Selective cross-metathesis of C-allyl-glycosides

Article abstract of DOI:10.1080/07328300500174887

The efficient and selective cross-metathesis (CM) of both the α- and β-anomers of C-allyl-glucose and N-acetyl-C-allyl-glucosamine with electron-deficient olefins is reported. The applicability of our CM approach in the synthesis of glycoside-conjugates i

Full text of DOI:10.1080/07328300500174887

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Selective Cross‐Metathesis of
C‐Allyl‐Glycosides
Mattie S. M. Timmer a , Marta Vinciano Chumillas a , Wilma E.
Donker‐Koopman b , Johannes M. F. G. Aerts b , Gijsbert A. van
derMarel a , Herman S. Overkleeft a & Jacques H. van Boom a
a Leiden Institute of Chemistry, Leiden University, Leiden, The
Netherlands
b Academic Medical Centre, University of Amsterdam, Amsterdam,
The Netherlands
Version of record first published: 16 Aug 2006
To cite this article: Mattie S. M. Timmer, Marta Vinciano Chumillas, Wilma E. Donker‐Koopman,
Johannes M. F. G. Aerts, Gijsbert A. van derMarel, Herman S. Overkleeft & Jacques H. van Boom
(2005): Selective Cross‐Metathesis of C‐Allyl‐Glycosides, Journal of Carbohydrate Chemistry, 24:4-6,
335-351
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Journal of Carbohydrate Chemistry, 24:335–351, 2005
Copyright # Taylor & Francis, Inc.
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300500174887
Selective Cross-Metathesis
of C-Allyl-Glycosides
Mattie S. M. Timmer and Marta Vinciano Chumillas
Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
Wilma E. Donker-Koopman and Johannes M. F. G. Aerts
Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Gijsbert A. van der Marel, Herman S. Overkleeft,
and Jacques H. van Boom†
Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
The efficient and selective cross-metathesis (CM) of both the a- and b-anomers of C-allyl-
glucose and N-acetyl-C-allyl-glucosamine with electron-deficient olefins is reported. The
applicability of our CM approach in the synthesis of glycoside-conjugates is illustrated
by the CM of a-C-allyl-glycosamine 2 with uridinyl vinylphosphonate 22, to produce
UDP-GlcNAc analog 23.
Keywords Synthesis, Cross-metathesis, C-glycosides, UDP-GlcNAc, Inhibitor
INTRODUCTION
Olefin metathesis has become an increasingly important and powerful tool in
organic chemistry.[1] The success of olefin metathesis is largely due to the deve-
lopment of stable, reactive, and functional group-tolerant precatalysts, the
most important examples of which are the ruthenium alkylidenes I and II
(Fig. 1).[2] The great potential of olefin metathesis is illustrated by the recent
advances in the synthesis of disubstituted olefins by cross-metathesis (CM)
reactions.[3] Although several types of alkenes have been applied in CM
Received April 10, 2005; accepted May 18, 2005.
†With deep sadness the authors inform the reader that our colleague, Jacques H. van
Boom, died on July 31, 2004 at the age of 67.
Address correspondence to Herman S. Overkleeft, Leiden Institute of Chemistry, Leiden
University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. E-mail: h.s.overkleeft@
chem.leidenuniv.nl
335

M. S. M. Timmer et al.
336
Figure 1: Olefin metathesis precatalysts.
using the first-generation ruthenium precatalysts I,[4] nonterminal and conju-
gated olefins in general are poor substrates in combination with this catalyst.
Since the emergence of the N-heterocyclic carbene (NHC) coordinated precata-
lysts,[5] such as the second-generation Grubbs’ precatalyst II, both nonterminal
and conjugated olefins can now participate in productive CM events.[6] Theor-
etically, CM of two differently substituted terminal alkenes (A and B) can lead
to the formation of up to six products (Sch. 1).
Besides the desired heterodimeric product(s) C, two undesired homodi-
meric products (D and E) can be formed, all as a mixture of E and Z isomers.
Major goals in the area of CM comprise the acquirement of product selectivity
and control over E/Z ratios. One of the first examples of a ruthenium complex
I-catalyzed CM is the heterodimerization of the electron-rich allyltrimethylsi-
lane[7] and a variety of aliphatic alkenes. Although high product selectivity was
obtained, the E/Z-selectivity was low. Blechert and coworkers have shown that
product selectivity can be increased by using Grubbs’ second-generation preca-
talyst II in the CM of sterically hindered terminal olefins, which proved to
undergo selective CM with a variety of commercially available terminal
olefins.[8] On the other hand, Grubbs and coworkers have developed a two-
step CM procedure in which terminal olefins are first homodimerized prior to
a second CM event with a second alkene, leading to heterodimers with con-
siderably improved reaction rates and high E-selectivity.[9] Recently, it has
become evident that a combination of aliphatic olefins with more electrophilic
alkenes, such as a,b-unsaturated esters, ketones, and phosphonates, leads to
good product selectivities.[10] The unreactive electron-poor alkene is prohibited
to undergo self-metathesis, while the aliphatic olefin can, after homodimeri-
zation, undergo a second metathesis event with the a,b-unsaturated alkene
to form the desired product. In this paper we report the ruthenium complex
II-catalyzed CM of C-allyl-glycosides, bearing an electron-rich double bond,
Scheme 1: Olefin cross-metathesis products.

Cross-Metathesis of C-Allyl-Glycosides
337
with electron-poor alkenes to give anomerically functionalized C-glycosides.
Some initial results in the assessment of inhibitory activity against N-acetyl-
glucosamine processing enzymes are presented.
RESULTS AND DISCUSSION
The C-allyl-glucosides (1–4), which we have selected for CM with a set of
commercially available a,b-unsaturated alkenes (5–7), are depicted in
Figure 2. Both the a- and b-anomers of C-allyl-D-glucose and N-acetyl-C-
allyl-D-glucosamine were readily accessible through known procedures.[11–14]
The a-C-allyl-glucopyranoside 1 was treated with 5 mol% of Grubbs’ preca-
talyst II and five equivalents of dimethyl vinylphosphonate (5) in DCM, under
an argon atmosphere. After refluxing for 14 hr, TLC-analyses showed complete
disappearance of 1 and the formation of a more polar compound. Work-up and
purification by silica gel column chromatography led to the isolation of pure
E-glucosylphosphonate 8 in 71% yield (entry 1, Table 1). We were quite
pleased to see that only a trace amount, as judged by the relative intensities
of the corresponding 1H NMR signals, of the Z-product was formed. Subjection
of N-acetyl-C-allyl-D-glucosamine 2 to the above-mentioned CM conditions
proceeded uneventfully to give E-glucosaminophosphonate 9 in a satisfying
yield of 72% (entry 2). The series of glyco-phosphonates was completed by a
similar treatment of the b-C-glucosides 3 and 4, which afforded phosphonates
10 and 11 yields of 85% and 84%, respectively (entries 3 and 4), again with only
trace amounts of the Z-isomers. Next, the set of glucosides (1–4) was subjected
to CM with tert-butyl acrylate (6). Again, selective CM was achieved resulting
in tert-butyl glucosylacrylates 12–15 (entries 5–8) in excellent yields, ranging
from 74% to 93%. Similar results were obtained in the CM of glucosides 1–4
with acrylic acid (7) and 3-glucosyl-acrylic acids 16–19 could be isolated in
Figure 2: C-allyl-glycosides and electron-deficient alkenes.

