Extending the scope of the Ferrier reaction: Fragmentation-rearrangement reactions of selectively substituted 1,2-cyclopropanated glucose derivatives

Article abstract of DOI:10.1016/j.carres.2012.01.006

Two further variations of the Ferrier-type allylic rearrangements of 1,2-cyclopropanated glucose derivatives bearing an acetoxylated carbon at the 1′-position are described. In the first, treatment of the cyclopropanated sugar with a nucleophile (ROH, PhS

Full text of DOI:10.1016/j.carres.2012.01.006

Carbohydrate Research 351 (2012) 49–55
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Extending the scope of the Ferrier reaction: fragmentation-rearrangement
reactions of selectively substituted 1,2-cyclopropanated glucose derivatives
⇑
Muganza Munyololo, David W. Gammon , Ilka Mohrholz
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
a r t i c l e i n f o
a b s t r a c t
Article history:
Two further variations of the Ferrier-type allylic rearrangements of 1,2-cyclopropanated glucose
derivatives bearing an acetoxylated carbon at the 10-position are described. In the first, treatment of
the cyclopropanated sugar with a nucleophile (ROH, PhSH, azide) and Lewis acid (BF3ꢀEt2O or Al(OTf)3),
Received 12 December 2011
Received in revised form 10 January 2012
Accepted 11 January 2012
Available online 21 January 2012
gives 2-C-vinyl glucosides in good yields and a-selectivities. Alternatively, treatment with a combination
of Lewis acid and acetic acid leads to a novel fragmentation-rearrangement to form a 2,3-dehydro-2-for-
myl-C-glycoside.
Keywords:
NuH,
Ferrier reaction
Cyclopropanated sugars
Glycals
BF3.Et2O
Nu
O
BnO
BnO
or Al(OTf)3,
CH2Cl2 or
CH3CN
R
H
H
H
H
OEt
O
OAc
R
O
O
OBn
O
H
H
BnO
BnO
BnO
BnO
Al(OTf)3,
Me
AcOH, H2O
OBn
OBn
BnO
BnO
O
CH2Cl2
(R = H)
R = H, Bu
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
Option A (Scheme 1) represents the classical and by far most
widely investigated Ferrier rearrangement involving an endo olefin,
and resulting mainly in 2,3-anhydroglycosides, with rare instances
of insertion of the incoming nucleophile at the site of the leaving
group.4 Option B also incorporates an endocyclic olefin, but has
the allylic leaving group external to the ring, resulting in the
formation of a 2-C-methylene glycoside.5 Option C could be classed
as an ‘exo-Ferrier’ rearrangement, and gives rise to branched 1-C-
vinyl-glycosides.6 These options are then supplemented by a series
of Ferrier-type fragmentations of 1,2-cyclopropanated sugars, most
of which are described in reviews of cyclopropanated sugars.2,3 In
option D the application of standard Ferrier conditions to the
otherwise-unsubstituted cyclopropanes results in ring-expansion
Since first reported in 1980s the Ferrier rearrangement of gly-
cals1 has continued to attract interest, as a basis for modification
of the sugar skeleton to provide key intermediates for the synthesis
of important natural products or templates for diversity-oriented
synthesis. The key features required for this reaction are an exo-
or endo- double bond at C-1, and a leaving group at the allylic
position. Explorations of the scope and range of the rearrangement
have focused on two broad aspects: the extensive array of catalysts
which promote the reaction together with the associated subtle
differences in reactivity and selectivity, and the synthetic scope
of the reaction inherent in the endo or exo orientation of the olefin,
or the replacement of the olefin by a cyclopropyl group.2,3 These
possibilities, and the outcomes of the Ferrier rearrangement, are
summarized in a generalized way in Scheme 1.
to form oxepines,7 while in option
E an acetonide-bearing
cyclopropanated sugar could be fragmented under Lewis acid catal-
ysis to yield 2-C-acetonyl glycosides.8 Option F illustrates the en-
hanced reactivity of lactonized cyclopropanes, which are easily
activated by Lewis acids in contrast to their ester counterparts.3
Finally, there is a single example in the literature, shown in option
G, where a 1,2-cyclopropanated sugar bearing an ‘allylic’ hydroxyl
⇑
Corresponding author.
E-mail address: david.gammon@uct.ac.za (D.W. Gammon).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2012.01.006

50
M. Munyololo et al. / Carbohydrate Research 351 (2012) 49–55
Table 1
OR1
A
B
O
R1OH
O
RO
RO
Results of treatment of acetate 2 with nucleophiles in the presence of a Lewis acid in
either CH2Cl2 or CH3CN at 40 °C
RO
RO
Lewis acid
Entry
Nucleophile
Catalyst
Solvent
Product
% Yield (a:b)
OR
O
1
2
3
4
5
6
7
8
BnOH
BnOH
PhSH
BF3ꢀEt2O
Al(OTf)3
BF3ꢀEt2O
Al(OTf)3
BF3ꢀEt2O
Al(OTf)3
BF3ꢀEt2O
Al(OTf)3
CH2Cl2
CH3CN
CH2Cl2
CH3CN
CH2Cl2
CH3CN
CH2Cl2
CH3CN
3a
3a
3b
3b
3c
3c
3d
3d
41% (1:0)
54% (1:1)
72% (1:1)
80% (1.2:1)
30% (1:0)
74% (1:0)
80% (2:1)
78% (2.2:1)
OR1
O
R1OH
RO
RO
RO
RO
OR
PhSH
Lewis acid
AllOH
AllOH
TMSN3
TMSN3
OR
O
OR
OR1
C
D
OR2
O
RO
RO
R1OH
RO
RO
OR
Lewis acid
OR
OR
O
OR
2. Results and discussion
H
OR1
R1OH
Lewis acid
RO
RO
O
RO
RO
The starting material, cyclopropanated exo ester 1, was readily
H
prepared by a literature procedure involving rhodium-catalyzed
addition of ethyl diazoacetate to benzylated D
-glucal,10 and this
OR
proved to be surprisingly resistant to direct Lewis-acid mediated
fragmentation (Scheme 2). This is in agreement with earlier reports
of the low reactivity of carboxylate-substituted cyclopropanated
sugars,11 and is in contrast to the reportedly high reactivity of an
analogous exocyclic ketone having the galacto-configuration,
which reportedly underwent facile Lewis acid-mediated fragmen-
tation to give the corresponding 30-oxopropylglycoside.12
In view of the low reactivity of 1 we proceeded to prepare cyclo-
propylcarbinyl acetate 2 with the acetate appropriately positioned
for the Ferrier-type reaction, by LAH reduction and subsequent
acetylation of 1 (Scheme 2). Initial treatment of 2 with benzyl alco-
hol and either BF3(OEt)2 or Al(OTf)3,13 in either dichloromethane or
acetonitrile, yielded the predicted benzyl 2-deoxy-2-C-vinylgluco-
sides 3a, with high selectivity as long as water was rigorously ex-
cluded. While the yields were modest, the combination of Al(OTf)3
in acetonitrile gave the best yield (57%, as opposed to 41% using
BF3ꢀEt2O in CH2Cl2). The formation of the 2-C-vinylglucosides was
readily apparent in the 1H NMR spectrum of the products which
showed characteristic downfield signals for the terminal olefin,
H
O
E
H
O
OR1
O
R1OH
RO
RO
RO
RO
O
catayst
H
OR
O
OR
O
A
F
A
B
RO
RO
RO
RO
B
catayst
O
O
O
O
O
H
H
Ar
H
OH
O
G
O
PPh3, DEAD
ArCO2H
RO
RO
RO
RO
O
OR
OR
Scheme 1. Summary of known variations of the Ferrier reaction of unsaturated or
cyclopropanated sugars. The group ‘R’ is in most cases either Bn or Ac, and the
alcohol R1OH is in many instances interchangeable with a variety of O-, S-, N- and
C-nucleophiles. The reagent ‘A–B’ in option F represents a reagent incorporating
both electrophilic and nucleophilic character.
