Efficient route to 20-32 membered macrocyclic crown diamides via ring closing metathesis

Article abstract of DOI:10.1016/j.tet.2004.07.004

RCM of the appropriate bis-allyloxyacetanilides and bis-o- allyloxyphenoxyacetanilides led to an efficient synthetic approach to the corresponding macrocylic polyoxadiamides with 20- to 32-membered ring sizes in good to excellent yields using Grubbs' cata

Full text of DOI:10.1016/j.tet.2004.07.004

Tetrahedron 60 (2004) 8429–8436
Efficient route to 20–32 membered macrocyclic crown diamides
via ring closing metathesis
*
Yehia A. Ibrahim, Haider Behbehani and Nasser S. Khalil
Chemistry Department, Faculty of Science, Kuwait University, PO Box 5969, Safat 13060, Kuwait
Received 1 April 2004; revised 11 June 2004; accepted 1 July 2004
Available online 4 August 2004
Abstract—RCM of the appropriate bis-allyloxyacetanilides and bis-o-allyloxyphenoxyacetanilides led to an efficient synthetic approach to
the corresponding macrocylic polyoxadiamides with 20- to 32-membered ring sizes in good to excellent yields using Grubbs’ catalyst.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Scheme 1 illustrates our synthetic route to the precursor
1,u-dienes 19–23 needed for the RCM synthesis of 1–5.
Thus, two routes were used to prepare compounds 19–23.
The first route involved acylation of o-aminophenol 11 with
allyloxyacetyl chloride to afford the o-allyloxyacetamido-
phenol 12. The latter was converted into its potassium salt
13 which was reacted with the appropriate dihalo or
ditosylate derivatives 14–18 in DMF to give the correspond-
ing 1,u-dienes 19–23 in 40–50% yields. Alternatively,
compounds 19–23 were obtained in 60–75% yields by
reacting the appropriate bis-amines 24–28 with allyloxy-
acetyl chloride. RCM of the dienes 19–23 proceeded
smoothly to give the corresponding macrocycles 1–5
in 62–93% yields with Grubbs’ catalyst I (2–2.5 mol%) in
refluxing CH2Cl2 for 3 h. The results are presented in
Table 1.
There exists increasing interest in the synthesis of crown
compounds and azacrown compounds due to their important
diverse applications in supramolecular chemistry.1,2 Of
particular interest are crown compounds incorporating
amide groups, since such groups modify the binding
properties of the crown compounds with respect to alkali
metal ions.2,3 Recently, we reported efficient synthetic
approaches towards polyaza-polyether-olefinic macrocyclic
compounds of potential utility in supramolecular chemistry,
using ring closing metathesis (RCM).4 Moreover, some of
our recently reported olefinic crown formazans prepared
efficiently via RCM showed interesting applications in
spectrophotometric determination of lithium ions.5 Appli-
cations of RCM techniques has proved to be one of the most
efficient synthetic approaches towards macrocyclic com-
pounds.6–16 However, application of such efficient macro-
cyclization technique for the synthesis of crown compounds
are still limited.4,10,17,18
On the other hand, the 1,u-dienes 36–40 were readily
obtained as outlined in Scheme 2. Thus, acylation of 24–28
with chloroacetyl chloride (29) afforded the corresponding
bis-chloroacetamide derivatives 30–34. Reacting the latter
with the potassium salt of o-allyloxyphenol (35) afforded
the desired 1,u-dienes 36–40. RCM of the dienes 36–40
proceeded smoothly to give the corresponding macrocycles
6–10 in 86–95% yields upon heating with Grubbs’ catalyst I
(1.5–2 mol%) in refluxing CH2Cl2 for 3 h. The results are
presented in Table 2.
The present work describes the synthesis of macrocyclic
polyethers containing amide groups inside the macrocyclic
ring via RCM using Grubbs’ catalyst I as the key
macrocyclization step. The results obtained provide an
efficient synthetic procedure towards macrocyclic crown
diamides 1–5 with 20–26 membered rings and macrocylic
polyoxadiamides 6–10 with 26–32 membered ring sizes
(Fig. 1).
In all RCM reactions, the progress of the reaction was
monitored by TLC and 1H NMR spectroscopic analysis
where no further increase in products was noticed after 3 h
of reflux in CH2Cl2. The RCM products 1–10 were shown
Keywords: Ring closing metathesis; 1,u-Dienes; Bis-anilides;
Diazapolyoxacycloalkenediones.
1
from their H and 13C NMR to consist of the E and Z
* Corresponding author. Tel.: C965-9464215; fax: C965-4816482.;
e-mail: yehiaai@kuc01.kuniv.edu.kw
isomers in different ratios as shown in Tables 1 and 2.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.004

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Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
Figure 1.
The E:Z isomers of the olefinic crown diamides were readily
1
where the CH] of the Z-isomer appears more downfield
than that of the E-isomer.
assigned and their ratios were determined4b from the H
NMR and 13C NMR spectra. The major products in most of
the RCM reactions were shown to be the E isomers with the
characteristic 13C NMR signal of the OCH2 (of the
OCH2CH]CHCH2O), which appears more downfield
than that for the corresponding Z isomer. On the contrary
The present work describes an efficient synthetic access to
macrocyclic crown-diamide derivatives, with potential
diverse applications in supramolecular chemistry and as
starting compounds for further synthetic transformations,
utilizing the RCM techniques for the macrocyclization
step. The examples of RCM presented here represent one of
the most efficient macrocyclization reaction techniques for
the synthesis of crown compounds. It also expands the
utility of RCM methodology and its application to the
synthesis of large-ring cyclic olefins with different func-
tional groups.
1
in the H NMR spectra, the OCH2 of E isomers appears as
essentially a singlet and more upfield than that of the Z
isomer which appears as a broad doublet (JZ3–5 Hz). Also,
in the 1H NMR spectra, the CH] of the E isomers appear as
broad singlets and more downfield than those of the Z
isomers which appear as triplets (Tables 1 and 2). An
1
exception occurs in the H NMR spectra of compound 7
Scheme 1.

Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
8431
Table 1. Catalyst %, yields, E/Z ratios and characteristic 1H NMR spectroscopy signals of macrocycles 1–5
Entry
Substrate
Mol% catalyst/
substrate
Yield (%)
Product E:Z
ratio
1HNMR of E/Z products
J (Hz)
NH
OCH2CH]
OCH2CH]
1
2
3
4
5
19
20
21
22
23
2
2.5
2
62
93
70
80
89
1
1:1
2
19:1
3
1:1
4
1:1
5
9.11
9.03
9.14
9.14
9.22
9.13
9.09
9.09
9.17
9.13
4.18 (m)
4.29 (dd)
4.19 (m)
4.19 (d)
4.20 (s)
4.25 (d)
4.21 (s)
4.25 (d)
4.11 (s)
4.07 (d)
6.04 (m)
5.94 (tt)
6.04 (m)
5.90 (t)
6.08 (s)
5.92 (t)
6.02 (s)
5.92 (t)
5.93 (br)
5.40 (t)
1.1, 3.8
4.2
3.4
2
3.6
2.5
1.3:1
4
Table 2. Catalyst %, yields, E/Z ratios and characteristic 1H NMR spectroscopy signals of macrocycles 6–10
Entry
Substrate
Mol% catalyst/
substrate
Yield %
Product E:Z
ratio
1H NMR of E/Z products
J (Hz)
NH
OCH2CH]
OCH2CH]
1
2
3
4
5
30
31
32
33
34
1.5
2.0
1.5
2.0
1.5
91
92
86
95
94
6
4:1
7
3:1
8
3:1
9
2:1
10
2:1
9.53
9.23
9.63
9.24
9.24
9.20
9.20
9.21
9.30
9.27
4.39 (s)
4.70 (d)
3.85 (s)
4.75 (d)
4.47 (dd)
4.80 (d)
4.66 (s)
4.83 (d)
4.29 (d)
4.55 (d)
6.06 (s)
5.87 (t)
5.64 (s)
5.90 (t)
6.13 (m)
5.92 (t)
6.15 (s)
5.95 (t)
5.94 (t)
5.69 (t)
3.5
3.2
1.1, 2.0
3.5
3.2
2.5
3.2
Scheme 2.
3. Experimental
super-conducting NMR spectrometer. Mass spectra were
measured on VG Auto-spec-Q (high resolution, high
performance, tri-sector GC/MS/MS) and with LCMS
using Agilent 1100 series LC/MSD with an API-
ES/APCI ionization mode. Microanalyses were per-
formed on LECO CHNS-932 Elemental Analyzer.
Allyloxyacetyl chloride19 and the bis-diamines 24–2820
were prepared as reported in the literature.
3.1. General
All melting points are uncorrected. IR spectra were
recorded in KBr disks using Perkin Elmer System 2000
FT-IR spectrophotometer. 1H NMR and 13C NMR
spectra were recorded on a Bruker DPX 400, 400 MHz

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Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
3.1.1. o-Allyloxyacetamidophenol 12. To a cold (5 8C)
solution of o-aminophenol (11) (1.3 g, 12 mmol) in sodium
hydroxide solution (12 mmol in 4 mL water) was added
allyloxyacetyl chloride17 (1.35 g, 10 mmol) dropwise with
stirring. The reaction mixture was kept stirring for 10 min
and the resulting precipitate was filtered off. The filtrate was
acidified with conc. HCl (1 mL) and the resulting colorless
crystals were collected, washed several times with water
and crystallized from EtOH/H2O to give 1.1 g (53%) of 12,
colorless crystals, mp 121–123 8C. IR: 3371, 3304, 3089,
2961, 2917, 2870, 2741, 1663, 1615, 1593, 1549, 1457,
1377, 1283, 1249, 1204, 1148, 1107, 1097, 981, 917, 756.
1H NMR (CDCl3) d 4.16 (s, 2H, CH2C]O), 4.19 (d, 2H,
JZ5.7 Hz, OCH2CH]), 5.35 (d, 1H, JZ10.4 Hz, CH2Z
CH), 5.41 (d, 1H, JZ17.8 Hz, CH2ZCH), 5.96 (m, 1H,
ZCH), 6.88 (dt, 1H, JZ1.1, 7.5 Hz), 7.06 (m, 2H), 7.17 (t,
1H, JZ7.5 Hz), 8.56, 8.99 (2s, 2H, NH, OH). LCMS; m/z:
208 (MC1). Anal. calcd for C11H13NO3 (207.2): C, 63.76;
H, 6.32; N, 6.76. Found: C, 63.57; H, 6.43; N, 6.86.
Yield 0.19 g (42%, A); colorless crystals, mp 93–95 8C. IR:
3385, 1690, 1601, 1534, 1454, 1250, 1207, 1114, 751. H
1
NMR (CDCl3) d 2.37 (quint, 2H, JZ6.1 Hz, OCH2CH2), 4.09
(s, 4H, CH2C]O), 4.09 (dd, 4H, JZ1.4, 6.8 Hz, CH2CH]),
4.27(t, 4H, JZ6.1 Hz, OCH2CH2), 5.23(m, 2H, CH2]), 5.35
(m, 2H, CH2]), 5.89 (m, 2H, CH]), 6.92 (dd, 2H, JZ1.3,
7.8 Hz), 7.01 (dt, 2H, JZ1.3, 7.8 Hz), 7.07 (dt, 2H, JZ1.7,
7.8 Hz), 8.43 (dd, 2H, JZ1.7, 7.8 Hz), 9.04 (s, 2H, NH).
LCMS;m/z:455(MC1). Anal. calcdforC25H30N2O6 (454.5):
C, 66.06; H, 6.65; N, 6.16. Found: C, 66.21; H, 6.71; N, 6.22.
3.2.3. 1,5-Bis(o-allyloxyacetamidophenoxy)-3-oxapen-
tane 21. Yield 0.23 g (47%, A), 0.3 g (61%, B); colorless
crystals, mp 55–56 8C. IR: 3383, 3070, 2937, 1690, 1601,
1534, 1485, 1453, 1333, 1253, 1209, 1116, 1046, 927, 751.
1H NMR (CDCl3) d 3.95 (t, 4H, JZ4.7 Hz, ArOCH2CH2O),
4.24 (t, 4H, JZ4.7 Hz, ArOCH2CH2O), 4.07 (s, 4H,
CH2C]O), 4.10 (dd, 4H, JZ1.2, 5.0 Hz, CH2CH]),
5.25, 5.36 (dd, 2H, JZ1.0, 10.6 Hz, CH2]), 5.36 (dd,
2H, JZ1.6, 17.2 Hz, CH2]), 5.94 (m, 2H, CH]), 6.92 (dd,
2H, JZ1.5, 8.0 Hz), 7.04 (m, 4H), 8.42 (dd, 2H, JZ1.5,
8.0 Hz), 9.04 (s, 2H, NH). 13C NMR (CDCl3) d 68.3, 69.9,
72.4, 111.6, 117.9, 120.0, 121.6, 124.0, 127.3, 133.4, 147.3,
167.6. LCMS; m/z: 485 (MC1). Anal. calcd for
C26H32N2O7 (484.6): C, 64.45; H, 6.66; N, 5.78. Found:
C, 64.54; H, 6.65; N, 6.00.
3.2. Bis-o-allyloxyacetamidophenoxy derivatives 19–23.
General procedures
A. Compound 12 (22 mmol) was added to a solution of
KOH (0.13 g, 2.2 mmol) in methanol (10 mL). The mixture
was then stirred at room temperature for 15 min and the
solvent was then removed in vacuo. To the remaining
potassium salt 13 was added DMF (5 mL) and the
appropriate dihalo or ditosylate derivatives 14–18
(1 mmol). The reaction mixture was then heated under
reflux for 5 min. The mixture was cooled, diluted with water
(20 mL) and the precipitate was collected, washed with cold
water and finally crystallized from petroleum ether (40–60).
