A tandem ring-closing metathesis cleavable linker system for solid-phase oligosaccharide synthesis

Article abstract of DOI:10.1055/s-2004-831301

A novel triene linker system, that can be cleaved by a tandem ring-closing metathesis (RCM) reaction, is presented. The tandem RCM cleavage, that regenerates the active ruthenium catalyst without the need of additives like ethylene, proceeded very clean and fast to liberate cyclopent-2-enyl mannosides from the solid support. A cyclopent-2-enyl mannoside was isomerized to the corresponding vinyl ether glycoside, which could be readily deprotected by iodine-mediated hydrolysis.

Full text of DOI:10.1055/s-2004-831301

LETTER
2155
A Tandem Ring-Closing Metathesis Cleavable Linker System for Solid-Phase
Oligosaccharide Synthesis
T
andem
R
CM Cleavab
a
le
L
inker ttie S. M. Timmer,1 Jeroen D. C. Codée,1 Herman S. Overkleeft, Jacques H. van Boom,†
Gijsbert A. van der Marel*
Leiden Institute of Chemistry, Gorlaeus Laboratories, P. O. Box 9502, 2300 RA Leiden, The Netherlands
Fax +31(071)5274307; E-mail: g.marel@chem.leidenuniv.nl
Received 4 May 2004
† With deep sadness the authors inform the reader that our colleague, Jacques H. van Boom, died July 31st, at the age of 67.
usually require basic conditions. The exciting progress in
Abstract: A novel triene linker system, that can be cleaved by a
the development of efficient and stable metathesis cata-
tandem ring-closing metathesis (RCM) reaction, is presented. The
lysts and their use in metathesis reactions,4 both in solu-
tion and on a solid support, have prompted several groups
tandem RCM cleavage, that regenerates the active ruthenium cata-
lyst without the need of additives like ethylene, proceeded very
clean and fast to liberate cyclopent-2-enyl mannosides from the sol- to investigate metathesis based linkers for solid-phase
synthesis.5 A major disadvantage in contemporary solid-
id support. A cyclopent-2-enyl mannoside was isomerized to the
corresponding vinyl ether glycoside, which could be readily depro-
tected by iodine-mediated hydrolysis.
phase protocols based on metathesis mediated cleavage,
however, is the propensity of the catalyst to remain, after
release of the target molecule from the resin, covalently
attached to either the solid-phase or the released molecule.
Key words: glycosylations, linker, metathesis, ruthenium, solid-
phase
Additives, such as styrene or ethylene, are required for re-
generation of the catalyst. The necessity of using these ad-
The development of novel methodologies for the solid-
phase assembly of oligosaccharides is one of the major re-
search aims in contemporary carbohydrate chemistry.2
The nature of the linker system, connecting the first syn-
thon to the solid support, is of profound importance in any
solid-phase synthesis.3 The linker should be easy to install
on a polymeric support, be completely stable to all reac-
tion conditions en route to the target molecule and be ef-
ficiently and selectively cleavable under conditions that
do not affect the integrity of the product. Solid-phase oli-
gosaccharide synthesis necessitates the use of a linker that
is stable in both acidic and basic media since the introduc-
tion of glycosidic bonds generally proceeds under Lewis
acidic conditions, while protecting group manipulations
ditives limits the efficiency of metathesis mediated
cleavage in solid-phase synthesis.5,6 In order to overcome
this drawback, we envisaged a tandem ring-closing met-
athesis based cleavable linker system (Scheme 1), that al-
lows release of the target molecule with concomitant
liberation of the catalytic species. The approach com-
mences with the synthesis of immobilized triene 1,
equipped with an allylic alcohol for ensuing solid-phase
assembly of oligosaccharides (1 to 2). Reaction of the gly-
cosylated resin 2 with either Grubbs’ second generation
ruthenium pre-catalyst 37 or ruthenium catalyst 4, gener-
ated after one catalytic cycle, gives ruthenium alkylidene
5 with the release of styrene or ethylene. The first ring-
closure results in resin bound ruthenium complex 7 with
[Ru]
R
O
O
O
O
O
[Ru]
3 (R = Ph)
4 (R = H)
4
glycosylation
RCM
RCM
8
[Ru]
styrene or
ethylene
[Ru]
7
6
Mes N
Ru
N Mes
Cl
OR
OH
OR
OR
5
1
2
Cl
Ph
P(Cy)3
3
Scheme 1 Tandem RCM linker system.
