Palladium catalysed tandem cyclisation-anion capture processes. Part 8 [1]: In situ and preformed organostannanes. Carbamyl chlorides and other starter species

Article abstract of DOI:10.1016/j.jorganchem.2005.11.045

A sequential one-pot process is reported involving in situ, palladium catalysed, formation of a series of tributylstannyl-1,2-carbo and heterocyclic dialkylidene-5-membered rings from the corresponding 1,6-diynes and Bu ₃SnH. These substrates a

Full text of DOI:10.1016/j.jorganchem.2005.11.045

Journal of Organometallic Chemistry 691 (2006) 1476–1487
www.elsevier.com/locate/jorganchem
Palladium catalysed tandem cyclisation–anion capture processes.
Part 8 [1]: In situ and preformed organostannanes.
Carbamyl chlorides and other starter species
a
a
a,
a
Usman Anwar , Mark R. Fielding , Ronald Grigg *, Visuvanathar Sridharan ,
b
Christopher J. Urch
a
Molecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, Chemistry Department, Leeds University, Leeds, Yorkshire LS2 9JT, UK
b
Syngenta, Jealottꢀs Hill Research Station, Bracknell, Berkshire RG42 6EY, UK
Received 18 November 2005; accepted 21 November 2005
Available online 19 January 2006
Abstract
A sequential one-pot process is reported involving in situ, palladium catalysed, formation of a series of tributylstannyl-1,2-carbo and
heterocyclic dialkylidene-5-membered rings from the corresponding 1,6-diynes and Bu3SnH. These substrates and other organostann-
anes are then combined with carbamyl chlorides and iodobenzenes containing proximate alkene and alkynyl groups in palladium catal-
ysed cyclisation–anion capture cascades affording a diverse range of heterocycles in good yield.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Cascade; Carbamyl chlorides; Organostannanes; Tributyltinhydride
1. Introduction
oxidative addition reaction between the starter or ‘‘zipper’’
species and Pd(0) to generate an organopalladium(II) spe-
cies. In monocyclisations the organopalladium(II) species
cyclises onto the terminating species (T). Exchange of
halide or triflate with the anion capture agent Y followed
by reductive elimination generates a regiospecifically func-
tionalised monocyclic product and regenerates Pd(0). In
polycyclisation processes, the initial Pd(II) intermediate
engages one or more relay species (R) before passing to
the terminating phase and anion capture.
Aryl iodides [3,4], allyl, benzyl halides/acetates [5],
vinyl halides/triflates [6], and propargyl halides/carbonate
[7] have been successfully utilised as starter species in
the palladium catalysed cyclisation–anion capture
processes.
Cascade ring forming processes via multiple insertions
with concomitant introduction of functionally by replacing
the b-hydride elimination step of a Heck reaction with a
group or atom transfer offer wide ranging opportunities
for substantially leveraging molecular complexity and
diversity. This concept has been developed into powerful,
widely applicable, highly regio- and stereo-selective palla-
dium catalysed cyclisation–anion capture methodology
[2,3]. The use of word ꢁanionꢀ for the group or atom
transfer/capture embraces both ionic and covalent sources
of Y (Table 1) and is felt to be more appropriate than
cross-coupling. Table 1 summarises the basic process which
comprises four segments.
The starter species is usually an appropriate halide (Cl,
Br, I) or triflate in which case the cascade begins with an
2. Results and discussion
In this paper, we describe the full detail of a new starter
species, carbamyl chlorides, and their monocyclisation–
anion capture processes [1,2] together with palladium
*
Corresponding author. Tel.: +44 1133436501; fax: +44 1133436501/
1133436530.
E-mail address: r.grigg@leeds.ac.uk (R. Grigg).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.11.045

U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
1477
Table 1
Potential combinations for (poly) cyclisation–anion capture processes
Starter species
Relay species (R)
Terminating species (T)
Y
Allyl
Alkene
Alkene
Anionic: H,CN, N3, TsNR, SO2Ph, CH(CO2R)2, enolates
Alkyl
Alkyne
Alkyne
Vinyl
1,2-Diene
1,3-Diene
1,2-Diene
1,3-Diene
Neutral: amines, MeOH/CO, acrylates, allenes
Allenyl
Carbamyl
Oxycarbonyl
Organometallics: RM [M = Sn(IV), B(III), Zn(II)]
catalysed cyclisation–anion capture with in situ generated
tributylstannyl 1,2-dialkylidenecyclopentanes anion cap-
ture agents.
iline with benzaldehyde gave 6 and carbamyl chloride for-
mation with phosgene gave 7 in good yield.
N
Ph
2.1. Carbamyl chloride starter species
Cl
O
Initially, we prepared 5-membered and 6-membered cyc-
lisation substrates containing an alkyne terminating spe-
cies. Thus, 1a,1b were prepared via reductive amination
of 2-iodoaniline with benzaldehyde or aniline with 2-iodo-
benzaldehyde [8]. Treatment of 1a,b with trimethylsilylacet-
ylene under Sonogashiraꢀs conditions [9] afforded the
desired TMS protected ethynyl derivatives 2a,b in high
yield. Deprotection with TBAF [10] afforded 3a,b in 89–
91% yield which were converted to the desired carbamyl
chloride products 4a,b on treatment with phosgene [11] in
toluene at 0 ꢁC (Scheme 1).
The carbamyl chlorides 4a,b both contains benzene rings
directly attached to the unsaturated group. We also made a
carbamyl chloride in which the alkyne is attached to an
alkyl chain. Thus, 5 was readily synthesised from N-ben-
zyl-N-3-butynyl amine and phosgene by the method men-
tioned above.
5
Catalytic cyclisation–anion capture of the carbamyl
chlorides was studied using tributylstannanes and a cata-
lyst system consisting of Pd(OAc)2 (10 mol%) and tri-2-
furylphosphane TFP (20 mol%) in toluene at 50 ꢁC. Ini-
tially, we assessed cyclisation onto proximate alkynes to
form Z-methylene oxindoles. The E- and Z-3-alkylideneox-
indole moieties are found in many tyrosine kinase inhibi-
tors [12], cyclin-dependent protein kinase inhibitors [13]
and antirheumatic compounds [14]. When 4a (1 mmol)
was treated with tributylphenylethynyltin (1.1 mmol),
Pd(OAc)2 (10 mol%) and TFP (20 mol%) in toluene at
50 ꢁC for 5 min the cyclisation–anion capture product 8
was obtained in 81% yield (Table 2, entry 1). A similar
result was obtained when 4a was reacted with 2-thienyl-
tributylstannane (Table 2, entry 2). In this case oxindole
9 was formed in excellent yield and repetition of this reac-
tion employing 1 mol% catalyst gave the product in 91%
yield indicating that further reductions in catalyst loading
A substrate containing a double bond was easily acces-
sible from commercially available 2-isopropenylaniline
(Scheme 2). Thus, reductive amination of 2-isopropenylan-
O
(i)
or
TMS
O
X
I
TMS
H
H
N
I
NH2
Ph
N
Ph
m
(ii) NaBH4
( )
( ) ( )
Pd(PPh3)4, CuI
Et3N, DMF, rt
( ) ( )
n
n
m
n
n =0, X = I
n = 1, X = H
a. n = 0, m = 1
b. n = 1, m = 0
91%
92%
2
1
a. n = 0, m = 1
b. n = 1, m = 0
TBAF
THF / H2O
O
Cl
Cl
Cl
H
O
N
N
Ph
m
( ) ( )
NaHCO3, DCM-H2O
0oC to rt
( )
n
( )
m
n
Ph
a. n = 0, m = 1
b. n = 1, m = 0
3
91%
89%
a. n = 0, m = 1
b. n = 1, m = 0
4
93%
50%
Scheme 1.