3.2.4. 1,8-Bis(o-allyloxyacetamidophenoxy)-3,6-dioxaoc-
tane 22. Yield, 0.23 g (43%, A), 0.4 g (75%, B), colorless
crystals, mp 63–64 8C. IR: 3384, 3070, 2875, 1690, 1601,
1534, 1485, 1454, 1332, 1290, 1253, 1209, 1177, 1137,
1
1116, 1046, 928, 750. H NMR (CDCl3) d 3.74 (s, 4H,
OCH2CH2O), 3.88 (t, 4H, JZ4.8 Hz, ArOCH2CH2O), 4.08
(s, 4H, CH2C]O), 4.12 (dd, 4H, JZ1.3, 4.2 Hz,
CH2CH]), 4.19 (t, 4H, JZ4.8 Hz, ArOCH2CH2O), 5.27
(dd, 2H, JZ1.3, 10.4 Hz, CH2]), 5.37 (m, 2H, CH2]),
5.95 (m, 2H, CH]), 6.89 (dd, 2H, JZ1.5, 8.0 Hz), 7.00 (m,
4H), 8.41 (dd, 2H, JZ1.5, 8 Hz), 9.04 (s, 2H, NH). 13C
NMR (CDCl3) d 68.2, 69.7, 69.8, 71.0, 72.3, 111.4, 118.0,
119.9, 121.6, 123.7, 129.8, 133.4, 147.4, 167.6. Anal. calcd
for C28H36N2O8 (528.6): C, 63.62; H, 6.86; N, 5.30. Found:
C, 63.75; H, 6.77; N, 5.41.
B. To a solution of each of the appropriate bis-amine
dihydrochlorides 24–2820 (1 mmol) in DCM (10 mL) at
0 8C was added dropwise TEA (3 mL) followed by a
dropwise addition of a solution of allyloxyacetyl chloride19
(0.28 g, 2.1 mmol) in DCM (10 mL) over a period of 30 min
at 0 8C. The reaction mixture was then kept stirring at room
temperature overnight. The mixture was then diluted with
DCM (50 mL) and washed with hydrochloric acid (2 M,
100 mL), then twice with saturated sodium carbonate
solution and finally with water. The organic layer was
then dried over anhydrous sodium sulfate and evaporated to
dryness. The remaining bis-anilides 19–23 were recrystal-
lized from petroleum ether (40–60).
3.2.5. 1,2-Bis(o-allyloxyacetamidophenoxymethyl)ben-
zene 23. Yield, 0.25 g (48%, A), 0.35 g, (68%, B); colorless
crystals, mp 72 8C. IR: 3387, 3069, 3028, 2935, 2892, 2852,
1689, 1600, 1534, 1484, 1454, 1331, 1290, 1250, 1205, 1114,
1046, 1006, 928, 750. 1H NMR (CDCl3) d 3.97 (dd, 4H, JZ
0.8, 5.6 Hz, CH2CH]), 4.01 (s, 4H, CH2C]O), 5.06 (d, 2H,
JZ10.4 Hz, CH2ZCH), 5.16 (dd, 2H, JZ1.1, 17.8 Hz,
CH2]CH), 5.23 (s, 4H, OCH2C6H4), 5.68 (m, 2H, CH]),
6.9–7.06 (m, 6H), 7.43 (m, 2H), 7.57 (m, 2H), 8.44 (dd, 2H,
JZ1.0, 8.0 Hz), 9.03 (s, 2H, NH). 13C NMR (CDCl3) d 68.2,
69.6, 72.2, 111.3, 117.9, 119.8, 121.7, 124.0, 127.1, 128.6,
128.8, 133.0, 134.4, 147.0, 167.4. LCMS; m/z: 517 (MC1).
Anal. calcd for C30H32N2O6 (516.6): C, 69.75; H, 6.24; N,
5.42. Found: C, 69.62; H, 6.31; N, 5.55.
3.2.1. 1,2-Bis(o-allyloxyacetamidophenoxy)ethane 19.
Yield 0.19 g (43%, A); 0.3 g (70%, B); colorless crystals,
mp 89–90 8C. IR: 3384, 1690, 1649, 1534, 1452, 1249,
1206, 1116, 926, 748. 1H NMR (CDCl3): d 3.87 (d, 4H, JZ
5.5 Hz, OCH2CH]), 4.02 (s, 4H, OCH2CH2O), 4.45 (s, 4H,
CH2C]O), 4.95 (d, 2H JZ10.4 Hz, CH2]), 5.14 (dd, 2H,
JZ1.3, 17.2 Hz, CH2]), 5.61 (m, 2H, CH]), 6.97 (d, 2H,
JZ7.6 Hz), 7.04 (t, 2H, JZ7.6 Hz), 7.10 (dt, 2H, JZ1.5,
7.6 Hz), 8.45 (dd, 2H, JZ1.5, 7.6 Hz), 9.08 (s, 2H, NH). 13C
NMR (CDCl3): d 67.2, 69.7, 72.2, 111.1, 117.6, 120.0,
121.8, 124.0, 127.4, 132.5, 147.2, 167.6. LCMS; m/z: 441
(MC1). Anal. calcd for C24H28N2O6 (440.5): C, 65.44; H,
6.41; N, 6.36. Found: C, 65.50; H, 6.32; N, 6.47.
3.3. Bis-o-chloroacetamidophenoxy derivatives 30–34.
General procedure
A mixture of the appropriate bis-amine dihydrochloride 24–
28 (10 mmol) and sodium carbonate (3.7 g, 35 mmol) in
3.2.2. 1,3-Bis(o-allyloxyacetamidophenoxy)propane 20.

Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
8433
water (15 mL) was stirred for 10 min, then DCM (20 mL)
was added and cooled to 5 8C. To this cold mixture was
added dropwise with stirring a solution of chloroacetyl
chloride (2.83 g, 25 mmol) in DCM (20 mL). The reaction
mixture was stirred for 1 h and the organic layer was
separated, evaporated in vacuo and the remaining precipi-
tate was recrystallized from ethanol to give colorless
crystals of compounds 30–34.
(CDCl3) d 4.12 (s, 4H, CH2C]O), 5.28 (s, 4H, CH2C6H4),
7.00 (d, 2H, JZ7.8 Hz), 7.05 (t, 2H, JZ7.8 Hz), 7.11 (dt,
2H, JZ1.3, 7.8 Hz), 7.46 (m, 2H), 7.59 (m, 2H), 8.36 (dd,
2H, JZ1.3, 8 Hz), 8.96 (s, 2H, NH). 13C NMR (DMSO-d6)
d 43.9, 68.1, 113.4, 121.2, 123.1, 125.9, 127.2, 128.6, 128.7,
135.2, 149.5, 165.3. LCMS; m/z: 473 (MC1), 475 (MC3),
477 (MC5). Anal. calcd for C24H22 Cl2N2O4 (473.4): C,
60.90; H, 4.68; N, 5.92. Found: C, 61.11; H, 4.85; N, 5.88.
3.3.1. 1,2-Bis(o-chloroacetamidophenoxy)ethane (30).
Yield 2.94 g (74%); colorless crystals, mp 197–199 8C.