SYNLETT 2004, No. 12, pp 2155–2158
0
1
.1
0
.2
0
0
4
Advanced online publication: 24.08.2004
DOI: 10.1055/s-2004-831301; Art ID: G15004ST
© Georg Thieme Verlag Stuttgart · New York

2156
M. S. M. Timmer et al.
LETTER
OR1
concomitant release of saccharide 6, having a cyclopente-
nyl protecting group at the reducing end. The following
RCM event leads to immobilized cyclopentene 8 and re-
lease of catalyst 4. Alternatively, the first RCM can take
place at the adjacent terminal double bond, resulting in the
release of saccharide and resin in reverse order. Since no
ethylene atmosphere is required in the overall metathesis
process and the active catalyst [Ru]=CH2 is regenerated
after each cleavage cycle, a fast and efficient cleavage re-
action is expected. We here present the synthesis of a dou-
ble ring-closing metathesis cleavable linker and its use in
the solid-phase assembly of a dimannoside.
OAc
O
BnO
BnO
BnO
ii
O
OBn
OR2
16
13 R1 = MMT, R2 = H
14 R1 = H, R2 = Bn
i
iii
OAc
O
BnO
BnO
BnO
The synthesis of the linker system starts with selective
mono epoxidation of cycloocta-1,5-diene (9) using m-
chloroperoxybenzoic acid (m-CPBA) to give epoxide 10
(Scheme 2). Acidic epoxide opening and ensuing oxida-
tive cleavage of the resulting diol yielded dialdehyde 11.
In the next step, a double Grignard reaction of dialdehyde
11 with vinylmagnesium bromide furnished, after purifi-
cation by silica gel chromatography, the linker core struc-
ture 12 in an overall yield of 83%.8 In order to allow
colorimetric determination of the loading on the resin,9
diol 12 was treated with mono-methoxytrityl chloride
(MMT-Cl) in pyridine to yield the mono MMT protected
linker 13.
OAc
BnO
BnO
BnO
O
17
O
+
O
CCl3
NH
15
OBn
18
Scheme 3 Solution phase double ring-closing metathesis. Reagents
and conditions: i) a. BnBr, NaH, DMF, b. TFA, TES, CH2Cl2, 87%;
ii) 15 (3 equiv), TMSOTf (0.3 equiv), CH2Cl2, –20 °C, 70%; iii) 3 (5
mol%), CH2Cl2, reflux, 17: 92%, 18: 85%.
Triene 16 was dissolved in dichloromethane (0.01 M) and
treated with ruthenium pre-catalyst 3 (5 mol%) at reflux
temperature. Monitoring of the reaction progress by TLC
analysis showed that the substrate was completely con-
verted into two new products within fifteen minutes.
Workup and purification led to the isolation of cyclopent-
2-enyl mannoside 17 and benzyloxy-cyclopentene 18 in
excellent yields.
O
O
i
ii
O
9
10
11
iii
OMMT
OH
Encouraged by these results we turned our attention to-
wards the solid-phase assembly of dimannoside 25
(Scheme 4). To this end, linker 13 was coupled to Merri-
field polystyrene resin 19 (1% cross-linked, loading 0.8
mmol/g) under the agency of sodium hydride and a cata-
lytic amount of TBAOTf. After stirring overnight at 50
°C, methanol was added to ensure capping of the remain-
ing chloromethyl groups and the resin was filtered,
washed (DMF, MeOH, CH2Cl2, Et2O) and dried to give
functionalized resin 20, the loading of which was deter-
mined to be 0.38 mmol/g.
iv
OH
OH
12
13
Scheme 2 Synthesis of linker system 13. Reagents and conditions:
i) m-CPBA, CH2Cl2, 0 ºC; ii) H5IO6, dioxane, H2O; iii) vinyl MgBr,
Et2O, THF, 83% (over 3 steps), iv) MMTCl, pyridine, 64%.
