Δ3-Aryl/heteroaryl substituted heterocycles via sequential Pd-catalysed termolecular cascade/ring closing metathesis (RCM)

Article abstract of DOI:10.1016/j.tet.2005.08.078

A novel sequential Pd-catalysed termolecular allenylation cascade/Ru catalysed RCM process affords a diverse range of Δ³-aryl/ heteroaryl substituted five-seven membered nitrogen and oxygen heterocycles. Further elaboration, via 1,3-dipolar cyc

Full text of DOI:10.1016/j.tet.2005.08.078

Tetrahedron 61 (2005) 10652–10666
D3-Aryl/heteroaryl substituted heterocycles via sequential
Pd-catalysed termolecular cascade/ring closing metathesis (RCM)
a
H. Ali Dondas,a,b Blandine Clique,a Bekir Cetinkaya,c Ronald Grigg,a, Colin Kilner,
*
James Morrisa and Visuvanathar Sridharana
aMolecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, School of Chemistry, Leeds University, Leeds LS2 9JT, UK
bDepartment of Chemistry, Faculty of Pharmacy, Mersin University, Yenisehir, 33342 Mersin, Turkey
c
˙
Chemistry Department, Science Faculty, Ege University, Bornova, Izmir, Turkey
Received 24 June 2005; revised 5 August 2005; accepted 19 August 2005
Available online 15 September 2005
Abstract—A novel sequential Pd-catalysed termolecular allenylation cascade/Ru catalysed RCM process affords a diverse range of D3-aryl/
heteroaryl substituted five–seven membered nitrogen and oxygen heterocycles. Further elaboration, via 1,3-dipolar cycloaddition, in selected
cases, afforded fused heterocyclic ring systems.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
good yields of bridged tricyclic heterocycles.15 In other
studies, we combined our palladium-catalysed cyclisation-
anion capture methodology with subsequent RCM as an
additional strategy for the synthesis of fused, spiro and
bridged ring heterocycles.16 Further studies showed N-allyl-
anilines,17 and isoquinoline and b-carboline enamines18
were viable RCM substrates with the first generation
catalyst 2. We now report in full a 3-component Pd-cata-
lysed cascade process employing an aryl/heteroaryl/vinyl
iodide 3, allene gas and an alkene tethered nucleophile 4,
which when coupled with RCM affords a novel and diverse
strategy for the synthesis of heterocycles 6 (Scheme 1).19–21
Multicomponent cascade reactions are highly attractive
from a drug discovery point of view.1,2 Products of high
complexity and diversity, which are often difficult to
synthesize in a stepwise linear fashion, can be quickly
accessed in a single reaction vessel. Our own efforts in this
area have recently focused on employing allenes as
3-carbon building blocks in Pd-catalysed molecular queuing
processes, which, combined with core organic reactions,
afford products, which are of high synthetic value. Recent
examples include termolecular Pd-catalysed allenylation/
1,3-dipolar cycloadditions,3,4 Pd/In Barbier type allylation,5
and Petasis/Pd termolecular queuing processes.6 Ring
closing metathesis continues to be a highly popular reaction
for the formation of carbo- and heterocyclic ring systems.7,8
This is largely to the discovery of air-stable, second
generation Ru catalysts, such as 1, which exhibit higher
thermal stability and wider functional group tolerance than
parent complex 2.9–11 The formation of previously
unattainable tri-and tetrasubstituted double bonds by 1 has
also extended the scope of this excellent reaction.12,13 Our
previous work in this area has involved combination of
RCM with a subsequent Heck reaction affording fused, spiro
and bridged ring heterocycles.14 Examples of strategies
involving a fluorous biphasic solvent system and polymer
support palladium catalyst were developed, which afforded
Scheme 1.
Our initial studies employed N-allylbenzene sulphonamide
as the nucleophile in the 3-component cascade and
Pd(OAc)2 (10 mol%) and PPh3 (20 mol%) as the catalyst
system. 1,6-Dienes 8–11 were obtained in 79–88% yield
Keywords: Ruthenium; Allene; Dipolar cycloaddition; Azomethine ylides.
*
Corresponding author. Tel.: C44 113 343 6501; fax: C44 113 233 6501;
e-mail: r.grigg@chem.leeds.ac.uk
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.078

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
10653
Table 1. 3-Pyrrolines via sequential pd catalysed cascade synthesis of N,N-diallylsulphonamides/RCM
Entry
Aryl/heteroaryl/vinyl
iodide
Pd-cascade producta
Yield (%)
RCM productb
Yield (%)c
1
86a/(86)d
74
73
8
9
12
13
2
3
79a/(72)d
85a/(68)d
85
75
14
10
4
88a/(70)d
11
15
a Reactions carried out in toluene at 80 8C for 18 h and employed 1 mmol aryl/heteroaryl/vinyl iodide, 10 mol% Pd(OAc)2, 20 mol% PPh3, 2 mol equiv
K2CO3, allene (1 bar) and 1 mol equiv of N-allylbenzene sulphonamide.
b Reactions carried out in toluene at 80 8C for 2–4 h and employed 5 mol% of catalyst 1.
c Isolated yield.
d Reactions carried out in toluene at 80 8C for 16 h and employed 1 mmol aryl/heteroaryl/vinyl iodide, 2 mol% Pd(OAc)2, 4 mol% of salt 7, 3 mol equiv
Cs2CO3, allene (0.5 bar) and 1 mol equiv of N-allylbenzene sulphonamide.
(Table 1).22 We have also utilized a low loading (2 mol%)
palladium/dihydroimidazol-2-ylidine catalyst system for the
synthesis of the 1,6-dienes.5,15 In this latter case, aryl/
heteroaryl/vinyl iodides (1 mmol) reacted with allene
(0.5 atm), Pd(OAc)2 (2 mol%), salt 7 (4 mol%), Cs2CO3
(3 mol equiv) and N-allylbenzene sulphonamide in toluene
at 70–80 8C over 16 h to give 8–11 (Table 1, entries 1–4) in
68–86% yield
can thus be incorporated into this process with equal
success. The poor yield in the Pd-cascade for entry 9 may be
the result of nucleophilic attack of 16 on the activated
carbonyl of the isatin. A limited investigation into nitrogen
protecting groups for methyl allylglycinate (Scheme 2)
showed the 2,4-dinitrobenzenesulfonyl (DNs) and Boc
groups to be incompatible with the Pd-cascade conditions.
However, the 4-nitrobenzenesulfonyl (Ns)24 group proved
to be suitable and nucleophile 17 was employed in the
3-component Pd-cascade process to afford 36–38 in
43–71% yield (Table 3). On subjecting 36–38 to 1
tetrahydropyridines 39–41 were formed in 76–98% yield
(Table 3). Facile removal of the Ns group afforded the
pipecolinic acid derivatives 42 and 43 in 83 and 70% yield,
respectively, (Scheme 3).
Subjecting dienes 8–11 to 1 in toluene at 80 8C afforded D3-
pyrrolidines 12–15 in 73–94% yield (Table 1). With the
process successfully established variation of the nucleophile
tether was investigated. Nucleophile 16 was readily
prepared in 86% yield from commercially available racemic
allyl glycinate (Scheme 2). Employing the above conditions
in the multi-component Pd-cascade afforded the a,u-dienes
18–26 in yields of 41–81% (Table 2). The addition of
tetraalkylammonium salt NEt4Cl was found to be beneficial
in this case.23 Subjecting 18–26 to 1 in toluene at 80 8C
afforded D3- tetrahydropyridines 27–35 in 75–96% yield.
Electron rich, deficient or sterically encumbered aryl groups
The free amino esters allowed further structural elaboration
through cycloaddition chemistry. Refluxing 42, benzalde-
hyde and N-methyl maleimide (NMM) in toluene afforded
a 3.5:1 mixture of endo and exo cycloadducts 44 and 45
(Scheme 4) arising from the syn-dipole formed from the
iminium ion generated in situ from 42 and benzaldehyde.25
The structure of the major isomer 44 was established by
X-ray crystallography (Fig. 1) and that of the minor isomer
45 by NOE studies and coupling constants. These structures
are in agreement with previous related work.26 Refluxing 42
and 43 with salicylaldehyde 46 afforded cycloadducts 47
and 48 in 56 and 54% yield, respectively.27 The relative
stereochemistry of 47 and 48 was assigned from chemical
Scheme 2.

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H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
Table 2. 3-Piperideines via sequential cascade synthesis of N-allyl-N-homoallylsulphonamides/RCM
Entry
Aryl/heteroaryl/vinyl
iodide
Pd-cascade producta
Yield (%)
RCM productb
Yield (%)c
1
81
77
27
28
18
19
2
3
80
70
75
75
29
20
4
70
84
30
31
21
22
5
6
71
68
71
96
32
23
7
8
80
72
83
74
33
34
24
25
9
41
83
35
26
a Reactions were carried out in toluene at 80 8C for 18 h and employed 1 mmol aryl/heteroaryl/vinyl iodide, 10 mol% Pd(OAc)2, 20 mol% PPh3, 2 mol equiv
K2CO3, allene (1 bar), 1 mol equiv NEt4Cl and 1 mol equiv 7.
b Reactions were carried out in toluene at 80 8C for 2–4 h and employed 5 mol% of catalyst 1.
c Isolated yield.

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
Table 3. Sequential Pd/Ru processes employing 4-nitrobenzenesulphonyl protection
10655
Entry
Aryl/heteroaryl/vinyl
iodide
Pd-cascade producta
Yield (%)
RCM productb
Yield (%)c
1
71
98
93
39
40
36
37
2
67
3
43
76
41
38
a Reactions carried out in toluene at 80 8C for 18 h and employed 1 mmol aryl/heteroaryl/vinyl iodide, 10 mol% Pd(OAc)2, 20 mol% PPh3, 2 mol equiv
K2CO3, allene (1 bar), 1 mol equiv NEt4Cl and 1 mol equiv 7.
b Reactions carried out in toluene at 80 8C for 2–4 h and employed 5 mol% of catalyst 1.
c Isolated yield.
Scheme 3.
shift values, coupling constants and NOE studies and is in
agreement with related work previously reported by our
group (Scheme 5).28
There has been comparatively little exploration of RCM
routes to benzoxepines although there are examples
involving both a,u-diene and ene-yne precursors.14,29
This lack of examples encouraged us to explore the alkene
tethered oxygen nucleophile 49 in our Pd cascade/RCM
process with three representative aryl iodides. The Pd-
cascade afforded dienes 53–55 in 78–80% yield (Table 4).
The RCM reaction of these dienes, utilizing 1, proved to
be more sluggish than for the formation of the five- and six-
membered N-heterocycles and reaction times of 18 h
were required to afford moderate yields of 56–58
(Table 4, 56–62%).
Figure 1. X-ray structure of 44.
Scheme 4.

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Scheme 5.
Table 4. Benzoxapines via sequential pd catalysed cascade synthesis/RCM
Entry
Aryl/heteroaryl/vinyl
iodide
Pd-cascade producta
Yield (%)
RCM productb
Yield (%)c
1
78
69
56
53
2
3
78
80
62
56
57
54
55
58
a Reactions were carried out in toluene at 80 8C for 18 h and employed 1 mmol aryl/heteroaryl iodide, 10 mol% Pd(OAc)2, 20 mol% PPh3, 2 mol equiv K2CO3,
allene (1 bar), and 1 mol equiv 7.
b Reactions were carried out in toluene at 80 8C for 18 h and employed 5 mol% of catalyst 1.
c Isolated yield.
In summary, a novel and diverse route accessing 3-aryl/
heteroaryl/vinyl substituted heterocycles has been
developed via the sequential employment of a chemo-
selective 3-component Pd-cascade/RCM sequence. An
investigation into the compatibility of other alkene-tethered
nucleophiles in this process is currently underway.
the compound in DCM onto a germanium plate. X-ray
structural data were collected on a Stadi 4-circle diffracto-
meter. Column chromatography was performed using silica
gel 60 (Merck, 230–400 mesh). Nuclear magnetic resonance
spectra were recorded on Bruker DPX250, DPX300 and
DPX500 instruments operating at 250, 300 and 500 MHz,
respectively. Solvents were dried according to established
methods,30 unless purchased dry from Aldrich in sure-seal
bottles. Palladium acetate was supplied by Johnson Matthey
and ruthenium alkylidene catalysts were purchased from
Strem and Aldrich and used as received. The term ether
refers to diethyl ether and the term petrol refers to the
40–60 8C boiling point fraction of petroleum ether. All the
compounds are named according to the IUPAC system
and names were obtained using the ACD/i-Lab software.
2. Experimental
Melting points were determined on a Reichert hot-stage
apparatus and are uncorrected. Mass spectral data were
obtained from a VG Autospec instrument operating at 70 eV
(EI and FAB) or ZD 2000 electrospray instrument (ES).
Accurate molecular masses were obtained from the EPSRC
Swansea Mass Spectroscopy service using perfluorotri-
butylamine or polyethylenimine as an internal standard.
Microanalyses were obtained using a Carbo Erba
MOD11016 instrument. IR spectra were determined on a
Nicolet Magna FT-IR 560 spectrometer. The IR samples
were prepared as thin films by evaporation of a solution of
2.1. General termolecular cascade procedure
With PPh3 ligands. Palladium acetate (23 mg, 0.1 mmol),
triphenylphosphine (53 mg, 0.2 mmol), potassium carbo-
nate (276 mg, 2 mmol), tetraethylammonium chloride