IR: 3384, 3295, 3136, 3070, 2957, 1675, 1600, 1537, 1454,
3.4. Compounds 36–40. General procedures
o-Allyloxyphenol (0.33 g, 2.2 mmol) was added to a
solution of KOH (0.13 g, 2.2 mmol) in methanol (5 mL).
The mixture was then stirred at room temperature for 15 min
and the solvent was then removed in vacuo. To the
remaining potassium salt 35 was added DMF (2 mL) and
the appropriate dichloro derivatives 30–34 (1 mmol). The
reaction mixture was then heated under reflux for 5 min.
The mixture was cooled, diluted with water (20 mL) and the
precipitate was collected, washed with cold water and
finally crystallized from petroleum ether (40–60) to give
colorless needles of compounds 36, 37. Compound 38–40
were purified by silica gel column chromatography [6:3:4
DCM/EtOAc/petroleum ether (40–60)].
1
1337, 1257, 1118, 1047, 751. H NMR (CDCl3) d 4.13 (s,
4H, OCH2CH2O), 4.50 (s, 4H, CH2C]O), 6.99 (dd, 2H,
JZ1.2, 8 Hz), 7.06 (dt, 2H, JZ1.5, 8 Hz), 7.14 (dt, 2H, JZ
1.5, 8 Hz), 8.37 (dd, 2H, JZ1.5, 8 Hz), 9.02 (s, 2H, NH).
LCMS; m/z: 397 (MC1), 399 (MC3), 401 (MC5). Anal.
calcd for C18H18Cl2N2O4 (397.3): C, 54.42; H, 4.57; N,
7.05. Found: C, 54.44; H, 4.50; N, 7.17.
3.3.2. 1,2-Bis(o-chloroacetamidophenoxy)propane (31).
Yield 3.36 g (82%); colorless crystals, mp 185–186 8C. IR:
3287, 3146, 3073, 3004, 2953, 2883, 1680, 1602, 1551, 1496,
1456, 1343, 1288, 1262, 1227, 1118, 998, 753, 680. 1H NMR
(CDCl3) d 2.43 (quint, 2H, JZ6 Hz, OCH2CH2CH2O), 4.21
(s, 4H, CH2C]O), 4.34 (t, 4H, JZ6 Hz, OCH2CH2), 6.96
(d, 2H, JZ7.8 Hz), 7.02 (t, 2H, JZ7.8 Hz), 7.12 (dt, 2H,
JZ1, 7.8 Hz), 8.35 (dd, 2H, JZ1, 7.8 Hz), 9.04 (s, 2H, NH).
LCMS; m/z: 411 (MC1), 413 (MC3), 415 (MC5). Anal.
calcd for C19H20Cl2N2O4 (411.3): C, 55.49; H, 4.90; N,
6.81. Found: C, 55.77; H, 5.07; N, 6.89.
3.4.1. 1,2-Bis[o-(o-allyloxyphenoxyacetamido)phenoxy]
ethane (36). Yield 0.42 g (67%); colorless crystals, mp
126–127 8C. IR: 3387, 3069, 2927, 1690, 1600, 1536, 1501,
1454, 1254, 1205, 1120, 1051, 929, 747. 1H NMR (CDCl3)
d 4.31 (s, 4H, OCH2CH2O), 4.43 (d, 4H, JZ5.1 Hz,
CH2CH]), 4.56 (s, 4H, CH2C]O), 5.20 (d, 2H, JZ
10.5 Hz, CH2]), 5.34 (d, 2H, JZ17.1 Hz, CH2]), 5.97
(m, 2H, ]CH), 6.80 (m, 4H), 6.87 (m, 4H), 6.98 (m, 6H),
8.34 (m, 2H), 9.13 (s, 2H, NH). LCMS; m/z: 625 (MC1).
Anal. calcd for C36H36N2O8 (624.7): C, 69.22; H, 5.81; N,
4.48. Found: C, 69.01; H, 5.90; N, 4.65.
3.3.3. 1,5-Bis(o-chloroacetamidophenoxy)-3-oxapentane
(32). Yield 4.05 g (92%); colorless crystals, mp 115–
117 8C. IR: 3375, 3062, 3003, 2928, 2876, 1677, 1604,
1
1536, 1488, 1459, 1408, 1338, 1256, 1117, 1051, 758. H
NMR (CDCl3) d 3.99 (t, 4H, JZ4.6 Hz, ArOCH2CH2O),
4.26 (t, 4H, JZ4.6 Hz, ArOCH2CH2O), 4.17 (s, 4H,
CH2C]O), 6.94 (d, 2H, JZ7.8 Hz), 7.02 (t, 2H, JZ
7.8 Hz), 7.10 (dt, 2H, JZ1.2, 7.8 Hz), 8.35 (dd, 2H, JZ1.2,
7.8 Hz), 9.07 (s, 2H, NH). 13C NMR (DMSO-d6) d 44.0,
69.2, 69.8, 113.6, 121.5, 122.1, 125.8, 127.6, 149.4, 165.2.
LCMS; m/z: 441 (MC1), 443 (MC3), 445 (MC5). Anal.
calcd for C20H22 Cl2N2O5 (441.3): C, 54.43, H, 5.02, N,
6.35. Found: 54.37, H, 5.05, N, 6.37.
3.4.2. 1,3-Bis[o-(o-allyloxyphenoxyacetamido)phenoxy]-
propane (37). Yield 0.38 g (60%); colorless crystals, mp
120 8C. IR: 3391, 3069, 2933, 1690, 1599, 1535, 1499,
1453, 1253, 1204, 1118, 1052, 927, 747. 1H NMR (CDCl3)
d 2.16 (quint, 2H, JZ6.0 Hz, OCH2CH2), 4.08 (t, 4H, JZ
6 Hz, OCH2CH2), 4.53 (d, 4H, JZ5.2 Hz, OCH2CH]),
4.64 (s, 4H, CH2C]O), 5.22 (d, 2H, JZ10.6 Hz, CH2]),
5.36 (d, 2H, JZ17.2 Hz, CH2]), 5.99 (m, 2H, ]CH), 6.73
(m, 2H), 6.96 (m, 12H), 8.36 (dd, 2H, JZ2.1, 7.3 Hz), 9.13
(s, 2H, NH). LCMS; m/z: 639 (MC1). Anal. calcd for
C37H38N2O8 (638.7): C, 69.58; H, 6.00; N, 4.39. Found: C,
69.48; H, 6.03; N, 4.28.