and distinctly resolved signals for the anomeric protons in the
a/
b mixture.
The scope of this Al(OTf)3 catalyzed Ferrier-type fragmentation
was then explored further by extending the range of simple nucle-
ophiles to include PhSH, AllOH, and TMSN3. In each case moderate
to good yields of the 2-C-vinylglucosides were obtained with selec-
group was treated under Mitsunobu conditions with benzoic acids
as nucleophile, to give 2-C-vinyl glycosyl benzoates.9
In the course of exploring general methodologies for
stereo-selective introduction of functionalized alkyl groups at C-2
of glucose, we were interested in establishing more general condi-
tions for the last-mentioned variation (option G) of the Ferrier
reaction, to allow for efficient formation of 2-C-vinyl, or more
generally, 2-C-alkenyl glycosides with a wider range of glycosidic
substituents. These investigations were not only successful in
establishing the more general methodologies, but also led to the
discovery of a new variation on the Ferrier rearrangement.
tivity toward the a-glucoside except in the case of reactions with
PhSH (Table 1). A preliminary attempt to apply this methodology
to the formation of disaccharides was not successful, with no
reaction observed when partially protected sugar alcohol 414 was
combined with acetate 2 and the Lewis acid. The outcomes of these
reactions are consistent with the mechanism of the Ferrier reaction,
in which Lewis acid-mediated elimination of the ‘allylic’ acetoxy
group is driven by formation of an oxocarbenium ion intermediate,
H
H
R
O
O
O
H
OAc
H O
BnO
BnO
BnO
BnO
BnO
BnO
(a)
(b)
OEt
H
OBn
H
OBn
OBn
2
1
3a R = OBn
O
OMe
OBn
3b
3c
R = SPh
R = OAll
HO
BnO
(b)
(c)
3d R = N3
no reaction
OBn
4
no reaction
Scheme 2. Reagents and conditions: (a) (i) LAH, THF; (ii) Ac2O, pyridine (71% over two steps); (b) nucleophile (BnOH, PhSH, AllOH or TMSN3), Lewis acid (BF3ꢀEt2O or
Al(OTf)3), solvent (CH2Cl2 or CH3CN) (see Table 1 in Supplementary data for details); (c) 4, Al(OTf)3), CH3CN or CH2Cl2.

M. Munyololo et al. / Carbohydrate Research 351 (2012) 49–55
51
H
H
H
R1
O
OAc
R1
O
R
O
O
H
H
BnO
BnO
BnO
BnO
BnO
BnO
R1
H
OBn
OBn
OBn
I
II
III
Scheme 3. Proposed route to 2-C-alkenylated sugars.
H
H
H
H
O
H
O
R
OAc
Bu
OAc
O
O
H
H
BnO
BnO
BnO
BnO
BnO
BnO
d,e
a
1
+
Bu
H
OBn
H
OBn
OBn
5 R = OH
6 R = N(Me)OMe
7 R = Bu
b
c
8a
8b
f
f
OBn
OBn
O
O
BnO
BnO
BnO
BnO
Bu
Bu
OBn
OBn
9b
9a
Scheme 4. Reagents and conditions: (a) KOH, EtOH, reflux, 1 h, quant.; (b) CDMT, NMM, MeNH–OMeꢀHCl, overnight, 96%; (c) n-BuLi, THF, ꢂ78 °C, 30 min, 74%; (d) LiAlH4,
Et2O, 1 h; (e) Ac2O, DMAP, TEA, THF, 30 min, 72% over two steps; (f) BnOH, Al(OTf)3, CH2Cl2, 40 °C, 1 h, 67% (9a) and 86% (9b).
H
(a)
(b)
OAc
(S)
O
C1
H
BnO
BnO
H
E2
9a
Bu
C2
Bu
H
OBn
AcO
H
8a
H
C1
C1
OAc
(R)
O
H
H
Bu
BnO
BnO
E1
9b
H
OAc
C2
AcO
NOT favoured
C2
Bu
H
OBn
Bu
H
H
8b
0
Figure 1. Stereoselectivity in the elimination step; the anti-periplanar arrangement of the departing acetoxy group and the C1–C1 bond is favoured for the S-isomer (a) but
not the R-isomer.
followed by trapping of this with a nucleophile. A more general pro-
cedure is thus now available for achieving a variation of the Ferrier
rearrangement identified as option G in Scheme 1.
major isomer 8a gave rise to a single benzyl glucoside 9a in a 67%
yield, having exclusively E-geometry in the extended olefinic side-
0
0
chain at C-2 as deduced from the large coupling (J2 ,3 = 15.3 Hz) in
The success of this Ferrier-type fragmentation using simple
nucleophiles prompted an investigation of the extension of this
methodology to the installation of more complex side chains at
C-2 of glucosides. We envisaged (Scheme 3) that ketone I, readily
obtainable from ester 1 could be converted to secondary acetate
II, which, on treatment under the conditions established earlier,
should give rise to glycosides III having a substituted olefin at-
tached at C-2. This would thus constitute a general approach to
the preparation of a range of 2-C-alkenylated glucose derivatives.