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
10657
(166 mg, 1 mmol) for 18–26 and toluene (8 ml) were added
to a Schlenk tube, containing a magnetic stirrer bar.
A solution of the nucleophile (1 mmol), and aryl iodide
(1–1.2 mmol) in toluene (2 ml) was then added. The tube
was then sealed and the mixture frozen in liquid nitrogen,
and degassed by vacuum pump. The solid mixture was then
allowed to reach room temperature, resulting in a liquid
mixture, followed by re-freezing and degassing for a second
time. Allene (1 bar) was then added to the Schlenk tube,
and the mixture heated in an oil bath at 80 8C for 40 h.
On completion of the reaction the excess gas was released
and the mixture filtered. Concentration of the filtrate in
vacuo afforded the crude product, which was purified by
flash chromatography.
2.1.3. N-Allyl-N-[2-(3nitrophenyl)allyl]benzenesulfona-
mide (10). The product was isolated as a pale yellow
solid (85%); mp 75–77 8C; (Found: C, 60.10; H, 5.15; N,
7.80; S, 8.80; C18H18N2O4S requires C, 60.30; H, 5.10; N,
7.80; S, 8.90%); nmax/cmK1 (CH2Cl2 solution) 1653
(C]C), 1636 (C]C), 1528 (NO2), 1347 (S]Oas), 1161
(S]Os), 998; dH (250 MHz; CDCl3) 8.23 (1H, d, JZ
1.9 Hz, PhNO2), 8.15 (1H, d, JZ8.4 Hz, PhNO2), 7.78–7.81
(3H, m, PhNO2 and PhSO2), 7.47–7.60 (4H, m, PhNO2 and
PhSO2), 5.60 (1H, s, CH2]), 5.36–5.50 (1H, m, CH]),
5.38 (1H, s, CH2]), 5.12 (1H, dd, JZ10.1, 0.8 Hz,
CHcisH]CH), 5.07 (1H, dd, JZ16.1, 1.1 Hz,
CHtransH]CH), 4.27 (2H, s, CH2–C]), 3.76 (2H, d, JZ
6.5 Hz, CH2–CH]); dC (50 MHz; CDCl3) 148.7, 141.3,
140.4, 140.1, 133.2, 133.1, 132.2, 129.9, 129.6, 127.6,
123.2, 121.9, 120.3, 119.4, 50.8, 50.2; m/z (%) 358 (1, MC),
210 (21, MKPhCCH2), 141 (29, PhSO2), 77 (100, Ph).
With in situ generated carbene ligands. N-Sulfonylpropar-
gylamine (1 mol equiv), aryl iodide (1.1 mol equiv),
palladium acetate (2 mol%), 1,3-dimesityl-4,5-dihydro-
imidazol-2-ylidine (4 mol%) and cesium carbonate
(3 mol equiv) were dissolved in toluene (10 ml) in a
Schlenk tube. The mixture was subjected to two freeze,
pump, thaw cycles, charged with allene (0.5 atm), stirred for
16–18 h at 70–80 8C, cooled, excess allene vented and the
solvent evaporated under reduced pressure. The crude
product was purified by flash chromatography.
2.1.4. N-[2-(4-Acetyl-phenyl)-allyl]-N-allyl-benzenesul-
fonamide (11). The product was isolated as a pale orange
solid. (88%); mp 100–102 8C; nmax/cmK1 (CH2Cl2 solution)
1682 (C]O), 1345 (S]Oas), 1162 (S]Os), 998 (CH), 925
(CH), 847 (PhCOMe); dH (250 MHz; CDCl3) 7.92 (2H, d,
JZ8.5 Hz, PhCOMe), 7.79 (2H, dd, JZ8.5, 1.3 Hz,
PhSO2), 7.44–7.53 (5H, m, PhCOMe and PhSO2), 5.57
(1H, s, CH2]), 5.30–5.50 (1H, m, CH]), 5.34–5.04
(2H, m, CHcisHtrans]C), 5.09 (1H, s, CH2]), 4.27 (2H, s,
CH2–C]), 3.74 (2H, d, JZ6.5 Hz, CH2–CH]), 2.62 (3H,
s, CH3); dC (50 MHz; CDCl3) 198.2 (C]O), 143.4, 142.2,
140.2, 136.9, 133.1, 132.3, 129.6, 128.9, 127.6, 127.1,
120.0, 118.8, 50.8, 49.9, 27.1; m/z (%) 355 (9, MC), 210
(77, MKPhCCH2), 141 (72, MKPhSO2), 77 (100, Ph), 43
(58, allyl); HRMS Found: 355.1242, C20H21NO3S requires
355.1245.
2.1.1. N-Allyl-N-(2-phenyl-allyl)-benzenesulfonamide
(8). The product was isolated as a pale yellow oil (86%);
(Found: C, 69.20; H, 5.90; N, 4.30; S, 10.20; C18H19NO2S
requires C, 69.00; H, 6.11; N, 4.50; S, 10.20%); nmax/cmK1
(CH2Cl2 solution) 1635 (C]C), 1344 (S]Oas), 1161
(S]Os), 991 (CH), 911; dH (250 MHz; CDCl3) 7.75 (2H,
dd, JZ8.5, 1.2 Hz, PhSO2), 7.25–7.47 (8H, m, Ph and
PhSO2), 5.52–5.38 (1H, m, CH]), 5.43 (1H, s, CH2]),
5.21 (1H, s, CH2]), 5.06 (1H, d, JZ10.1 Hz,
CHcisH]CH), 5.04 (1H, d, JZ16.2 Hz, CHHtrans]CH),
4.24 (2H, s, CH2–C]), 3.73 (2H, d, JZ6.5 Hz, CH2–
CH]); dC (50 MHz; CDCl3) 142.9, 140.4, 138.9, 133.1
132.6, 129.6, 128.9, 128.5, 127.7, 126.9, 119.9, 116.9,
50.9, 49.9; m/z (%) 313 (10, MC), 210 (70, MKPhCCH2),
172 (41, MKPhSO2), 141 (74, PhSO2), 118 (79,
PhC]CH2CH3), 77 (100, Ph).
2.2. General ring closing metathesis procedure
Grubbs’ second generation catalyst (5 mol%) was added to a
magnetically stirred solution of the diene (0.13 mmol), in
anhydrous toluene (40 ml) and the mixture stirred under
an argon atmosphere at 80 8C for 2–4 h. Concentration in
vacuo afforded the crude product as a brown oil, which was
purified by flash chromatography.
2.2.1. 1-Benzenesulfonyl-3-phenyl-2,5-dihydro-1H-pyr-
role (12). The product was isolated as a pale yellow solid
(34 mg, 74%); mp 120–122 8C; nmax/cmK1 (CH2Cl2
solution) 1446 (Ph C]C), 1339 (S]Oas), 1167 (S]Os),
830 (CH); dH (250 MHz; CDCl3) 7.89 (2H, dd, JZ8.2,
1.5 Hz, PhSO2), 7.53–7.58 (3H, m, PhSO2), 7.29–7.33 (5H,
m, Ph), 6.01 (1H, qi, JZ2.1 Hz, CH]), 4.29–4.34 and
4.48–4.53 (4H, m, CH2–C] and CH2–CH]); dC (50 MHz;
CDCl3) 137.7, 137.4, 133.3, 132.8, 129.7, 129.1, 128.9,
127.8, 125.8, 119.3, 56.1, 55.3; m/z (%) 285 (8, MC), 144
(54, MKPhSO2), 77 (93, Ph), 41 (100, allyl).
2.1.2. N-Allyl-N-(2-thiophen-2-yl-allyl)benzenesulfona-
mide (9). The product was isolated as a pale yellow oil
(79%); (Found: C, 59.90; H, 5.20; N, 4.10; S, 20.00;
C16H17NO2S2 requires C, 60.20; H, 5.36; N, 4.40; S,
20.10%); nmax/cmK1 (CH2Cl2 solution) 1653 (C]C), 1341
(S]Oas), 1163 (S]Os), 998 (CH), 900 (CH); dH (250 MHz;
CDCl3) 7.83 (2H, dd, JZ8.4, 1.5 Hz, PhSO2), 7.46–7.55
(3H, m, PhSO2), 6.94 (1H, dd, JZ5.1, 3.7 Hz, thienyl-H),
7.14 (1H, d, JZ5.1 Hz, thienyl-H), 7.22 (1H, d, JZ3.5 Hz,
thienyl-H), 5.52 (1H, s, CH2]), 5.47–5.38 (1H, m,
CH]), 5.09 (1H, s, CH2]), 5.07 (1H, d, JZ10.0 Hz,
CHHcis]CH), 5.03 (1H, dd, JZ16.2, 1.1 Hz,
CHtransH]CH), 4.19 (2H, s, CH2–C]), 3.82 (2H, d,
JZ6.5 Hz, CH2–CH]); dC (50 MHz; CDCl3) 142.2,
140.4, 136.2, 133.1, 132.3, 129.6, 128.1, 127.7, 125.2,
120.0, 115.1, 50.8, 50.1; m/z (%) 319 (6, MC), 210 (50,
MKPhCCH2), 178 (52, MKPhSO2), 141 (66, PhSO2), 124
(100, thiophen-C]CH2CH3), 109 (56, thiophen-C]CH2),
77 (95, Ph).
2.2.2. 1-Benzenesulfonyl-3-thiophen-2-yl-2,5-dihydro-
1H-pyrrole (13). The product was isolated as a colourless
solid (38 mg, 82%); mp 105–107 8C; Found: C, 57.50; H,
4.35; N, 4.60; S, 21.90; C16H15NO2S requires C, 57.70; H,
4.50; N, 4.80; S, 22.00%; nmax/cmK1 (CH2Cl2 solution)
1339 (S]Oas), 1166 (S]Os), 830 (CH); dH (250 MHz;
CDCl3) 7.88 (2H, dd, JZ7.8, 1.4 Hz, PhSO2), 7.54–7.59