3.3.4. 1,8-Bis(o-chloroacetamidophenoxy)-3,6-dioxaoc-
tane (33). Yield 4.0 g (83%); colorless crystals, mp 99–
100 8C. IR: 3382, 3136, 3068, 3010, 2950, 2874, 1683,
1605, 1538, 1488, 1453, 1409, 1337, 1292, 1257, 1209,
1
1117, 1047, 929, 751. H NMR (CDCl3) d 3.77 (s, 4H,
3.4.3. 1,5-Bis[o-(o-allyloxyphenoxyacetamido)phenoxy]-
3-oxapentane (38). Yield 0.36 g (54%); pale yellow oil. IR:
3387, 3068, 2930, 2868, 1690, 1600, 1535, 1499, 1455,
1255, 1205, 1120, 1051, 928, 793, 749. 1H NMR (CDCl3) d
3.76 (br, 4H, ArOCH2CH2O), 4.02 (br, 4H, ArOCH2CH2O),
4.56 (d, 4H, JZ4.8 Hz, OCH2CH]), 4.62 (s, 4H,
CH2C]O), 5.22 (d, 2H, JZ10.5 Hz, CH2]), 5.37 (d, 2H,
JZ17.3 Hz, CH2]), 6.01 (m, 2H, ]CH), 6.78 (d, 2H, JZ
7.5 Hz), 6.90 (m, 4H), 7.01 (m, 8H), 8.40 (d, 2H, JZ
7.6 Hz), 9.21 (s, 2H, NH). 13C NMR (CDCl3) d 68.5, 69.7,
69.8, 70.5, 111.7, 114.2, 117.4, 117.9, 120.3, 121.4, 121.6,
123.7, 124.2, 127.2, 133.0, 147.4, 147.6, 149.3, 166.8. LC/
MS; m/z: 669 (MC1). Anal. calcd for C38H40N2O9 (668.8):
OCH2CH2O), 3.90 (t, 4H, JZ4.6 Hz, ArOCH2CH2O), 4.19
(s, 4H, CH2C]O), 4.22 (t, 4H, JZ4.6 Hz, ArOCH2CH2O),
6.91 (d, 2H, JZ7.8 Hz), 7.00 (t, 2H, JZ7.8 Hz), 7.09 (dt,
2H, JZ1.1, 7.8 Hz), 8.34 (dd, 2H, JZ1.1, 7.8 Hz), 9.08 (s,
2H, NH). LCMS; m/z: 485 (MC1), 487 (MC3), 487 (MC
5). Anal. calcd for C22H26Cl2N2O6 (485.4): C, 54.44; H,
5.40; N, 5.77. Found: C, 54.45; H, 5.53; N, 5.98.
3.3.5. 1,2-Bis[o-(chloroacetamido)phenoxymethyl]ben-
zene (34). Yield 3.65 g (77%); colorless crystals, mp 155–
157 8C. IR: 3392, 3062, 3005, 2957, 2909, 2861, 1680,
1
1601, 1486, 1457, 1296, 1257, 1119, 1026, 749. H NMR

8434
Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
C, 68.25; H, 6.03; N, 4.19. Found: C, 67.98; H, 5.97; N,
4.38.
(s, 4H, CH2C]O), 5.94 (tt, 2H, JZ1.1, 3.8 Hz, ]CH), 6.86
(dd, 2H, JZ1.5, 8 Hz), 7.06 (m, 4H), 8.42 (dd, 2H, JZ1.5,
8 Hz), 9.03 (s, 2H, NH). LCMS: m/zZ413 (MC1). Anal.
calcd for C22H24N2O6 (412.5): C, 64.07; H, 5.87; N, 6.79.
Found: C, 64.06; H, 5.92; N, 6.97.
3.4.4. 1,8-Bis[o-(o-allyloxyphenoxyacetamido)phenoxy]-
3,6-dioxaoctane (39). Yield 0.38 g (53%); pale yellow oil,
RfZ0.67. IR: 3387, 3069, 2925, 2876, 1688, 1600, 1534,
1501, 1455, 1256, 1209, 1120, 1050, 998, 929, 750. 1H NMR
(CDCl3) d 3.50 (s, 4H, OCH2CH2O), 3.72 (t, 4H, JZ4.8 Hz,
ArOCH2CH2O), 4.13 (t, 4H, JZ4.8 Hz, ArOCH2CH2O),
4.59 (d, 4H, JZ5.2 Hz, OCH2CH]), 4.65 (s, 4H,
CH2C]O), 5.24 (d, 2H, JZ10.4 Hz, CH2]), 5.39 (d, 2H,
JZ17.3 Hz, CH2]), 6.04 (m, 2H, ]CH), 6.91 (m, 6H),
6.99–7.09 (m, 8H), 8.41 (d, 2H, JZ7.8 Hz), 9.23 (s, 2H,
NH). LCMS; m/z: 713 (MC1). Anal. calcd for
C40H44N2O10 (712.8): C, 67.40, H, 6.22, N, 3.93. Found:
C, 67.40, H, 6.11, N, 4.05.
3.5.2. Compound 2. (E and Z): 79 mg (93%); colorless
crystals, mp 191–193 8C, (RfZ0.32). IR: 3374, 2963, 2889,
2870, 1681, 1603, 1542, 1490, 1456, 1408, 1336, 1291,
1
1252, 1212, 1115, 1040, 1016, 966, 817, 751. H NMR
(CDCl3) (E isomer): d 2.35 (quintet, 2H, JZ7 Hz,
OCH2CH2), 4.16 (s, 4H, CH2C]O), 4.19 (m, 4H,
CH2CH]), 4.24 (t, 4H, JZ7 Hz, OCH2CH2), 6.04 (m,
2H, ]CH), 6.90 (d, 2H, JZ7.8 Hz), 7.04 (m, 4H), 8.45 (d,
2H, JZ7.8 Hz), 9.14 (s, 2H, NH). 13C NMR (CDCl3) (E
isomer): d 28.9, 65.1, 71.0, 71.6, 111.2, 119.7, 121.6, 124.0,
127.4, 127.9, 146.6, 167.15. 1H NMR (CDCl3) (Z isomer): d
2.35 (quintet, 2H, JZ7 Hz, OCH2CH2), 4.16 (s, 4H,
CH2C]O), 4.19 (d, 4H, JZ4.2 Hz, CH2CH]), 4.24 (t,
4H, JZ7 Hz, OCH2CH2), 5.90 (t, 2H, JZ4.2 Hz, ]CH),
6.90 (d, 2H, JZ8 Hz), 7.04 (m, 4H), 8.39 (d, 2H, JZ8 Hz),
9.14 (s, 2H, NH). 13C NMR (CDCl3) (Z isomer): d 29.6,
65.5, 67.1, 70.8, 111.5, 119.7, 121.6, 124.04, 127.3, 128.4,
147.2, 167.2. MS: m/zZ426 (MC, 70%). Anal. calcd for
C23H26N2O6 (426.5): C, 64.78; H, 6.15; N, 6.57. Found: C,
64.50; H, 6.22; N, 6.61.