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U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
O
(i) PhCHO
Cl
Cl
Cl
NaHCO3, DCM-H2O
0 0C to rt
(ii) NaBH4, MeOH
NH
Ph
NH2
N
O
Ph
76%
61%
7
6
Scheme 2.
Table 2
Cyclisation–anion capture processes of carbamyl chloridesa
Entry
1
Carbamyl chloride
R–M
Product
Yield (%)b
81
4a
Ph
SnBu3
Ph
O
N
Ph
8
2
3
4a
88
76
S
SnBu3
S
O
N
N
Ph
9
4a
SnBu3
O
O
N
Ph
Ph
11
10
4
:
3
4
4b
87
60
SnBu3
S
S
O
NPh
12
5
6
5
O
SnBu3
O
O
N
Ph
13
7
7
84
50
S
SnBu3
S
O
N
N
Ph
14
15
7
PhB(OH)2
Ph
O
Ph
a
Reactions were carried out in toluene at 50 ꢁC with carbamyl chloride (1 mmol) and organotin (1.1 mmol). Catalyst system: 10 mol% Pd(OAc)2 and
20 mol% TFP.
b
Isolated yield.

U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
1479
R
R
PdCl
PdCl
O
RPdCl
O
O
N
N
N
Ph
10
R = H or Bu3Sn
Ph
Ph
R
R
ClPd
ClPd
-RPdCl
O
O
O
N
N
N
11
Ph
Ph
Ph
Scheme 3.
are possible. Treatment of 4a with tributyl(vinyl)tin,
Pd(OAc)2 (10 mol%) and TFP (20 mol%) in toluene at
50 ꢁC for 5 min afforded a mixture of geometrical isomers
10 and 11 in a 4:3 ratio (Table 2, entry 3). Isomerisation
of 10 to 11 may occur via p-allyl palladium intermediates
(Scheme 3) [15].
anion capture reagent [18] resulted in 15 in 50% yield (Table
2, entry 7). This reaction was considerably slower (50 h,
90 ꢁC) than those involving organostannane anion capture
reagents. The carbamyl chloride cyclisation onto proximate
alkynes was, as expected, regio- and stereo-selective and
results in the formation of two new bonds and one ring in
these cases. In all cases the processes employing organo trib-
utylstannanes proceeded in excellent yield.
We also briefly studied the cyclisation–anion capture of
4b. Thus, 4b was reacted with 2-thienyl-tributylstannane
under essentially same conditions as above affording iso-
quinolinone 12 in 87% yield (Table 2, entry 4). This demon-
strates that 6-ring and 5-ring closure occur very rapidly at
50 ꢁC and that cyclisation is unlikely to be the rate deter-
mining step in these reactions. In the event of cyclisation
occurring at a similar rate to direct capture then significant
amounts of direct capture byproduct would be isolated. We
have not detected any such byproduct in the above pro-
cesses. Compound 5 was also successfully employed in
the cyclisation–anion capture processes (Table 2, entry 5).
Initially, on treatment of 5 with Pd(OAc)2, TFP and tribu-
tyl(2-furyl)tin in toluene at 50 ꢁC, a low yield of product 13
was obtained (35%). However on changing the ligand, to
tris-t-butylphosphane and the solvent to THF we found
that the reaction proceeded in 60% yield over 48 h at room
temperature. Such ligands promote oxidative addition to
the acyl chlorine bond by increasing the nucleophilic nature
of Pd(0) and also favour the reductive elimination step [16].
Others have recently reported a closely related process
affording a-alkylidene-b-lactams [17].
2.2. In situ generated anion capture agents
The basic strategy makes use of the known regio-selec-
tive palladium catalysed hydrostannylation of terminal
alkynes bearing a b- or c-heteroatom (Scheme 4) [19].
This strategy has proved extremely powerful in generating
complex organotin(IV) anion capture species in situ via
regio-selective hydrostannylation of appropriate alkynes
as part of a temperature controlled cyclisation–anion cap-
ture cascade [20–22]. Following the success of the palla-
dium catalysed cyclisation–anion capture with in situ
generated vinylstannanes, we decided to investigate anion
capture with in situ generated tributylstannyl 1,2-
dialkylidenecyclopentanes.
Our synthetic plan focused on generating 17 in situ
from 16 followed by the addition of an appropriate zipper
and subsequent heating to trigger the cyclisation–anion
capture cascade process to furnish 18 (Scheme 5).
Recently, Lautens et al. [23] reported a new catalytic
approach to the synthesis 16 using palladium. They found
upon treatment of a wide range of terminal 1,6-diynes 16
with Bu3SnH in the presence of Pd(OH)2/C (Pearl-
mans catalyst) triggered a hydrostannylation/cyclisation
We also explored the cyclisation–anion capture processes
of 7. Thus, cyclisation onto the isopropenyl group of 7 to
form 14 (Table 2, entry 6) is much slower (4 h), but proceeds
in excellent yield (84%). The use of phenyl boronic acid as
Pd(0)
Bu3Sn
XR
+
+
Bu3SnH
Bu3Sn
0oC to rt
XR
X = O, NR1
XR
major
minor
Scheme 4.

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U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
I
X
Z
Bu3SnH
Y
SnBu3
X
X
Z
Pd(0) / PR3Δ
Pd(0)
Y
18
X = O, NR, CR
17
16
2
Scheme 5.
sequence generating 17 in excellent yield. They further
showed that addition of triphenylphosphane retarded
the reaction and that slow addition of Bu3SnH was neces-
sary to obtained a good yield of 17. Transition metals are
known to catalyse the decomposition of Bu3SnH to
Bu6Sn2 and H2 [24] and this side reaction can be pre-
vented by slow addition of Bu3SnH via a syringe pump.
A possible catalytic cycle for the synthesis of 17 is illus-
trated in Scheme 6 [23].
1,6-Diynes 19–22 were prepared in high yield using a
standard alkylation procedure [25]. We selected 23–26
as cyclisation precursors (‘‘zippers’’) [18] generating 5-
membered and 6-membered products. Initially 1,6-diyne
19 was reacted with Bu3SnH, added via a syringe pump
over 90 min, in the presence of tris(dibenzylideneace-
tone)dipalladium in THF at room temperature. After
2.5 h, the reaction mixture was examined using 1H
NMR spectroscopy and the exclusive formation of the
tributylstannyl dialkylidenecyclopentane was confirmed.
The presence of 3 singlets at d 4.9, 5.2 and 5.8 corre-
sponding to the olefinic protons clearly indicated the for-
mation of 27. THF was then removed after the initial
hydrostannylation/cyclisation and Aryl iodide 23 and
tris-2-furyl phosphane were then added and the mixture
heated to 95 ꢁC in toluene for 16 h to furnish 28 in
67% yield (Scheme 7). Having established the conditions
for the cyclisation–anion capture processes, a series of
cascade reactions were performed involving aryl iodides
24, 25 and carbocyclic 1,6-diyne 19. Aryl iodides cyclised
efficiently with the capture of tributylstannyl dialkylid-
enecyclopentane derivative generated in situ from 19 to
give the corresponding products 29, 30 in 64–70% yield
(Table 3, entries 2 and 3). The hydrostannylation/cyclisa-
tion of 20 followed by reaction with aryl iodides 23–26
H
Pd
SnBu3
H
S
Bu3Sn
S
SnBu3
H
Bu3SnH
Pd
Pd
Pd(0)
or
X
X
X
X
PdSnBu3S2
PdHS2
SnBu3
X
X
SnBu3
X
Scheme 6.
CO2Me
CO2Me
SnBu3
Bu3SnH
28 / TFP
19
toluene, 95oC, 16h
Pd2dba3, toluene rt 5h
O
MeO2C CO2Me
67%
28
27
Scheme 7.