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(3H, m, PhSO2), 7.22 (1H, d, JZ5.3 Hz, thienyl-H), 6.96
(1H, dd, JZ5.3, 3.5 Hz, thienyl-H), 6.88 (1H, m, thienyl-H),
6.01 (1H, qi, JZ2.0 Hz, CH]), 4.25–4.34 and 4.43–4.45
(4H, m, CH2–C] and CH2–CH]); dC (50 MHz; CDCl3)
137.3, 136.4, 133.3, 132.2, 129.7, 128.0, 127.8, 125.9,
125.2, 118.6, 55.8, 55.7; m/z (%) 291 (9, MC), 150 (100,
MKPhSO2), 77 (56, Ph).
4.10–4.02 (1H, dt, JZ9.0, 6.8 Hz NCH), 3.5 (3H, s, CH3),
2.47 (2H, t, JZ6.8 Hz, CH2); dC (63 MHz, CDCl3) 171.6
(C]O), 140.1, 133.3, 131.6, 129.5, 127.6, 120.3, 55.6, 52.9,
37.9; m/z (ES) 292 (MCCNa).
2.3.2. Methyl 2-{[(4-nitrophenyl)sulfonyl]amino}pent-4-
enoate (17).31 Prepared by the above N-sulfonyl protection
procedure on a 0.05 mol scale. Purification by flash
chromatograpy eluting with DCM afforded the product
(8.65 g, 55%) as a pale yellow solid. Crystallisation from
DCM/petrol afforded colourless needles, mp 134–136 8C; Rf
0.15; (Found: C, 45.80; H, 4.40; N, 8.75. C12H14N2O6S
requires C, 45.85; H, 4.50; N, 8.90%); nmax/cmK1 (film)
1741 (C]O), 1539 (NO2), 1350 (S]Oas), 1171 (S]Os);
dH (250 MHz, CDCl3) 8.35 (2H, d, JZ9.0 Hz, ArH), 8.04
(2H, d, JZ9.0 Hz, ArH), 5.61 (1H, ddt, JZ16.9, 10.4,
7.2 Hz, CH]CH2), 5.32 (1H, d, JZ8.6 Hz, NH), 5.18–5.08
(2H, m, CH]CH2), 4.13 (1H, dt, JZ8.6, 5.9 Hz, NCH),
2.55–2.49 (2H, m, CH2); m/z (ES) 337 (MCCNa).
2.2.3. 1-Benzenesulfonyl-3-(3-nitro-phenyl)-2,5-dihydro-
1H-pyrrole (14). The product was isolated as a colourless
solid (49 mg, 93%); mp 130–132 8C; Found: C, 58.50; H,
4.50; N, 8.20; S, 9.90; C16H15NO2S requires C, 58.20; H,
4.27; N, 8.50; S, 9.70; nmax/cmK1 (CH2Cl2 solution) 3088,
2918, 1530 (NO2), 1348 (S]Oas), 1166 (S]Os), 830 (CH);
dH (250 MHz; CDCl3) 8.12–8.22 (2H, m, PhNO2), 7.91 (2H,
dd, JZ8.2, 1.5 Hz, PhSO2), 7.55–7.64 (5H, m, PhSO2 and
PhNO2), 6.01 (1H, t, JZ2.1 Hz, CH]), 4.37–4.40 and
4.51–4.55 (4H, m, CH2–C] and CH2–CH]); dC (50 MHz;
CDCl3) 148.9, 137.2, 135.9, 134.4, 133.5, 131.6, 130.2,
129.8, 127.8, 123.4, 122.8, 120.6, 56.1, 55.1; m/z (%) 330
(34, MC), 189 (100, MKPhSO2), 143 (54, MKPhSO2 and
NO2), 115 (68, MKPhNO2 and OPh), 77 (86, Ph).
2.3.3. Methyl 2-[(2-phenyl-2-propenyl)(phenylsulfonyl)
amino]-4-pentenoate (18). Prepared by the general
termolecular cascade procedure on a 1 mmol scale, using
1.2 mmol of the aryl iodide and a reaction time of 40 h.
Purification by flash chromatograpy eluting with DCM
afforded the product (312 mg, 81%) as a colourless oil; Rf
0.34; (Found: C, 65.15; H, 6.15; N, 3.90. C21H23NO4S
requires C, 65.45; H, 6.00; N, 3.65%); nmax/cmK1 (film)
1741 (C]O), 1447, 1345 (S]Oas), 1158 (S]Os) 1091,
916; dH (250 MHz, CDCl3) 7.85–7.81 (2H, m, SO2PhH),
7.61–7.46 (3H, m, SO2PhH), 7.38–7.28 (5H, m, PhH), 5.78
(1H, ddt, JZ16.7, 9.8, 6.8 Hz, CH]CHH), 5.85 (1H, d, JZ
0.9 Hz, ]CHH), 5.41 (1H, d, JZ0.9 Hz, ]CHH), 5.00
(1H, d, JZ16.7 Hz, CH]CHHtrans), 4.98 (1H, d, JZ
9.8 Hz, CH]CHcisH), 4.48 (1H, dd, JZ8.0, 6.9 Hz, NCH),
4.42 (1H, d, JZ16.0 Hz, NCHH), 4.36 (1H, d, JZ16.0 Hz,
NCHH), 3.89 (s, 3H, CH3), 2.64–2.58 (1H, m, ]CHCHH),
2.43–2.35 (m, 1H, ]CHH); dC (63 MHz, CDCl3) 170.8
(C]O), 144.0, 139.9, 139.2, 133.7, 133.2, 129.3, 128.8,
128.4, 128.1, 126.8, 118.7, 116.5, 59.8 (NCH), 52.2
(OCH3), 50.2 (NCH2), 35.2 (]CHCH2); m/z (%) (EI)
385 (4, MC), 326, (43, MKCO2Me), 284 (78), 244 (34,
MKSO2Ph), 144 (45), 117 (95), 77 (100, Ph).
2.2.4. 1-[4-(1-Benzenesulfonyl-2,5-dihydro-1H-pyrrol-3-
yl)-phenyl]-ethanone (15). The product was isolated as a
colourless solid (32 mg, 75%); mp 145–147 8C; Found: C,
66.20; H, 5.30; N, 4.10; S, 9.60; C18H17NO3S requires C,
66.00; H, 5.23; N, 4.30; S, 9.80; nmax/cmK1 (CH2Cl2
solution) 2919, 1680 (C]O), 1339 (S]Oas), 1166 (S]Os),
828 (CH); dH (250 MHz; CDCl3) 7.94 (4H, m, PhSO2 and
PhCOMe), 7.55–7.60 (3H, m, PhSO2), 7.37 (2H, d, JZ
8.5 Hz, PhCOMe), 6.18 (1H, t, JZ2.1 Hz, CH]), 4.33–
4.37 and 4.50–4.55 (4H, m, CH2–C] and CH2–CH]),
2.60 (3H, s, CH3); dC (50 MHz; CDCl3) 197.3 (C]O),
137.1, 137.0, 136.9, 133.4, 129.8, 129.2, 127.7, 125.9,
122.3, 56.1, 55.1, 27.0; m/z (%) 327 (23, MC), 186
(100, MKPhSO2), 170 (57, MKPhSO2 and O), 144 (42,
MKPhSO2N(CH2)2), 115 (43, MKPhCOMe and OPh), 77
(57, Ph), 43 (63, COMe).
2.3. General allyl glycinate ester formation and
N-sulfonyl protection
2.3.1. Methyl 2-[(phenylsulfonyl)amino]-4-pentenoate
(16). Thionyl chloride (1.35 ml, 0.0181 mol) was added
dropwise to a stirred solution of allyl glycinate (2.09 g,
0.0181 mol) in methanol (150 ml) at 0 8C and the solution
was allowed to warm to ambient temperature. After 1 h the
methanol was removed and the residue dissolved in DCM
(100 ml). Benzenesulfonyl chloride (2.35 ml, 0.0181 mol)
dissolved in DCM (20 ml) was added to the reaction mixture
followed by triethylamine (5.7 ml, 0.056 mol). After 16 h
the mixture was washed with water (2!20 ml), dried
(MgSO4), filtered and the filtrate concentrated. Purification
of the residue by flash chromatography eluting with DCM
afforded the product (3.8 g, 78%), which crystallised from
DCM/petrol as colourless needles, mp 75–76 8C; Rf 0.13;
(Found: C, 53.40; H, 5.45; N, 4.95. C12H15NO4S requires C,
53.50; H, 5.60; N, 5.20%); nmax/cmK1 (Nujol) 3291 (NH),
1741 (C]O), 1331 (S]Oas), 1163 (S]Os), 1092; dH
(250 MHz, CDCl3) 7.88–7.83 (2H, m, ArH), 7.62–7.47 (3H,
m, ArH), 5.62 (1H, ddt, JZ18.0, 14.3, 6.8 Hz, CH]CH2),
5.27 (1H, d, JZ9.0 Hz, NH), 5.13–5.04 (2H, m, CH]CH2),
2.3.4. Methyl 2-{[2-(3-methylphenyl)-2-propenyl]-
(phenylsulfonyl)amino}-4-pentenoate (19). Prepared by
the general termolecular cascade procedure on a 1 mmol
scale, using 1.2 mmol of the aryl iodide and a reaction time
of 34 h. Purification by flash chromatograpy eluting with
DCM afforded the product (318 mg, 80%) as a colourless
oil; Rf 0.24; (Found: C, 66.25; H, 6.40; N, 3.50.
C22H25NO4S requires C, 66.15; H, 6.30; N, 3.50%); nmax
/
cmK1 (film) 1742 (C]O), 1447, 1437, 1345 (S]Oas), 1159
(S]Os), 1091, 919; dH (250 MHz, CDCl3) 7.85–7.81 (2H,
m, SO2PhH), 7.59–7.49 (3H, m, SO2PhH), 7.26–7.12 (4H,
m, ArH), 5.63 (1H, ddt, JZ16.8, 9.7, 6.9 Hz, CH]CHH),
5.46 (1H, d, JZ0.8 Hz, ]CHH), 5.39 (1H, d, JZ0.8 Hz,
]CHH), 5.01 (1H, d, JZ16.8 Hz, CH]CHHtrans), 5.00
(1H, d, JZ9.7 Hz, CH]CHcisH), 4.48 (1H, dd, JZ8.0,
6.8 Hz, NCH), 4.48 (1H, d, JZ17.5 Hz, NCHH), 4.38 (1H,
d, JZ17.5 Hz, NCHH), 3.40 (3H, s, OCH3), 2.64–2.60 (1H,
m, ]CHCHH), 2.43–2.34 (1H, m, ]CHCHH), 2.34 (3H, s,
ArCH3); dC (63 MHz, CDCl3) 170.9 (C]O), 144.1, 138.3,