The Weinreb amide 6 (Scheme 4) was selected as a potentially
versatile synthetic intermediate allowing for preparation of a range
of ketones. It was easily obtained from ester 1 via the corresponding
acid 5 using a published procedure.15 As ‘proof of concept’ amide 6
was then converted to n-butyl ketone 7 by treatment with n-butyl
lithium.16 LAH-reduction of the ketone followed by acetylation gave
a separable 2:1 mixture of diastereomeric acetates 8a and 8b in a
combined yield of 72%. At this stage it was not possible to determine
the absolute configuration of each, although this was inferred from
the outcomes of the subsequent reactions when each was treated in
turn with benzyl alcohol and Al(OTf)3 in dichloromethane. The
the 1H NMR spectrum for doublets at dH 5.65 and 5.50 ppm, for H-
30 and H-20, respectively, and predominantly as the
a-anomer, as
judged by the signal for H-1 at dH 4.81 (J1,2 = 3.4 Hz). However, when
the minor isomer 8b was treated under the same conditions, it gave
rise to a mixture of glucosides 9b in a 87% yield, again predomi-
nantly as
isomers.
a
-anomer but this time as a ꢁ1:1 mixture of E- and Z-
These results, as illustrated by means of Newman projections in
Figure 1, suggest that the major isomer 8a has the S-configuration at
the acetoxylated carbon. This was deduced from the supposition
that stereoselectivity in this reaction requires an E2 elimination,
which in turn requires the C–OAc bond to be anti peri-planar to
Me
O
Al(OTf)3, AcOH, H2O
CH2Cl2, reflux
BnO
BnO
2
O
10
Scheme 5.

52
M. Munyololo et al. / Carbohydrate Research 351 (2012) 49–55
H
H
O
O
H
O
OH
OH
O
LA
H2O
H+
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
OAc
OBn
2
OBn
IV
OBn
V
OBn
VI
rotate C2-C3 and
isomerize to
conjugated enone
OH
O
BnO
LA
Me
BnO
BnO
O
BnO
BnO
BnO
O
BnO
VII
O
BnO
O
10
LA
VIII
Scheme 6. A possible mechanism for the formation of 10.
0
the C1–C1 bond, an arrangement which is sterically favoured in the
S-isomer (Fig. 1a) but not in the R-isomer (Fig. 1b).
ceric ammonium sulfate solution. Silica gel chromatography was
performed using Merck Kieselgel 60 70–230 mesh for gravity col-
umns and 230–400 mesh for flash chromatography. NMR spectra
were recorded in CDCl3 solution, unless otherwise stated, on
either a Varian Mercury-300 (1H 300.13, 13C 75.5 MHz) or Varian
Unity-400 (1H 400.13; 13C 100.6 MHz) spectrometer, with
(CH3)4Si as an internal standard. High resolution mass spectra
were recorded by LC ESI-MS at the Central Analytical Facility of
the University of Stellenbosch. Melting points were recorded on
The foregoing results suggest a general methodology for instal-
lation of an alkenyl substituent at C-2 of glucose, although only the
E-isomer is obtainable in a controlled way, and this only if stereo-
selective reduction of the intermediate ketones can be achieved.
In the course of the investigations of the reactivity of acetate 2
described above, it was observed that when water was not rigor-
ously excluded, a persistent minor side-product was formed. This
was duly isolated, and its structure confirmed by detailed 1H and
13C NMR studies as well as HRMS as carbaldehyde 10, a product
that had been previously prepared17 by an unrelated route from
benzylated 2-formylglycal. Upon further investigation (Scheme 5)
we found that 10 could be deliberately and exclusively formed in
a 59% yield, with no evidence for formation of 2-C-vinyl glycoside,
by treatment of acetate 2 with a combination of aqueous acetic
acid and Al(OTf)3 in dichloromethane at reflux.
a
Kofler hotstage microscope (Reichart Thermovar) and are
uncorrected. Elemental analysis was carried out on a Thermo
Flash EA1112 CHNS elemental analyzer. Infrared spectra were
recorded on a Perkin-Elmer Paragon 1000 FT-IR spectrometer
using chloroform as solvent.
3.2. 1,5-Anhydro-2-deoxy-1,2-C-(exo-acetoxymethylmethylene)
-3,4,6-tri-O-benzyl-a-D-glucitol (2)
Consideration of the conditions required for the formation of
carbaldehyde 10 suggests that the reaction may proceed as out-
lined in Scheme 6, where the initially-formed oxocarbenium ion
IV is intercepted by water to give hemiacetal V which is in equilib-
rium with aldehyde VI; rotation of the C2–C3 bond and isomeriza-
tion lead to conjugated enone VII, which can undergo Lewis acid
catalyzed intramolecular conjugate addition to form intermediate
enolate VIII, which in turn yields 10 after elimination of the b-ben-
zyloxy group. This then constitutes yet another variation of the
Ferrier rearrangement, adding to its already formidable scope,
and provides access to an unusually functionalized, chiral sugar
To a stirred suspension of LiAlH4 (2.03 g, 5.37 mmol) in dry Et2O
(40 mL) was slowly added a solution of ethyl ester 1 (2.7 g,
5.37 mmol) in Et2O (10 mL). The reaction mixture was stirred for
1 h at 25 °C when TLC showed the reaction was complete. The
reaction mixture was then diluted with Et2O, cooled to 0 °C, and
quenched by careful and slow addition of water (8 mL) and 15% aque-
ous NaOH (8 mL). A further portion of water (24 mL) was added and
the mixture was left to warm up to room temperature for 15 min.