U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
1481
Table 3
Cyclisation–anion capture with in situ generated carbocyclic
organostannanes
Entry
Aryl
iodide
1,6-Diyne
Product
Yield
(%)a
O
O
N
O
MeO2C CO2Me
1
23
19
67
CO2Me
CO2Me
Ph
22
19
20
21
I
I
I
I
O
N
28
O
N
O
N
O
SO2Ph
2
24
19
64
CO2Me
CO2Me
Me
23
24
25
26
29
30
We next turned our attention to 1,6-diynes bearing a
nitrogen or oxygen atom in the 4-position. Diynes 21 and
22 underwent clean hydrostannylation/cyclisation with
the exclusive formation of the corresponding cyclised trib-
SO2Ph
3
4
25
19
70
70
CO2Me
CO2Me
1
utylstannyl derivatives as determined by H NMR spec-
O
troscopy. Moderate to good yields of products were
obtained when the resulting tributylstannyldialkylidene tet-
rahydrofuran (Table 4, entries 1 and 3) and pyrrolidine
(Table 4, entries 2 and 4) were incorporated into the cas-
cade process.
N
Me
23
20
O
O
O
31
Table 4
Cyclisation–anion capture with in situ generated herterocyclic
organostannanes
5
24
20
62
O
Entry
Aryl
iodide
1,6-Diyne
Product
Yield
(%)a
O
1
23
21
62
O
N
32
SO2Ph
6
25
20
72
O
O
O
O
35
2
3
23
26
26
22
21
22
62
62
70
Ph
N
O
N
O
N
33
Me
36
7
26
20
62
O
O
O
O
O
37
34
a
Isolated yield.
4
Ph
gave the corresponding products 31–34 in 62–72% yield
(Table 3, entries 4–7). Overall this protocol results in
the formation of two new rings (5,5 and 6,5), two new
C–C bonds and one stereocentre.
38
a
Isolated yield.

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U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
3. Summary
48.4 mmol) added and the mixture stirred at r.t. for
16 h [10]. The solution was then diluted with ether
(150 ml), washed with sat. aq. ammonium chloride
(160 ml), water (200 ml), brine (160 ml), dried (MgSO4),
filtered and the filtrate evaporated to dryness. The residue
was chromatographed eluting with EtOAc–pentane mix-
tures to afford the product (overall yields reported), gen-
erally as a clear, pale yellow oil.
We have developed a powerful palladium catalysed cyc-
lisation–anion capture processes affording 3,3-disubstituted
and Z-3-methyleneoxindoles, and heterocyclic1,3-dienes.
The reactions occur in good yield and afford products with
functionality offering considerable further synthetic oppor-
tunities such as Michael additions and cycloadditions.
4. Experimental
4.1.1. N-benzyl-2-ethynylaniline (3a)
The product (3.07 g, 82%) was obtained as a colourless
oil. (Found: C, 86.65; H, 6.50; N, 6.75. C15H13N requires:
C, 86.95; H, 6.30; N, 6.75%); mmax/cmÀ1 1601, 1575, 1508,
1452, 1324 and 1282; dH (250 MHz), 7.59 (dd, J = 7.6,
1.7 Hz, 1H, ArH), 7.36–7.16 (m, 7H, ArH), 6.79 (dd,
J = 7.7, 1.2Hz, 1H, ArH), 5.40 and 4.39 (AB, 2· d,
J = 14.3 Hz, 2· 1H, NCH2Ph) and 3.32 (s, 1H, C–H);
m/z (%) 207(M+, 80), 130(53) 91(100) and 65(24).
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 perflu-
orotributylamine or polyethylenimine as an internal stan-
dard. 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 the compound in DCM onto a germanium plate.
Nuclear magnetic resonance spectra were recorded on Bru-
ker DPX250, DPX300 and DPX500 instruments operating
at 250, 300 and 500 MHz, respectively. The following
abbreviations are used: s = singlet, d = doublet, t = triplet,
q = quartet, qi = quintet, m = multiplet, dd = doublet of
doublets, ddd = double doublet of doublets, ddt = double
doublet of triplets, b = broad. Solvents were dried accord-
ing to established methods, unless purchased dry from
Aldrich in sure-seal bottles. The term ether refers to diethyl
ether and the term petrol refers to the 40–60 ꢁC 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 version 4.5.
Experimental for compounds 19–22 and 23–26 have
been reported earlier [25,18].
4.1.2. N-(2-ethynylbenzyl)aniline (3b)
The product (3.07 g, 82%) was obtained as a pale yellow
gum. (Found: C, 86.70; H, 6.35; N, 6.85. C15H13N requires:
C, 86.95; H, 6.30; N, 6.75%); mmax/cmÀ1 1696, 1684, 1653,
1498, 1369, 1353 and 1264; dH (250 MHz), 7.52 (dd,
J = 7.5, 1.3 Hz, 1H, ArH), 7.41 (dd, J = 7.6 Hz, 0.6 Hz,
1H, ArH), 7.31 (td, J = 7.4, 1.4 Hz, 1H, ArH), 7.25–7.22
(m, 1H, ArH), 7.17 (t, J = 7.5 Hz, 2H, ArH), 6.71 (t,
J = 7.3 Hz, 1H, ArH), 6.63 (dd, J = 7.7, 0.8 Hz, 2H,
ArH), 4.51 (d, J = 5.7 Hz, 2H, NCH2Ar) and 4.22 (bs,
1H, NH); m/z (%) 207(M+, 100).
4.2. General procedure for carbamyl chloride formation [11]
The amine (7.21 mmol) was dissolved in DCM (92 ml)
and sat. aq. sodium bicarbonate (92 ml) added. The result-
ing biphasic solution was then cooled to 0 ꢁC and phosgene
(1.93 M in toluene, 9.0 ml, 17.37 mmol) added dropwise
over 5 min to the rapidly stirred solution. The mixture
was left stirring for 10 min, the organic phase separated
and the aqueous layer washed with DCM (2 · 50 ml).
The combined organic phase was dried (MgSO4), filtered
and the filtrate evaporated to dryness. The residue was
chromatographed eluting with ether–pentane mixtures or
used without further purification.
4.1. General procedure for Sonagashira coupling-
deprotection [9]
The iodoaniline (20.0 mmol) and trimethylsilylacetylene
(4.58 ml, 32.4 mmol) were added to DMF (120 ml). To
this solution was added triethylamine (6 ml, 43.1 mmol),
copper(I) iodide (760 mg, 4 mmol) and tetraakis(triphe-
nylphosphane)palladium(0) (480 mg, 0.45 mmol) and the
solution stirred at r.t. for 16 h. Water (100 ml) was added
to the mixture and the aqueous phase extracted with ether
(2 · 100 ml). The combined organic phase was washed
with water (4 · 60 ml), dried (MgSO4) and evaporated
to dryness. The residue was then passed through a column
of silica eluting with 1:1 v/v diethyl ether–pentane or pure
ether. The product fractions were combined and evapo-
rated to dryness and the residual pale brown oil was dis-
solved in THF (170 ml), the solution cooled to 0 ꢁC,
tetrabutylammonium fluoride (48.38 ml, 1.0 M in THF,
4.2.1. 2-Ethynylbenzyl(phenyl)carbamyl chloride (4b)
The product (0.95 g, 49%) was obtained as a pale pink
oil. (Found: C, 71.10; H, 4.55; N, 5.2. C16H12NClO
requires: C, 71.25; H, 4.45; N, 5.2%); mmax/cmÀ1 1732,
1494, 1376, 1228, 1198 and 965; dH (250 MHz), 7.45–7.22
(m, 7H, ArH), 7.07–7.06 (m, 2H, ArH), 5.13 (s, 2H,
NCH2Ph) and 3.11 (s, 1H, CH); m/z (%) 270 (M+
35Cl + H, 66), 234(48), 207(36) and 115(100).
4.2.2. Benzyl(2-ethynylphenyl)carbamyl chloride (4a)
The product (3.51 g, 93%) was isolated as colourless
prisms from diethyl ether–hexane, m.p. 34–36 ꢁC. (Found:

U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
1483
C, 71.15; H, 4.60; N, 5.15. C16ClH12NO requires: C, 71.25;
4.3.2. (3Z)-1-benzyl-3-(2-thienylmethylene)-1,3-dihydro-
2H-indol-2-one (9)
H, 4.45; N, 5.20%); mmax/cmÀ1 1734, 1487, 1376, 1201, 1199
and 849; dH (250 MHz), 7.59 (dd, J = 7.6, 1.7 Hz, 1H,
ArH), 7.36–7.16 (m, 7H, ArH), 6.79 (dd, J = 7.7, 1.2 Hz,
1H, ArH), 5.40 and 4.39 (AB, 2· d, J = 14.3 Hz, 2· 1H,
NCH2Ph) and 3.32 (s, 1H, CH); m/z (%) 269 (M+ 35Cl,
4), 233(24), 204(13), 143(65) and 91(100).
The product (279 mg, 88%) was obtained as pale orange
rods from EtOAc–hexane, m.p. 128–129 ꢁC. (Found: C,
74.80; H, 4.80; N, 4.25. C20H15NOS Æ 0.25H2O requires:
C, 74.65; H, 4.80; N, 4.35%); mmax/cmÀ1 1686, 1615, 1469,
1343, 1170 and 1104; dH (250 MHz), 7.85 (d, J = 3.4 Hz,
1H, thienyl H), 7.79 (s, 1H, @CH), 7.66 (d, J = 5.1 Hz,
1H, thienyl H), 7.54 (d, J = 7.4 Hz, 1H, ArH), 7.36–7.14
(m, 7H, ArH), 7.04 (t, J = 7.5 Hz, 1H, ArH), 6.74 (d,
J = 7.7 Hz, 1H, ArH) and 5.04 (s, 2H, NCH2Ph); m/z
(%) 317(M+, 100).
4.2.3. Benzyl(3-butynyl)carbamyl chloride (5)
The product (1.06 g, 96%) was obtained as a colourless
oil. (Found: C, 64.85; H, 5.50; N, 6.25. C12H12NClO
requires: C, 65.00; H, 5.40; N, 6.30%); mmax/cmÀ1 1728,
1456, 1400, 1185, 1156 and 1032; dH (250 MHz, 1:1 mixture
of rotamers), 7.41–7.19 (m, 5H, ArH), 4.85 and 4.70 (s, 2H,
NCH2Ph), 3.58 and 3.50 (t, J = 7.1 Hz, 2H, NCH2), 2.51
(td, J = 7.1, 2.7 Hz, 2H, NCH2CH2) and 2.07 and 2.04 (t,
J = 2.7 Hz, 1H, CH); m/z (%) 222 (M + H+ 35Cl, 71),
186(7), 129(8) and 91(100).
4.3.3. (3Z)-1-benzyl-3-(2-propenylidene)-1,3-dihydro-2H-
indol-2-one (10)
The product (112 mg, 43% from carbamyl chloride;
39 mg, 15% from aryl iodide) was obtained as an orange
gum. (Found (HRMS): 545.2210 (2M + Na+). C18H15NO
requires: 545.2205); mmax/cmÀ1 1701, 1607, 1466, 1354,
1179 and 934; dH (250 MHz), 7.63 (d, J = 7.5 Hz, 1H,
ArH), 7.40 (d, J = 12.1 Hz, 1H, @CHc), 7.35–7.24 (m,
6H, ArH/CH@CH2), 7.16 (td, J = 7.7, 1.3 Hz, 1H, ArH),
7.01 (td, J = 7.7, 1.0 Hz, 1H, ArHa), 6.71 (d, J = 7.8 Hz,
1H, ArHb), 5.92 (dd, J = 15.5, 1.0 Hz, 1H, @CH2), 5.81
(dd, J = 10.7, 1.6 Hz, 1H, @CH2) and 4.97 (s, 2H,
NCH2Ph); m/z (%) 262(M + H+, 29), 91(100), 81(17),
69(30) and 55(44).
4.2.4. Benzyl(2-isopropenyl)carbamyl chloride (7)
The product (1.85 g, 76%) was obtained as a colourless
oil. (Found: C, 71.30; H, 5.80; N, 4.85. C17ClH16NO
requires: C, 71.45; H, 5.60; N, 4.90%); mmax/cmÀ1 1734,
1489, 1375, 1222, 1195 and 908; dH (250 MHz), 7.33–7.05
(m, 7H, ArH), 7.03–6.99 (dd, J = 5.1, 3.6 Hz, 1H, ArH),
6.71 (dd, J = 7.9, 1.6 Hz, 1H, ArH), 5.40 and 4.09 (AB,
2· d, J = 14.3 Hz, 2· 1H, NCH2Ph), 5.32 (qu.,
J = 1.5 Hz, 1H, @CH2), 5.14 (q, J = 0.8 Hz, 1H, @CH2)
and 2.16 (q, J = 0.9 Hz, 3H, CH3); m/z (%) 250(M À Cl,
29) and 229(9).
Hc
nOe data:
irradiated H
Hb
enhancement / %
Ha
4.3. General procedure for cyclisation–anion capture
a
c
O
b
7.9
7.7
N
The carbamyl chloride (1.0 mmol), palladium(II) ace-
tate (22.4 mg, 10 mol%), trisubstituted phosphane
(20 mol%) and tributylstannane (1.1 mmol) were added
to toluene or THF (15–20 ml) and the mixture heated to
at 23–90 ꢁC for 0.1–30 h. The solution was then evapo-
rated to dryness, the residue dissolved in diethyl ether
(50 ml) and 10% aq. potassium fluoride (50 ml) solution
added. The biphasic mixture was rapidly stirred at r.t.
for 16 h, the diethyl ether layer separated and evaporated
to dryness. The residue was chromatographed eluting with
EtOAc–pentane or diethyl ether–pentane mixtures to
afford the product.
Ph
4.3.4. (3E)-1-benzyl-3-(2-propenylidene)-1,3-dihydro-2H-
indol-2-one (11)
The product (85 mg, 33% from carbamyl chloride;
143 mg, 55% from aryl iodide) was obtained as an orange
gum. (Found (HRMS): 284.1057(M + Na+). C18H15NO
requires: 284.1051); mmax/cmÀ1 1695, 1610, 1469, 1347,
1169 and 1008; dH (250 MHz), 8.15 (dt, J = 17.0,
11.4 Hz, 1H, CHc@CH2), 7.43 (d, J = 7.1 Hz, 1H, ArH),
7.32–7.11 (m, 6H, ArH), 7.17 (d, J = 11.4 Hz, 1H, @CHd),
6.98 (td, J = 7.6, 1.0 Hz, 1H, ArHa), 6.68 (d, J = 7.8 Hz,
1H, ArHb), 5.80–5.68 (m, 2H, @CH2) and 4.94 (s, 2H,
NCH2Ph); m/z (%) 262(M + H+, 29), 249(8), 232(5),
183(5) and 91(100).
4.3.1. (3Z)-1-benzyl-3-(3-phenyl-2-propynylidene)-1,3-
dihydro-2H-indol-2-one (8)
The product (271 mg, 81%) was obtained as pale orange
prisms from diethyl ether–pentane, m.p. 127–128 ꢁC.
(Found: C, 85.90; H, 5.20; N, 3.90. C24H17NO requires:
C, 85.95; H, 5.05; N, 4.20%); mmax/cmÀ1 1705, 1611, 1469,
1357, 1172 and 1103; dH (250 MHz), 7.67 (m, J = 2.3 Hz,
2H, ArH), 7.48 (d, J = 7.4 Hz, 1H, ArH), 7.39–7.17 (m,
9H, ArH), 6.99 (m, 1H, ArH), 6.87 (s, 1H, @CH), 6.69
(d, J = 7.8 Hz, 1H, ArH) and 4.99 (s, 2H, NCH2Ph); m/z
(%) 335(M+, 100), 258(39) and 91(89).
nOe data:
irradiated H
H
He
enhancement / %
Hc
Hb
a
9.7
-
c
18.9
-
e
-
6.1
Hd
b
d
Ha
O
N
Ph