Acidolysis of the MMT group by dichloroacetic acid lib-
erated the secondary hydroxyl function for the ensuing
glycosylation sequence with trichloroacetimidate manno-
side 15. The presence of the 2-O-acetyl function not only
ensures the selective formation of an a-glycosidic bond,
but also allows selective deprotection for ensuing chain
extension. Glycosylation of the solid support 21 was ac-
complished by treatment of the resin with 3 equivalents of
mannosyl donor 15 and a catalytic amount of TMSOTf
(0.3 equivalents) at –20 °C. After the resin was filtered,
washed and dried, the condensation was repeated to en-
sure complete glycosylation. Deacetylation of the resin-
bound mannoside 22 was achieved by treatment of the
resin with sodium methoxide in dichloromethane/metha-
nol. Glycosylation of the free hydroxyl in immobilized
The efficiency of the tandem RCM cleavage of the triene
linker system was first assessed in solution (Scheme 3). In
order to mimic the polystyrene resin, the MMT group in
linker 13 was replaced with a benzyl ether. Treatment of
13 with sodium hydride and benzyl bromide in the pres-
ence of a catalytic amount of tetra-n-butylammonium tri-
flate (TBAOTf) and subsequent acidic cleavage of the
MMT ether in the presence of the cation scavenger trieth-
yl silane (TES) led to the isolation of benzyl ether 14 in
87% yield. The linker was functionalized with 2-O-acetyl-
3,4,6-tri-O-benzyl mannose by trimethylsilyl triflate
(TMSOTf) mediated glycosylation of 14 with trichloro-
acetimidate 1510 to give model substrate 16 in 70% yield.
Synlett 2004, No. 12, 2155–2158 © Thieme Stuttgart · New York

LETTER
Tandem RCM Cleavable Linker
2157
OAc
O
OAc
BnO
BnO
BnO
BnO
O
BnO
BnO
i
i
Cl
O
OR
O
O
19
17
26
OR
ii
20 R = MMT
21 R = H
ii
OAc
O
BnO
BnO
BnO
iii
OH
OAc
O
27
BnO
BnO
BnO
OR
Scheme 5 Isomerization and hydrolysis of cyclopentenyl manno-
side 17. Reagents and conditions: i) (PPh3)3RhCl (25 mol%), DBU
(25 mol%), EtOH, reflux, 78%; ii) I2, THF–H2O (4:1, v/v), 20 min,
BnO
v
O
O
BnO
BnO
BnO
BnO
O
BnO
O
n
O
22 R = Ac, n = 1
23 R = H, n = 1
24 R = Ac, n= 2
iv
Synthesis of Linker 12.
25
iii
meta-Chloroperoxybenzoic acid (100 mmol, 22.0 g, 70–75%) was
slowly added to a cooled (0 °C) and stirred mixture of 1,5-cyclooc-
tadiene (100 mmol, 10.8 g, 12.3 mL) in CH2Cl2 (250 mL). After the
initial exothermic reaction had subsided, the mixture was allowed to
warm to r.t. and stirring was continued for 15 min. The white pre-
cipitate was filtered and the filtrate was evaporated under reduced
pressure. The residue was taken up in CH2Cl2 (100 mL) and filtered
again. Evaporation of the filtrate gave epoxide 10 as colorless oil,
which was used without further purification. To a cooled (ice bath)
and stirred mixture of the epoxide 10 in dioxane (200 mL) was add-
ed dropwise (over 15 min) a solution of H5IO6 (100 mmol, 22.5 g)
in H2O (100 mL). The ice-bath was removed and stirring was con-
tinued for 1 h. The aqueous layer was extracted with CH2Cl2
(3 × 100 mL) and the combined organic layers were washed with
sat. aq NaHCO3 and brine, dried (MgSO4), filtered and evaporated
to give dialdehyde 11 as a colorless syrup. To a cooled (ice bath)
and vigorously stirred mixture of the 4-octenedial in dry Et2O (400
mL) was added dropwise, over 15 min, a solution of vinylmagne-
sium chloride (220 mmol, 130 mL, 1.7 M in THF). The ice bath was
removed and stirring was continued for 1 h. Under vigorous stirring
sat. aq NH4Cl (400 mL) was slowly added. The organic layer was
separated and washed with sat. aq NH4Cl and brine, dried (MgSO4),
filtered and concentrated. Purification of the residue by silica gel
column chromatography gave homogeneous 12 (16.0 g, 83 mmol,
83%) as a colorless syrup. IR (thin film): 3314, 2928, 2866, 1427,
Scheme 4 Solid-phase synthesis of a model disaccharide. Reagents
and conditions: i) 13, NaH, TBAOTf, DMF, 50 ºC, 16 h, then: MeOH,
50 ºC, 1h; ii) 3% DCA, CH2Cl2; iii) 15 (3 equiv), TMSOTf (0.3
equiv), CH2Cl2, –20 ºC; iv) NaOMe (10 equiv), MeOH, CH2Cl2; v) 3
(10 mol%), CH2Cl2, reflux, 67%.
mannoside 23, using the same conditions as mentioned
before, gave the immobilized disaccharide 24. Treatment
of resin 24 with 10 mol% of Grubbs’ catalyst 3 in reflux-
ing dichloromethane for two hours gave, after flash col-
umn chromatography, homogeneous disaccharide 25 in a
satisfying 67% yield, which corresponds with an average
yield of 90% per step.