3.4.5. 1,2-Bis[o-(o-allyloxyphenoxyacetamido)phenoxy-
methyl]benzene (40). Yield 0.5 g (71%), colorless semi-
solid. IR: 3391, 3068, 2922, 2856, 1690, 1600, 1535, 1501,
1
1455, 1255, 1206, 1119, 1049, 997, 928, 749. H NMR
(CDCl3) d 4.36 (d, 4H, JZ5.3 Hz, OCH2CH]), 4.59 (s, 4H,
CH2C]O), 5.10 (d, 2H, JZ10.4 Hz, CH2]), 5.18 (s, 4H,
OCH2C6H4), 5.25 (d, 2H, JZ17.4 Hz, CH2]), 5.87 (m, 2H,
]CH), 6.84 (m, 6H), 6.89 (m, 2H), 6.99 (m, 6H), 7.16 (m,
2H), 7.43 (m, 2H), 8.42 (m, 2H), 9.23 (s, 2H, NH). 13C NMR
(CDCl3) d 68.4, 69.4, 70.2, 111.8, 113.8, 116.9, 117.7,
120.4, 121.2, 121.6, 123.5, 124.3, 127.2, 128.4, 128.6,
132.9, 134.3, 147.1, 147.3, 149.1, 166.8. LC/MS; m/z: 701
(MC1). Anal. calcd for C42H40N2O8 (700.8): C, 71.99, H,
5.75, N, 4.00. Found: C, 71.99, H, 5.69, N, 4.19.
3.5.3. Compound 3. (E and Z): 64 mg (70%); colorless
crystals, mp 141–142 8C, (RfZ0.35). IR: 3378, 3061, 2933,
2855, 1686, 1601, 1535, 1485, 1453, 1252, 1116, 752. H
1
NMR (CDCl3) (E isomer): d 3.94 (t, 4H, JZ4.2 Hz,
ArOCH2CH2O), 4.16, 4.20 (2s, 4H, 4H, CH2C]O,
CH2CH]), 4.23 (t, 4H, JZ4.2 Hz, ArOCH2CH2O), 6.08
(s, 2H, ]CH), 6.91 (m, 2H), 7.04 (m, 4H), 8.43 (m, 2H),
9.22 (s, 2H, NH). 13C NMR (CDCl3) (E isomer): d 68.9,
69.6, 70.8, 71.5, 112.1, 119.8, 121.8, 124.0, 128.1, 128.7,
3.5. Ring closing metathesis of 19–23, 36–40. General
procedure
A solution of each of the substrates 19–23, 36–40
(0.2 mmol) in DCM (25 mL) and Grubbs’ catalyst (2.5–
4 mg, ca. 1.5–2.5 mol% of the substrate) was heated under
reflux for 3 h. The reaction mixture was then mixed with
silica gel (100–200 mm, 0.5 g), stirred for 30 min, filtered
and the silica was extracted twice with DCM (50 mL). After
removing the solvent from the DCM extract, the remaining
products were analyzed by 1H NMR (Tables 1 and 2).
Compounds 1, 3, 4, 8 were purified by preparative thin layer
chromatography [6:3:4 DCM/EtOAc/petroleum ether (40–
60)]. All macrocycles 1–10 were characterized by their Rf
values on TLC using the same solvent mixture where both E
and Z isomers gave the same spot. The E and Z isomers of
compound 10 were separated by fractional crystallization by
leaving a CH2Cl2 solution of the mixture in a closed
atmosphere containing petroleum ether (40–60). Other
1
147.2, 167.4. H NMR (CDCl3) (Z isomer): d 3.99 (t, 4H,
JZ4.8 Hz, ArOCH2CH2O), 4.07 (s, 4H, CH2C]O), 4.23 (t,
4H, JZ4.8 Hz, ArOCH2CH2O), 4.25 (d, 4H, JZ3.4 Hz,
CH2CH]), 5.92 (t, 2H, JZ3.4 Hz, ]CH), 6.91 (m, 2H),
7.04 (m, 4H), 8.43 (m, 2H), 9.13 (s, 2H, NH). 13C NMR
(CDCl3) (Z isomer): d 67.4, 68.6, 70.2, 70.8, 111.7, 119.8,
121.7, 124.0, 127.4, 127.8, 147.1, 167.1. LC/MS: m/zZ457
(MC1). Anal. calcd for C24H28N2O7 (456.5): C, 63.15; H,
6.18; N, 6.14. Found: C 63.38, H 6.30, N 6.29.
3.5.4. Compound 4. (E and Z): 80 mg (80%); colorless
crystals, mp 137–138 8C, (RfZ0.30). IR: 3379, 3023, 2929,
1690, 1600, 1535, 1454, 1252, 1116, 798. 752 cmK1
.
1HNMR (CDCl3) (E isomer): d 3.79 (s, 4H, OCH2CH2O),
3.92 (t, 4H, JZ4.1 Hz, ArOCH2CH2O), 4.14 (s, 4H,
CH2C]O), 4.20 (t, 4H, JZ4.1 Hz, ArOCH2CH2O), 4.21
(s, 4H, CH2CH]), 6.02 (s, 2H, ]CH), 6.89 (m, 2H), 6.99
(m, 2H), 7.07 (m, 2H), 8.43 (m, 2H), 9.09 (s, 2H, NH). 13C
NMR (CDCl3) (E isomer): d 68.5, 69.7, 70.4, 70.9, 71.3,
1
isomers were identified by their H and 13C NMR in their
mixture.
3.5.1. Compound 1. (E and Z): Yield 51 mg (62%);
colorless crystals, mp 169–171 8C, (RfZ0.32). IR: 3387,
3066, 2960–2904, 2852, 1691, 1601, 1536, 1483, 1456,
1332, 1256, 1201, 1120, 746. 1H NMR (CDCl3) (E isomer):
d 4.14 (s, 4H, OCH2CH2), 4.18 (m, 4H, CH2CH]), 4.54 (s,
4H, CH2C]O), 6.04 (m, 2H, ]CH), 6.88 (dd, 2H, JZ1.5,
7.8 Hz), 7.06 (m, 4H), 8.45 (dd, 2H, JZ1.5, 7.8 Hz), 9.11 (s,
1
111.3, 119.8, 121.5, 124.1, 128.4, 128.9, 147.3, 167.4. H
NMR (CDCl3) (Z isomer): d 3.80 (s, 4H, OCH2CH2O), 3.91
(t, 4H, JZ4.1 Hz, ArOCH2CH2O), 4.12 (s, 4H, (s, 4H,
CH2C]O), 4.21 (t, 4H, JZ4.1 Hz, ArOCH2CH2O), 4.25
(d, 4H, JZ3.6 Hz, CH2CH]), 5.92 (t, 2H, JZ3.6 Hz,
]CH), 6.99 (m, 2H), 7.07 (m, 2H), 8.43 (m, 2H), 9.09 (s,
2H, NH). 13C NMR (CDCl3) (Z isomer): d 67.4, 68.6, 70.0,
70.5, 70.9, 110.9, 119.6, 121.4, 124.1, 128.1, 128.7, 147.3,
1
2H, NH). H NMR (CDCl3) (Z isomer): d 4.12 (s, 4H,
OCH2CH2), 4.29 (dd, 4H, JZ1.1, 3.8 Hz, CH2CH]), 4.50

Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
8435
167.2. LCMS: m/zZ501 (MC1). Anal. calcd for
C22H32N2O8 (500.5): C, 62.39; H, 6.44; N, 5.60. Found:
C, 62.56; H, 6.59; N, 5.78.