1484
U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
4.3.5. (4Z)-2-phenyl-4-(2-thienylmethylene)-1,4-dihydro-3
(2H)-isoquinolinone (12)
(1.15 mmol) in dry THF (11.5 ml) at room temperature
under an atmosphere of nitrogen, followed by dropwise
addition of Bu3SnH (0.396 ml, 1.50 mmol) via a syringe
pump over 90 min. The resulting solution was stirred for
a further 1 h before being concentrated in vacuo to give
the dienylstannane as a dark brown oil which was dissolved
in dry toluene (15 ml) and aryl iodide (1.15 mmol) and
tris(2-furyl)phosphane (26.7 mg, 10 mol%) added. The
resulting mixture was stirred and heated at 80–100 ꢁC (oil
bath temperature) for 16–17 h then cooled to room temper-
ature and concentrated in vacuo. The residue was dissolved
in ether (10 ml) and stirred at room temperature for 2 h
with 20% aqueous potassium fluoride (5 ml). The organic
layer was separated, dried (MgSO4), filtered and the
filtrate concentrated. The residue purified by flash
chromatography.
The product (250 mg, 87%) was obtained as pale yellow
prisms from diethyl ether–pentane, m.p. 180–182 ꢁC.
(Found: C, 75.60; H, 4.95; N, 4.30. C20H15NOS requires:
C, 75.70; H, 4.75; N, 4.40%); mmax/cmÀ1 1653, 1595, 1408,
1286, 1216 and 1203; dH (250 MHz), 7.64 (d, J = 7.4 Hz,
1H, ArH), 7.49–7.24 (m, 10H, ArH/@CH), 7.19 (dd,
J = 7.3, 0.5 Hz, 1H, ArH), 7.06 (dd, J = 5.1, 3.7 Hz, 1H,
furyl H) and 4.86 (s, 2H, NCH2Ar); m/z (%)
318(M + H+, 100), 288(26) and 207(17).
4.3.6. (3Z)-1-benzyl-3-(2-furylmethylene)-2-pyrrolidinone
(13)
The product (76 mg, 60%) was obtained as colourless
prisms from diethyl ether–hexane, m.p. 62–63 ꢁC. (Found:
C, 75.85; H, 5.95; N, 5.50. C16H15NO2 requires: C, 75.90;
H, 5.95; N, 5.55%); mmax/cmÀ1 1678, 1442, 1421, 1272,
1084 and 1008; dH (250 MHz), 7.87 (d, J = 3.5 Hz, 1H,
furyl H), 7.40 (d, J = 1.1 Hz, 1H, furyl H), 7.38–7.26 (m,
5H, ArH), 6.61 (t, J = 2.3 Hz, 1H, @CH), 6.50–6.47 (m,
1H, ArH), 4.55 (s, 2H, NCH2Ph), 3.33 (t, J = 6.9 Hz, 2H,
NCH2) and 2.85 (td, J = 7.0, 2.3 Hz, 2H, NCH2CH2);
m/z (%) 254(M + H+, 100), 91(43) and 69(21).
4.4.1. Dimethyl(3Z)-3-[2-(3-methyl-2,3-dihydro-1-benzo-
furan-3-yl)ethylidene]-4-methylene-1,1-cyclopentanedi-
carboxylate (28)
Prepared from diyne (19) (239 mg, 1.15 mmol) and aryl
iodide (23) (315 mg, 1.15 mmol) by the general procedure
over 16 h at 90 ꢁC. The crude product was subjected to
flash chromatography eluting with 1:4 v/v ether/petroleum
ether to afford the product (276 mg, 67%) which crystal-
lised from ether–petroleum ether as colourless needles,
m.p. 115–118 ꢁC. (Found C, 70.80; H, 6.95. C21H24O5
requires: C, 70.75; H, 6.80%); d (250 MHz), 1.37 (s, 3H,
Me), 2.50–2.71 (m, 2H, @CHCH2), 2.96 and 3.02 (2· s,
2· 2H, C(CH22)), 3.71 and 3.72 (2· s, 2· 3H, 2· OMe),
4.15 and 4.34 (2· d, 2· 1H, J = 9.0 Hz, OCH2), 5.13 and
5.17 (2· s, 2· 1H, @CH2), 5.41 (t, 1H, J = 7.0 Hz,
@CHCH2), 6.77 (d, 1H, J = 8.0 Hz, ArH), 6.85 (t, 1H,
J = 6.0 Hz, ArH) and 7.06–7.15 (m, 2H, ArH); m/z (%)
356(M+, 22), 281(25), 224(77), 178(30), 133(100) and
105(59).
4.3.7. 1-Benzyl-3-methyl-3-(2-thienylmethyl)-1,3-dihydro-
2H-indol-2-one (14)
The product (279 mg, 84%) was obtained as colourless
prisms from diethyl ether, m.p. 118–119 ꢁC. (Found: C,
75.45; H, 5.70; N, 4.05. C21H19NOS requires: C, 75.65;
H, 5.70; N, 4.20%); mmax/cmÀ1 1709, 1612, 1489, 1467,
1455 and 1359; dH (250 MHz), 7.29 (dd, J = 6.9, 1.2Hz,
1H, ArH), 7.18–7.14 (m, 5H, ArH), 7.10 (td, J = 7.0,
1.5 Hz, 1H, ArH), 6.96 (dd, J = 5.1, 1.1 Hz, 1H, thienyl
H), 6.79–6.76 (m, 1H, ArH), 6.73–6.70 (m, 1H, ArH),
6.63 (d, J = 3.3 Hz, 1H, thienyl H), 6.49 (dd, J = 6.9,
1.4 Hz, 1H, ArH), 5.06 and 4.50 (AB, 2· d, J = 15.9 Hz,
2· 1H, NCH2Ph), 3.53 and 3.30 (AB, 2· d, J = 14.2 Hz,
2· 1H, CH2) and 1.55 (s, 3H, CH3); m/z (%)
334(M + H+, 100), 252(25) and 236(77).
4.4.2. Dimethyl(4Z)-3-methylene-4-{2-[3-methyl-1-
(phenylsulfonyl)-2,3-dihydro-1H-indol-3-yl]ethylidene}-1,1-
cyclopentanedicarboxylate (29)
Prepared from diyne (19) (239 mg, 1.15 mmol) and aryl
iodide (24) (474 mg, 1.15 mmol) by the general procedure
over 17 h at 100 ꢁC. Work up followed by flash chromatog-
raphy eluting with 3:2 v/v ether/petroleum ether afforded
the product (366 mg, 64%) which crystallised from ether/
petroleum ether as colourless prisms, m.p. 112–114 ꢁC.
(Found C, 65.20; H, 5.95; N, 2.65. C27H29NO6S requires:
C, 65.45; H, 5.90; N, 2.85%); d (250 MHz), 1.12 (s, 3H,
Me), 2.31 and 2.42 (2· dd, 2· 1H, J = 7.0, 16.0 Hz,
@CHCH2), 2.86 and 3.01 (2· s, 2· 2H, C(CH2)2), 3.57
and 3.78 (2· d, 2· 1H, J = 10.0 Hz, NCH2), 3.72 and
3.73 (2· s, 2· 3H, 2· OCH3), 5.02 and 5.08 (2· s, 2· 1H,
@CH2), 5.18 (t, 1H, J = 7 Hz, @CHCH2), 6.95–7.05 (m,
2H, ArH), 7.21 (m, 1H, ArH), 7.41–7.56 (m, 3H, ArH),
7.66 (d, 1H, J = 8.0 Hz) and 7.81 (m, 2H, ArH). m/z (%)
495(M+, 14), 420(18), 354(6), 272(100), 163(9), 130(58)
and 77(74).
4.3.8. 1,2-Dibenzyl-3-methyl-1,3-dihydro-2H-indol-2-one
(15)
The product (79 mg, 47%) was obtained as a pale yellow
oil. dH (250 MHz), 7.28–7.03 (m, 9H, ArH), 6.89 (dd,
J = 6.9, 1.5 Hz, 2H, ArH), 6.63 (dd, J = 7.8, 2.3 Hz, 2H,
ArH), 6.42–6.38 (m, 1H, ArH), 5.02 and 4.45 (AB, 2· d,
J = 16.0 Hz, 2· 1H, NCH2Ph), 3.25 and 3.13 (AB, 2· d,
J = 13.0 Hz, 2· 1H, PhCH2) and 1.55 (s, 3H, CH3); m/z
(%) 328(M + H+, 100), 252(20), 236(33) and 91(70).
4.4. General procedure for cyclisation–anion capture with
in situ generated tributylstannyl-1,2-dialkylidenecyclo-
pentanes
Tris(dibenzylideneacetone)dipalladium (26.3 mg, 2.5
mol%) was added to a stirred solution of the 1,6-diyne