The anomeric cyclopentenyl group in the released disac-
charide allows a variety of functionalizations. Evidently
the cyclopent-2-enyl group can function as an anomeric
protecting group, which upon hydrogenation will result in
the formation of an inert cyclopentane cap. Furthermore,
the cyclopent-2-ene moiety can be rearranged to furnish
the cyclopent-1-enyl isomer, which is susceptible to acid-
ic cleavage to provide the anomeric deprotected glyco-
side. Isomerization of the cyclopent-2-ene moiety in
mannoside 17 under influence of Wilkinson’s catalyst and
1,8-diazabicyclo[5.4.0]undec-7-ene gave the substituted
vinyl ether 26 (Scheme 5). Treatment of the vinyl ether
with iodine in aqueous THF resulted in smooth deblock-
ing of the anomeric center to provide anomeric free man-
noside 27.
1053, 991, 918, 678, 661 cm–1. H NMR (200 MHz, CDCl3): d =
1
5.88 (ddd, J = 17.2 Hz, J = 10.3 Hz, J = 6.0 Hz, 2 H, H-2 and H-11),
5.49–5.34 (m, 2 H, H-6 and H-7), 5.24 (dt, J = 17.2 Hz, J = 1.5 Hz,
2 H, H-1a and H-12a), 5.11 (dt, J = 10.3 Hz, J = 1.4 Hz, 2 H, H-1b
and H-12b), 4.12 (app tq, J = 1.5 Hz, J = 6.5 Hz, 2 H, H-3 and H-
10), 2.45–2.33 (m, 4 H, H-5 and H-8), 2.24–2.11 (m, 4 H, H-4 and
H-9), 2.72 (br s, 2 H, OH). 13C NMR (50 MHz, CDCl3): d = 140.7
(C-2 and C-11), 129.0 (C-6 and C-7), 113.6 (C-1 and C-12), 71.4
(C-3 and C-10), 36.2 (C-4 and C-9), 22.5 (C-5 and C-8).
In summary, a tandem ring-closing metathesis cleavable
triene linker system was designed and could be prepared
in a high yielding three-step reaction sequence, starting
from 1,5-cyclooctadiene. Both the solution and solid-
phase ring-closing metathesis proceeded very clean and
fast to liberate the target cyclopent-2-enyl mannosides.
Application of the linker system in the solid-phase assem-
bly of more complex oligosaccharides and glycoconju-
gates will be reported in due course.
Cyclopent-2-enyl 2-O-(2-O-acetyl-3,4,6-tri-O-benzyl-a-D-man-
nopyranosyl)-3,4,6-tri-O-benzyl-a-D-mannopyranoside (25).
Grubbs’ catalyst 3 (2.3 mg, 10 mol%) was added to a dry suspension
of resin 24 (27 mmol) in CH2Cl2 (2 mL), under an argon atmosphere.
After refluxing for 2 h, the resin was filtered and washed with
CH2Cl2, MeOH and CH2Cl2. Concentration of the mother liquor
gave the crude product, which was purified by silica gel column
chromatography (light petroleum ether–20% EtOAc in light petro-
leum ether) to give homogeneous cyclopentenyl dimannoside 25
(17 mg, 17 mmol, 67%). IR (thin film): 2924, 2862, 2361, 2341,
1744, 1497, 1454, 1366, 1234, 1134, 1084, 1049, 980, 914, 826,
Synlett 2004, No. 12, 2155–2158 © Thieme Stuttgart · New York