Table 1: CM of C-allyl-glycosides with electron-deficient alkenes.a
Entry
Alkenes
Product
Yieldb
Entry
Alkenes
Product
Yieldb
1
1
5
71
7
3
6
87
2
3
2
3
5
5
72
85
8
9
4
1
6
7
74
82

4
4
5
84
10
2
7
81
5
6
1
2
6
6
90
93
11
12
3
4
7
7
78
72
aReagents and conditions: II (5 mol%), DCM, reflux, Ar, 14 hr.
bYield of isolated products.

M. S. M. Timmer et al.
340
72% to 82% (entries 9–12). The outcome of this study clearly demonstrates that
CM is an efficient approach to carbohydrate derivatives that are functionalized
differently at the anomeric center. Application of more intricate electrophilic
alkenes should allow the synthesis of advanced C-glycoside-conjugates. In
this framework, we set out to apply our CM approach to the synthesis of
UDP-GlcNAc analog 23 (Sch. 2).
The required uridinyl vinylphosphonate 22 was readily obtained via a
phosphorylation strategy developed earlier in our laboratory.15 Condensation
of 20,30-benzoyl-uridine 20 with the cyanoethyl (CNE)-protected phosphorami-
dite 21 using 1H-tetrazole as the activating agent followed by in situ oxidation
of the intermediate phosphine with tert-butyl hydrogenperoxide led to the
isolation of uridinyl vinylphosphonate 22 in 73% over the two steps. Unfortu-
nately, treatment of uridinyl phosphonate 22 and a-C-allyl-glucosamide 2
with precatalyst II under the earlier mentioned conditions only led to trace
amounts of the expected product 23. These results are in accordance with
the study of Lera et al. on the CM of CNE-protected vinylphosphonates.[6d]
It occurred to us that the use of copper(I) chloride, applied by Blechert and
coworkers in their CM studies of acrylonitrile,[16] could have a beneficial
Scheme 2: Synthesis of UDP-GlcNAc analog 24. Reagents and conditions: (i) 1H-tetrazole (3)
equiv.), MeCN, RT, Ar, then tBuOOH, 08C, 5 min, 73%. (ii) II (5 mol%), CuCl (20 mol%), DCM,
reflux, Ar, 3 hr, 58%, E/Z ¼ 8:1. (iii) NaOMe, MeOH, RT, 16 hr, 75% (24), 95% (25), 95% (26).

Cross-Metathesis of C-Allyl-Glycosides
341
effect on the yield of 23. Gratifyingly, execution of the CM of 2 and 22 with
5 mol% Grubbs0 precatalyst II in combination with 20 mol% copper(I) chloride
gave the protected UDP-GlcNAc conjugate 23 as an 8:1 mixture of E- and
Z-isomers, in 58% yield. HPLC purification led to the homogeneous E-isomer,
the identity of which was fully ascertained by NMR and HRMS. To determine
the inhibitory potential of the a,b-unsaturated phosphonates, compound 23 as
well as the a- and b-glucosamine phosphonates 9 and 11 were deprotected
under basic conditions to give neoglycosides 24, 25, and 26.
The inhibitory potency of 24, 25, and 26 was tested toward human
b-hexosamidase purified from spleen and recombinant human chitinase
(chitotriosidase), an endo-b-D-N-acetylglucosaminidase.[17] The outcome of
these studies showed that compounds 25 and 26 are only weak inhibitors at
1 mM concentrations, whereas for compound 24 no inhibition was observed.
Studies on the inhibitory activities of 24–26 in a standard N-acetyl-D-
glucosaminyltransferase[18] assay revealed that none of these compounds
was able to inhibit N-acetyl-D-glucosaminyltransferase activity.
CONCLUSION
In conclusion, we have presented a short and efficient synthesis of anomerically
functionalized a- and b-C-glycosides, from inexpensive, readily available
precursors by way of a ruthenium-based olefin CM reaction. The viability
of this procedure is exemplified in the synthesis of UDP-GlcNAc analog 24
and both a- and b-glucosamine-phosphonates 25 and 26. Biologic screening
indicates that these compounds are poor inhibitors of human lysosomal b-
hexosaminidase isolated from spleen, recombinant human chitinase, and an
N-acetyl-D-glucosaminyltransferase.
EXPERIMENTAL
General Methods and Materials
All reactions were performed dry, under an inert atmosphere and at
ambient temperature unless stated otherwise. Toluene (purum), ethyl
acetate (puriss.), and light petroleum ether (puriss.) were obtained from
¨
Riedel-de Haen and distilled prior to use. Acetonitrile, dichloromethane, and
˚
diethyl ether (Biosolve) were stored on 4A molecular sieves. THF (Biosolve)
was distilled from LiAlH4 prior to use. Acrylic acid (Merck) was distilled
prior to use. tert-Butyl acrylate (Aldrich), tert-butyl hydroperoxide (Fluka),
dimethyl vinylphosphonate (Fluka), methanol (Biosolve), 1H-tetrazole
(Acros), and triethylamine (Acros) were used as received. All solvents were
removed by evaporation under reduced pressure. Reactions were monitored