U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
1485
4.4.3. Dimethyl(3Z)-3-[2-(1,3-dimethyl-2-oxo-2,3-dihydro-
1H-indol-3-yl)ethylidene]-4-methylene-1,1-cyclopentanedi-
carboxylate (30)
15), 272(100), 132(18) and 83(7); mmax(film) 2956, 1727,
1695, 1168, 1093 and 957 cmÀ1
.
Prepared from diyne (19) (248 mg, 1.15 mmol) and aryl
iodide (25) (346 mg, 1.15 mmol) by the general procedure
over 17 h at 100 ꢁC. Work up followed by flash chromatog-
raphy eluting with 3:2 v/v ether/petroleum ether afforded
the product (305 mg, 70%) which crystallised from ether/
petroleum ether as colourless prisms, m.p. 107–109 ꢁC.
(Found: C, 68.65; H, 6.80; N, 3.35. C22H25NO5 requires:
C, 68.90; H, 6.55; N, 3.65%); d (250 MHz), 1.39 (s, 3H,
Me), 2.66–2.88 (m, 6H, @CHCH2, C(CH2)2), 3.23 (s, 3H,
NMe), 3.65 and 3.70 (2· s, 2· 3H, 2· OMe), 5.11–5.16
(m, 3H, @CH2, @CHCH2), 6.86 (d, 1H, J = 8.0 Hz,
ArH), 7.01 (t, 1H, J = 7.0 Hz, ArH) and 7.16–7.21 (m,
2H, ArH); m/z (%) 383(M+, 32), 352(28), 276(18),
223(49), 161(100) and 103(18).
4.4.6. (2Z)-2[2-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-
3-yl)ethylidene]-8,8-dimethyl-3-methylenespiro[4.5]decane-
6,10-dione (33)
Prepared from diyne (20) (248 mg, 1.15 mmol) and aryl
iodide (25) (346 mg, 1.15 mmol) by the general procedure
over 17 h at 100 ꢁC. Work up followed by flash chromatog-
raphy eluting with 7:3 v/v ether/petroleum ether to afford
the product (364 mg, 72%) which crystallised from ether/
petroleum ether as colourless prisms, m.p. 111–113 ꢁC
(Found: C, 76.65; H, 7.65; N, 3.30. C25H29NO3 requires:
C, 76.70; H, 7.45; N, 3.60%); d (250 MHz) 0.96 and 0.97
(2· s, 2· 3H, Me2C), 1.38 (s, 3H, Me), 2.54 and 2.56 (2·
s, 2· 3H, Me2C(CH2)2), 2.65–2.89 (m, 6H, @CHCH2,
C(CH2)2), 3.22 (s, 3H, NMe), 5.09–5.19 (m, 3H, @CH2,
@CHCH2), 6.85 (d, 1H, J = 8.0 Hz, ArH), 7.07 (t, 1H,
J = 8.0 Hz, ArH) and 7.19 and 7.32 (m, 2H, ArH); m/z
(%) 391(M+, 80), 373(9), 307(17), 250(22), 213(27),
161(100), 129(19) and 55(8).
4.4.4. (2Z)-8,8-dimethyl-2-[2-(3-methyl-2,3-dihydro-1-
benzofuran-3-yl)ethylidene]-3-methylenespiro[4.5]decane-
6,10 dione (31)
Prepared from diyne (20) (248 mg, 1.15 mmol) and
aryl iodide (23) (315 mg, 1.15 mmol) by the general pro-
cedure over 16 h at 90 ꢁC. Work up followed by flash
chromatography eluting with 3:7 v/v ether/petroleum
ether afforded the product (296 mg, 70%) which crystal-
lised from ether/petroleum ether as colourless needles,
m.p. 125–127 ꢁC. (Found: C, 79.05; H, 7.70. C24H28O3
requires: C, 79.10; H, 7.75%); d (250 MHz) 0.96 and
1.01 (2· s, 2· 3H, Me2C), 1.37 (s, 3H, Me), 2.52–2.65
(m, 6H, @CHCH2, Me2C(CH2)2), 2.82 and 2.91 (2· s,
2· 2H, C(CH2)2), 4.15 and 4.35 (2· d, 2· 1H,
J = 7 Hz, OCH2), 5.11 and 5.15 (2· s, 2 · 1H, @CH2),
5.35 (t, 1H, J = 7.0 Hz, @CHCH2), 6.79 (d, 1H,
J = 8.0 Hz, ArH), 6.87 (t, 1H, J = 7.0 Hz, ArH) and
7.06–7.16 (m, 2H, ArH); m/z (%) 364(M+, 14), 280(6),
232(6), 133(100), 105(34) and 77(7).
4.4.7. (2Z)-8,8-dimethyl-2-[2-(4-methyl-3,4-dihydro-1H-
isochromen-4yl)ethylidene]-3-methylenespiro[4.5]decane-
6,10-dione (34)
Prepared from diyne (20) (248 mg, 1.15 mmol) and aryl
iodide (26) (331 mg, 1.15 mmol) by the general procedure
over 17 h at 90 ꢁC. Work up followed by flash chromatog-
raphy eluting with 2:3 v/v ether/petroleum ether afforded
the product (281 mg, 62%) which crystallised from ether/
petroleum ether as colourless needles, m.p. 117–119 ꢁC
(Found C, 79.10; H, 8.10. C25H30O3 requires: C, 79.35;
H, 8.00%); d (250 MHz) 0.96 and 1.00 (2· s, 2· 3H,
Me2C), 1.27 (s, 3H, Me), 2.52–2.73 (m, 6H, @CHCH2,
Me2C(CH2)2), 2.81 and 2.90 (2· s, 2· 2H, C(CH2)2), 3.35
and 3.75 (2· d, 2· 1H, J = 11 Hz, OCH2), 4.78 (s, 2H,
OCH2Ar), 5.11 and 5.23 (2· s, 2· 1H, @CH2), 5.37 (t,
1H, J = 7.0 Hz, @CHCH2), 6.95 (m, 1H, ArH) and 7.13–
7.30 (m, 4H, ArH); m/z (%) 378(M+, 19), 361(11), 247(5),
147(18), 57(74) and 43(100).
4.4.5. (3Z)-8,8-dimethyl-2-methylene-3-{2-[3-methyl-1-
(phenylsulfonyl)-2,3-dihydro-1H-indol-3-yl]ethylidene}-
spiro[4.5]decane-6,10-dione (32)
Prepared from diyne (20) (248 mg, 1.15 mmol) and aryl
iodide (24) (346 mg, 1.15 mmol) by the general procedure
over 17 h at 100 ꢁC. Work up followed by flash chromatog-
raphy eluting with 7:3 v/v ether/petroleum ether afforded
the product (390 mg, 62%) which crystallised from ether/
petroleum ether as colourless prisms, m.p. 104–106 ꢁC.
(Found: C, 71.65; H, 6.70; N, 2.85. C30H33NO4S requires:
C, 71.55; H, 6.60; N, 2.80%); d (250 MHz) 0.97 and 1.01
(2· s, 2· 3H, Me2C), 1.12 (s, 3H, Me), 2.32 and 2.50 (2·
dd, 2· 1H, J = 7.0, 16.0 Hz, @CHCH2), 2.58–2.65 (m,
4H, Me2C(CH2)2), 2.73 and 2.88 (2· s, 2· 2H, C(CH2)2),
3.56 and 3.78 (2· d, 2· 1H, J = 10.0 Hz, NCH2), 5.00
and 5.06 (2· s, 2· 1H, @CH2), 5.15 (t, 1H, J = 7.0 Hz,
@CHCH2), 6.96–7.03 (m, 2H, ArH), 7.21 (m, 1H, ArH),
7.40–7.58 (m, 3H, ArH), 7.65 (d, 1H, J = 8.0 Hz, ArH)
and 7.80–7.85 (m, 2H, ArH); m/z (%) (FAB) 504(M+ + 1,
4.4.8. 3-Methyl-3-[(2E)-2-(4-methylenedihydro-3(2H)-
furanylidene)ethyl]-2,3-dihydro-1-benzofuran (35)
Prepared from diyne (21) (108 mg, 1.15 mmol) and aryl
iodide (23) (315 mg, 1.15 mmol) by the general procedure
over 16 h at 90 ꢁC. Work up followed by flash chromatog-
raphy eluting with 1:4 v/v ether/petroleum ether afforded
the product (184 mg, 62%) as a colourless oil. (Found: C,
78.95, H, 7.10. C16H18O2 requires: C, 79.30; H, 7.50%); d
(250 MHz), 1.42 (s, 3H, Me), 2.59–2.71 (m, 2H, @CHCH2),
4.19 and 4.39 (2· d, 2H, J = 9.0 Hz, OCH2), 4.38 and 4.44
(2· s, 2· 2H, O(CH2)2), 5.11 and 5.28 (2· s, 2· 1H, @CH2),
5.46 (t, 1H, J = 7.0 Hz, @CHCH2), 6.81 (d, 1H,
J = 8.0 Hz, ArH), 6.89 (t, 1H, J = 7.0 Hz, ArH) and
7.08–7.16 (m, 2H, ArH); m/z (%) 242(M+, 18), 233(63),
205(12), 165(18), 133(100), 105(51) and 77(10); mmax(film)
2958, 1733, 1596, 1480, 1229, 976 and 831 cmÀ1
.