Magnesium sulfate was added and the slurry stirred again for
15 min, then the Et2O phase was recovered and concentrated under
vacuum to give alcohol (1.63 g, 3.5 mmol). This was immediately
acetylated, without further purification, by dissolving in THF
(20 mL) and adding Ac2O (1.92 mL, 20.4 mmol), DMAP (41.4 mg,
0.34 mmol), and TEA (1.87 mL, 13.6 mmol). When TLC showed that
the reaction was complete (30 min at room temperature) the reac-
tion mixture was diluted in dichloromethane and poured into ice-
water with stirring. The organic layer was separated and washed suc-
cessively with water and brine, dried over MgSO4, filtered, and then
concentrated under vacuum. The crude product was purified by
column chromatography on silica gel (EtOAc/petroleum ether 2:8),
to give acetate 2 as an oil (1.26 g, 71% over two steps). IR (CHCl3/
cmꢂ1) 1734, 1452, 1364; 1H NMR (400 MHz, CDCl3): dH 7.38–7.27
(15H, m, Ar-H), 4.77 (2H, 2d, J 10.7 Hz,11.5 Hz, Ph–CH2–), 4.63 (1H,
d, J 11.8 Hz, Ph–CH–), 4.58 (1H, d, J 11.6 Hz, Ph–CH–), 4.56 (1H, d, J
12 Hz, Ph–CH–), 4.55 (1H, d, J 11.1 Hz, Ph–CH–), 3.90 (2H, d, J
7.5 Hz, H-30), 3.79 (1H, dt, J 3.7, 6.0 Hz, H-6a), 3.7–3.66 (2H, m, H-
3,4), 3.58–3.52 (3H, m, H-1,5,6b), 2.07 (3H, s, COCH3), 1.46–1.43
(1H, m, H-20), 1.04–1.01 (1H, m, H-2); 13C NMR (100 MHz, CDCl3):
dC 170.8(C@O), 138.2, 137.9, 128.2, 128.1, 127.7, 127.5, 127.4,
127.3, 78.4, 76.6 (C-1), 76.1, 73.2, 73.1, 70.9, 69.6, 64.4 (C-30), 53.9,
23.0 (CH3), 20.7 (C-20), 20.2 (C-2); Found: C,73.39; H, 6.54; calcd for
derivative having a synthetically useful
a,b-unsaturated aldehyde
allowing for further elaboration. General conditions have thus been
established for achieving the Ferrier rearrangement of 1,2-cyclo-
propanated sugars bearing an acetoxylated carbon at the 20-posi-
tion, to give 2-C-alkenyl sugars. In addition, a new variation of
the Ferrier reaction has been described in which treatment of a
cyclopropanated sugar with a combination of Lewis acid and acetic
acid induced a fragmentation-rearrangement to give a 2,3-unsatu-
rated-2-carbaldehyde derivative of a sugar.
3. Experimental
3.1. General conditions
Commercially obtained compounds and reagents were used as
received. Air- and moisture-sensitive reactions were performed
under nitrogen atmosphere. Solvents used were of AR grade or
dried according to common procedures. Reaction progress was
monitored by thin layer chromatography (TLC) on pre-coated Sil-
ica Gel 60 F254 plates of thickness 0.25 mm (Merck) and was
visualized under UV light or by overlaying with ethanolic acidic

M. Munyololo et al. / Carbohydrate Research 351 (2012) 49–55
53
C31H34O6: C, 74.08; H, 6.82; [M+Na] calcd for C31H34NaO6: 525.2253;
found for C31H34NaO6: 525.2244.
(C-1
a
), 85.7, 84.3, 80.9, 79.5, 78.9, 78.4, 75.2, 75, 74.9, 74.7, 73.4
), 52.7 (C-2b). Anal. Calcd for
35H36O4S: C, 76.06; H, 6.56; S, 5.80. Found: C, 76.51; H, 6.73; S,
(C-1b), 72, 69.4, 68.8, 53 (C-2
C
a
3.3. General procedures for Ferrier-type rearrangements of 2
5.50. [M+Na] calcd for C35H36NaO4S: 575.2232; found for
C35H36NaO4S: 575.2250.
Method A: To a solution of 2 (200 mg, 0.4 mmol) in CH2Cl2
(5 mL) at 0 °C was added alcohol (3.0 equiv) and BF3ꢀEt2O
(2.0 mmol, 5.1 equiv). The reaction mixture was stirred at 40 °C
until TLC showed completion of the reaction, whereupon the reac-
tion mixture was diluted with EtOAc, then the EtOAc phase was
washed with aq NaCl, separated, dried over Na2SO4, and the sol-
vent removed under vacuum. The residue was purified by silica
gel column chromatography (EtOAc/petroleum ether mixtures) to
give the corresponding product.
Method B: To a solution of 2 (200 mg, 0.4 mmol) in CH3CN
(5 mL) at 25 °C was added alcohol (3.0 equiv) and Al(OTf)3
(2.0 mmol, 5.1 equiv). The reaction mixture was stirred at 40 °C
until TLC showed completion of the reaction, whereupon the reac-
tion mixture was diluted with EtOAc, then the EtOAc phase washed
with aq NaCl, separated, dried over Na2SO4, and the solvent re-
moved under vacuum. The residue was purified by silica gel col-
umn chromatography (EtOAc/petroleum ether mixtures) to give
the corresponding product.
3.6. Allyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-vinyl-a-D-
glucopyranoside (3c)
Compound 2 (200 mg, 0.4 mmol) was treated with allyl alcohol
(0.125 mL, 2.5 mmol) using Method B to give 2-C-vinylglucoside 3c
as an oil (352 mg, 74%). 1H NMR (400 MHz, CDCl3): dH 7.36–7.16
(15H, m, Ph-H), 5.95–5.80 (2H, m, H-20, OCH2CHCH2), 5.31–5.13
(4H, m, H-30, OCH2CHCH2), 4.83 (1H, d, J 10.8 Hz, Ph-CH–), 4.77
(1H, d, J 3.3 Hz, H-1), 4.69–4.62 (3H, m, Ph-CH2–, Ph-CH–), 4.51
(2H, d, J 11.66 Hz, Ph-CH2–), 4.16 (1H, tdd, J 1.5, 5.1, 13.2 Hz,
H-6a), 3.94 (1H, tdd, J 1.4, 5.8, 13.1 Hz, H-6b), 3.86 (2H, m, H-
3,5), 3.78 (1H, dd, J 3.9, 10.6 Hz, H-4) 3.68 (2H, dd, J 1.7, 10.5 Hz,
OCH2CHCH2), 2.58 (1H, m, H-2); 13C NMR (CDCl3, 75 MHz): dC
138.5, 138.4, 138.1, 135.3 (C-20), 134 (OCH2CHCH2), 128.3, 128.2,
128, 127.8, 127.6, 118.7 (C-30), 116.8 (OCH2CHCH2), 99.7 (C-1),
80.6, 78.7, 74.9, 74.8, 73.4, 71, 69.9, 67.9, 52.6 (C-2). Elemental
Anal. Calcd for C32H36O5: C, 78.53; H, 7.04. Found: C, 78.05; H,
6.87. [M+Na] calcd for
C32H36NaO5: 523.2480.