M. S. M. Timmer et al.
342
by TLC analysis using DC-fertigfolien (Schleicher & Schuell, F1500, LS254)
with detection by UV-absorption (254 nm), by spraying with an aqueous
solution of KMnO4 (7%) and KOH (2%), by spraying with 20% H2SO4 in
ethanol followed by charring at ꢀ1508C, or by spraying with a solution of
.
.
(NH4)6Mo7O24 4H2O (25 g/L) and (NH4)4Ce(SO4)4 2H2O (10 g/L) in 10%
sulfuric acid followed by charring at ꢀ1508C. Column chromatography was
performed on Merck silicagel (0.040–0.063 nm). Mass spectra were recorded
on a PE/Sciex API 165 instrument and HRMS (SIM mode) were recorded on
a TSQ Quantum (Thermo Finnigan) fitted with an accurate mass option, inter-
polating between PEG-calibration peaks. H, 13C-APT, and 31P NMR spectra
1
were recorded on a Jeol JNM-FX-200 (200/50.1/81.1 MHz), a Bru¨ker WM-
300 (300/75.1/121 MHz), a Bru¨ker AV-400 (400/100/162 MHz), or a Bru¨ker
DMX-600 (600/150/242 MHz) spectrometer. Chemical shifts are given in
ppm (d) relative to tetramethylsilane (1H NMR and 13C NMR) or 85% H3PO4
(31P NMR). Coupling constants (J) are given in Hz. Where indicated, NMR
peak assignments were made using COSY and NOESY experiments. All pre-
sented 13C-APT and 31P spectra are proton decoupled. Optical rotations were
measured on a Propol automatic polarimeter (Sodium D line, l ¼ 589 nm)
and ATR-IR spectra were recorded on a Shimadzu FTIR-8300 fitted with a
single bounce DurasamplIR diamond crystal ATR-element.
General procedure for the cross-metathesis of glycosides 1–4 with
electron-deficient alkenes 5–7. The electron-deficient alkene (5 equiv.) and
Grubbs’ second-generation precatalyst II (0.05 equiv.) were added to a solution
of the C-allyl-glycoside in DCM (5 mL/mmol) under an argon atmosphere.
After refluxing for 14 hr, the mixture was concentrated and purified by silica
gel column chromatography (ethyl acetate ! 5% methanol in ethyl acetate).
Dimethyl E-3-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)-propenyl-
phosphonate (8). Cross-metathesis of 1 (140mg, 0.376 mmol) and dimethyl
vinylphosphonate (2mmol) using the general procedure described above
yielded
8
as
a
colorless oil (128 mg, 0.267 mmol, 71%, E/Z ¼ 16:1):
[a]2D0 ¼ þ68.28 (c ¼ 1.0, CHCl3); IR (thin film) 2955, 1738, 1636, 1435, 1373,
1213, 1142, 1097, 1024, 980, 939, 907, 826 cm21; H NMR (400 MHz, CDCl3): d
1
6.74 (ddt, J2,P ¼ 21.9, J1,2 ¼ 17.2, J2,3a ¼ J2,3b ¼ 6.6, 1H, H-2), 5.81 (ddt,
4
4
0
0
0
0
J1,P ¼ 20.0, J1,3a ¼ J1,3b ¼ 1.6, 1H, H-1), 5.30 (dd, J2 ,3 ¼ 9.2, J3 ,4 ¼ 8.5, 1H,
H-30), 5.10 (dd, J1 ,2 ¼ 5.6, 1H, H-20), 4.97 (dd, J4 ,5 ¼ 9.1, 1H, H-40), 4.36 (ddd,
0
0
0
0
2
J1 ,3a ¼ 5.6, J1 ,3b ¼ 4.3, 1H, H-10), 4.26 (dd, J5 ,6a ¼ 5.7, J6a ,6b ¼ 12.3, 1H,
0
0
0
0
0
0
H-6a0), 4.05 (dd, J5 ,6b ¼ 2.7, 1H, H-6b0), 3.86 (ddd, 1H, H-50), 3.724
(d, J ¼ 11.0, 3H, CH3OP), 3.722 (d, J ¼ 11.0, 3H, CH3OP), 2.73 (ddddd,
J3a,P ¼ 22.8, J3a,3b ¼ 2.4, 1H, H-3a), 2.73 (ddddd, J3b,P ¼ 16.0, 1H, H-3b), 2.11
(s, 3H, CH3), 2.07 (s, 3H, CH3), 2.048 (s, 3H, CH3), 2.045 (s, 3H, CH3); 13C
NMR (100.6 MHz, CDCl3): d 170.7, 170.0, 169.5, 169.4 (C55O), 148.1
(d, JP ¼ 5.4, C-2), 119.1 (d, JP ¼ 189, C-1), 71.0 (C-10), 69.9 (C-30), 69.8 (C-20),
0
0

Cross-Metathesis of C-Allyl-Glycosides
343
69.3 (C-50), 68.5 (C-40), 61.9 (C-60), 52.3 (d, JP ¼ 5.7, CH3OP), 30.9 (d, JP ¼ 23.3,
C-4), 20.60 (CH3); 31P NMR (162 MHz, CDCl3): d 20.4; ESI-MS (m/z): 481.1
[M þ H]þ, 503.1 [M þ Na]þ, 983.4 [2M þ Na]þ; HRMS m/z calcd. for
C19H29O12P: 481.1469, obsd: 481.1479.
Dimethyl E-3-(2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-a-D-gluco-
pyranosyl)-propenylphosphonate (9). Cross-metathesis of 2 (123 mg,
0.332 mmol) and dimethyl vinylphosphonate (2 mmol) using the general pro-
cedure described above yielded 9 as a colorless oil (115 mg, 0.240 mmol, 72%,
E/Z ¼ 19:1): [a]2D0 ¼ þ 42.08 (c ¼ 1.0, CHCl3); IR (thin film) 2955, 1744, 1670,
1
1635, 1541, 1437, 1369, 1229, 1030, 988, 908, 826, 725, 646 cm21; H NMR
(400 MHz, CDCl3): d 6.67 (ddt, J2,P ¼ 22.0, J1,2 ¼ 17.2, J2,3a ¼ J2,3b ¼ 6.6, 1H,
0
H-2), 6.47 (d, JNH,2 ¼ 8.3, 1H, NH), 5.72 (dd, J1,P ¼ 20.6, 1H, H-1), 4.99
(t, J2 ,3 ¼ J3 ,4 ¼ 6.7, 1H, H-30), 4.84 (t, J4 ,5 ¼ 6.7, 1H, H-40), 4.31 (dd,
0
0
0
2
0
0
0
J5 ,6a ¼ 6.6, J6a ,6b ¼ 12.2, 1H, H-6a0), 4.23 (m, 2H, H-10 and H-20), 4.01 (dd,
0
0
0
0
J5 ,6b ¼ 3.4, 1H, H-6b0), 3.87 (dt, 1H, H-50), 3.66 (d, JP ¼ 11.0, 3H, CH3OP),
3.65 (d, JP ¼ 11.0, 3H, CH3OP), 2.54 (m, 1H, H-3a), 2.41 (m, 1H, H-3b), 2.05
(s, 3H, CH3), 2.03 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.93 (s, 3H, CH3); 13C NMR
(100.6 MHz, CDCl3): d 170.5, 170.2, 169.8, 168.8 (C55O), 148.7 (d, JP ¼ 4.9,
C-2), 118.3 (d, JP ¼ 188, C-1), 70.8 (C-10), 69.7 (C-50), 69.3 (C-30), 67.6 (C-40),
61.0 (C-60), 52.1 (d, JP ¼ 4.5, CH3OP), 49.7 (C-20), 32.4 (d, JP ¼ 22.7, C-3),
22.8, 20.6, 20.5, 20.4 (CH3); 31P NMR (162 MHz, CDCl3): d 20.4; ESI-MS
(m/z): 480.0 [M þ H]þ, 502.2 [M þ Na]þ, 981.3 [2M þ Na]þ; HRMS m/z calcd.
for C19H30NO11P: 480.1629, obsd: 480.1645.
0
0
E-Dimethyl 3-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-propenyl-
phosphonate (10). Cross-metathesis of 3 (137 mg, 0.368 mmol) and dimethyl
vinylphosphonate (2 mmol) using the general procedure described above
yielded 10 as a colorless oil (150 mg, 0.313 mmol, 85%, E/Z ¼ 24:1):
[a]2D0 ¼ 2 4.88 (c ¼ 1.0, CHCl3); IR (thin film) 2943, 1744, 1636, 1437, 1215,
1140, 1099, 1026, 990, 908, 827 cm21; 1H NMR (400 MHz, CDCl3): d 6.77 (ddt,
J2,P ¼ 22.0, J1,2 ¼ 17.2, J2,3a ¼ J2,3b ¼ 6.7, 1H, H-2), 5.72 (ddt, J1,P ¼ 20.4,
4
4
J1,3a ¼ J1,3b ¼ 1.5, 1H, H-1), 5.18 (t, J2 ,3 ¼ J3 ,4 ¼ 9.5, 1H, H-30), 5.04
0
0
0
0
(t, J4 ,5 ¼ 9.5, 1H, H-40), 4.90 (t, J1 ,2 ¼ 9.5, 1H, H-20), 4.23 (dd, J5 ,6a ¼ 5.2,
0
0
0
0
0
0
2
J6a ,6b ¼ 12.3, 1H, H-6a0), 4.08 (dd, J5 ,6b ¼ 2.3, 1H, H-6b0), 3.72 (d, J ¼ 11.0,
0
0
0
0
6H, CH3OP), 3.66 (ddd, 1H, H-50), 3.59 (ddd, J1 ,3a ¼ 4.2, J1 ,3b ¼ 7.5, 1H,
H-10), 2.47 (m, 2H, H-3a and H-3b), 2.09 (s, 3H, CH3), 2.05 (s, 3H, CH3), 2.03
(s, 3H, CH3), 2.00 (s, 3H, CH3); 13C NMR (100.6 MHz, CDCl3): d 170.5,
170.2, 169.5, 169.4 (C ¼ O), 148.3 (d, JP ¼ 5.3, C-2), 118.8 (d, JP ¼ 188, C-1),
76.0 (C-10), 75.6 (C-50), 74.1 (C-30), 71.5 (C-20), 68.3 (C-40), 62.0 (C-60),
52.2 (d, JP ¼ 5.2, CH3OP), 36.0 (d, JP ¼ 22.9, C-4), 20.53, 20.47 (CH3); 31P
NMR (162 MHz, CDCl3): d 20.7; ESI-MS (m/z): 481.2 [M þ H]þ, 503.1
[M þ Na]þ, 983.4 [2M þ Na]þ; HRMS m/z calcd. for C19H29O12P: 481.1469,
obsd: 481.1479.
0
0