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
10659
133.7, 133.1, 129.3, 129.1, 128.7, 127.5, 123.8, 118.7,
116.2, 59.9 (NCH), 52.2 (OCH3), 50.2 (NCH2), 35.2
(]CHCH2), 21.9 (ArCH3); m/z (%) (FAB) 400 (69,
MCCH), 399 (19, MC), 340 (27, MKCO2Me), 259
(100), 258 (34, MKSO2Ph), 158 (20), 131 (47), 77 (13,
C6H5).
(278 mg, 71%), as a viscous, pale yellow oil, Rf 0.15;
(Found: C, 58.30; H, 5.35; N, 3.80. C19H21NO4S requires C,
58.30; H, 5.40; N, 3.60%); nmax/cmK1 (film) 1740 (C]O),
1447, 1437, 1343 (S]Oas), 1160 (S]Os), 1191, 1091, 923;
dH (250 MHz, CDCl3) 7.87–7.83 (2H, m, SO2PhH), 7.64–
7.49 (3H, m, SO2PhH), 7.20 (1H, dd, JZ5.1, 1.0 Hz, ArH),
7.13 (1H, dd, JZ3.7, 1.0 Hz, ArH), 6.98 (1H, dd, JZ5.1,
3.7 Hz, ArH), 5.65 (1H, ddt, JZ16.9, 9.9, 6.9 Hz,
CH]CHH), 5.58 (1H, s, ]CHH), 5.30 (1H, s, ]CHH),
4.99–5.04 (2H, m, CH]CHcisHtrans), 4.53 (1H, t, JZ
7.4 Hz, NCH), 4.42 (1H, d, JZ17 Hz, NCHH), 4.35 (1H, d,
JZ17 Hz, NCHH), 3.40 (3H, s, CH3), 2.64–2.56 (1H, m,
]CHCHH), 2.49–2.40 (1H, m, ]CHCHH); dC (63 MHz,
CDCl3), 170.8 (C]O), 142.5, 139.8, 137.5, 133.6, 133.3,
129.4, 128.0, 127.9, 125.1, 124.5, 118.8, 114.7, 59.9 (NCH),
52.3 (OCH3), 49.7 (NCH2), 35.3 (]CHCH2); m/z (ES) 414
(MCC Na).
2.3.5. Methyl 2-{[2-(2-naphthyl)-2-propenyl](phenyl-
sulfonyl)amino}-4-pentenoate (20). Prepared by the
general termolecular cascade procedure on a 1 mmol
scale, using 1.1 mmol of aryl iodide, Pd2(dba)3
(0.05 mmol) and a reaction time of 44 h. Purification by
flash column chromatography eluting with 4:1 v/v petrol/
ethyl acetate afforded the product (295 mg, 69%) as a
viscous, pale yellow oil; Rf 0.22; (Found: C, 68.75; H, 5.95;
N, 3.20. C23H25NO4S requires C, 68.95; H, 5.80; N, 3.20%);
nmax/cmK1 (film) 1742 (C]O), 1447, 1347 (S]Oas), 1158
(S]Os), 1091, 921; dH (250 MHz, CDCl3) 8.11–8.08 (1H,
m, ArH), 7.83–7.79 (4H, m, ArH), 7.54–7.43 (6H, m, ArH),
7.28 (1H, dd, JZ7.5, 1.2 Hz, ArH), 5.82 (1H, d, JZ1.4 Hz,
]CHCHD), 5.72 (1H, ddt, JZ16.9, 10.2, 6.8 Hz,
CH]CHH), 5.32, (1H, d, JZ1.4 Hz, ]CHH), 5.12 (1H,
d, JZ10.2 Hz, CH]CHcisH), 5.09 (1H, d, JZ16.9 Hz,
CH]CHHtrans), 4.59 (1H, dd, JZ8.2, 5.5 Hz, NCH), 4.32
(1H, d, JZ18.5 Hz, NCHH), 4.19 (1H, d, JZ18.5 Hz,
NCHH), 3.39 (3H, s, CH3), 2.67–2.58 (1H, m, ]CHCHH),
2.49–2.38 (1H, m, ]CHCHH); dC (63 MHz, CDCl3) 170.9
(C]O), 144.6, 139.7, 138.8, 134.0, 133.3, 133.2, 131.8,
129.3, 128.7, 128.3, 128.0, 126.8, 126.3, 126.1, 125.8,
125.6, 119.0, 117.5, 60.2 (NCH), 52.3 (OCH3), 52.0
(NCH2), 35.4 (]CHCH2); m/z (ES) 458 (MCCNa).
2.3.8. Methyl 2-{[2-(-methoxyphenyl)-2-propenyl]-
(phenylsulfonyl)amino}-4-pentenoate (23). Prepared by
the general termolecular cascade procedure on a 1 mmol
scale, using 1.2 mmol of aryl iodide and a reaction time of
42 h. Purification by flash chromatography eluting with
DCM afforded the product (259 mg, 63%), as a colourless
oil, Rf 0.11; (Found: C, 63.50; H, 6.20; N, 3.40.
C22H25NO5S requires C, 63.60; H, 6.05; N, 3.35%); nmax
/
cmK1 (film) 1741 (C]O), 1514, 1342 (S]Oas), 1249
(O–Me), 1159 (S]Os), 1090, 1030, 836; dH (500 MHz,
CDCl3) 7.84–7.82 (2H, m, SO2PhH), 7.58–7.56 (1H, m,
SO2PhH), 7.51–7.48 (2H, m, SO2PhH), 7.31 (2H, d, JZ
8.9 Hz, ArH), 6.84 (2H, d, JZ8.9 Hz, ArH), 5.61 (1H, ddt,
JZ16.5, 9.7, 6.9 Hz, CH]CHH), 5.39 (1H, d, JZ0.8 Hz,
]CHH), 5.29 (1H, d, JZ0.8 Hz, ]CHH), 4.99 (1H, d, JZ
9.7 Hz, CH]CHcisH), 4.98 (1H, d, JZ16.5 Hz,
CH]CHHtrans), 4.45 (1H, dd, JZ8.1, 6.7 Hz, NCH), 4.38
(1H, d, JZ16.6 Hz, NCHH), 4.34 (1H, d, JZ16.6 Hz,
NCHH), 3.81 (3H, s, CH3), 3.39 (3H, s, CH3), 2.66–2.61
(1H, m, ]CHCHH), 2.40–2.35 (1H, m, ]CHCHH); dC
(125 MHz, CDCl3), 170.4 (C]O), 159.5, 142.9, 139.7,
133.5, 132.7, 131.2, 128.9, 127.7, 127.6, 118.2, 114.8,
113.8, 59.5 (CH3), 55.3 (NCH), 51.8 (CH3), 50.0 (NCH2),
34.8 (]CHCH2); m/z (%) (EI) 415 (17, MC), 356 (20,
MKCO2Me), 274 (100, MKSO2Ph), 174 (88), 147 (86),
133 (78).
2.3.6. Methyl 2-{[2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra-
hydro-5-pyrimidinyl)-2-propenyl](phenylsulfonyl)
amino}-4-pentenoate (21). Prepared by the general
termolecular cascade procedure on a 1 mmol scale, using
1.2 mmol of aryl iodide and a reaction time of 40 h.
Purification by flash chromatography eluting with 9:1 v/v
ether/ethyl acetate afforded the product (314 mg, 70%) as a
colourless oil; Rf 0.27; (Found: C, 56.30; H, 5.75; N, 9.45.
C21H26N2O6S requires C, 56.35; H, 5.65; N, 9.40%), nmax
/
cmK1 (film) 1741 (MeOC]O), 1702 (N–C]O), 1655
(N(N)C]O), 1448, 1340 (S]Oas), 1266, 1159 (S]Os),
1091; dH (250 MHz, CDCl3) 7.82 (2H, m, SO2PhH), 7.60–
7.48 (3H, m, SO2PhH), 7.27 (1H, d, JZ0.8 Hz, ]CH), 5.73
(1H, ddt, JZ16.9, 10.1, 6.8 Hz, CH]CHH), 5.49 (1H, d,
JZ0.8 Hz, ]CHH), 5.39 (1H, s, ]CHH), 5.05 (1H, ddd,
JZ16.9, 2.9, 1.4 Hz, CH]CHHtrans), 5.01 (1H, dd, JZ
10.1, 1.4 Hz, CH]CHcisH), 4.50 (1H, dd, JZ8.3, 6.8 Hz,
NCH), 4.28 (1H, d, JZ16.3 Hz, NCHH), 4.19 (1H, d, JZ
16.3 Hz, NCHH), 3.46 (3H, s, CH3), 3.44 (3H, s, CH3), 3.42
(3H, s, CH3), 2.75–2.66 (1H, m, ]CHCHH), 2.57–2.45
(1H, m, ]CHCHH); dC (63 MHz, CDCl3), 170.8 (C]O),
162.7 (C]O), 151.8 (C]O), 142.0, 139.6, 138.5, 134.1,
133.2, 129.2, 128.2, 120.0, 118.4, 112.5, 60.4 (NCH), 52.4
(OCH3), 50.6 (NCH2), 37.5 (NCH3), 34.8 (NCH3), 28.4
(]CHCH2); m/z (ES) 470 (MCCNa).
2.3.9. Methyl 2-{[2-(1-methyl-1H-indol-5-yl)-2-propenyl]
(phenylsulfonyl)amino}-4-pentanoate (24). Prepared by
the general termolecular cascade procedure on a 1 mmol
scale, using 1.2 mmol of aryl iodide and a reaction time of
40 h. Purification by flash chromatography, eluting with
DCM yielded the product (353 mg, 80%) as a viscous
colourless oil, Rf 0.1; (Found: C, 66.00; H, 5.95; N, 6.25.
C24H26N2O4S requires C, 65.75; H, 5.95; N, 6.25%); nmax
/
cmK1 (film) 1741 (C]O), 1446, 1336 (S]Oas), 1159
(S]Os), 1091; dH (250 MHz, CDCl3) 7.87–7.82 (2H, m,
SO2PhH), 7.58–7.45 (4H, m, ArH), 7.26 (2H, br s, ArH),
7.05 (1H, d, JZ3.1 Hz, ArH), 6.44 (1H, d, JZ3.1 Hz, ArH),
5.63 (1H, ddt, JZ17.0, 10.3, 6.9 Hz, CH]CHH), 5.46 (1H,
d, JZ1.0 Hz, ]CHH), 5.35 (1H, d, JZ1.0 Hz, ]CHH),
5.03–4.95 (2H, m, CH]CHcisHtrans), 4.49 (1H, dd, JZ8.2,
6.6 Hz, NCH), 4.46 (2H, br s, NCH2), 3.79 (3H, s, CH3),
3.39 (3H, s, CH3), 2.70–2.64 (1H, m, ]CHCHH), 2.45–
2.38 (1H, m, ]CHCHH); dC (63 MHz, CDCl3), 171.0
2.3.7. Methyl 2-{(phenylsulfonyl)[2-(2-thienyl)-2-pro-
penyl]amino}-4-pentenoate (22). Prepared by the general
termolecular cascade procedure on a 1 mmol scale, using
1.2 mmol of aryl iodide and a reaction time of 38 h.
Purification by flash chromatography afforded the product

10660
H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
(C]O), 144.7, 140.1, 136.9, 133.9, 133.0, 130.6, 129.8,
129.2, 128.7, 128.1, 120.9, 119.1, 118.6 (]CH2), 114.8
(]CH2), 109.4, 101.8, 59.3 (NCH), 52.2 (OCH3), 50.8
(NCH2), 35.3 (]CHCH2), 33.3 (NCH3); m/z (ES) 461
(MCCNa).
2.3.12. Methyl 5-phenyl-1-(phenylsulfonyl)-1,2,3,6-tetra-
hydropyridine-2-carboxylate (27). Prepared by the
general ring closing metathesis procedure on a 0.13 mmol
scale and a reaction time of 3 h. Purification by flash column
chromatography eluting with 1:1 v/v petrol/ether to afforded
the product (36 mg, 77%) as a viscous, colourless oil. Rf
0.25; (Found: C, 63.65; H, 5.40; N, 4.00; C19H19NO4S
requires C, 63.85; H, 5.35; N, 3.90%); nmax/cmK1 (film)
1744 (C]O), 1447, 1342 (S]Oas), 1202, 1164 (S]Os),
1097; dH (500 MHz, CDCl3) 7.78–7.76 (2H, m, SO2PhH),
7.51–7.49 (1H, m, SO2PhH), 7.45–7.41 (2H, m, SO2PhH),
7.25–7.18 (5H, m, PhH), 5.94–5.96 (1H, br m, ]CH), 4.86
(1H, dd, JZ5.5, 3.0 Hz, NCH), 4.50 (1H, ddd, JZ16.4, 3.9,
1.9 Hz, NCHH), 4.09 (1H, ddd, JZ16.4, 5.3, 3.0 Hz,
NCHH), 3.40 (3H, s, CH3), 2.66–2.64 (2H, br m,
]CHCH2); dC (75 MHz, CDCl3) 171.2 (C]O), 139.5,
138.6, 134.1, 133.1, 129.3, 128.9, 128.3, 127.6, 125.6,
119.7, 52.7 (NCH), 52.6 (OCH3), 43.9 (NCH2), 28.5
(]CHCH2); m/z (%) (EI) 357 (11, MC), 298 (40,
MKCO2Me), 216 (48, MKSO2Ph), 156 (100), 129 (44),
77 (70, Ph).
2.3.10. Methyl 2-{[2-(2-methyl-4-nitrophenyl)-2-pro-
penyl](phenylsulfonyl)amino}-4-pentenoate (25). Pre-
pared by the general termolecular cascade procedure on a
1 mmol scale, using 1.1 mmol aryl iodide and Pd2(dba)3
(0.05 mmol, 92 mg) in place of Pd(OAc)2 and a reaction
time of 40 h. Purification by flash column chromatography
eluting with 4:1 v/v petrol/ethyl acetate afforded the product
(322 mg, 72%) as a viscous pale yellow oil, which solidified
on standing. Crystallisation from DCM/petrol afforded
colourless needles, mp 67–69 8C; Rf 0.18; (Found: C,
59.35; H, 5.60; N, 6.20; C22H24N2O6S requires C, 59.45;
H, 5.45; N, 6.30%); nmax/cmK1 (film) 1742 (C]O), 1519
(C–NO2), 1447, 1346 (S]Oas), 1311, 1158 (S]Os), 1091,
926; dH (500 MHz; CDCl3) 8.04 (1H, d, JZ2.4 Hz, ArHE),
7.98 (1H, dd, JZ8.4, 2.4 Hz, ArH), 7.81–7.79 (2H, m,
SO2Ph), 7.58–7.58 (1H, m, SO2PhH), 7.50–7.47 (2H, m,
SO2PhH), 7.24 (1H, d, JZ8.4 Hz, ArH), 5.69 (1H, ddt, JZ
17.0, 10.2, 6.8 Hz, CH]CHH), 5.66 (1H, d, JZ0.8 Hz,
]CHH), 5.14 (1H, d, JZ0.8 Hz, ]CHH), 5.11 (1H, ddd,
JZ10.2, 2.9, 1.4 Hz, CH]CHcisH), 5.08 (1H, d, JZ
17.0 Hz, CH]CHHtrans), 4.53 (1H, dd, JZ8.4, 6.5 Hz,
NCH), 4.14 (1H, dt, JZ18.3, 1.6 Hz, NCHH), 4.09 (1H, dt,
JZ18.3, 6 Hz, NCHH), 3.43 (1H, s, OCH3), 2.65–2.59 (1H,
m, ]CHCHH), 2.42 (1H, s, ArCH3), 2.42–2.38 (1H, m,
]CHCHH); dC (125 MHz, CDCl3) 170.4 (C]O), 147.2,
146.9, 143.9, 139.3, 137.5, 133.0, 132.7, 129.9, 129.0,
127.6, 125.0, 120.8, 118.8, 117.4, 59.6 (NCH), 51.9
(OCH3), 50.32 (NCH2), 35.0 (]CHCH2), 19.8 (ArCH3);
m/z (ES) 467 (MCC Na).
2.3.13. Methyl 5-(3-methylphenyl)-1-(phenylsulfonyl)-1,
2,3,6-tetrahydropyridine-2-carboxylate (28). Prepared by
the general ring closing metathesis procedure on a
0.14 mmol scale and reaction time of 2 h. Purification by
flash chromatography eluting with 4:1 v/v petrol/ethyl
acetate afforded the product (38 mg, 75%) as a colourless
oil, which crystallised on standing to afford colourless
needles, mp 59–61 8C; Rf 0.23; (Found: C, 64.80; H, 5.95;
N, 3.85. C20H21NO4S requires C, 64.65; H, 5.70; N, 3.75%);
nmax/cmK1 (film) 1744 (C]O), 1447, 1340 (S]Oas), 1202,
1163 (S]Os), 1098, 1032, 971; dH (250 MHz, CDCl3),
7.86–7.82 (2H, m, SO2PhH), 7.62–7.48 (3H, m, SO2PhH),
7.25–7.22 (4H, m, ArH), 6.03–6.00 (1H, br m, ]CH), 4.93
(1H, t, JZ4.3 Hz, NCH), 4.51 (1H, dd, JZ16.4, 2.0 Hz,
NCHH), 4.14 (1H, ddd, JZ16.4, 5.0, 2.8 Hz, NCHCH),
3.46 (3H, s, OCH3), 2.73–2.72 (2H, br m, ]CHCH2), 2.35
(3H, s, ArCH3); dc (63 MHz, CDCl3) 171.2 (C]O), 139.5,
138.6, 134.2, 133.1, 129.4, 129.1, 128.8, 128.5 127.6, 126.3,
122.7, 119.5, 52.7 (NCH), 52.6 (OCH3), 44.0 (NCH2), 28.6
(]CHCH2), 21.9 (PhCH3); m/z (%) (EI) 371 (27, MC), 312
(54, MKCO2Me), 230 (86, MKSO2Ph), 170 (10), 77 (60,
Ph).
2.3.11. Methyl 2-{[2-(1-methyl-2,3-dioxo)-2,3-dihydro-
1H-indole-5-yl]prop-2-enyl(phenylsulfonyl)amino}pent-
4-enoate (26). Prepared by the general termolecular cascade
procedure on a 1 mmol scale, using 1.2 mmol of aryl iodide
and a reaction time of 48 h. Purification by flash
chromatography eluting with 2:3 v/v ethyl acetate/petrol
affords the product (193 mg, 41%), as red solid, which
crystallised from DCM/petrol as red needles, mp 116–
118 8C; Rf 0.2; (Found: C, 61.35; H, 5.25; N, 5.85.
C24H24N2O6S requires C, 61.55; H, 5.15; N, 6.0%); nmax
/
2.3.14. Methyl 5-(2-naphthyl)-1-(phenylsulfonyl)-1,2,3,6-
tetrahydropyridine-2-carboxylate (29). Prepared by the
general ring closing metathesis procedure on a 0.14 mmol
scale and a reaction time of 5 h. Purification by flash
chromatography eluting with 4:1 v/v petrol/ethyl acetate
afforded the product (43 mg, 75%), which crystallised from
petrol/DCM as colourless needles, mp 144–146 8C; Rf 0.21;
(Found: C, 67.65; H, 5.20; N, 3.70. C23H21NO4S requires C,
67.80; H, 5.20; N, 3.45%); nmax/cmK1 (film) 1742 (C]O),
1447, 1341 (S]Oas), 1201, 1164 (S]Os), 1095; dH
(250 MHz, CDCl3) 7.86–7.76 (5H, m, ArH), 7.62–7.41
(6H, m, ArH), 7.23 (1H, dd, JZ7.0, 1.6 Hz, ArH), 5.78 (1H,
bdd, JZ5.5, 2.3 Hz, ]CH), 5.06 (1H, dd, JZ6.3, 2.0 Hz,
NCH), 4.39 (1H, br d, JZ16.5 Hz, NCHH), 4.08 (1H, dd,
JZ16.5, 2.2 Hz, NCHH), 3.56 (3H, s, CH3), 2.93–2.73 (2H,
br m, ]CHCH2); dC (63 MHz, CDCl3), 171.4 (C]O),
139.2, 137.9, 134.8, 134.0, 133.1, 131.8, 129.3, 128.8,
128.5, 127.7, 126.7, 126.3, 125.6, 125.4, 122.8, 122.4, 52.7
cmK1 (film) 1740 (MeOC]O), 1619, 1593, 1331 (S]Oas),
1267, 1160 (S]Os), 1091; dH (250 MHz, CDCl3) 7.84–7.81
(2H, m, SO2PhH), 7.72 (1H, dd, JZ8.3, 2.0 Hz, ArH), 7.65–
7.49 (4H, m, SO2PhH and ArH), 6.89 (1H, d, JZ8.3 Hz,
ArH), 5.60 (1H, ddt, JZ16.9, 9.8, 6.9 Hz, CH]CHH), 5.49
(1H, s, ]CHH), 5.45 (1H, s, ]CHH), 5.02 (1H, d, JZ
16.9 Hz CH]CHHtrans), 5.02 (1H, d, JZ9.8 Hz
CH]CHcisH), 4.48 (1H, t, JZ7.4 Hz, NCH), 4.41 (1H, d,
JZ16.9 Hz, NCHH), 4.30 (1H, d, JZ16.9 Hz, NCHH),
3.41 (3H, s, CH3), 3.27 (3H, s, CH3), 2.67–2.55 (1H, m,
]CHCHH), 2.42–2.30 (m, 1H, ]CHCHH); dC (63 MHz,
CDCl3) 183.7 (C]O), 170.6 (C]O), 158.7 (C]O), 151.2,
142.4, 139.6, 136.9, 135.2, 133.4, 129.4, 128.0, 123.5,
118.9, 117.7, 117.3, 110.3, 59.7 (NCH), 52.4 (OCH3), 50.0
(NCH2), 35.2 (]CHCH2), 26.8 (N–CH3); m/z (%) (EI); 468
(57, MC), 409 (72, MKCO2Me), 327 (82, MKSO2Ph), 200
(55), 144 (70), 77 (100).