C32H36NaO5: 523.2460; found for
3.4. Benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-vinyl-
a-
D
-
glucopyranoside (3a)
3.7. Azido 3,4,6-tri-O-benzyl-2-deoxy-2-C-vinyl-a/b-D-
Compound 2 (200 mg, 0.4 mmol) was treated with benzyl
alcohol (0.123 mL, 1.2 mmol) using Method B to give the 2-C-vi-
glucopyranoside (3d)
nyl-a
-glycoside 3a as an oil (117 mg, 54%). 1H NMR (400
Compound 2 (200 mg, 0.4 mmol) was treated with TMSN3
(0.18 mL, 1.78 mmol) using Method to give the 2-C-vinyl
glucoside 3d as an oil (154 mg, 80%,
:b = 2.2:1). IR (CHCl3/cmꢂ1
2114 (N3); 1H NMR (400 MHz, CDCl3): dH 7.38–7.20 (15H, m,
Ph-H), 5.75–5.61 (1H, m, H-20a, b), 5.42–5.26 (1.66H, m, H-1
0a,b), 4.85 (1H, d, J 11.0 Hz, Ph-CH–), 4.73 (1H, d, J 10.8 Hz,
Ph-CH–), 4.67 (1H, d, J 12.4 Hz, Ph-CH–), 4.62 (1H, d, J 10.9
MHz, CDCl3): dH 7.42–7.26 (18H, m, Ph-H), 7.21 (2H, m, Ph-H),
5.93 (1H, td, J 9.5, 17.1 Hz, H-20), 5.28 (1H, dd, J 1.5, 17.2 Hz, H-
30a), 5.23 (1H, dd, J 1.9, 10.2 Hz, H-3’b), 4.88 (1H, d, J 3.6 Hz,
H-1), 4.87 (1H, d, J 10.6 Hz, Ph-CH–), 4.74 (1H, d, J 11.4 Hz, Ph-
CH–), 4.72 (1H, d, J 10.4 Hz, Ph-CH–), 4.71 (1H, d, J 10.6 Hz,
Ph-CH–), 4.69 (1H, d, J 12.1 Hz, Ph-CH–), 4.56 (1H, d, J 12.8
Hz, Ph-CH–), 4.56 (1H, d, J 10.1 Hz, Ph-CH–), 4.50 (1H, d, J
12.0 Hz, Ph-CH–), 3.94 (2H, m, H-3, 6a), 3.81 (1H, dd, J 3.9,
10.6 Hz, H-6b), 3.71 (2H, m, H-4,5), 2.64 (1H, m, H-2); 13C NMR
(75 MHz, CDCl3): dC 138.4, 138.3, 138, 137.5, 135.1 (C-20), 128.2,
128.12, 128.1, 127.8, 127.6, 127.5, 127.4, 118.6 (C-30), 99.8 (C-1),
80.5, 78.6, 74.8, 74.6, 73.3, 71, 69, 67.7, 52.5 (C-2); Anal. Calcd
for C36H38O5: C, 78.52; H, 6.96. Found: C, 78.88; H, 6.34. [M+Na]
calcd for C35H38NaO5: 573.2617; found for C35H38NaO5: 573.2634.
B
a
)
a,
3
Hz, Ph-CH–), 4.60 (1H, d, J 12.3 Hz, Ph-CH–), 4.56 (1H, d, J
10.9 Hz, Ph-CH–), 4.55 (1H, d, J 12.1 Hz, Ph-CH–), 4.50 (0.33H, d, J
9.6 Hz, H-1b), 4.03–3.96 (0.66H, m, H-4a), 3.86–3.65 (3.63H, m,
H-3 ,5 ,b,6 a,b,6ba,b), 3.61–3.55 (0.33H, m, H-4b), 3.55–3.47
a
a
a
(0.33H, m, H-3b), 2.69–2.59 (0.66H, m, H-2a), 2.53–2.42 (0.33H,
m, H-2b); 13C NMR (75 MHz, CDCl3): dC 138.2, 138, 137.9, 134
(C-20a), 133 (C-20b), 128, 127.8, 127.7, 127.69, 127.64, 120.6
(C-30a), 120.1 (C-30b), 91.4 (C-1
a
), 89 (C-b), 79.9, 76.7, 78.1, 77.9,
77.5, 75, 74.9, 73.6, 73.5, 73.3, 68.7, 68.5, 53 (C- ), 51.5 (C-2b). Ele-
a
3.5. Phenyl 3,4,6-tri-O-benzyl-2-deoxy-1-thio-2-C-vinyl-
glucopyranoside (3b)
a
/b-D
-
mental Anal. Calcd for C29H31N3O4: C, 71.73; H, 6.43; N, 8.65.
Found: C, 71.26; H, 6.48; S, 8.18. [M+Na] calcd for C29H31N3NaO4:
508.2212; found for C29H31N3NaO4: 508.2216.
Compound 2 (200 mg, 0.4 mmol) was treated with thiophenol
(0.2 mL, 1.7 mmol) using Method B to give 2-C-vinyl thioglycoside
3.8. 1,5-Anhydro-2-deoxy-1,2-C-(exo-carboxymethylene)-3,4,6-
tri-O-benzyl-a-D-glucitol (5)
3b as
a
crystalline solid (157 mg, 72%,
a
:b = 1:1). 1H NMR
(400 MHz, CDCl3): dH 7.57–7.55 (0.918H, m, SPh-H-b), 7.51–7.49
(1.08H, m, SPh-H-
a
), 7.36–7.28 (8.10H, m, Ph-H-
a
), 7.27–7.24
To a stirred solution of 1 (286 mg, 0.57 mmol) in ethanol (5 mL)
was added aqueous KOH (3 M, 2 mL). The reaction mixture was
stirred under gentle reflux for 1 h and then cooled to 0 °C and made
slightly acidic by the addition of aqueous HCl (2 M) with stirring.