M. S. M. Timmer et al.
344
Dimethyl E-3-(2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-b-D-gluco-
pyranosyl)-propenylphosphonate (11). Cross-metathesis of 4 (93 mg,
0.25 mmol) and dimethyl vinylphosphonate (1.25 mmol) using the general pro-
cedure described above yielded 11 as a colorless oil (99 mg, 0.21 mmol, 84%,
E/Z ¼ 12:1): [a]2D0 ¼ –20.08 (c ¼ 0.1, CHCl3); IR (thin film) 2916, 1734, 1651,
1
1560, 1452, 1373, 1236, 1078, 1034, 980, 907, 835 cm21; H NMR (400 MHz,
CDCl3): d 6.97 (ddt, J2,P ¼ 22.1, J2,3 ¼ 17.2, J2,3a ¼ J2,3b ¼ 6.6, 1H, H-2), 5.89
4
4
0
(d, JNH,2 ¼ 9.3, 1H, NH), 5.72 (ddt, J1,P ¼ 20.9, J1,3a ¼ J1,3b ¼ 1.5, 1H,
2
H-1), 5.04 (m, 2H, H-30 and H-40), 4.21 (dd, J5 ,6a ¼ 5.2, J6a ,6b ¼ 12.3, 1H,
0
0
0
0
H-6a0), 4.08 (dd, J5 ,6b ¼ 2.3, 1H, H-6b0), 4.03 (ddd, J2 ,3 ¼ 9.6, J1 ,2 ¼ 10.1,
0
0
0
0
0
0
1H, H-20), 3.72 (d, 6H, (CH3O)2P), 3.60 (ddd, J4 ,5 ¼ 9.6, 1H, H-50), 3.45 (ddd,
0
0
J1 ,3a ¼ 3.9, J1 ,3b ¼ 8.0, 1H, H-10), 2.53 (m, 2H, H-3a and H-3b), 2.09 (s, 3H,
CH3), 2.04 (s, 3H, CH3), 2.03 (s, 3H, CH3), 1.95 (s, 3H, CH3); 13C NMR
(100.6 MHz, CDCl3): d 171.5, 170.7, 170.3, 169.3 (C55O), 149.7 (d, JP ¼ 5.1,
C-3), 123.3 (d, JP ¼ 188, C-2), 77.8 (C-10), 75.7 (C-50), 74.1 (C-30), 68.4 (C-40),
62.3 (C-60), 53.7 (C-20), 52.3 (CH3O), 36.5 (d, J ¼ 22.8, C-4), 23.1, 20.7, 20.6
(CH3); ESI-MS (m/z): 480.1 [M þ H]þ, 502.2 [M þ Na]þ, 959.6 [2M þ H]þ,
981.6 [2M þ Na]þ; HRMS m/z calcd. for C19H30NO11P: 480.1629, obsd:
480.1688.
0
0
E-4-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)-but-2-enoic
acid
tert-butyl ester (12). Cross-metathesis of 1 (138 mg, 0.371 mmol) and tert-
butyl acrylate (2 mmol) using the general procedure described above yielded
12 as a white solid (158 mg, 0.335 mmol, 90%, E/Z ¼ 14:1): [a]2D0 ¼ þ68.28
(c ¼ 1.0, CHCl3); IR (thin film) 2950, 1742, 1711, 1653, 1437, 1367, 1213,
1
1151, 1092, 1030, 980, 912, 847 cm21; H NMR (400 MHz, CDCl3): d 6.78 (dt,
4
4
J2,3 ¼ 15.6, J3,4a ¼ J3,4b ¼ 6.8, 1H, H-3), 5.88 (ddd, J2,4a ¼ 1.2, J2,4b ¼ 1.5,
1H, H-2), 5.32 (t, J2 ,3 ¼ J3 ,4 ¼ 9.2, 1H, H-30), 5.11 (dd, J1 ,2 ¼ 5.6, 1H, H-20),
0
0
0
0
0
0
4.96 (t, 1H, H-40), 4.35 (ddd, J1 ,4a ¼ 10.2, J1 ,4b ¼ 4.8, 1H, H-10), 4.24 (dd,
0
0
2
J5 ,6a ¼ 5.9, J6a ,6b ¼ 12.2, 1H, H-6a0), 4.07 (dd, J5 ,6b ¼ 2.5, 1H, H-6b0), 3.86
(ddd, 1H, H-50), 2.68 (dddd, 1H, H-4a), 2.45 (dddd, 1H, H-4b), 2.09 (s, 3H,
CH3), 2.06 (s, 3H, CH3), 2.05 (s, 3H, CH3), 2.04 (s, 3H, CH3), 1.47 (s, 9H,
t-Bu); 13C NMR (100.6 MHz, CDCl3): d 170.6, 170.0, 169.4, 165.1 (C55O, C-1),
141.5 (C-3), 125.8 (C-2), 80.4 (Cq t-Bu), 71.3 (C-10), 69.9 (C-50), 69.8 (C-30),
69.0 (C-20), 68.8 (C-40), 62.0 (C-60), 28.7 (C-4), 28.0 (CH3 t-Bu), 20.6 (CH3);
ESI-MS (m/z): 473.2 [M þ H]þ, 495.4 [M þ Na]þ, 945.5 [2M þ H]þ, 967.6
[2M þ Na]þ; HRMS m/z calcd. for C22H32O11: 473.2017, obsd: 473. 2068.
0
0
0
0
0
0
E-4-(2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-a-D-glucopyranosyl)-
but-2-enoic acid tert-butyl ester (13). Cross-metathesis of 2 (140 mg,
0.377 mmol) and tert-butyl acrylate (2 mmol) using the general procedure
described above yielded 13 as a white solid (165 mg, 0.350 mmol, 93%,
E/Z ¼ 10:1): [a]2D0 ¼ þ42.88 (c ¼ 1.0, CHCl3); IR (thin film) 2980, 2936, 1740,
1712, 1684, 1653, 1541, 1437, 1367, 1221, 1153, 1090, 1034, 980,