1486
U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
4.4.9. (3E)-1-benzyl-3-[2-(3-methyl-2,3-dihydro-1-
References
benzofuran-3-yl)ethylidene]-4-methylenepyrrolidine (36)
Prepared from diyne (22) (210 mg, 1.15 mmol) and aryl
iodide (23) (315 mg, 1.15 mmol) by the general procedure
over 16 h at 100 ꢁC. Work up followed by flash chromatog-
raphy eluting with 1:1 v/v ether/petroleum ether afforded
the product (257 mg, 62%) as a viscous colourless oil.
(Found C, 83.00; H, 7.15; N, 3.85. C23H25NO requires:
C, 83.35; H, 7.60; N, 4.25%); d (250 MHz), 1.36 (s, 1H,
Me), 2.58–2.66 (m, 2H, @CHCH2), 3.22 and 3.30 (2· s,
2· 2H, N(CH2)2), 3.59 (s, 2H, NCH2Ph), 4.16 and 4.39
(2· d, 2· 1H, J = 8.0 Hz, OCH2), 5.09 and 5.20 (2· s, 2·
1H, @CH2), 5.41 (t, 1H, J = 7.0 Hz, @CHCH2), 6.79 (d,
1H, J = 8.0 Hz, ArH), 6.88 (t, 1H, J = 7.0 Hz, ArH) and
7.20–7.31 (m, 5H, ArH); m/z (%) 331(M+, 14), 316(6),
198(37), 133(92), 91(100) and 65(13).
[1] Part 7: A. Casachi, R. Grigg, V. Sridharan, Tetrahedron 57 (2001)
607;
Preliminary communication on carbamyl chlorides:M.R. Fielding, R.
Grigg, C.J. Urch, J. Chem. Commun. (2000) 2239.
[2] R. Grigg, V. Sridharan, Pure Appl. Chem. 70 (1998) 1047.
[3] R. Grigg, V. Sridharan, J. Organomet. Chem. 576 (1999) 65.
[4] R. Grigg, E. Mariani, V. Sridharan, Tetrahedron Lett. (42) (2001)
8677;
M.F. Fielding, R. Grigg, V. Sridharan, M. Thornton-Pett, C.J. Urch,
Tetrahedron 57 (2001) 7737;
R. Grigg, W.S. MacLachlan, D.T. MacPherson, V. Sridharan, S.
Suganthan, Tetrahedron 57 (2000) 10335;
P.F. Diaz, L. Gendre, B. Charpentier, Tetrahedron 54 (1998) 4579;
R. Grigg, I. Koppen, M. Rasparini, V. Sridharan, Chem. Commun.
(2001) 964;
L.E. Overman, M.D. Rosen, Angew. Chem., Int. Ed. 39 (2000) 4596.
[5] R. Grigg, S. Sukirthalingam, V. Sridharan, Tetrahedron Lett. 32
(1991) 2545;
R. Grigg, V. Sridharan, S. Sukirthalingam, Tetrahedron Lett. 32
(1991) 3885;
4.4.10. 4-Methyl-4-[(2E)-2-(4-methylenedihydro-3(2H)-
furanylidene)ethyl]-3,4-dihydro-1H-isochromene (37)
Prepared from diyne (21) (108 mg, 1.15 mmol) and aryl
iodide (26) (331 mg, 1.15 mmol) by the general procedure
over 16 h at 90 ꢁC. Work up followed by flash chromatogra-
phy eluting with 1:4 v/v ether/petroleum ether afforded the
product (183 mg, 62%) as a viscous yellow oil. (Found: C,
79.25; H, 7.7. C17H20O2 requires: C, 79.65, H, 7.85%); d
(250 MHz), 1.30 (s, 3H, Me), 2.62 and 2.82 (2· dd, 1H,
J = 7.0, 16.0 Hz), 3.58 and 3.80 (2· d, 2H, J = 11.0 Hz,
OCH2), 4.37 and 4.44 (2· s, 2· 2H, O(CH2)2), 4.81 (s, 2H,
OCH2Ar), 5.11 and 5.38 (2· s, 2· 1H, @CH2), 5.48 (t, 1H,
J = 7.0 Hz, @CHCH2), 6.98 (d, 1H, J = 8.0 Hz, ArH) and
7.14–7.31 (m, 3H, ArH); m/z (%) 256(M+, 10), 225(14),
197(18), 178(27), 165(67), 147(100), 119(90), 77(13) and
W. Oppolzer, Angew. Chem., Int. Ed. 28 (1989) 39;
B.M. Trost, J.I. Luengo, J. Am. Chem. Soc. 110 (1988) 8239.
[6] S. Suffert, Angew. Chem., Int. Ed. 43 (2004) 2826;
C.H. Oh, Y. Lim, Tetrahedron Lett. 44 (2003) 267;
C.W. Lee, K.S. Oh, K.S. Kim, K.H. Ahn, Org. Lett. 2 (2000) 1213;
M. Ishilana, A. Hino, T. Yaginuma, I. Agata, N. Katagiri, Tetrahe-
dron 56 (2000) 193;
R.C. Larock, X. Han, J. Org. Chem. 64 (1999) 1875.
[7] J. Bohmer, R. Grigg, J.D. Marchbank, Chem. Commun. (2002) 768;
A.G. Steining, A. de Meijere, Eur. J. Org. Chem. (1999) 1333;
W. Oppolzer, A. Pimm, B. Stammen, W. Hulme, Helv. Chim. Acta
80 (1997) 623;
R. Grigg, R. Rasul, D. Wilson, Tetrahedron Lett. 37 (1996) 4609.