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
10661
(NCH), 52.6, (OCH3), 46.4 (NCH2), 28.7 (]CHCH2); m/z
(%) (EI) 407 (44, MC), 348 (25, MKCO2Me), 266 (100,
MKSO2Ph), 206 (73), 179 (76), 165 (50), 141 (42), 77 (80).
16.3, 1.9 Hz, NCHH), 3.80 (3H, s, CH3), 3.46 (3H, s, CH3),
2.74–2.71 (2H, br m, ]CHCH2); dC (63 MHz, CDCl3)
171.2 (C]O), 159.8, 139.5, 133.4, 133.1, 131.1, 129.3,
127.6, 126.6, 118.1, 114.3, 55.7 (OCH3), 52.8 (NCH), 52.6
(OCH3), 44.0 (NCH2), 28.5 (]CHCH2); m/z (ES) 410
(MCCNa).
2.3.15. Methyl 5-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra-
hydro-5-pyrimidinyl)-1-(phenylsulfonyl)-1,2,3,6-tetra-
hydropyridine-2-carboxylate (30). Prepared by the
general ring closing metathesis procedure on a 0.12 mmol
scale and a reaction time of 3 h. Purification by flash column
chromatography eluting with 3:2 v/v petrol/ethyl acetate
afforded the product (48 mg, 84%), which crystallised from
DCM/petrol as colourless needles, mp 196–198 8C; Rf 0.1;
(Found: C, 54.40; H, 5.05; N, 9.85. C19H21N3O6S requires
C, 54.40; H, 5.05; N, 10.0%); nmax/cmK1 (film) 1742
(MeOC]O), 1702 (NC]O), 1652 (N(N)C]O), 1448,
1339 (S]Oas), 1164 (S]Os), 1095; dH (250 MHz, CDCl3)
7.88–7.83 (2H, m, SO2PhH), 7.62–7.47 (3H, m, SO2PhH),
7.06 (1H, s, ArH), 6.10–6.07 (1H, br m, ]CHB), 4.88 (1H,
dd, JZ5.6, 2.9 Hz, NCH), 4.43 (1H, d, JZ16.3 Hz,
NCHH), 4.05 (1H, ddd, JZ16.3, 4.9, 3.2 Hz, NCHH),
3.51 (3H, s, CH3), 3.41 (3H, s, CH3), 3.34 (3H, s, CH3),
2.65–2.63 (2H, br m, ]CHCH2); dC (63 MHz, CDCl3)
171.1 (C]O), 162.3 (C]O), 151.6 (C]O), 140.0, 139.6,
133.1, 129.4, 128.6, 127.6, 122.7, 112.8, 52.7 (NCH),
52.5 (OCH3), 43.7 (NCH2), 37.5 (CH3), 28.5 (CH3),
28.1 (]CHCH2) m/z (%) (EI) 419 (9, MC), 278 (68,
MKSO2Ph), 218 (100), 77 (25, Ph).
2.3.18. Methyl 5-(1-methyl-1H-indole-5-yl)-1-(phenylsul-
fonyl)-1,2,3,6-tetrahydropyridine-2-carboxylate (33).
Prepared by the general ring closing metathesis procedure
on a 0.12 mmol scale and a reaction time of 5 h. Purification
by flash column chromatography eluting with 4:1 v/v ether/
petrol affords the product (41 mg, 85%) as a colourless oil,
which solidified on standing, mp 138–140 8C; Rf 0.35;
(Found: C, 64.25; H, 5.55; N, 6.90; C22H22N2O4S requires
C, 64.35; H, 5.40; N, 6.80%); nmax/cmK1 (film) 1743
(C]O), 1446, 1339 (S]Oas), 1201, 1161 (S]Os), 1097;
dH (250 MHz, CDCl3) 7.87–7.83 (2H, m, SO2PhH),
7.57–7.46 (4H, m, 3!SO2PhH and ArH), 7.26 (1H, d,
JZ8.6 Hz, ArHE) 7.19 (1H, dd, JZ8.6, 1.7 Hz, ArH), 7.05
(1H, d, JZ3.1 Hz, ArH), 6.46 (1H, d, JZ3.1 Hz, ArH),
6.00–5.97 (1H, m, ]CH), 4.95 (1H, t, JZ4.2 Hz, NCH),
4.60 (1H, dd, JZ16.3, 1.9 Hz, NCHH), 4.21 (1H, ddd, JZ
16.3, 5.0, 2.8 Hz, NCHH), 4.17 (3H, s, CH3), 3.45 (3H, s,
CH3), 2.76–2.73 (2H, br m, ]CHCH2); m/z (ES) 433
(MCCNa).
2.3.19. Methyl 5-(2-methyl-4-nitrophenyl)-1-(phenylsul-
fonyl)-1,2,3,6-tetrahydropyridine-2-carboxylate (34).
Prepared by the general ring closing metathesis procedure
on a 0.12 mmol scale and a reaction time of 5 h. Purification
by flash chromatography eluting with 1:4 v/v ethyl acetate/
petrol afforded the product (35 mg, 74%), which crystallised
from petrol/DCM as colourless needles, mp 154–156 8C; Rf
0.1; (Found: C, 57.90; H, 4.90; N, 6.50. C22H24N2O6S
requires C, 57.70; H, 4.85; N, 6.75%); nmax/cmK1 (film)
1743 (C]O), 1518 (NO2), 1447, 1344 (S]Oas), 1289,
1021, 1166 (S]Os), 1095; dH (500 MHz, CDCl3) 8.04 (1H,
d, JZ2.4 Hz, ArH), 7.99 (1H, dd, JZ8.4, 2.4 Hz, ArH),
7.81–7.79 (2H, m, SO2PhH), 7.60–7.58 (1H, m, SO2PhH)
7.53–7.50 (2H, m, SO2PhH), 7.17 (1H, d, JZ8.4 Hz, ArH),
5.65–5.62 (1H, m, ]CH), 4.97 (1H, dd, JZ6.7, 1.8 Hz,
NCH), 4.22–4.18 (1H, m, NCHH), 3.96–3.92 (1H, m,
NCHH), 3.52 (3H, s, OCH3), 2.78–2.72 (2H, m, ]CHCH2),
2.28 (3H, s, ArCH3); dC (125 MHz, CDCl3) 170.6 (C]O),
147.4, 145.9, 138.7, 137.8, 134.1, 132.9, 129.8, 129.0,
127.2, 125.1, 122.5, 120.9, 52.3 (NCH), 52.0 (OCH3), 44.8
(NCH2), 28.0 (]CHCH2), 19.6 (ArCH3); m/z (%) (EI) 416
(2, MC), 357 (75, MKCO2Me), 275 (93, MKSO2Ph), 215
(61), 141 (53, SO2Ph), 77 (100, C6H5).
2.3.16. Methyl 1-(phenylsulfonyl)-5-(2-thienyl)-1,2,3,6-
tetrahydropyridine-2-carboxylate (31). Prepared by the
general ring closing metathesis procedure on a 0.13 mmol
scale and a reaction time of 3 h. Purification by flash column
chromatography eluting with DCM affords the product
(33 mg, 71%) as a viscous colourless oil; Rf 0.15; (Found: C,
55.90; H, 4.90; N, 3.60; C17H17NO4S2 requires C, 56.20; H,
4.7; N, 3.85%); nmax/cmK1 (film) 1743 (C]O), 1447, 1339
(S]Oas), 1202, 1164 (S]Os), 1098. dH (250 MHz, CDCl3),
7.86–7.82 (2H, m, SO2PhH), 7.63–7.49 (3H, m, SO2PhH),
7.16 (1H, dd, JZ5.0, 0.8 Hz, ArH), 7.05–6.93 (2H, m, ArH
and ArH), 6.09–6.06 (1H, br m, ]CH), 4.25 (1H, t, JZ
4.5 Hz, NCH), 4.71 (1H, dd, JZ16.1, 1.9 Hz, NCHH), 4.17
(dd, 1H, JZ16.1, 1.9 Hz, NCHH), 3.40 (3H, s, CH3), 2.71–
7.76 (2H, br m, ]CHCH2). dC (63 MHz, CDCl3) 171.0
(C]O), 142.1, 139.5, 133.2, 129.4, 128.5, 127.8, 127.5,
124.4, 122.6, 118.8, 52.8 (NCH), 52.7 (OCH3), 43.6
(NCH2), 28.2 (]CHCH2); m/z (%) (EI) 363 (6, MC), 304
(18, MKCO2Me,), 222 (72, MKSO2 Ph,), 162 (100), 77
(59, Ph).
2.3.17. Methyl 5-(4 methoxyphenyl)-1-(phenylsulfonyl)-
1,2,3,6-tetrahydropyridine-2-carboxylate (32). Prepared
by the general ring closing metathesis procedure on a
0.12 mmol scale and a reaction time of 2 h. Purification by
flash column chromatography eluting with 4:1 v/v ether/
petrol afforded the product (43 mg, 96%) as a viscous,
colourless oil; Rf 0.35; (Found: C, 61.85; H, 5.75, N, 3.55.
2.3.20. Methyl 5-(1-methyl-2,3,dioxo-2,3-dihydro-1H-
indol-5-yl)-1-(phenylsulfonyl)-1,2,3,6-tetrahydropyri-
dine-2-carboxylate (35). Prepared by the general ring
closing metathesis procedure on a 0.12 mmol scale and a
reaction time of 3 h. Purification by flash column
chromatography eluting with 3:2 v/v ethyl acetate/petrol
afforded the product (39 mg, 83%) as red needles, mp 175–
177 8C; Rf 0.2; (Found: C, 57.85; H, 5.05; N, 5.75.
C22H20N2O6S with 1 equiv of H2O requires C, 57.65; H,
4.85; N, 6.36%); nmax/cmK1 (film) 1739 (MeO–C]O),
1620, 1338 (S]Oas), 1164 (S]Os), 1098; dH (250 MHz,
CDCl3) 7.86–7.83 (2H, m, SO2PhH), 7.65–7.50 (5H, m, 3!
C20H21NO5S requires C, 62.00; H, 5.46; N, 3.62%); nmax
/
cmK1 (film) 1744 (C]O), 1514, 1341 (S]Oas), 1248
(OCH3), 1163 (S]Os), 1097, 1024; dH (250 MHz, CDCl3),
7.86–7.82 (2H, m, SO2PhH), 7.58–7.51 (3H, m, SO2PhH),
7.23 (2H, d, JZ8.9 Hz, ArH), 6.85 (2H, d, JZ8.9 Hz, ArH),
5.96–5.93 (1H, br m, ]CH), 4.92 (1H, t, JZ4.2 Hz, NCH),
4.48 (1H, dd, JZ16.3, 1.9 Hz, NCHH), 4.11 (1H, dd, JZ