Cross-Metathesis of C-Allyl-Glycosides
345
912, 849 cm21
;
1H NMR (400 MHz, CDCl3):
d
6.81 (dt, J2,3 ¼ 15.7,
0
J3,4a ¼ J3,4b ¼ 7.2, 1H, H-3), 6.34 (d, JNH,2 ¼ 8.6, 1H, NH), 5.86 (d, 1H, H-2),
5.07 (t, J2 ,3 ¼ J3 ,4 ¼ 6.9, 1H, H-30), 4.91 (t, J4 ,5 ¼ 6.9, 1H, H-40), 4.37 (dd,
0
0
0
0
0
0
2
J5 ,6a ¼ 7.4, J6a ,6b ¼ 12.1, 1H, H-6a0), 4.30 (m, 2H, H-10 and H-20), 4.10 (dd,
0
0
0
0
J5 ,6b ¼ 3.3, 1H, H-6b0), 3.95 (ddd, 1H, H-50), 2.48 (m, 2H, H-4a and H-4b),
2.09 (s, 3H, CH3), 2.087 (s, 3H, CH3), 2.04 (s, 3H, CH3), 1.99 (s, 3H, CH3),
1.47 (s, 9H, t-Bu); 13C NMR (100.6 MHz, CDCl3): d 170.4, 170.3, 169.7, 168.8,
165.0 (C55O, C-1), 142.0 (C-3), 125.4 (C-2), 80.1 (Cq t-Bu), 70.7, 70.0, 69.7,
67.7 (C-10, C-30, C-40, C-50), 61.8 (C-60), 51.0 (C-20), 30.2 (C-4), 27.9 (CH3 t-Bu),
22.8, 20.54, 20.47, 20.39 (CH3); ESI-MS (m/z): 472.2 [M þ H]þ, 494.2
[M þ Na]þ, 943.7 [2M þ H]þ, 965.5 [2M þ Na]þ; HRMS m/z calcd. for
C22H33NO10: 472.2177, obsd: 472.2212.
0
0
E-4-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-but-2-enoic acid tert-
butyl ester (14). Cross-metathesis of 3 (135 mg, 0.363 mmol) and tert-butyl
acrylate (2 mmol) using the general procedure described above yielded 14 as
a white solid (148 mg, 0.314 mmol, 87%, E/Z ¼ 21:1): [a]2D0 ¼ –4.48 (c ¼ 1.0,
CHCl3); IR (thin film) 2937, 1747, 1712, 1653, 1435, 1367, 1213, 1153, 1101,
1
1030, 980, 907, 849 cm21; H NMR (400 MHz, CDCl3): d 6.79 (dt, J2,3 ¼ 15.7,
0
0
0
0
J3,4a ¼ J3,4b ¼ 6.9, 1H, H-3), 5.78 (d, 1H, H-2), 5.16 (t, J2 ,3 ¼ J3 ,4 ¼ 9.5, 1H,
H-30), 5.03 (t, J4 ,5 ¼ 9.5, 1H, H-40), 4.89 (t, 1H, H-20), 4.22 (dd, J5 ,6a ¼ 5.2,
0
0
0
0
2
J6a ,6b ¼ 12.3, 1H, H-6a0), 4.07 (dd, J5 ,6b ¼ 2.2, 1H, H-6b0), 3.65 (ddd, 1H,
0
0
0
0
H-50), 3.55 (dt, J1 ,4a ¼ 6.0, J1 ,4b ¼ 9.5, 1H, H-10), 2.39 (m, 2H, H-4a and
H-4b), 2.08 (s, 3H, CH3), 2.03 (s, 3H, CH3), 2.01 (s, 3H, CH3), 1.98 (s, 3H,
CH3), 1.46 (s, 9H, t-Bu); 13C NMR (100.6 MHz, CDCl3): d 170.5, 170.2, 169.4,
169.3, 165.3 (C55O, C-1), 141.5 (C-3), 125.5 (C-2), 80.2 (Cq t-Bu), 76.3 (C-10),
75.6 (C-50), 74.1 (C-30), 71.7 (C-20), 68.5 (C-40), 62.1 (C-60), 34.1 (C-4), 28.0
(CH3 t-Bu), 20.6, 20.5 (CH3); 31P NMR (162 MHz, CDCl3): d 21.7; ESI-MS
(m/z): 473.4 [M þ H]þ, 495.2 [M þ Na]þ, 967.6 [2M þ Na]þ; HRMS m/z calcd.
for C22H32O11: 473.2017, obsd: 473.2062.
0
0
E-4-(2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-b-D-glucopyranosyl)-
but-2-enoic acid tert-butyl ester (15). Cross-metathesis of 4 (129 mg,
0.348 mmol) and tert-butyl acrylate (2 mmol) using the general procedure
described above yielded 15 as a white solid (121 mg, 0.257 mmol, 74%,
E/Z ¼ 20:1): [a]2D0 ¼ –19.28 (c ¼ 0.5, CHCl3); IR (thin film) 2937, 1740, 1703,
1653, 1558, 1435, 1367, 1221, 1157, 1105, 1043, 988, 945, 901, 853, 818 cm21
;
1H NMR (400 MHz, CDCl3): d 6.83 (dt, J2,3 ¼ 15.7, J3,4a ¼ J3,4b ¼ 6.7, 1H,
H-3), 6.01 (d, JNH,2 ¼ 9.5, 1H, NH), 5.80 (d, 1H, H-2), 5.05 (m, 2H, H-30and
0
2
H-40), 4.23 (dd, J5 ,6a ¼ 5.4, J6a ,6b ¼ 12.3, 1H, H-6a0), 4.08 (dd, J5 ,6b ¼ 2.4,
0
0
0
0
0
0
1H, H-6b0), 4.07 (m, 1H, H-20), 3.63 (ddd, J4 ,5 ¼ 7.8, 1H, H-50), 3.59 (ddd,
0
0
J1 ,2 ¼ 11.7, J1 ,4a ¼ 4.8, J1 ,4b ¼ 7.1, 1H, H-10), 2.46 (m, 2H, H-4a and H-4b),
2.08 (s, 3H, CH3), 2.03 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.93 (s, 3H, CH3), 1.47
(s, 9H, t-Bu); 13C NMR (100.6 MHz, CDCl3): d 171.4, 170.6, 170.2, 169.2,
0
0
0
0