The solution was then extracted with EtOAc and the combined ex-
tracts washed with brine, dried (MgSO4), and evaporated under re-
duced pressure. Filtration of the residue through a short silica gel
column (1:4 EtOAc/petroleum ether) gave acid 5 in quantitative
(8.10H, m, Ph-H-b), 5.90 (0.541H, td, J 9.6, 16.9 Hz, H-20a), 5.68
(0.46H, td, J 9.6 Hz, 16.9 Hz, H-20b), 5.47 (0.54H, d, J 5.0 Hz,
H-1
4.86 (0.541H, d, J 11.0 Hz, Ph-CH-
Ph-CH- ,b), 4.73 (1H, d, J 16.3 Hz, Ph-CH-
a
), 5.30 (2H, m, H-30a, b), 4.87 (0.46H, d, J 10.9 Hz, Ph-CH-b),
a
), 4.74 (1H, d, J 16.1 Hz,
a
a,b), 4.64 (0.54H, d, J
12.0 Hz, Ph-CH-b), 4.64 (0.46H, d, J 7.5 Hz, H-1b), 4.63 (0.54H, d, J
11.4 Hz, Ph-CH-b), 4.58 (0.459H, d, J 10.8 Hz, Ph-CH-b), 4.57
(0.54H, d, J 11.9 Hz, Ph-CH-
a
), 4.48 (0.541H, d, J 11.9 Hz, Ph-CH-
), 3.87–3.48 (5H, m, H-3,4,5,6a,6b ,b), 2.99 (0.54H, ddd, J 4.8,
); 13C NMR (75 MHz, CDCl3): dC 138.4, 138.38,
yield. mp:71–73 °C; IR (CHCl3/cmꢂ1 1760 (C@O); 1H NMR
)
a
a
(400 MHz, CDCl3): dH 7.31–7.20 (15H, m, Ar-H), 4.71 (2H, d, J
11.6 Hz, Ph-CH2–), 4.61–4.50 (4H, m, 2 ꢃ Ph-CH2–), 4.00 (1H, dd,
J 2.1, 7.3 Hz, H-1), 3.78 (1H, dd, J 2.7, 6.2 Hz, H-3), 3.72–3.66 (2H,
m, H-4,6a), 3.60 (2H, dd, J 5.3, 7.5 Hz, H-5, 6b), 1.99 (1H, dd, J 2.0,
5.5 Hz, H-2’), 1.83 (1H, ddd, J 2.1,5.6, 7.5 Hz, H-2), 13C NMR
9.4, 10.5 Hz, H-2
a
138.3, 138.2, 138.1, 138.09, 135.1 (C-20a), 134.2 (C-20b), 132, 131,
128.8, 128.7, 128.4, 128.4, 128.34, 128.3, 128, 127.9, 127.8, 127.7,
127.67, 127.6, 127.5, 127.3, 127, 119.6 (C-30b), 119.3 (C-30a), 89.6

54
M. Munyololo et al. / Carbohydrate Research 351 (2012) 49–55
(100 MHz, CDCl3): dC 176.4 (C@O), 138.0, 128.4, 128.3, 127.8,
127.7, 127.69, 127.63, 76.2, 75.19, 74.4, 73.4, 73.3, 71.5, 69.2,
58.2 (C-1), 25.4 (C-2), 24.1 (C-20); Found: C, 73.55; H, 7.06 calcd
for C29H30O6: C, 73.40; H, 6.37. [M+Na] calcd for C29H30O6:
497.1940; found for C29H30NaO6: 497.1954.
(5 mL). The reaction mixture was stirred for 1 h at 25 °C when TLC
showed the reaction was complete, and it was then diluted with
ether, cooled to 0 °C, and quenched by careful, slow addition of
water (5 mL) and 15% aqueous NaOH (5 mL). A further portion of
water (15 mL) was added and the mixture was left to warm up
to room temperature for 15 min. Magnesium sulfate was added
as a drying agent and the slurry stirred again for 15 min, the mix-
ture was decanted to remove the salts formed since the use of frit
was difficult due to its blockage by the salt. The solvent was re-
moved to yield the crude product (64 mg, 0.115 mmol). This was
immediately acetylated by stirring at room temperature with
Ac2O (0.07 mL, 0.69 mmol), DMAP (1.6 mg, 0.012 mmol) and TEA
(0.07 mL, 0.46 mmol) in THF (10 mL), with reaction complete after
30 min as judged by TLC. The reaction mixture was diluted in
CH2Cl2 and poured into ice-water with stirring. The organic layer
was separated and washed successively with water and brine,
dried over MgSO4, filtered, and then concentrated under reduced
pressure. The crude product was purified by column chromatogra-
phy on silica gel (EtOAc/petroleum ether 2:8) to give the two iso-
mers in a 72% yield over two steps, 8a (44 mg, 48%) and 8b
(20 mg, 24%).
3.9. 1,5-Anhydro-2-deoxy-1,2-C-[exo-(N-methyl-N-methoxy)
amidocarboxymethylene]-3,4,6-tri-O-benzyl-a-D-glucitol (6)
To a solution of acid 5 (650 mg, 1.4 mmol) in THF (8 mL), at
room temperature, were added 2-chloro-4,6-dimethoxy-[1,3,5]tri-
azine (288 mg, 1.64 mmol) and N-methylmorpholine (0.382 mL,
4.11 mmol). A white precipitate was formed during stirring for
1 h, and N,O-dimethylhydroxylamine hydro-chloride (133 mg,
1.4 mmol) was added. The mixture was stirred overnight and then
quenched with H2O (15 mL) and extracted with diethyl ether
(2 ꢃ 7 mL). The combined organic phases were washed with satu-
rated aqueous Na2CO3 (2 ꢃ 15 mL) followed by 1 N HCl (15 mL)
and brine (15 mL). The organic layer was dried over anhydrous
Na2SO4 to give, after evaporation of solvent, amide 6 as a white
solid (682 mg, 96%); mp: 87–89 °C; IR (CHCl3/cmꢂ1) 1660, 1450,
1415; 1H NMR (400 MHz, CDCl3): dH 7.34–7.27 (15H, m, Ar-H),
4.72 (1H, d, J 11.7 Hz, Ph-CH–), 4.68 (1H, d, J 11.3 Hz, Ph-CH–),
4.57–4.50 (4H, m, 2 ꢃ Ph-CH2–), 3.90 (1H, dd, J 2.1, 7.2 Hz, H-1),
3.81–3.74 (2H, m, H-3,4), 3.71 (1H, dd, J 6.0, 10.3 Hz, H-6a), 3.65
(3H, s, OCH3–), 3.61–3.55 (2H, m, H-5,6b), 3.16 (3H, s, CH3–),
2.54–2.43 (1H, br s, H-20), 1.86 (1H, ddd, J 2.1, 5.8, 7.5 Hz, H-2);
13c NMR (100 MHz, CDCl3): dC 171.7 (C@ON(OCH3)(CH3), 138.2,
138.1, 137.9, 128.4, 128.35, 128.32, 127.8, 127.65, 127.61, 76.2,
75.6, 74.6, 73.43. 73.1, 71.2, 69.3, 61.6 (N–OCH3), 57.6(C-1),
32.5(N-CH3), 23.9 (C-2), 22.2 (C-20); Found: C, 72.46; H, 6.50; N,
2.14; calcd for C31H35NO6: C, 71.93; H, 6.82; N, 2.71. [M+Na] calcd
for C31H35NNaO6: 540.2344; found for C31H35NNaO6: 540.2344.