[8] Y.T. Park, I.H. Lee, Y.H. Kim, J. Heterocyclic Chem. 31 (1994)
1625.
[9] T. Sakamoto, K. Yoshinori, I. Shigeki, H. Yamanaka, Chem. Pharm.
Bull. 35 (1987) 1823.
43(26); mmax(film) 2953, 1727, 1489, 1386 and 1097 cmÀ1
.
[10] A. Padwa, K.E. Krumpe, M.D. Weingarten, J. Org. Chem. 60 (1995)
5595.
4.4.11. (3E)-1-benzyl-3-[2-(4-methyl-3,4-dihydro-1H-
[11] J.S. Norwick, S. Insaf, J. Am. Chem. Soc. 119 (1997) 10903.
[12] L. Sun, C. Liang, S. Shirazian, Y. Zhou, T. Miller, J. Cui, J.Y.
Fukuda, J.Y. Chu, A. Nematalla, X. Wang, H. Chen, A. Sistla, T.C.
Luu, F. Tang, J. Wei, C. Tang, J. Med. Chem. 46 (2003) 1116.
[13] C.L. Woodard, Z. Li, A.K. Kathcart, J. Terell, L. Gerena, M.L.
Sanchez, D.E. Kyle, A.K. Bhattacharjee, D.A. Nichols, W. Ellis,
S.T. Prigge, J.A. Geyer, N.C. Waters, J. Med. Chem. 46 (2003) 3877.
[14] R.P. Robinson, L.A. Reiter, W.E. Barth, A.M. Campeta, K. Cooper,
B.J. Cronin, R. Destito, K.M. Donahue, F.C. Falkner, E.F. Fiese,
D.L. Johnson, A.V. Kuperman, T.E. Liston, D. Malloy, J.J. Martin,
D.Y. Mitchell, F.W. Rusek, S.L. Shamblin, C.F. Wright, J. Med.
Chem. 39 (1996) 10.
[15] B. Bosnich, P.B. Mackenzie, Pure Appl. Chem. 54 (1982) 189;
R. Grigg, V. Savic, Tetrahedron Lett. 37 (1996) 6565.
[16] A.F. Littke, G.C. Fu, Angew. Chem., Int. Ed. Engl. 38 (1998) 3387.
[17] M. Toyofuku, S.I. Fujiwara, T. Shin-ike, H. Kuniyasu, K. Nobuaki,
J. Am. Chem. Soc. 127 (2005) 9706.
isochromen-4-yl)ethylidene]-4-methylenepyrrolidine (38)
Prepared from diyne (22) (210 mg, 1.15 mmol) and aryl
iodide (26) (331 mg, 1.15 mmol) by the general procedure
over 17 h at 90 ꢁC. Work up followed by flash chromatogra-
phy eluting with 1:1 v/v ether/petroleum ether afforded the
product (277 mg, 70%) as a viscous colourless oil. (Found:
C, 83.30; H, 7.90; N, 4.20. C24H27NO requires: C, 83.45;
H, 7.90; N, 4.05%); d (250 MHz), 1.29 (s, 3H, Me), 2.56
and 2.78 (2· dd, 2· 1H, J = 7.0, 16.0 Hz, @CHCH2), 3.19
and 3.31 (2· s, 2· 2H, N(CH2)2), 3.56 and 3.76 (2· d, 2·
1H, J = 11.0 Hz, OCH2), 3.59 (s, 2H, NCH2Ph), 4.78 (s,
2H, OCH2Ar), 5.09 and 5.30 (2· s, 2· 1H, @CH2), 5.41 (t,
1H, J = 7.0 Hz, @CHCH2), 6.95 (m, 1H, ArH) and 7.11–
7.32 (m, 8H, ArH); m/z (%) 345(M+, 13), 330(6), 254(7),
198(77), 147(27), 119(37), 91(100) and 65(13); mmax(film)
[18] R. Grigg, J.M. Sansano, V. Santhakumar, V. Sridharan, R. Than-
gavelanthum, M. Thorn-Pett, D. Wilson, Tetrahedron 53 (1997)
11803;
2956, 1733, 1700, 1456, 1289 and 1026 cmÀ1
.
B. Burns, R. Grigg, V. Sridharan, P. Stevenson, S. Sukirthlingam, T.
Worakun, Tetrahedron Lett. 37 (1996) 695.
[19] M. Lautens, C. Meyer, A. Lorenz, J. Am. Chem. 118 (1996) 10676;
H.X. Zhang, F. Guibe, G. Balavoine, J. Org. Chem. 55 (1990) 1857.
[20] A. Casachi, R. Grigg, J.M. Sansano, D. Wilson, J. Redpath,
Tetrahedron 56 (2000) 7541.
Acknowledgements
WethankLeedsUniversity, EPSRCandSyngentaforsup-
port and the Johnson Matthey loan scheme for Pd(OAc)2.

U. Anwar et al. / Journal of Organometallic Chemistry 691 (2006) 1476–1487
1487
[21] A. Casachi, R. Grigg, J.M. Sansano, Tetrahedron 57 (2001) 607;
A. Casachi, R. Grigg, J.M. Sansano, Tetrahedron 56 (2000) 7553.
[22] R. Grigg, M.F. Jones, M. McTiernan, V. Sridharan, Tetrahedron 57
(2001) 7979.
[24] W.P. Neuman, The Organic Chemistry of Tin, Wiley, New York,
1970.
[25] Y. Yamamoto, H. Kitahara, R. Ogawa, J. Org. Chem. 63 (1998)
9610;
[23] M. Lautens, N. Smith, D. Ostrovsky, J. Org. Chem. 62 (1997) 8970.
R. Grigg, R. Scott, P. Stevenson, Tetrahedron Lett. 23 (1982) 2691.