M. S. M. Timmer et al.
346
165.6 (C55O, C-1), 142.7 (C-3), 125.0 (C-2), 80.2 (Cq t-Bu), 77.9 (C-10), 75.5 (C-50),
74.1 (C-40), 68.6 (C-30), 62.4 (C-60), 53.7 (C-20), 34.3 (C-4), 28.0 (CH3 t-Bu), 23.0,
20.6, 20.5 (CH3); ESI-MS (m/z): 417.2 [M þ H]þ, 439.1 [M þ Na]þ, 833.3
[2M þ H]þ, 855.2 [2M þ Na]þ; HRMS m/z calcd. for C22H33NO10: 472.2177,
obsd: 472.2218.
E-4-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)-but-2-enoic acid (16).
Cross-metathesis of 1 (115 mg, 0.309 mmol) and acrylic acid (2 mmol) using
the general procedure described above yielded 16 as a white solid (105 mg,
0.252 mmol, 82%, E/Z ¼ 10:1): [a]2D0 ¼ þ 68.08 (c ¼ 0.2, CHCl3); IR (thin film)
2925, 1744, 1655, 1437, 1369, 1215, 1099, 1032, 982, 907 cm21 1H NMR
;
(400 MHz, CDCl3): d 7.01 (dt, J2,3 ¼ 15.7, J3,4a ¼ J3,4b ¼ 7.0, 1H, H-3), 5.98
4
4
(dt, J2,4a ¼ J2,4b ¼ 1.5, 1H, H-2), 5.32 (t, J2 ,3 ¼ J3 ,4 ¼ 9.0, 1H, H-30), 5.11
0
0
0
0
(t, J1 ,2 ¼ 5.5, 1H, H-20), 4.95 (t, 1H, J4 ,5 ¼ 9.0, H-40), 4.37 (ddd, J1 ,4a ¼ 10,
0
0
0
0
0
2
J1 ,4b ¼ 4.4, 1H, H-10), 4.24 (dd, J5 ,6a ¼ 6.2, J6a ,6b ¼ 12.2, 1H, H-6a0), 4.07
0
0
0
0
0
2
(dd, J5 ,6b ¼ 2.6, 1H, H-6b0), 3.88 (ddd, 1H, H-50), 2.74 (ddd, J4a,4b ¼ 15.9,
1H, H-4a), 2.74 (ddd, 1H, H-4a), 2.08 (s, 3H, CH3), 2.07 (s, 3H, CH3), 2.05
(s, 3H, CH3), 2.04 (s, 3H, CH3); 13C NMR (100.6 MHz, CDCl3): d 170.9, 170.7,
169.8, 169.5, (C55O, C-1), 145.6 (C-3), 123.5 (C-2), 71.0 (C-10), 69.9 (C-30), 69.8
(C-20), 69.4 (C-50), 68.6 (C-40), 62.1 (C-60), 29.2 (C-4), 21.0, 20.63, 20.61, 20.5
(CH3); ESI-MS (m/z): 417.2 [M þ H]þ, 439.2 [M þ Na]þ, 833.3 [2M þ H]þ,
855.2 [2M þ Na]þ; HRMS m/z calcd. for C18H24O11: 417.1391, obsd: 417.1392.
0
0
E-4-(2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-b-D-glucopyranosyl)-
but-2-enoic acid (17). Cross-metathesis of 2 (134 mg, 0.361 mmol) and acrylic
acid (2 mmol) using the general procedure described above yielded 17 as a
white solid (122 mg, 0.292 mmol, 81%, E/Z ¼ 8:1): [a]2D0 ¼ þ48.88 (c ¼ 0.5,
CHCl3); IR (thin film) 3292, 2926, 1740, 1655, 1537, 1433, 1373, 1229, 1090,
1
1034, 984, 914 cm21; H NMR (400 MHz, CDCl3): d 8.24 (bs, 1H, COOH), 7.00
0
(dt, J2,3 ¼ 15.6, J3,4a ¼ J3,4b ¼ 7.0, 1H, H-3), 6.23 (d, JNH,2 ¼ 8.6, 1H, NH),
4
4
0
0
0
0
5.94 (dt, J2,4a ¼ J2,4b ¼ 1.5, 1H, H-2), 5.00 (dd, J2 ,3 ¼ 5.8, J3 ,4 ¼ 6.3, 1H,
2
H-30), 4.90 (t, J4 ,5 ¼ 5.8, 1H, H-40), 4.42 (dd, J5 ,6a ¼ 7.8, J6a ,6b ¼ 12.1, 1H,
0
0
0
0
0
0
H-6a0), 4.32 (m, 2H, H-10 and H-20), 4.09 (dd, J5 ,6b ¼ 3.9, 1H, H-6b0), 3.97
0
0
(ddd, 1H, H-50), 2.57 (dddd, J1 ,4a ¼ 8.7, 1H, H-4a), 2.43 (dddd, J1 ,4b ¼ 4.0,
1H, H-4b), 2.11 (s, 3H, CH3), 2.10 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.01 (s, 3H,
CH3); 13C NMR (100.6 MHz, CDCl3): d 170.8, 170.6, 170.21, 170.17, 168.9
(C55O, C-1), 145.9 (C-3), 123.3 (C-2), 71.4 (C-50), 69.44 (C-10), 69.38 (C-30),
67.4 (C-40), 61.0 (C-60), 49.9 (C-20), 31.0 (C-4), 23.1, 20.8, 20.7, 20.5 (CH3);
ESI-MS (m/z): 416.1 [M þ H]þ, 438.0 [M þ Na]þ, 831.4 [2M þ H]þ, 853.3
[2M þ Na]þ; HRMS m/z calcd. for C18H25NO10: 416.1551, obsd: 416.1592.
0
0
E-4-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-but-2-enoic acid (18).
Cross-metathesis of 3 (162 mg, 0.435 mmol) and acrylic acid (2 mmol) using
the general procedure described above yielded 18 as a white solid (141 mg,