10662
H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
SO2PhH and ArH), 6.87 (1H, d, JZ8.4 Hz, ArH), 6.09–6.01
(1H, br m, ]CH), 4.94 (1H, t, JZ4.2 Hz, NCH), 4.44 (1H,
dd, JZ16.3, 1.9 Hz, NCHH), 4.11 (1H, dd, JZ16.3, 1.9 Hz,
NCHH), 3.47 (3H, s, CH3), 3.26 (3H, s, CH3), 2.76 (2H, br s,
]CHCH2). dC (63 MHz, CDCl3) 183.1 (C]O), 170.2
(C]O), 157.9 (C]O), 150.5, 138.5, 134.6, 134.0, 132.6,
131.6, 128.8, 126.9, 121.6, 119.9, 117.2, 109.8, 52.0 (NCH),
52.8 (OCH3), 43.0 (NCH2), 27.5 (]CCH2), 26.1 (CH3); m/z
(ES) 463 (MCCNa); HRMS found 463.0940,
[C22H20N2O6SCNa] requires 463.0961.
2.3.23. Methyl 2-{[(4-nitrophenyl)sulfonyl][2-(1-methyl-
2,3,-dioxo-2,3,-dihydro-1H-indol-5-yl)prop-2-enyl]amino}-
pent-4-enoate (38). Prepared by the general termolecular
cascade procedure on a 2.0 mmol scale, using 2.0 mmol of aryl
iodide and a reaction time of 48 h. Pd2(dba)3 (0.05 mmol) was
used in place of Pd(OAc)2. Purification by flash column
chromatography eluting with 7:3 v/v petrol/ethyl acetate
afforded the product (380 mg, 43%) as red needles, mp 141–
143 8C; Rf 0.21; (Found: C, 55.90; H, 4.45; N, 8.05.
C24H23N3O8S requires C, 56.15; H, 4.50; N, 8.20%); nmax
/
cmK1 (film) 1741 (MeO–C]O), 1620, 1529 (NO2), 1349
(S]Oas), 1165 (S]Os) 1092; dH (250 MHz, CDCl3) 8.35 (2H,
d, JZ8.9 Hz, ArH), 8.01 (2H, d, JZ8.9 Hz, ArH), 7.68 (1H, dd,
JZ8.2, 1.9 Hz, ArHI), 7.58 (1H, d, JZ1.9 Hz, ArH), 6.88 (1H,
d, JZ8.2 Hz, ArH), 5.63 (1H, ddt, JZ16.7, 9.8, 6.9 Hz,
CH]CHH), 5.5 (1H, s, ]CHH), 5.4 (1H, s, ]CHH), 5.02–
5.09 (2H, m, CH]CHcisHtrans), 4.54 (1H, t, JZ7.4 Hz, NCH),
4.44 (1H, d, JZ16.8 Hz, NCHH), 4.26 (1H, d, JZ16.8 Hz,
NCHH), 3.49 (3H, s, CH3), 3.28(3H, s, CH3), 2.61–2.73(1H, m,
]CHCHH), 2.36–2.50 (1H, m, ]CHCHH); dC (75 MHz,
CDCl3) 183.6 (C]O), 170.3 (C]O), 158.6 (C]O), 151.4,
150.6, 145.3, 141.8, 136.7, 134.8, 133.1, 129.3, 124.5, 123.4,
119.4, 117.8, 110.4, 60.4 (NCH), 52.7 (OCH3), 50.4 (NCH2),
35.3 (]CHCH2), 23.0 (NCH3); m/z (ES) 536 (MCCNa).
2.3.21. Methyl 2-{[(4-nitrophenyl)sulfonyl](2-phenyl-
prop-2-enyl)amino}pent-4-enoate (36). Prepared by the
general termolecular cascade procedure on a 1 mmol scale,
using 1.2 mmol of aryl iodide and a reaction time of 42 h.
Purification by flash chromatography eluting with 4:1 v/v
petrol/ether afforded the product (611 mg, 71%), which
crystallised from DCM/petrol as colourless needles, mp
81–83 8C. Rf 0.2; (Found: C, 58.70; H, 5.15; N, 6.40;
C21H22N2O6S requires C, 58.60; H, 5.15; N, 6.50%); nmax
/
cmK1 (film) 1742 (C]O), 1530 (NO2), 1350 (S]Oas),
1163 (S]Oas), 1090; dH (500 MHz, CDCl3) 8.27 (2H, d,
JZ8.9 Hz, ArH), 7.97 (2H, d, JZ8.9 Hz, ArHE), 7.30–7.26
(5H, m, ArH), 5.69–5.61 (1H, ddt, JZ16.8, 9.8, 6.8 Hz,
CH]CHH), 5.44 (1H, s, ]CHH), 5.34 (1H, s, ]CHH),
5.07–5.03 (2H, m, CH]CHcisHtrans), 4.54 (1H, t, JZ
7.4 Hz, NCH), 4.43 (1H, d, JZ16.6 Hz, NCHH), 4.35 (1H,
d, JZ16.6 Hz, NCHH), 3.50 (3H, s, CH3), 2.74–2.68 (1H,
m, ]CH–CHH), 2.52–2.46 (1H, m,]CHH); dC (125 MHz,
CDCl3) 170.1 (C]O), 150.0, 145.5, 143.1, 138.6, 133.0,
129.0, 128.5, 128.2, 126.4, 124.0, 118.7, 117.0, 60.1 (NCH),
52.1 (OCH3), 50.3 (N–CH2), 34.8 (]CHCH2); m/z (ES) 453
(MCCNa).
2.3.24. Methyl 1-[(4-nitrophenyl)sulfonyl]-5-phenyl-1,2,
3,6-tetrahydropyridine-2-yl(propan-1-one) (39). Pre-
pared by the general ring closing metathesis procedure on
a 0.05 mmol scale and a reaction time of 1 h. Purification by
flash column chromatography eluting with 3:2 v/v petrol/
ether afforded the product (206 mg, 98%) as colourless
needles, mp 112–114 8C. Rf 0.19; (Found: C, 56.65; H, 4.75;
N, 6.95. C19H18N2O6S requires C, 56.71; H, 4.50; N,
6.95%); nmax/cmK1 (film) 1743 (C]O), 1530 (NO2), 1349
(S]Oas), 1167 (S]Oas), 1097; dH (250 MHz, CDCl3), 8.37
(2H, d, JZ8.6 Hz, ArH), 8.03 (2H, d, JZ8.6 Hz, ArH),
7.38–7.26 (5H, m, ArH), 6.10–6.06 (1H, br m, ]CH), 4.98
(1H, dd, JZ5.5, 2.8 Hz, NCH), 4.57 (1H, dd, JZ16.1,
1.7 Hz, NCHH), 4.13 (1H, ddd, JZ16.1, 5.3, 3.2 Hz,
NCHH) 3.54 (3H, s, CH3), 2.81–2.77 (2H, br m,
]CHCH2); dC (63 MHz, CDCl3) 170.6 (C]O), 150.4,
145.1, 138.2, 133.8, 129.1, 128.9, 128.6, 125.5, 124.6,
119.9, 53.1, 52.9, 44.0, 28.6; m/z (%) (EI) 402 (3, MC), 343
(6, MKCO2Me), 216 (40), 156 (100, SO2PhNO2), 129 (32).
2.3.22. Methyl 2-{[2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)prop-2-enyl][(4-nitrophenyl
sufonyl)]amino}pent-4-enoate (37). Prepared by the
general termolecular cascade procedure on a 2.9 mmol
scale, using 3.3 mmol of aryl iodide and a reaction time of
46 h. Purification by flash chromatography eluting with
1:1 v/v ethyl acetate/ether afforded the product (960 mg,
67%), which crystallised from DCM/petrol as colourless
needles, mp 140–142 8C. Rf 0.17; (Found: C, 51.25; H, 5.00;
N, 11.45. C21H24N4O8S requires C, 51.20; H, 4.90; N,
11.40%); nmax/cmK1 (film) 1742 (MeO–C]O), 1702
(N–C]O), 1653 (N(N)C]O), 1531 (NO2), 1350
(S]O2), 1161 (S]O3); dH (CDCl3 250 MHz) 8.35 (2H,
d, JZ9.0 Hz, ArH), 8.02 (2H, d, JZ9.0 Hz, ArH), 7.27 (1H,
s, ArH), 5.71 (1H, ddt, JZ16.9, 10.2, 6.6 Hz, CH]CHH),
5.43 (1H, d, JZ1.0 Hz, ]CHH), 5.38 (1H, d, JZ1.0 Hz,
]CHH), 5.11 (1H, ddd, JZ16.9, 3.1, 1.5 Hz,
CH]CHHtrans), 5.05 (1H, ddd, JZ10.2, 2.6, 1.7 Hz,
CH]CHcis) 4.58 (1H, dd, JZ8.7, 6.4 Hz, NCH), 4.24
(2H, s, NCH2), 3.51 (3H, s, CH3), 3.43 (3H, s, CH3), 3.33
(3H, s, CH3), 2.81–2.69 (1H, m, ]CHCHH); 2.64–2.52
(1H, m, ]CHCHH); dC (63 MHz, CDCl3) 170.5 (C]O),
162.7 (C]O), 152.5 (C]O), 150.2, 145.1, 141.8, 138.7,
133.7, 129.5, 124.3, 119.8 (]CH2), 118.8 (]CH2), 112.7,
61.0 (NCH), 52.6 (OCH3), 50.4 (NCH2), 37.5 (NCH3),
34.8 (]CHCH2), 28.4 NCH3; m/z (EI) 492 (4, MC),
433 (21, MKCO2Me), 387 (100), 369 (47), 306 (100,
MKSO2PhNO2).
2.3.25. Methyl 5-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra-
hydropyrimidin-5-yl)-1-[(4-nitorphenyl)sulfonyl]-1,2,3,
6-tetrahydropyridine-2-carboxylate (40). Prepared by the
general ring closing metathesis procedure on a 0.16 mmol
scale and a reaction time of 1 h. Purification by flash
chromatography eluting with 3:2 v/v ethyl acetate/petrol
afforded the product (702 mg, 93%) as colourless needles,
mp 221–223 8C; Rf 0.14; (Found: C, 49.05; H, 4.40; N,
12.20. C19H20N4O8S requires C, 49.15; H, 4.35; N,
12.05%); nmax/cmK1 (film) 1742 (MeO–C]O), 1702 (N–
C]O), 1653 (N(N)C]O), 1530 (NO2), 1350 (S]Oas),
1167 (S]Os); dH (CDCl3, 250 MHz) 8.36 (2H, d, JZ
8.9 Hz, ArH), 8.06 (2H, d, JZ8.9 Hz, ArH), 7.08 (1H, s,
ArH), 5.98–5.94 (1H, br m, ]CH), 4.91 (1H, dd, JZ6.6,
1.65 Hz, NCH), 4.61 (1H, d, JZ16.6 Hz, NCHH), 4.06–
3.99 (1H, m, NCHH), 3.58 (3H, s, CH3), 3.41 (3H, s, CH3),
3.34 (3H, s, CH3), 2.70–2.61 (2H, br m, ]CHCH2); dC
(63 MHz, CDCl3) 170.6 (C]O), 162.4 (C]O), 151.6