2158
M. S. M. Timmer et al.
LETTER
737, 698 cm–1. 1H NMR (400 MHz, CDCl3): d = 7.40–7.12 (m, 30
H, CH Ph), 5.98–5.89 (m, 1 H, H-2¢), 5.84–5.76 (m, 1 H, H-3¢), 5.53
(br s, 1 H, H-2¢), 5.08 (br s, 1 H, H-1¢), 5.02 (br s, 1 H, H-1), 4.86–
4.36 (m, 13 H, H-1¢¢ and CH2 Bn), 4.02–3.65 (m, 11 H, H-2, H-3,
H-4, H-5, H-6, H-3¢, H-4¢, H-5¢ and H-6¢), 2.48–2.32 (m, 1 H, H-
4a¢¢), 2.27–2.98 (m, 5 H, H-4b¢¢, 5a¢¢ and CH3 Ac), 1.80–1.64 (m, 1
H, H-5b¢¢). 13C NMR (100 MHz, CDCl3): d = 170.1 (CO Ac), 138.5,
138.44, 138.40, 138.2, 138.0 (Cq Ph), 136.0, 135.5 (C-3¢¢), 131.5,
130.1 (C-2¢¢), 128.3, 128.14, 128.06, 127.8, 127.6, 127.53, 127.46,
127.3 (CH Ph), 99.5 (C-1¢), 97.1 (C-1), 83.3, 82.7, 79.7, 78.1, 75.2,
74.8, 74.4, 71.8, 71.7, 68.7 (C-2, C-3, C-4, C-5, C-2¢, C-3¢, C-4¢, C-
5¢), 75.2, 75.1, 73.4, 73.3, 71.9 (CH2 Bn), 69.3, 69.0 (C-6 and C-6¢),
31.1, 30.7, 30.5, 29.7 (C-4¢¢ and C-5¢¢), 21.1 (CH3 Ac). HRMS: m/z
calcld for C61H66O12Na: 1013.4451; found: 1013.4476.
Carbohydrate Libraries; Seeberger, P. H., Ed.; Wiley: New
York, 2001. (h) Khersonsky, S. M.; Ho, C. M.; Garcia, M.
A. F.; Chang, Y. T. Curr. Top. Med. Chem. 2003, 3, 617.
(i) Franzen, R.; Tois, J. Comb. Chem. High Throughput
Screening 2003, 6, 433. (j) Plante, O. J.; Seeberger, P. H.
Curr. Opin. Drug Discovery Dev. 2003, 6, 521.
(3) (a) Gordon, K.; Balasubramanian, S. J. Chem. Technol.
Biotechnol. 1999, 74, 835. (b) Brown, A. R.; Hermkens, P.
H. H.; Ottenheijm, H. C. J.; Rees, D. C. Synlett 1998, 817.
(4) (a) Ivin, K. J.; Mol, J. C. Olefin Metathesis and Olefin
Metathesis Polymerization, 1st ed.; Academic Press:
London, 1997. (b) Fürstner, A. Top. Catal. 1997, 4, 285.
(c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl.
1997, 36, 2037. (d) Grubbs, R. H.; Chang, S. Tetrahedron
1998, 54, 4413. (e) Armstrong, S. K. J. Chem. Soc., Perkin
Trans. 1 1998, 371. (f) Ivin, K. J. J. Mol. Catal. A 1998, 133,
1. (g) Pandit, U. K.; Overkleeft, H. S.; Borer, B. C.;
Bieräugel, H. Eur. J. Org. Chem. 1999, 959. (h) Wright, D.
L. Curr. Org. Chem. 1999, 3, 211. (i) Blechert, S. Pure
Appl. Chem. 1999, 71, 1393. (j) Jørgensen, P.; Hadwiger,
P.; Madsen, R.; Stütz, A. E.; Wrodnigg, T. M. Curr. Org.
Chem. 2000, 4, 565. (k) Roy, R.; Das, S. K. Chem. Commun.
2000, 519. (l) Fürstner, A. Angew. Chem. Int. Ed. 2000, 39,
3013. (m) Hoveyda, A. H.; Schrock, R. R. Chem.–Eur. J.
2001, 7, 945. (n) Schrock, R. R.; Hoveyda, A. H. Angew.
Chem. Int. Ed. 2003, 42, 4592. (o) Connon, S. J.; Blechert,
S. Angew. Chem. Int. Ed. 2003, 42, 1900.
Cyclopent-1-enyl 2-O-acetyl-3,4,6-tri-O-benzyl-a-D-manno-
pyranoside (26).
