61.9 [SO2CH(Br)Ph],
68.7 (C6), 73.4, 75.2, 75.7, 75.9 (4 ϫ CH2Ph), 77.0, 77.5, 79.2, 85.7,
85.8, (C1, C2, C3, C4, C5), 127.5, 127.8, 128.0, 128.1, 128.5 (ϫ
2) 128.8 128.9, 130.4, 130.5 (arom. CH), 131.1 [subst. arom. C of
CH(Br)Ph], 136.9, 137.4, 137.6, 137.9 (subst. arom. C); found [M ϩ
NH4]ϩ 779.1648. C41H41BrO7S·NH4 requires 779.1654. Ϫ Further
elution gave the less mobile diastereomer 14b as a colourless oil
(0.019 g), Rf ϭ 0.33 (DCM). [α]2D0 ϭ Ϫ9.8 (c ϭ 0.9, CHCl3); δH
(270 MHz, CDCl3): 3.63Ϫ3.85 (m, 5 H, 3-H, 4-H, 5-H, 6-HA, 6-
HB), 4.05 (t, J ϭ 9.2 Hz, 1 H, 2-H), 4.53, 4.64 (AB, J ϭ 12.1 Hz,
2 H, CH2Ph), 4.59, 4.82 (AB, J ϭ 10.9 Hz, 2 H, CH2Ph), 4.71,
4.89 (AB, J ϭ 9.9 Hz, 2 H, CH2Ph), 4.86, 4.94 (AB, J ϭ 10.9 Hz,
2 H, CH2Ph), 4.97 (d, J1,2 ϭ 9.2 Hz, 1 H, 1-H), 6.05 [s, 1 H,
CH(Br)Ph], 7.16Ϫ7.20 (m, 2 H, 2 ϫ arom. H), 7.25Ϫ7.44 (m, 21
H, 21 ϫ arom. H), 7.61Ϫ7.64 (m, 2 H, 2 ϫ arom. H); δC
(67.9 MHz, CDCl3): 58.7 [SO2CH(Br)Ph], 68.5 (C6), 73.2, 75.2,
75.4, 75.9 (4 ϫ CH2Ph), 77.2, 77.5, 79.9, 86.1, 87.7 (C1, C2, C3,
C4, C5), 127.6, 127.7, 127.8 (ϫ 2), 128.0, 128.4, 128.5, 128.6, 128.8,
CCDC-174420 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, UK; fax (internat.): ϩ44Ϫ1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
Acknowledgments
We are grateful to the Government of Papua New Guinea for the
award of a HEP fellowship (F. K. G.), the University of York for
a studentship (D. E. P.) and Chiroscience for a postdoctoral fellow-
ship (P. V. M.). We also thank Dr. T. Dransfield (University of
York) for obtaining mass spectroscopic data and C. J. Boxwell, S.
P. Foxon, and J. Turkenburg (University of York) for the X-ray
crystal structure determination of 13a.
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Eur. J. Org. Chem. 2002, 1305Ϫ1322
1321

F. K. Griffin, D. E. Paterson, P. V. Murphy, R. J. K. Taylor
FULL PAPER
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