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
10663
(C]O), 150.4, 145.4, 140.4, 128.9, 124.6, 122.6, 112.6,
2.4. Intermolecular cycloaddition
53.0 (NCH), 52.9 (OMe), 43.8 (NCH2), 37.5 (NCH3), 28.5
(]CHCH2), 27.9 (NCH3); m/z (%) (FAB) 465 (100, MC
HC), 279 (31, MKSO2PhNO2), 218 (24).
Benzaldehyde (22 ml, 0.2 mmol), and N-methyl maleimide
(25 mg, 0.23 mmol) were added to a stirred solution of 42
(45 mg, 0.2 mmol) in toluene (6 ml). The reaction mixture
was immersed in a pre-heated oil bath at 110 8C and stirred
under a nitrogen atmosphere for 54 h. Concentration in
vacuo gave the crude product, which comprised 3.5:1
mixture of 44 and 45. Preparative HPLC (Luna C18/7:3 v/v
MeCN/H2O, 0.6 ml/min, detection at 254 nm) afforded pure
44 and 45 in 80% combined yield.
2.3.26. Methyl 5-(1,3-dimethyl-2,4,-dioxo-1,2,3,4-tetra-
hydropyrimidin-5-yl)-1-[(4-nitrophenyl)sulfonyl]-1,2,3,
6-tetrahydropyridine-2-carboxylate (41). Prepared by the
general ring closing metathesis procedure on a 0.058 mmol
scale and a reaction time of 1 h. Purification by flash column
chromatography eluting with 1:1 v/v ethyl acetate/petrol
afforded the product (216 mg, 76%) as red needles, mp 224–
226 8C; Rf 0.16; (Found: C, 54.40; H, 3.90; N, 8.45.
C22H19N3O8S requires C, 54.45; H, 3.95; 8.65%); nmax/cmK1
(film) 1740 (MeO–C]O), 1621, 1530 (NO2), 1349
(S]Oas) 1168 (S]Os); dH (250 MHz, CDCl3), 8.39 (2H,
d, JZ9.0 Hz, ArH), 8.03 (2H, d, JZ9.0 Hz, ArH), 7.56 (2H,
dd, JZ7.3, 1.8 Hz, ArH), 7.54 (1H, s, ArH), 6.88 (1H, dd,
JZ7.3, 1.8 Hz, ArH), 6.11–6.09 (1H, br m, ]CH), 4.98
(1H, t, JZ4.2 Hz, NCH), 4.48 (1H, dd, JZ16.2, 1.9 Hz,
NCHH), 4.08 (m, 1H, NCHH), 3.54 (3H, s, CH3), 3.27
(3H, s, CH3), 2.83 (2H, br s, ]CHCH2); m/z (ES) 508
(MCC Na).
2.4.1. endo-Methyl 2-methyl-1,3-dioxo-4,7-diphenyl 1,2,
3,3a,4,6,9,9b-octahydro-9aH-pyrrolo[3,4-a]indolizine-
9a-carboxylate (44). Crystallisation from DCM/petrol
afforded colourless needles, mp 105–107 8C; Rf 0.17;
(Found: C, 72.15; H, 5.65; N, 6.50. C25H24N2O4 requires
C, 72.10; H, 5.80; N, 6.75%); nmax/cmK1 (film) 1750
(MeOC]O), 1702 (N–C]O), 1435, 1286; dH (500 MHz,
C6D6), 7.16–7.03 (7H, m, ArH), 6.97–6.96 (3H, m, ArH),
6.02 (1H, m, ]CH), 4.80 (1H, d, JZ9.7 Hz, NCHC), 3.82–
3.80 (1H, m, NCHHj), 3.79–3.77 (1H, m, NCHH) 3.38 (1H,
ddd, JZ17.5, 6.5, 2.9 Hz, ]CHCHH), 3.25 (3H, s, Me),
3.22 (1H, ddd, JZ17.5, 6.4, 1.7 Hz, ]CHCHH), 3.07 (1H,
dd, JZ9.7, 7.9 Hz, PhCHCHB), 2.84 (1H, d, JZ7.9 Hz,
NCCHA), 2.56 (3H, s, Me); dC (63 MHz, CDCl3) 175.5
(C]O), 175.4 (C]O), 173.7 (C]O), 139.2, 137.4, 135.1,
131.0, 129.0, 128.7, 128.3, 127.8, 125.3, 120.6, 68.5, 68.3,
52.6, 51.1, 49.7, 48.7 (NCH2), 31.8 (]CHCH2), 25.3; m/z
(%) (EI) 416 (1, MC), 357 (100, MKCO2Me);
2.3.27. Methyl 5-phenyl-1,2,3,6-tetrahydropyridine-2-
carboxylate (42). A solution of 39 (215 mg, 0.5 mmol)
and benzene thiol (62 ml, 0.6 mmol) in DMF (4 ml) was
added to a suspension of K2CO2 (0.208 g, 1.5 mmol) in
DMF (3 ml) and the mixture stirred for 3 h at room
temperature, quenched with 10% NaHCO3 solution (6 ml)
and extracted with ether (3!5 ml). The combined organic
extracts were washed with water (5 ml), dried (MgSO4),
filtered and the filtrate concentrated in vacuo. Purification of
the residue by flash chromatography eluting with ether
afforded the product (88 mg, 83%) as pale yellow needles,
mp 46–48 8C; Rf 0.1; (Found: C, 71.60; H, 7.20; N, 6.35.
NOE data:
Signal irradiated
Enhancement (%)
HC
C13H15NO2 requires C, 71.85; H, 6.95; N, 6.45%); nmax
/
cmK1 (film) 3342 (NH), 1738 (C]O), 1435, 1202, 1174; dH
(300 MHz, CDCl3) 7.33–7.23 (5H, m, ArH), 6.16–6.13 (1H,
br m, ]CH), 3.90–3.80 (2H, m, NCH2), 3.77 (3H, s, CH3),
3.65 (1H, dd, JZ9.1, 5.0 Hz, NCH), 2.55–2.45 (2H, m,
]CHCH2); dC (75 MHz, CDCl3) 174.2 (C]O), 139.9,
136.8, 128.8, 127.7, 125.3, 121.5, 55.0 (OCH3), 52.6
(NCH), 46.5 (NCH2), 29.0 (]CHCH2); m/z (EI) 217 (21,
MC), 158 (100, MKCO2Me), 91 (38).
HA
HB
HD
5.6
HA
HB
HC
8.5
12.1
9.5
17.7
2.4.2. exo-Methyl 2-methyl-1,3-dioxo-4,7-diphenyl 1,2,3,
3a,4,6,9,9b-octahydro-9aH-pyrrolo[3,4-a]indolizine-9a-
carboxylate (45). Crystallisation from CH3CN/H2O
afforded colourless needles, mp 212–214 8C, Rf 0.27;
(Found: C, 71.90; H, 5.55; N, 6.50. C25H24N2O4 requires
C, 72.10; H, 5.80; N, 6.75%); nmax/cmK1 (film) 1769
(MeOC]O), 1693 (N–C]O), 1496, 1443, 1380, 1076; dH
(500 MHz, C6D6), 7.58–7.57 (2H, m, ArH), 7.23–7.20 (2H,
m, ArH), 7.14–7.12 (1H, m, ArH), 7.03–6.97 (5H, m, ArH),
6.10–6.09 (1H, m, ]CH), 4.88 (1H, d, JZ5.2 Hz, NCHG),
3.63–3.60 (1H, m, NCHAHB), 3.43–3.34 (2H, m, NCHAHB
and ]CHCHCHD), 3.20 (3H, s, CO2Me), 2.80 (1H, d, JZ
9.8 Hz, CHE), 2.77 (1H, dd, JZ9.8, 5.2 Hz, CHF), 2.73 (3H,
s, NMe), 2.45–2.40 (1H, m, CHCHCHD); dC (75 MHz,
CDCl3) 175 (C]O), 174.4 (C]O), 171.3 (C]O), 139.7,
137.7, 133.4, 128.0, 127.3, 127.1, 126.4, 126.3, 123.8,
120.5, 68.4 (CCO2Me), 66.5 (NCH), 53.2, 52.4, 50.9, 46.1
(NCH2), 35.2 (]CHCH2), 23.9 (NCH3); m/z (ES) 416 (M);
2.3.28. Methyl 5-(1,3,-dimethyl-2,4-dioxo-1,2,3,4-tetra-
hydropyrimidin-5-yl)-1,2,3,6-tetrahydropyridine-2-car-
boxylate (43). Prepared by the above method, on a
1.4 mmol scale and a reaction time of 18 h. Purification
by flash chromatography eluting with 9:1 v/v DCM/MeOH
afforded the product (266 mg, 70%) as a pale yellow solid,
mp 76–78 8C; Rf 0.28; (Found: C, 55.75; H, 5.80; N, 15.20.
C13H15NO2 requires C, 55.25; H, 6.10; N, 15.05%); nmax
/
cmK1 (film) 1701 (C]O), 1653, 1437, 1293; dH (250 MHz,
CDCl3), 7.08 (1H, s, ArH), 6.15–6.14 (1H, br m, ]CH),
3.76 (3H, s, CH3), 3.69 (2H, br s, NCH2), 3.64 (1H, dd, JZ
9.2, 5.2 Hz, NCH), 3.42 (3H, s, CH3), 3.35 (3H, s, CH3),
2.50–2.32 (2H, m, ]CHCH2); m/z (%) (FAB) 280 (100,
MC), 220 (10, MKCO2Me,), 193 (6).