Cross-Metathesis of C-Allyl-Glycosides
347
0.339 mmol, 78%, E/Z ¼ 10:1): [a]2D0 ¼ –7.68 (c ¼ 1.0, CHCl3); IR (thin film)
1
2926, 1744, 1655, 1435, 1367, 1213, 1142, 1101, 1032, 980, 908, 845 cm21; H
NMR (400 MHz, CDCl3): d 8.33 (bs, 1H, COOH), 7.03 (dt, J2,3 ¼ 15.7,
4
J3,4a ¼ J3,4b ¼ 7.0, 1H, H-3), 5.90 (dt, J2,4a ¼ 4J2,4b ¼ 1.5, 1H, H-2), 5.19
(t, J2 ,3 ¼ J3 ,4 ¼ 9.5, 1H, H-30), 5.05 (t, J4 ,5 ¼ 9.5, 1H, H-40), 4.92 (t, 1H,
0
0
0
0
0
0
2
H-20), 4.24 (dd, J5 ,6a ¼ 5.3, J6a ,6b ¼ 12.3, 1H, H-6a0), 4.09 (dd, J5 ,6b ¼ 2.3,
0
0
0
0
0
0
1H, H-6b0), 3.67 (ddd, 1H, H-50), 3.59 (ddd, J1 ,4a ¼ 4.8, J1 ,4b ¼ 7.1, 1H, H-10),
2.46 (m, 2H, H-4a and H-4b), 2.09 (s, 3H, CH3), 2.04 (s, 3H, CH3), 2.03
(s, 3H, CH3), 2.00 (s, 3H, CH3); 13C NMR (100.6 MHz, CDCl3): d 170.8, 170.7,
170.3, 169.6, 169.5 (C55O, C-1), 145.7 (C-3), 123.3 (C-2), 76.2 (C-10), 75.7
(C-50), 74.1 (C-30), 71.7 (C-20), 68.5 (C-40), 62.1 (C-60), 34.2 (C-4), 20.63, 20.59,
20.56, 20.54 (CH3); ESI-MS (m/z): 417.2 [M þ H]þ, 439.1 [M þ Na]þ, 833.3
[2M þ H]þ, 855.2 [2M þ Na]þ; HRMS m/z calcd. for C18H24O11: 417.1391,
obsd: 417.1397.
0
0
E-4-(2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-b-D-glucopyranosyl)-
but-2-enoic acid (19). Cross-metathesis of 4 (133 mg, 0.358 mmol) and acrylic
acid (2 mmol) using the general procedure described above yielded 19 as a
white solid (108 mg, 0.260 mmol, 72%, E/Z ¼ 19:1): [a]2D0 ¼ –21.08 (c ¼ 0.2,
CHCl3); IR (thin film) 2924, 2855, 1744, 1705, 1657, 1543, 1430, 1373, 1229,
1
1096, 1038, 980, 905 cm21; H NMR (400 MHz, CDCl3): d 7.03 (dt, J2,3 ¼ 15.6,
0
J3,4a ¼ J3,4b ¼ 7.0, 1H, H-3), 6.90 (d, 1H, H-2), 5.81 (d, JNH,2 ¼ 9.2, 1H, NH),
5.07 (t, J2 ,3 ¼ J3 ,4 ¼ 9.4, 1H, H-30), 5.03 (t, J4 ,5 ¼ 9.4, 1H, H-40), 4.23 (dd,
0
0
0
0
0
0
2
J5 ,6a ¼ 5.3, J6a ,6b ¼ 12.2, 1H, H-6a0), 4.09 (dd, J5 ,6b ¼ 2.3, 1H, H-6b0), 4.06
0
0
0
0
0
0
(app q, J1 ,2 ¼ 9.4, 1H, H-20), 3.61 (ddd, 1H, H-50), 3.43 (ddd, J1 ,4a ¼ 4.0,
0
0
0
J1 ,4b ¼ 7.8, 1H, H-10), 2.52 (m, 2H, H-4a and H-4b), 2.09 (s, 3H, CH3), 2.04
0
(s, 3H, CH3), 2.03 (s, 3H, CH3), 1.95 (s, 3H, CH3); 13C NMR (100.6 MHz,
CDCl3): d 172.8, 170.7, 170.3, 169.6, 169.5 (C55O, C-1), 147.2 (C-3), 123.3
(C-2), 78.0 (C-10), 75.7 (C-50), 74.2 (C-30), 68.4 (C-40), 62.1 (C-60), 53.8 (C-20),
34.2 (C-4), 23.1, 20.7, 20.6 (CH3); ESI-MS (m/z): 427.3 [M þ H]þ, 494.5
[M þ Na]þ, 943.6 [2M þ H]þ, 965.5 [2M þ Na]þ; HRMS m/z calcd. for
C18H25NO10: 416.1551, obsd: 416.1614.
Cyanoethyl (20,30-dibenzoyl-uridin-50-yl) vinylphosphonate (22).
1H-Tetrazole (84 mg, 1.2 mmol, 3 equiv.) was added to a solution of 20,30-diben-
zoyl-uridine (180 mg, 0.398 mmol) and phosphine 21 (160 mg, 0.603 mmol, 2
equiv.) in dry acetonitrile (5 mL), under an argon atmosphere. After 31P
NMR showed complete disappearance of the starting material, the mixture
was cooled (08C) and tert-butyl-hydrogenperoxide (0.11 mL, 5.5 M in nonane)
was added and allowed to react for 5 min. The mixture was diluted with
ethyl acetate, washed with sat. aq. NaHCO3 and brine, dried (MgSO4), and con-
centrated. Silica gel column chromatography (ethyl acetate ! 5% MeOH in
ethyl acetate) afforded homogeneous 22 (172 mg, 0.289 mmol, 73%, 1:1
mixture of diastereoisomers) as a white solid: [a]2D0 ¼ –61.68 (c ¼ 0.5, CHCl3);

M. S. M. Timmer et al.
348
IR (thin film) 2924, 2853, 1719, 1690, 1636, 1601, 1585, 1452, 1381, 1261, 1178,
1092, 1068, 1024, 1001, 906, 812, 727, 708 cm21; 1H NMR (200 MHz, CDCl3): d
10.15 (bs, 1H, H-3), 7.98–7.79 (m, 4H, Bz), 7.67–7.11 (m, 7H, Bz and H-6),
6.64–6.02 (m, 4H, CHCH2, and H-10), 5.94–5.58 (m, 3H, H-5, H-20 and H-30),
4.64–4.19 (m, 4H, H-40, H-5a0, H-5b0 and CH2O CNE), 2.79 (t, J ¼ 6.0, 2H,
CH2CN); 13C NMR (100.6 MHz, CDCl3): d 165.2 (C55O Bz), 163.2 (C-4), 150.4
(C-2), 140.0 (C-6), 138.2 (CH2 Vi), 133.6, 129.6, 128.1 (CH Bz), 128.0 (C Bz),
124.3 (CH Vi), 116.6 (CN), 103.4 (C-5), 87.5 (C-10), 81.0 (C-40), 73.2 (C-20),
70.6 (C-30), 64.9 (C-50), 60.5 (CH2O CNE), 19.7 (CH2CN CNE); 31P NMR
(162 MHz, CDCl3): d 19.8, 19.5; ESI-MS (m/z): 596.2 [M þ H]þ, 618.2
[M þ Na]þ; HRMS m/z calcd. for C28H26N3O10P: 596.1492, obsd: 596.1503.
Cyanoethyl 20,30-dibenzoyl-uridin-50-yl 3-(2-acetamido-3,4,6-tetra-
O-acetyl-2-deoxy-a-D-glucopyranosyl)-propenylphosphonate (23).
A
mixture of Grubbs’ second-generation precatalyst II (2.1 mg, 0.05 equiv.) and
copper(I) chloride (1 mg, 0.20 equiv.) was added to a dry solution of vinyl-
phosphonate 22 (50 mmol, 30 mg) and C-allyl-glycoside 2 (37 mg, 0.10 mmol, 2
equiv.) in DCM (1 mL) under an argon atmosphere. After refluxing for 3 hr,
the mixture was concentrated and purified by silica gel column chromato-
graphy to yield 23 (27 mg, 29 mmol, 58%, E/Z ¼ 8:1, 1:1 mixture of diastereoi-
somers). The E-isomer could be isolated by HPLC-purification: [a]2D0 ¼ –48.08
(c ¼ 0.1, CHCl3); IR (thin film) 2924, 2853, 1726, 1693, 1650, 1601, 1452,
1420, 1379, 1315, 1261, 1238, 1178, 1094, 1068, 1034, 1001, 810, 712 cm21
;
1H NMR (600 MHz, CDCl3): d 7.96 (m, 2H, Bz), 7.92 (m, 2H, Bz), 7.68 (m, 1H,
H-6), 7.59 (m, 2H, Bz), 7.42 (m, 2H, Bz), 7.38 (m, 2H, Bz), 6.92 (m, 1H, H-2’),
6.25 (m, 1H, H-10), 5.99 (m, 1H, H-100), 5.89–5.80 (m, 2H, H-5 and H-30), 5.75
(m, 1H, H-20), 5.13 (m, 1H, H-600), 4.94 (m, 1H, H-700), 4.60 (m, 1H, H-40), 4.46
(m, 2H, H-5a0 and H-5b0), 4.36 (m, 1H, H-9a00), 4.34–4.27 (m, 4H, H-40, H-500
and CH2O CNE), 4.10 (m, 1H, H-9b00), 3.95 (m, 1H, H-800), 2.87 (m, 2H,
CH2CN CNE), 2.76 (m, 1H, H-3a00), 2.51 (m, 1H, H-3b00), 2.10 (s, 3H, CH3
AcO), 2.08 (s, 3H, CH3 AcO), 2.08 (s, 3H, CH3 AcO), 2.00 (s, 3H, CH3 AcN);
13C NMR (150.9 MHz, CDCl3): d 172.1, 171.7, 171.1, 170.3 (C55O Ac), 165.9
(C55O Bz), 164.7 (C-4), 152.2 (C-200), 151.0 (C-2), 141.5 (C-6), 134.3, 130.1,
128.8 (CH Bz), 128.7 (C Bz), 117.9 (C-100), 117.5 (CN), 103.5 (C-5), 88.2 (C-10),
81.3 (C-40), 73.9 (C-20), 71.1 (C-30), 71.0 (C-400), 70.6 (C-800), 70.1 (C-600), 68.9
(C-700), 65.2 (C-50), 62.0 (C-900), 61.3 (CH2O CNE), 50.4 (C-500), 31.1 (C-300), 22.6
(CH3 AcN), 20.8 (CH3 AcO), 20.0 (CH2CN CNE); 31P NMR (162 MHz, CDCl3):
d 20.2, 19.9; ESI-MS (m/z): 939.5 [M þ H]þ, 1877.9 [2M þ H]þ; HRMS m/z
calcd. for C43H47N4O18P: 939.2403, obsd: 939.2696.
Uridin-50-yl
3-(2-amino-2-deoxy-a-D-glucopyranosyl)-propenyl-
phosphonate (24). Sodium methoxide (cat.) was added to a solution of phos-
phonate 23 (7 mg, 7.4 mmol) in MeOH (0.5 mL). After stirring for 16 hr, the
mixture was neutralized (Dowex-Hþ), filtered, and concentrated. Precipitation