(Ph3P)3RhCl (22 mg, 25 mol%) and DBU (3.5 mL, 25 mol%) were
added to a solution of 17 (52 mg, 0.093 mmol) in abs. EtOH (1.5
mL). The resulting mixture was refluxed until TLC analysis (light
petroleum ether/EtOAc, 4/1, v/v) showed complete conversion of
the starting material into a higher running product. Concentration of
the reaction mixture and purification of the residue by silica column
chromatography (light petroleum ether–20% EtOAc in light petro-
leum ether) gave homogeneous vinyl ether 26 (41.0 mg, 0.073
20
mmol, 78%). [a]D +28.0 (c 0.6, CHCl3). IR (thin film): 2928,
2855, 2361, 2341, 1744, 1651, 1497, 1454, 1366, 1231, 1103, 1045,
1
984, 910, 795, 737, 698 cm–1. H NMR (300 MHz, CDCl3): d =
(p) Leeuwenburgh, M. A.; Van der Marel, G. A.; Overkleeft,
H. S. Curr. Opin. Chem. Biol. 2003, 7, 757.
7.33–7.13 (m, 15 H, CH Ph), 5.42 (br s, 1 H, H-2), 5.30 (br s, 1 H,
H-1), 4.88–4.44 (m, 7 H, H-2¢ and CH2 Bn), 4.05–3.66 (m, 5 H, H-
3, H-4, H-5 and H-6), 2.37–2.23 (m, 4 H, H-3¢ and H-5¢), 2.16 (s, 3
H, CH3 Ac), 1.28–1.21 (m, 2 H, H-4¢). 13C NMR (75.5 MHz,
CDCl3): d = 170.4 (CO Ac), 155.5 (C-1¢¢), 138.3, 138.2, 137.9 (Cq
Ph), 128.4, 128.3, 128.02, 127.95, 127.83, 127.81, 127.7, 127.61,
127.56 (CH Ph), 99.6 (C-2¢), 96.1 (C-1), 78.0 (C-3), 75.2 (CH2 Bn),
74.0 (C-4), 73.4, 71.9 (CH2 Bn), 71.8 (C-5), 68.6 (C-6), 68.3 (C-2),
31.4, 29.0 (C-3¢ and C-5¢), 21.1 (CH3 Ac), 20.9 (C-4¢). HRMS: m/z
calcd for C37H38O7Na: 581.2509; found: 581.2512.
(5) (a) Knerr, L.; Schmidt, R. R. Synlett 1999, 1802. (b) Knerr,
L.; Schmidt, R. R. Eur. J. Org. Chem. 2000, 2803.
(c) Andrade, R. B.; Plante, O. J.; Melean, L. G.; Seeberger,
P. H. Org. Lett. 1999, 1, 1811. (d) Melean, L. G.; Haase, W.
C.; Seeberger, P. H. Tetrahedron Lett. 2000, 41, 4329.
(e) Palmacci, E. R.; Plante, O. J.; Hewitt, M. C.; Seeberger,
P. H. Helv. Chim. Acta 2003, 86, 3975. (f) Kanemitsu, T.;
Seeberger, P. H. Org. Lett. 2003, 5, 4541.
(6) Van Maarseveen, J. H.; Den Hartog, J. A. J.; Engelen, V.;
Finner, E.; Visser, G.; Kruse, C. G. Tetrahedron 1993, 49,
3665.
(7) (a) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H.
Tetrahedron Lett. 1999, 40, 2247. (b) Trnka, T. M.;
Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.;
Choi, T. L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am.
Chem. Soc. 2003, 125, 2546.
Acknowledgment
This work was financially supported by the Netherlands Technolo-
gy Foundation (STW). The authors thank Kees Erkelens and Fons
Lefeber for their assistance with NMR measurements.
(8) A combination of literature procedures was used:
(a) Nagarkatti, J. P.; Ashley, K. R. Tetrahedron Lett. 1973,
14, 4599. (b) Hoye, T. R.; Suhadolnik, J. C. Tetrahedron
1986, 42, 2855. (c) Meier, H.; Mayer, W.; Kolshorn, H.
Chem. Ber. 1987, 120, 685. (d) Ruan, Z.; Mootoo, D. R.
Tetrahedron Lett. 1999, 40, 49. (e) Dabideen, D.; Ruan, Z.;
Mootoo, D. R. Tetrahedron 2002, 58, 2077.
(9) The loading was determined by spectroscopic analysis of a
suspension of resin (2.0–3.0 mg) in 3% TCA in CH2Cl2 (50
mL): B = A477·V/(elm), where B = loading (mmol/g),
A = absorbance at l = 477 nm, V = volume (mL), e = 56·103
M–1m–1, l = pathway length (cm), m = mass of resin (g). See
also: Will, D. W.; Langner, D.; Knolle, J.; Uhlmann, E.
Tetrahedron 1995, 51, 12069.
References
(1) These authors contributed equally to this work.
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