10664
H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
6.12–6.11 (1H, m, ]CH), 4.25 (1H, d, JZ7.1 Hz, NCH),
3.96 (1H, dd, JZ10.6, 4.7 Hz, OCHH), 3.93 (1H, d, JZ
15.4 Hz, NCHH), 3.90 (1H, dd, JZ10.6, 8.1 Hz, OCHH),
3.74 (3H, s, CH3), 3.57 (d, 1H, JZ15.4 Hz, NCHH) 3.38
(3H, s, CH3), 3.33 (3H, s, CH3), 2.97 (1H, ddd, JZ16.6, 6.3,
2.0 Hz, ]CHCHH), 2.60–2.56 (1H, m, OCH2CH), 2.41
(1H, dd, JZ13.3, 8.5 Hz, NCCHH), 2.21 (1H, d, JZ
16.6 Hz, ]CHCHH), 1.71 (1H, dd, JZ13.3, 5.3 Hz,
NCCHH); m/z (%) (FAB) 424 (49, MCCH), 464 (55,
MKCO2Me);
NOE data:
Signal irradiated
Enhancement (%)
HA
5.7
HB
HC
HD
HE
HG
6.9
HA
HC
HE
HG
25.0
31.7
15.2
3.3
2.5. Intramolecular cycloaddition
2.5.1. Methyl-10-phenyl-6a,8,11,12a,tetrahydro-6H-
chromeno[3,4-b]indolizine-7a(7H)-carboxylate (47).
Salicylic aldehyde 46 (92 mg, 0.57 mmol) in toluene
(2 ml) was added to a solution of 42 (112 mg, 0.52 mmol)
in toluene (8 ml). The reaction mixture was immersed in a
pre-heated oil bath at 110 8C and stirred under a nitrogen
atmosphere for 26 h. Concentration in vacuo afforded a
yellow gum, which was purified by flash column chroma-
tography eluting with DCM to afford 47 (101 mg, 56%),
which crystallised from DCM/petrol as colourless plates,
mp 157–159 8C; Rf 0.34; nmax/cmK1 (film) 1727 (C]O),
1488, 1224, 1192, 1172; dH (500 MHz, C6D6), 7.31–7.29
(2H, m, ArH), 7.26 (1H, dd, JZ7.5, 1.6 Hz, ArH), 7.18–
7.04 (m, 5H, ArH), 6.81 (1H, td, JZ7.5, 1.5 Hz, ArH), 5.98
(1H, ddd, JZ6.4, 4.0, 1.8 Hz ]CH), 4.45 (1H, d, JZ
6.7 Hz, NCH), 4.28 (1H, br d, JZ15.7 Hz, NCHH), 4.06
(1H, br d, JZ15.7 Hz, NCHH), 3.77 (1H, dd, JZ10.7,
8.5 Hz, OCHH) 3.67 (1H, dd, JZ10.7, 4.4 Hz, OCHH),
3.33 (3H, s, CH3), 2.98 (1H, ddd, JZ16.4, 6.4, 1.8 Hz,
]CCHH), 2.28–2.23 (1H, m, CH2CH), 2.14–2.07 (2H, m,
]CCHH and CHCHH), 1.43 (1H, dd, JZ13.3, 5.0 Hz,
CHCHH); dC (75 MHz, CDCl3) 176.0 (C]O), 156.3, 140.1,
136.8, 131.6, 129.0, 128.7, 127.6, 125.6, 123.1, 121.7,
120.9, 117.8, 68.6 (OCH2), 65.3 (NC), 58.3 (NCH), 51.9,
47.8 (CH2), 38.3 (CH2), 37.2 (CH2), 34.9; m/z (%) (EI) 361
(1, MC), 302 (100, MKCO2Me). HRMS found 362.1747.
C23H24NO3 requires 362.1756.
NOE data:
Signal irradiated
Enhancement (%)
HB
HA
6.8
HC
3.4
HA
HB
9.6
2.5.3. 2-Allylphenyl-2-(thienyl)prop-2-en-1yl ether (53).
Prepared by the general termolecular cascade procedure
employing 2-allyphenol as the nucleophile on a 2 mmol
scale, using 2.5 mmol of aryl iodide and a reaction time of
16 h. Purification by flash chromatograpy eluting with 19:1
v/v petrol/ether afforded the product (398 mg, 78%) as a
colourless liquid; Rf 0.05; (Found: C, 74.90; H, 6.15;
C16H16OS. requires C, 74.95; H, 6.30%); nmax/cmK1 (film)
1638, 1600, 1586, 1488, 1231, 1090; dH (250 MHz, CDCl3)
7.25 (1H, d, JZ4.0 Hz, ArH), 7.18 (2H, d, JZ7.7 Hz, ArH
and ArH), 7.13 (1H, d, JZ3.7 Hz, ArH) 7.02 (1H, dd, JZ
4.0, 3.7 Hz, ArH) 6.93 (2H, t, JZ7.7 Hz, ArH and ArH),
5.98 (1H, ddt, JZ16.9, 10.2, 6.7 Hz, CH]CHH), 5.62 (1H,
s, ]CHH), 5.38 (1H, s, ]CHH), 5.03 (1H, d, JZ16.9 Hz,
CH]CHHtrans), 5.02 (1H, d, JZ10.2 Hz, CH]CHcisH),
4.87 (2H, s, OCH2), 3.42 (2H, d, JZ6.7 Hz, CH2); dC
(63 MHz, CDCl3) 156.5, 142.4, 137.5, 137.4, 130.4, 129.5,
127.8, 127.7, 125.0, 124.3, 121.4, 115.9, 113.3, 112.1, 70.0
(OCH2), 34.8 (CH2); m/z (%) (EI) 256 (14, MC), 215 (39),
123 (100), 79 (50).
2.5.2. Methyl 10-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra-
hydropyrimidin-5-yl)-6a,8,11,12a-tetrahydro-6H-chro-
meno[3,4-b]indolizine-7a (7H)-carboxylate (48).
Salicylic aldehyde 46 (70 mg, 0.43 mmol) in toluene
(2 ml) was added to a solution of 43 (100 mg, 0.36 mmol)
in toluene (8 ml). The reaction mixture was immersed in a
pre-heated oil bath at 110 8C and stirred under a nitrogen
atmosphere for 34 h. Work up (as above) followed by flash
column chromatography eluting with 3:2 v/v ethyl acetate/
petrol afforded 48 (82 mg, 54%), which crystallised from
DCM/petrol as colourless plates, mp 238–240 8C; Rf 0.25;
(Found: C, 65.40; H, 6.00; N, 9.70. C23H25N3O5 requires C,
65.25; H, 5.95; N, 9.90%) nmax/cmK1 (film) 1725 (MeO–
C]O), 1701 (N–C]O), 1652 (N(N)C]O), 1488, 1453,
1224, 1174, 1196; dH (500 MHz, CDCl3) 7.22 (1H, dd, JZ
7.5, 1.7 Hz, ArHF) 7.18 (1H, td, JZ7.5, 1.7 Hz, ArHG),
6.98 (1H, s, ArHE), 6.94–6.90 (2H, m, ArHH and ArHI),
2.5.4. 2-Allylphenyl-2-(4-nitrophenyl)prop-2-en-1-yl
ether (54). Prepared by the general termolecular cascade
procedure employing 2-allyphenol as the nucleophile on a
2 mmol scale, using 2.5 mmol of aryl iodide and a reaction
time of 21 h. Purification by flash chromatography eluting
with 9:1 v/v petrol/ether afforded the product (460 mg,
78%), which crystallised from DCM/petrol as colourless
needles, mp 51–53 8C; Rf 0.16; (Found: C, 73.05; H, 6.00;
N, 4.50. C18H17NO3 requires C, 73.20; H, 5.80; N, 4.75%);
nmax/cmK1 (film) 1597, 1505 (NO2), 1492, 1343 (NO2),
1243; dH (250 MHz, CDCl3) 8.20 (2H, d, JZ8.9 Hz, ArH),
8.14 (2H, d, JZ8.9 Hz, ArH), 7.22 (1H, d, JZ8.0 Hz, ArH),
7.16 (1H, d, JZ8.0 Hz, ArH), 6.94 (2H, t, JZ8.0 Hz, ArH),
5.87 (1H, ddt, JZ17.2, 10.7, 6.6 Hz, CH]CHH), 5.76 (1H,
s, ]CHH), 5.68 (1H, s, ]CHH), 4.95 (1H, d, JZ10.7 Hz,
CH]CHcisH), 4.94 (1H, d, JZ17.2 Hz, CH]CHHtrans
)

H. A. Dondas et al. / Tetrahedron 61 (2005) 10652–10666
10665
4.92 (2H, s, OCH3), 3.29 (2H, d, JZ6.6 Hz, CH2); dC
(63 MHz, CDCl3) 156.2, 147.8, 145.3, 142.3, 137.1, 130.6,
129.4, 127.8, 127.4, 124.1, 121.7, 118.9, 115.9, 111.9, 69.9
(OCH2), 34.7 (CH2); m/z (%) (EI) 295 (18, MC), 131 (42),
115 (100), 77 (35).
2.6.3. 3-(4-Methoxyphenyl)-2,5-dihydro-1-benzoxepine
(58). Prepared by the modified general RCM procedure on
a 0.46 mmol scale and a reaction time of 22 h. Purification
by flash chromatography eluting with 1:1 v/v DCM/petrol
afforded the product (68 mg, 56%), which crystallised from
hexane as colourless needles, mp 72–74 8C; Rf 0.35; nmax
/
cmK1 (film) 1603, 1491, 1254, 1229, 1030; dH (300 MHz,
CDCl3) 7.24–7.02 (4H, m, ArH), 7.18 (2H, d, JZ8.7 Hz,
ArH), 6.83 (2H, d, JZ8.7 Hz, ArH), 6.05 (1H, br t, JZ
5.5 Hz, ]CH), 4.90 (2H, d, JZ2.1 Hz, OCH2), 3.62 (2H, d,
JZ5.5 Hz, CH2); dC (75 MHz, CDCl3) 159.5, 158.9, 138.3,
135.4, 133.1, 129.2, 128.4, 127.6, 124.4, 123.8, 121.5,
114.2, 73.2 (OCH2), 55.7 (OCH3), 31.9 (CH2); m/z (%) (EI)
252 (100, MC), 237 (82, MKCH3) 131 (45); HRMS found
252.1143, C17H16O2 requires 252.1145.
2.5.5. 1-Allyl-2{[2-(4-methoxyphenyl)prop-2-en-1-yl]
oxy}benzene (55). Prepared by the general termolecular
cascade procedure employing 2-allyphenol as the nucleo-
phile on a 3 mmol scale, using 3.5 mmol of aryl iodide and a
reaction time of 30 h. Purification by flash chromatograpy
eluting with 19:1 v/v petrol/ether afforded the product
(680 mg, 80%) as a colourless liquid; Rf 0.4; (Found: C,
81.10; H, 7.10; C19H20O2 requires C, 81.40; H, 7.19%);
nmax/cmK1 (film) 1635, 1607, 1513, 1491, 1243, 1031; dH
(250 MHz, CDCl3) 7.42 (2H, d, JZ8.7 Hz, ArH), 7.23–7.14
(2H, m, ArH), 6.95–6.83 (2H, m, ArH), 6.86 (2H, d, JZ
8.7 Hz, ArH), 5.98 (1H, ddt, JZ17.0, 10.3, 6.7 Hz,
CH]CHH), 5.51 (1H, s, ]CHH), 5.39 (1H, s, ]CHH),
5.04–4.97 (2H, m, CX]HcisHtrans), 4.87 (2H, s, OCH2),
3.36 (2H, d, JZ6.7 Hz, CH2); dC (63 MHz, CDCl3) 159.8,
156.6, 143.0, 137.4, 131.4, 130.3, 129.5, 127.7, 127.6,
121.2, 115.8, 114.2, 113.2, 112.1, 70.3 (OCH2), 55.7
(OCH3), 34.8 (CH2); m/z (ES) 281 (MCCH).
2.7. Single-crystal X-ray analysis for 44
Crystallographic data for 44 was measured on a Nonius
Kappa CCD area-detector diffractometer using f and
u-scans and graphite monochromated Mo Ka radiation
˚
(lZ0.71073 A). The structure was solved by direct methods
using SHELXS-8632 and were refined by full-matrix least-
squares (based on F2) using SHELXL-97.33 The weighting
scheme used was wZ[s2(Fo2)C(0.1235P)2C0.0127P]K1
where PZ(F2oC2F2c)/3. All non-hydrogen atoms were
refined with anisotropic displacement parameters whilst
hydrogen atoms were constrained to predicted positions
2.6. Modified ring closing metathesis procedure
2.6.1. 3-(2-Thienyl)-2,5-dihydro-1-benzoxepine (56).
Catalyst 1 (22 mg, 2.5 mm) was added to a magnetically
stirred solution of 53 (130 mg, 0.5 mmol), in anhydrous
toluene (120 ml). The mixture then stirred under an argon
atmosphere at 80 8C for 16 h. Concentration in vacuo
afforded a brown oil, which was purified by flash
chromatography eluting with 7:3 v/v petrol/DCM to afford
the product (68 mg, 59%), which crystallised from DCM/
hexane as colourless needles, mp 84–86 8C; Rf 0.35;
(Found: C, 73.35; H, 5.40. C14H12OS requires C, 73.65;
H, 5.30%); nmax/cmK1 (film) 1614, 1440, 1254, 1234; dH
(250 MHz, CDCl3) 7.26–7.02 (5H, m, ArH), 6.94 (1H, dd,
JZ5.1, 3.5 Hz, ArH), 6.84 (1H, d, JZ3.5 Hz, ArH), 6.34
(1H, br t, JZ5.7 Hz, ]CH), 4.93 (2H, d, JZ1.8 Hz,
OCH2), 3.62 (2H, d, JZ5.7 Hz, CH2); dC (63 MHz, CDCl3)
129.1, 128.5, 127.7, 124.7, 124.0, 123.9, 122.2, 121.5, 72.6
(OCH2), 31.6 (CH2); m/z (%) (EI) 228 (100, MC), 165 (27),
131 (47), 97 (44).
using a riding model. The residuals wR2 and R1, given
1
2
2 2
2 2
below, are defined as wR2Z(S[w(FoKFc) ]/S[wFo] ) ⁄ and
R1ZSkFojKjFck/SjFoj.
2
Crystal data for 44. C25H24N2O4, 0.33!0.20!0.10 mm,
MZ416.46, monoclinic, space group P21/n, aZ6.4754(1),
˚
bZ12.1259(2), cZ30.0988(6) A, bZ93.3630(10)8, UZ
2359.29(7) A , ZZ2, DcZ1.172 Mg mK3, mZ0.08 mmK1
,
3
˚
F(000)Z880, TZ150(2) K.
Data collection. 1.36 %q%268; 4602 independent
reflections were collected [RintZ0.082]; 3209 reflections
with IO2s(I).
Structure refinement. Number of parametersZ283, good-
ness of fit, sZ1.084; wR2Z0.1980, R1Z0.0611.
Full supplementary crystallographic data, which include
hydrogen co-ordinates, thermal parameters and complete
bond lengths and angles, have been deposited at the
Cambridge Crystallographic Data Centre (CCDC 275316)
and are available on request.
2.6.2. 3-(4-Nitrophenyl)-2,5-dihydro-1-benzoxepine (57).
Prepared by the modified general RCM procedure on a
0.46 mmol scale and a reaction time of 23 h. Purification by
flash chromatography eluting with 1:1 v/v DCM/petrol
afforded the product (76 mg, 62%), which crystallized from
petrol/DCM as pale yellow needles, mp 94–96 8C; Rf 0.3;
(Found: C, 71.65; H, 5.05. N, 5.10; C16H13NO3 requires C,
71.90; H, 4.90; N, 5.25%); nmax/cmK1 (film) 1652, 1516
(NO2), 1343 (NO2), 1229; dH (250 MHz, CDCl3) 8.17 (2H,
d, JZ8.8 Hz, ArH), 7.37 (2H, d, JZ8.8 Hz, ArH), 7.27–
7.05 (4H, m, ArH), 6.31 (1H, br t, JZ5.7 Hz, ]CH), 4.95
(2H, d, JZ1.7 Hz, OCH2), 3.70 (2H, d, JZ5.7 Hz, CH2), dC
(63 MHz, CDCl3) 158.8, 147.3, 147.0, 137.3, 134.2, 129.4,
128.9, 128.8, 127.0, 124.7, 124.2, 121.5, 72.3 (OCH2), 32.1
(CH2); m/z (%) (EI) 267 (100, MC), 252 (47), 220 (36), 131
(71), 91 (49).
Acknowledgements
We thank GlaxoSmithKline and the EPSRC for their support.
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