Cross-Metathesis of C-Allyl-Glycosides
349
from MeOH/ether gave homogeneous 24 (3 mg, 5.4 mmol, 73%). 1H NMR
00
(400 MHz, MeOD): d 7.82 (d, 1H, J5,6 ¼ 8.1, H-6), 6.26 (ddt, 1H, J2 ,P ¼ 19.7,
J2 ,1 ¼ 16.9, J2 ,3 ¼ 6.8, H-200), 5.76 (d, 1H, J1 ,2 ¼ 4.8, H-10), 5.61 (dd, 1H,
00 00
00 00
0
0
J1 ,P ¼ 18.4, H-100), 5.60 (d, 1H, H-5), 4.01 (dd, 1H, J2 ,3 ¼ 5.2, H-20), 3.99 (dd,
00
0
0
1H, J3 ,4 ¼ 3.0, H-30), 3.95 (dt, 1H, J4 ,5 ¼ 5.7, J3 ,4 ¼ 4.2, H-400), 3.91–3.87
0
0
00 00
00 00
(m, 1H, H-40), 3.83–3.71 (m, 2H, H-50), 3.74 (dd, 1H, J5 ,6 ¼ 10.4, H-500), 3.55
00 00
(dd, 1H, J9a ,9b ¼ 11.9, J8 ,9a ¼ 2.7, H-9a00), 3.47 (dd, 1H, J8 ,9b ¼ 5.2,
00
00
00
00
00
00
H-9b00), 3.44 (dd, 1H, J6 ,7 ¼ 8.4, H-600), 3.25 (ddd, 1H, J7 ,8 ¼ 9.1, H-800), 3.13
(dd, 1H, H-700), 2.46–2.34 (m, 1H, H-3a00), 2.16–2.07 (m, 1H, H-300), 1.89
(s, 3H, NAc); 31P NMR (162 MHz, CDCl3): d 14.5; ESI-MS (m/z): 552.1
[M þ H]þ, 574.2 [M þ Na]þ.
00 00
00 00
Dimethyl E-3-(2-acetamido-2-deoxy-a-D-glucopyranosyl)-propenyl-
phosphonate (25). Deprotection of 9 as described for 23 gave 25 as a colorless
oil (115 mg, 0.240 mmol, 95%): IR (thin film): 3393, 2912, 2853, 2359, 2341,
1
1635, 1558, 1456, 1188, 1036, 880 cm21; H NMR (200 MHz, MeOD): d 6.71
(m, 1H, H-2), 5.70 (m, 1H, H-1), 3.78–3.62 (m, 4H, OMe and H-4), 3.59–3.49
(m, 4H, OMe and H-5), 3.36–3.07 (m, 5H, H-6, H-7, H-8 and H-9), 2.53–2.28
(m, 2H, H-3), 1.89 (s, 3H, NAc); 13C NMR (50.1 MHz, MeOD): d 173.6
(CO Ac), 152.9 (C-2), 118.9 (C-1), 75.3, 73.6, 73.4, 72.2 (C-4, C-6, C-7, C-8),
63.2 (C-9), 53.7 (MeOP), 50.4 (C-5), 31.2 (C-3), 22.6 (CH3 Ac); ESI-MS (m/z):
354.1 [M þ H]þ, 376.2 [M þ Na]þ, 707.4 [2M þ H]þ, 729.4 [2M þ Na]þ.
Dimethyl E-3-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-propenyl-
phosphonate (26). Deprotection of 11 as described for 23 gave 26 as a color-
less oil (115 mg, 0.240 mmol, 95%): IR (thin film): 3391, 2359, 2338, 1636,
1558, 1188, 1038, 880 cm21 1H NMR (400 MHz, MeOD): d 7.93 (d, 1H,
;
JNH,5 ¼ 9.5, NH), 6.85 (ddt, 1H, J2,P ¼ 22.3, J1,2 ¼ 17.2, J2,3 ¼ 6.8, H-2), 5.75
2
2
(ddt, 1H, J1,P ¼ 22.2, J1,3 ¼ 1.5, H-1), 3.83 (dd, 1H, J9a,9b ¼ 12.0,
J8,9a ¼ 2.3, H-9a), 3.71 (d, 3H, JMe,P ¼ 11.2, MeOP), 3.70 (d, 3H, JMe,P ¼ 11.2,
MeOP), 3.63 (dd, 1H, J8,9b ¼ 5.7, H-9b), 3.62 (ddd, 1H, J4,5 ¼ 10.1, J5,6 ¼ 9.8,
H-5), 3.39 (ddd, 1H, J3a,4 ¼ 3.8, J3b,4 ¼ 7.2, H-4), 3.37 (dd, 1H, J6,7 ¼ 8.6,
4
H-6), 3.28 (dd, 1H, J7,8 ¼ 9.8, H-7), 2.55 (ddddd, 1H, J3a,P ¼ 2.0,
4
2J3a,3b ¼ 15.2, H-3a), 2.41 (ddddd, 1H, J3b,P ¼ 2.5, H-3a), 1.97 (s, 3H, CH3
Ac); 13C NMR (100 MHz, MeOD): d 173.6 (CO Ac), 153.0 (C-2), 119.0 (C-1),
71.0, 70.6, 70.1, 68.9 (C-4, C-6, C-7, C-8), 62.8 (C-9), 54.8 (MeOP), 50.4 (C-5),
31.1 (C-3), 22.3 (CH3 Ac); ESI-MS (m/z): 354.1 [M þ H]þ, 376.2 [M þ Na]þ,
707.4 [2M þ H]þ, 729.4 [2M þ Na]þ.
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