3.5.8. Compound 8. (E and Z): 110 mg (86%); colorless
crystals, mp 138–140 8C (RfZ0.36). IR 3387, 3070, 2930,
2854, 1688, 1600, 1535, 1501, 1454, 1255, 1207, 1120,
1049, 748. 1H NMR (CDCl3) (E isomer): d 3.90 (t, 4H, JZ
4.7 Hz, ArOCH2CH2O), 4.02 (t, 4H, JZ4.7 Hz, ArOCH2-
CH2O), 4.47 (dd, 4H, JZ1.1, 2.0 Hz, OCH2CH]), 4.63 (s,
4H, CH2C]O), 6.13 (m, 2H, ]CH), 6.78 (m, 2H), 6.87 (m,
2H), 7.01 (m, 10H), 8.41 (m, 2H), 9.24 (s, 2H, NH). 13C
NMR (DEPT) (CDCl3) (E isomer): d 68.5 (CH2), 68.8
(CH2), 69.8 (2CH2), 111.7 (CH), 113.9 (CH), 115.7 (CH),
120.5 (CH), 121.4 (CH), 121.5 (CH), 123.2 (CH), 124.3
(CH), 127.1 (C), 128.1 (CH), 147.4 (C), 147.6 (C), 148.7
(C), 166.4 (C). 1H NMR (CDCl3) (Z isomer): d 3.80 (t, 4H,
JZ4.7 Hz, ArOCH2CH2O), 3.98 (t, 4H, JZ4.7 Hz,
ArOCH2CH2O), 4.65 (s, 4H, CH2C]O), 4.80 (d, 4H, JZ
3.5 Hz, OCH2CH]), 5.92 (t, 2H, JZ3.5 Hz, ]CH), 6.78
(m, 2H), 6.87 (m, 2H), 7.01 (m, 10H), 8.44 (m, 2H), 9.20 (s,
2H, NH). 13C NMR (DEPT) (CDCl3) (Z isomer): d 65.2
(CH2), 68.8 (CH2), 69.8 (CH2), 69.9 (CH2), 111.6 (CH),
113.9 (CH), 115.7 (CH), 120.1 (CH), 121.4 (CH), 121.6
(CH), 123.27 (CH), 124.2 (CH), 127.1 (C), 128.2 (CH),
147.3 (C), 147.6 (C), 148.4 (C), 166.4 (C). LCMS: m/z: 641
(MC1). Anal. calcd for C36H36N2O9 (640.7): C, 67.49; H,
5.66; N, 4.73. Found: C, 67.59; H, 5.84; N, 4.75.
3.5.5. Compound 5. (E and Z): 87 mg (89%); colorless
crystals, mp 202–204 8C, (RfZ0.53). IR: 3382, 3014, 2919,
2845, 1687, 1601, 1534, 1453, 1249, 1204, 1115, 1014, 752.
1H NMR (CDCl3) (E isomer): d 4.11 (s, 8H, CH2C]O,
CH2CH]), 5.36 (s, 4H, OCH2C6H4), 5.93 (br, 2H, ]CH),
6.80 (m, 2H), 7.03 (m, 4H), 7.39 (m, 2H), 7.47 (m, 2H), 8.40
(m, 2H), 9.17 (s, 2H, NH). 13C NMR (CDCl3) (E isomer): d
68.5, 69.7, 70.6, 111.1, 119.9, 121.6, 124.0, 127.1, 128.0,
1
128.2, 128.6, 134.3, 146.7, 167.1. H NMR (CDCl3) (Z
isomer): d 4.03 (s, 4H, CH2C]O), 4.07 (d, 4H, JZ4 Hz,
CH2CH]), 5.22 (s, 4H, OCH2C6H4), 5.40 (t, 2H, JZ4 Hz,
]CH), 6.95 (m, 2H), 7.04 (m, 4H), 7.48 (m, 2H), 7.56 (m,
2H), 8.45 (m, 2H), 9.13 (s, 2H, NH). 13C NMR (CDCl3) (Z
isomer): d 67.6, 68.1, 70.5, 111.4, 119.6, 121.8, 124.0,
127.3, 128.04, 128.7, 129.1, 134.1, 146.9, 167.3. LCMS: m/
zZ488 (MC). Anal. calcd for C28H28N2O6 (488.6): C,
68.84; H, 5.78; N, 5.73. Found: C, 68.60; H, 5.81; N, 5.67.
3.5.6. Compound 6. (E and Z): 109 mg (91%); colorless
crystals, mp 214 8C, (RfZ0.38). IR: 3380, 3070, 3005,
2926, 1691, 1599, 1537, 1500, 1452, 1254, 1206, 1120,
3.5.9. Compound 9. (E and Z): 130 mg (95%); colorless
crystals, mp 202–204 8C, (RfZ0.31). IR: 3385, 3065, 2928,
2865, 1690, 1601, 1537, 1500, 1454, 1254, 1206, 1119,
1
1043, 749. H NMR (CDCl3) (E isomer): d 4.33 (s, 4H,
OCH2CH2O), 4.39 (s, 4H, OCH2CH]), 4.63 (s, 4H,
CH2C]O), 6.06 (s, 2H, ]CH), 6.81–7.06 (m, 14H), 8.42
(dd, 2H, JZ1.0 Hz, 7.7), 9.53 (s, 2H, NH). 13C NMR
(CDCl3) (E isomer) d 66.5, 68.6, 69.7, 112.0, 113.6, 115.9,
120.1, 121.3, 122.8, 123.2, 124.2, 127.9, 147.1, 147.2,
147.5, 149.1, 166.4. 1H NMR (CDCl3) (Z isomer): d 4.30 (s,
4H, OCH2CH2O), 4.57 (s, 4H, CH2C]O), 4.70 (d, 4H, JZ
3.5 Hz, OCH2CH]), 5.87 (t, 2H, JZ3.5 Hz, ]CH), 6.85–
7.06 (m, 14H), 8.38 (dd, 2H, JZ2.2 Hz, 7.5), 9.23 (s, 2H,
NH). 13C NMR (CDCl3) (Z isomer): d 65.3, 66.5, 69.2,
113.6, 114.9, 115.6, 120.3, 121.4, 121.7, 122.7, 123.1,
124.1, 147.2, 147.3, 147.7, 148.5, 166.5. LCMS: m/zZ597
(MC1, 100%). Anal. calcd for C34H32N2O8 (596.6): C,
68.45; H, 5.41; N, 4.70. Found: C, 68.71; H, 5.90; N, 4.90.