Compound 8a: IR (CHCl3/cmꢂ1) 1743 (C@O), 1270, 1048; 1H
NMR (400 MHz, CDCl3): dH 7.38–7.26 (15H, m, Ar-H), 4.79 (1H, d,
J 11.6 Hz, Ph-CH–), 4.78 (1H, d, J 11.8 Hz, Ph-CH–), 4.59–4.50 (4H,
m, 4 ꢃ Ph-CH–), 4.35 (1H, td, J 6.5, 9.1 Hz, H-1), 3.77 (1H, td, J
3.50, 5.99, 6.01, H-5), 3.68 (1H, dd, J 6.1, 10.4 Hz, H-6a), 3.61 (1H,
dd, J 3.6, 7.5 Hz, H-3), 3.56–3.50 (4H, m, H-30,4,6b), 2.07 (3H, s, -
COCH3), 1.73–1.66 (2H, m, H-20, 60a), 1.38–1.26 (5H, m, H-2,40a,
b,50a,60b), 1.20–1.16 (1H, m, H-50b), 0.93 (3H, t, J 7.1 Hz, –CH3);
13C NMR (100 MHz, CDCl3): dC 170.7 (C@O), 138.4, 138.1 (2 ꢃ C),
128.4, 128.3, 128.2, 127.9, 127.67, 128.61, 78.7, 77.1, 76.4, 75.1,
73.4 (C-1), 73.2, 70.5, 69.8, 54.1, 34.1, 29.0, 27.4, 22.5, 21.1, 20.53
(–COCH3), 13.8 (–CH2–CH3). Found: C, 75.57; H, 7.93; calcd for
C
35H42O6: C, 75.24; H, 7.58. [M+Na] calcd for C35H42NaO6:
3.10. 1,5-Anhydro-2-deoxy-1,2-C-exo-(20-oxo-hexylidene)-3,4,6-
581.2879; found for C35H42NaO6: 581.2872.
tri-O-benzyl-
a
-
D
-glucitol (7)
Compound 8b: IR (CHCl3/cmꢂ1) 1744 (C@O), 1270, 1048; 1H
NMR (400 MHz, CDCl3): dH 7.38–7.26 (15H, m, Ar-H), 4.77 (1H, d,
J 11.6 Hz, Ph-CH–), 4.76 (1H, d, J 11.8 Hz, Ph-CH–), 4.64–4.52 (4H,
m, 4 ꢃ Ph-CH–), 4.39 (1H, ddd, J 5.4, 7.4, 8.4 Hz, H-1), 3.81 (1H,
dt, J 3.8, 6.0, H-5), 3.71–3.67 (2H, m, H-4,6a), 3.63 (1H, dd, J 2.4,
7.2 Hz, H-3), 3.57–3.54 (2H, m, H-30, 6b), 2.07 (3H, s, –COCH3),
1.67–1.62 (2H, m, H-20,60a), 1.38–1.29 (5H, m, H-2,40a,b,50a,60b),
1.01–0.96 (1H, m, H-50b), 0.94 (3H, t, J 7.1 Hz, –CH3); 13C NMR
(100 MHz, CDCl3): dC 170.7 (C@O), 138.4, 138.18, 138.14, 128.4,
128.36, 128.32, 127.9, 127.7, 128.6, 78.4, 76.46, 76.42, 73.8, 73.36
(C-1), 73.33, 71.3, 69.7, 53.3, 33.6, 28.1, 27.4, 22.5, 21.1, 20.35
(–COCH3), 13.9 (–CH2–CH3). Found: C, 75.12; H, 7.20; calcd for
To a solution of amide 6 (100 mg, 0.19 mmol) in dry THF (5 mL)
at ꢂ78 °C was added a solution of n-BuLi (2.5 M, 0.72 mL, 3.6 mmol).
After 1 h at ꢂ78 °C the amide was fully consumed. The reaction mix-
ture was then diluted with diethylether, water added, the ether
layer recovered, and the aqueous layer re-extracted with ether.
The combined organic extracts were dried over MgSO4, filtered,
and concentrated in vaccuo. Purification of the crude product by col-
umn chromatography (petroleum ether–ethyl acetate mixtures)
afforded ketone 7 (73 mg, 74%) as an oil. IR (CHCl3/cmꢂ1) 1690
(C@O); 1H NMR (400 MHz, CDCl3): dH 7.33–7.18 (15H, m, Ar-H),
4.68 (1H, d, J 8.1 Hz, Ph-CH–), 4.65 (1H, d, J 8.4 Hz, Ph-CH–), 4.56–
4.47 (4H, m, 2 ꢃ Ph-CH2–), 3.82 (1H, dd, J 1.9, 7.1 Hz, H-1), 3.72
(2H, td, J 2.9, 6.1, 6.2 Hz, H-3,4), 3.66 (1H, dd, J 6.0, 10.3 Hz, H-6a),
3.65 (2H, dt, J 4.8, 4.8, 8.8 Hz, H-5, 6b), 2.49 (2H, dd, J 7.6, 15.2, –
CH2CH2CH2CH3), 2.28 (1H, dd, J 1.9, 5.6 Hz, H-2’), 1.95–1.90 (1H,
m, H-2), 1.59–1.49 (2H, m, –CH2CH2CH3), 1.30 (2H, dd, J 7.4,
14.9 Hz, –CH2CH3), 0.88 (3H, t, J 7.3 Hz, –CH3); 13C NMR (100 MHz,
CDCl3): dC 207.4 (C@O), 138.2, 138.1, 137.9, 128.4, 128.3, 127.8,
127.79, 127.73, 127.6, 76.1, 75.4, 74.5, 73.4. 73.2, 71.3, 69.2, 60.3
(C-1), 43.7 (–CH2CH2CH2CH3), 32.3 (C-20), 26.3 (C-2), 26.1
(–CH2CH2CH3), 22.3 (–CH2CH3), 13.8 (CH3–). Found: C, 77.06; H,
7.43; calcd for C33H38O5: C, 77.01; H, 7.44. [M+Na] calcd for
C33H38NaO5: 537.2617; found for C33H38NaO5: 537.2592.
C34H40O5: C, 75.24; H, 7.58. [M+Na] calcd for C35H42NaO6:
581.2879; found for C35H42NaO6: 581.2872.
3.12. Benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(E)-10-hexenyl]-
a/
b-D
-glucopyranoside 9a
Compound 8a (40 mg, 0.07 mmol) was treated with BnOH
(0.022 mL, 0.21 mmol) using Method B to give a crude product
which was purified by chromatography on silica gel to give the
E-alkene 9a, predominantly as the
a-glycoside with only traces
of the b isomer, as an oil (29 mg, 67%). 1H NMR (400 MHz, CDCl3):
dH 7.39–7.26 (20H, m, Ar-H), 5.65 (1H, td, J 6.6, 15.4 Hz, H-30), 5.50
(1H, tdd, J 1.2, 9.1, 15.3 Hz, H-20), 4.86 (1H, d, J 10.9 Hz, Ph-CH–),
4.81 (1H, d,
J
3.4 Hz, H-1), 4.74–4.63 (4H, m, 4 ꢃ Ph-CH–),
3.11. 1,5-Anhydro-2-deoxy-1,2-C-exo-(20-acetoxyhexylidene)-
3,4,6-tri-O-benzyl-a-D-glucitol (8a,b)
4.57–4.48 (3H, m, 3 ꢃ Ph-CH–), 3.93–3.64 (5H, m, H-3,4,5,6a, b),
2.57 (1H, ddd, J 3.4,9.2, 10.6 Hz, H-2), 2.09–2.04 (2H, m, H-40a,b),
1.37–1.29 (4H, m, H-50a,b,H-60a, b), 0.91 (3H, t, J 7.1 Hz, -CH3);
13C NMR (100 MHz, CDCl3): dC 138.7, 138.5, 138.2, 137.9, 134.8
(C-30), 128.3, 128.2, 127.7, 127.84, 127.80, 127.6, 127.56, 127.51,
To a stirred suspension of LiAlH4 (7 mg, 0.17 mmol) in dry Et2O
(5 mL) was added slowly a solution of 7 (73 mg, 0.14 mmol) in Et2O

M. Munyololo et al. / Carbohydrate Research 351 (2012) 49–55
55
126.6 (C-20), 100.3 (C-1), 81.0, 78.8, 74.9, 74.8, 73.4, 71.2, 69.08,
69.01, 51.6 (C-2), 32.3, 31.4, 22.2, 13.9 (–CH3). Found: C, 78.90;
H, 7.40; calcd for C40H46O5: C, 79.18; H, 7.64; [M+Na] calcd for
above, gave 10 as an oil (54 mg, 59%). 1H NMR (400 MHz, CDCl3):
dH 9.40 (1H, s, CHO), 7.35–7.23 (10H, m, Ar-H), 6.74 (1H, s, H-3),
4.67 (2H, dd, J 3.0, 12.2 Hz, Ph-CH2), 4.57 (2H, dd, J 4.7, 12.1 Hz,
Ph-CH2), 4.52 (1H, ddd, J 1.8, 2.5, 6.5 Hz, H-1), 4.26 (1H, dt, J 2.0,
8.6 Hz, H-4), 3.75 (2H, dd, J 2.0, 10.8 Hz, H-6a,b), 3.45–3.40 (1H,
ddd, J 2.0, 4.6, 8.7 Hz, H-5), 1.39 (3H, d, J 6.6 Hz, CH3); 13C NMR
(100 MHz, CDCl3): dC 191.8 (CHO), 147.4 (C-3), 144.3 (C-2), 138.1,
137.3, 128.5, 128.3, 128.1, 128.0, 127,9, 127.6, 75.9, 73.5, 72.1;
70.9, 70.6 (C-1), 69.0, 19.6 (CH3). The spectroscopic data were con-
sistent with the published data.17
C40H46NaO5: 629.3243; found for C40H46NaO5: 629.3234.
3.13. Benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[(E/Z)-10-hexenyl]-
/b- -Glucopyranoside 9b
a
D
Compound 8b (20 mg, 0.036 mmol) was treated with BnOH
(0.011 mL, 0.107 mmol) using Method B to give a crude product
which was purified by chromatography on silica gel to give an
inseparable mixture of E and Z alkenes 9b as an oil (19 mg, 86%,
Acknowledgments
E:Z = 1:1, predominantly as the
a-glycoside with only traces of
the b isomer). 1H NMR (400 MHz, CDCl3): dH 7.39–7.26 (20H, m,
Ar-H), 5.67–5.59 (1H, m, H-30), 5.53 (1H, tt, J 1.2, 7.8 Hz, H-20),
4.86 (1H, d, J 10.9 Hz, Ph-CH–), 4.82 (0.5H, d, J 3.5 Hz, H-1-Z),
4.79 (0.5H, d, J 3.5 Hz, H-1-E), 4.74–4.63 (4H, m, 4 ꢃ Ph-CH–),
4.57–4.48 (3H, m, 3 ꢃ Ph-CH–), 3.93–3.64 (5H, m, H-3,4,5,6a,b),
2.98 (0.5H, dt, J 3.3, 10.1 Hz, H-2-Z), 2.57 (1H, ddd, J 3.4, 9.2,
10.6 Hz, H-2-E), 2.09–2.04 (2H, m, H-4a,b), 1.37–1.29 (4H, m,
H-50a,b, H-60a,b), 0.91 (1.5H, t, J 7.1 Hz, –CH3-Z), 0.88 (1.5H, t, J
5.3 Hz, -CH3-E); 13C NMR (100 MHz, CDCl3): dC 138.8 (C-Z), 138.7
(C-E), 138.55 (C-Z), 138.51 (C-E), 138.2 (C-E), 138.1 (C-Z), 137.9
(C-E), 137.8 (C-Z), 134.8 (C-30E), 133.8 (C-Z), 128.3, 128.2, 128.1,
127.94, 127.91, 127.85, 127.80, 127.68, 127.68, 127.62, 127.56,
127.52, 127.4, 126.6 (C-20E), 126.2 (C-20Z), 100.3 (C-1-E), 99.6
(C-1-Z), 81.5 (C-Z), 81.0 (C-E), 78.87 (C-Z), 78.81 (C-E), 74.95
(C-E), 74.91 (C-Z), 74.8 (C-E), 74.5 (C-Z), 73.5 (C-Z), 73.4 (C-E),
71.2 (C-E), 71.1 (C-Z) 69.2 (C-Z), 69.08 (C-E), 69.01 (C-E), 68.9 (C-
Z) 51.6 (C-2-E), 45.8 (C-2-Z), 32.3 (C-E), 31.9 (C-Z) 31.4 (C-E), 27.5
(C-Z), 22.3 (C-Z), 22.2 (C-E), 13.95 (–CH3-Z) 13.9 (–CH3-E). Found:
C, 78.80; H, 7.20; calcd for C40H46O5: C, 79.18; H, 7.64. [M+Na]
calcd for C40H46NaO5: 629.3243; found for C40H46NaO5: 629.3217.
This work was funded by Grants from the National Research
Foundation of South Africa and the University of Cape Town. The
award of an Eric Abrahams Refugee Scholarship to MM by the Uni-
versity of Cape Town is also gratefully acknowledged.
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Al(OTf)3 (20 mg, 0.06 mmol) and AcOH (0.3 mL, 5.2 mmol) were
added to a solution of 2 (100 mg, 0.2 mmol) in CH2Cl2 (5 mL) and,
after reaction monitoring and workup according to Method B