1
1049, 747. H NMR (CDCl3) (E isomer): d 3.57 (s, 4H,
OCH2CH2O), 3.74 (t, 4H, JZ4.8 Hz, ArOCH2CH2O), 4.14
(t, 4H, JZ4.8 Hz, ArOCH2CH2O), 4.66 (s, 8H, CH2C]O,
CH2CH]), 6.15 (s, 2H, ]CH), 6.86–7.07 (m, 14H), 8.42
(d, 2H, JZ7.7 Hz), 9.20 (s, 2H, NH). 13C NMR (CDCl3) (E
isomer): d 68.6, 68.7, 69.4, 69.8, 70.9, 112.0, 114.2, 115.7,
120.4, 121.5, 121.6, 123.2, 124.3, 127.3, 128.3, 147.5,
147.7, 148.7, 166.6. 1H NMR (CDCl3) (Z somer): d 3.50 (s,
4H, OCH2CH2O), 3.73 (t, 4H, JZ4.8 Hz, ArOCH2CH2O),
4.12 (t, 4H, JZ4.8 Hz, ArOCH2CH2O), 4.64 (s, 4H,
CH2C]O), 4.83 (d, 4H, JZ3.2 Hz, CH2CH]), 5.95 (t,
2H, JZ3.2 Hz, ]CH), 6.86–7.07 (m, 14H), 8.42 (d, 2H,
JZ7.7 Hz), 9.21 (s, 2H, NH). 13C NMR (CDCl3) (Z
isomer): d 65.2, 68.6, 69.5, 69.8, 70.9, 111.7, 114.0,
115.9, 120.4, 121.5, 121.6, 123.3, 124.3, 127.2, 128.5,
147.4, 147.6, 147.7, 166.6. LCMS: m/zZ685 (MC1). Anal.
calcd for C38H40N2O10 (684.8): C, 66.66; H, 5.89; N, 4.09.
Found: C, 66.59; H, 5.73; N, 4.20.
3.5.7. Compound 7. (E and Z): 112 mg (92%); colorless
crystals, mp 220 8C, (RfZ0.30). IR: 3385, 3067, 2923,
1689, 1600, 1537, 1500, 1455, 1290, 1256, 1210, 1117,
1045, 1001, 911, 745. 1H NMR (CDCl3) (E isomer): d 2.23
(quint, 2H, JZ5.4 Hz, OCH2CH2), 3.85 (s, 4H,
OCH2CH]), 4.20 (t, 4H, JZ5.4 Hz, OCH2CH2), 4.57 (s,
4H, CH2C]O), 5.64 (s, 2H, ]CH), 6.53 (d, 2H, JZ8 Hz),
6.66 (d, 2H, JZ8 Hz), 6.86–7.14 (m, 10H), 8.37 (d, 2H, JZ
7.8 Hz), 9.63 (s, 2H, NH). 13C NMR (CDCl3) (E isomer) d
29.3, 63.3, 68.0, 73.1, 110.8, 113.5, 119.95, 120.2, 120.8,
121.3, 124.4, 124.6, 126.65, 128.0, 147.7, 148.4, 149.8,
167.0. 1H NMR (CDCl3) (Z isomer): d 2.27 (quint, 2H, JZ
6.5 Hz, OCH2CH2), 4.12 (t, 4H, JZ6.5 Hz, OCH2CH2),
4.65 (s, 4H, CH2C]O), 4.75 (d, 4H, JZ3.2 Hz, CH2CH]),
5.90 (t, 2H, JZ3.2 Hz, ZCH), 6.74 (m, 2H), 7.01 (m, 10H),
7.12 (m, 2H), 8.37 (m, 2H), 9.24 (s, 2H, NH). 13C NMR
(CDCl3) (Z isomer) d 29.0, 65.5, 65.7, 69.0, 110.8, 114.1,
114.9, 120.0, 121.1, 121.8, 123.1, 124.3, 126.7, 128.2,
147.2, 147.4, 148.3, 166.3. LCMS; m/z: 611 (MC1). Anal.
calcd for C35H34N2O8 (610.7): C, 68.84; H, 5.61; N, 4.59.
Found: C, 68.98; H, 5.51; N, 4.70.
3.5.10. Compound 10. (E and Z): 127 mg (94%); colorless
crystals, mp 110 8C, (RfZ0.38). IR 3380, 3065, 2923, 2855,
1690, 1600, 1540, 1501, 1455, 1384, 1255, 1208, 1118,
1048, 921, 744. 1H NMR (CDCl3) (E isomer): d 4.29 (d, 4H,
JZ2.5 Hz, OCH2CH]), 4.58 (s, 4H, CH2C]O), 5.25 (s,
4H, OCH2C6H4), 5.94 (t, 2H, JZ2.5 Hz, ]CH), 6.81–7.09
(m, 16H), 7.37 (m, 2H), 8.41 (m, 2H), 9.30 (s, 2H, NH). 13C
NMR (CDCl3) (E isomer): d 68.2, 68.4, 70.0, 112.3, 113.2,
116.0, 120.3, 121.2, 121.6, 123.3, 124.3, 127.4, 128.3,
1
128.4, 129.2, 134.5, 147.1, 147.2, 148.7, 166.8. H NMR
(CDCl3) (Z isomer): d 4.55 (d, 4H, JZ3.2 Hz, OCH2CH]),
4.62 (s, 4H, CH2C]O), 5.26 (s, 4H, OCH2C6H4), 5.69 (t,
2H, JZ3.2 Hz, ]CH), 6.85–6.95 (m, 10H), 7.3 (m, 4H),
7.11 (m, 2H), 7.43 (m, 2H), 8.45 (m, 2H), 9.27 (s, 2H, NH).
13C NMR (CDCl3) (Z isomer): d 65.0, 68.4, 69.2, 112.0,
113.2, 114.9, 120.3, 121.3, 121.8, 122.9, 124.3, 127.3,

8436
Y. A. Ibrahim et al. / Tetrahedron 60 (2004) 8429–8436
3. Goodall, M.; Kelly, P. M.; Parker, D.; Gloe, K.; Stephan, H.
J. Chem. Soc., Perkin Trans. 2 1997, 59–69 and references
cited therein.
127.8, 127.9, 128.2, 134.0, 146.9, 147.2, 148.2, 166.4.
LCMS: m/zZ673 (MC1). Anal. calcd for C40H36N2O8
(672.7): C, 71.42; H, 5.39; N, 4.16. Found: C, 71.30; H,
5.32; N, 3.92.
4. (a) Ibrahim, Y. A.; Behbehani, H.; Ibrahim, M. R. Tetrahedron
Lett. 2002, 43, 4207–4210. (b) Behbehani, H.; Ibrahim,
M. R.; Ibrahim, Y. A. Tetrahedron Lett. 2002, 43,
6421–6426. (c) Ibrahim, Y. A.; Behbehani, H.; Ibrahim,
M. R.; Abrar, N. M. Tetrahedron Lett. 2002, 43,
6971–6974.
Acknowledgements
The support of the University of Kuwait received through
research grant no. SC10/02 and the facilities of ANALAB
and SAF (grants no. GS01/01, GS03/01) are gratefully
acknowledged.
5. Abrar, N. M. M.Sc. Thesis. Kuwait University, January, 2004.
6. Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995,
28, 446–552 and references therein.
7. Xu, Z.; Johannes, C. W.; Salman, S. S.; Hoyveda, A. H. J. Am.
Chem. Soc. 1996, 118, 10926–10927.
8. Clark, J. S.; Kettle, J. G. Tetrahedron Lett. 1997, 38, 123–126.
9. Fu¨rstner, A.; Langemann, K. J. Org. Chem. 1996, 61,
3942–3943.
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