Skeletal diversity via Pd(0) catalysed three-component cascades of allene and halides or triflates with protected hydroxylamines and formamide

Article abstract of DOI:10.1016/j.tet.2012.01.099

The reactions of allene gas (1 atm) and of 1,1-dimethylallene with a range protected hydroxylamines and formamide with aryl/heteroaryl iodides, bromides and triflates under Pd(0) catalysis lead to a skeletally diverse range of products in good yield. The

Full text of DOI:10.1016/j.tet.2012.01.099

Tetrahedron 68 (2012) 3103e3111
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Skeletal diversity via Pd(0) catalysed three-component cascades of allene
and halides or triflates with protected hydroxylamines and formamide
*
Elghareeb E. Elboray, Chuanjun Gao, Ronald Grigg
Molecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, School of Chemistry, Leeds University, Leeds LS2 9JT, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The reactions of allene gas (1 atm) and of 1,1-dimethylallene with a range protected hydroxylamines and
formamide with aryl/heteroaryl iodides, bromides and triflates under Pd(0) catalysis lead to a skeletally
diverse range of products in good yield. The cascades tolerate both electron withdrawing and electron
donating substrates and 1,1-dimethylallene reacts regioselectively in all cases.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 8 November 2011
Received in revised form 9 January 2012
Accepted 31 January 2012
Available online 4 February 2012
Keywords:
Mono- and di-protected hydroxylamines
Catalytic cascades
Aryl/heteroaryl bromides
Iodides
Triflates
Iodouracil
1. Introduction
We now report a series of three-component cascades in which
The hydroxylamine functional group has garnered multiple
synthetic applications1,2 as well as prompting studies of its biology
and potential uses in theraputics.3 We have a long standing interest
in hydroxylamines and oximes both as precursors of nitrones, and
their subsequent zero waste 1,3-dipolar cycloadditions4 and as
participants in palladium catalysed cascade reactions. We have
previously reported both solid phase (Wang resin) and solution
phase palladium catalysed, relay switched,5 three-component
cyclisationecarbonylationehydroxylamine cascades (Scheme 1)
and demonstrated that five-component processes are accessible
when R1¼H. The carbon monoxide functions as the relay switch in
these processes.6 The latter process results in the formation of six
new bonds, two rings and two tetrasubstituted C-centres.5
allene(s) act as the relay switch whilst mono- and bis- protected
hydroxylamines 1e3 and the formamide 4 are employed as
nucleophiles.
1.1. Cascades employing allene gas and monoprotected
hydroxylamine 1
Preliminary experiments with nucleophile 1 showed that its use
in excess enhanced the yield of the three-component product 5 and
suppressed formation of the five-component product 6 (Scheme 2).
Reactions were carried out in DMF at 80 ꢀC for 16 h and employed
allene (1 atm), 1 (2e3 mol equiv), Pd2(dba)3 (2.5 mol %), tris-(2-
furyl)phosphine (TFP) (10 mol %) and K2CO3 (2 mol equiv) (Table 1).
The disparate aryl/heteroaryl halides 7e13 were all converted into
their corresponding three-component cascade products in excellent
yield by using an excess of O-benzylhydroxylamine 1 and 1 atm of
allene. Thus 2-iodothiophene 8 furnished the desired product 15
in 90% yield (Table 1, entry 2) whilst 5-iodo-1,3-dimethyluracil 11
Scheme 1.
* Corresponding author. E-mail address: r.grigg@leeds.ac.uk (R. Grigg).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.099

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E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
Following our earlier report on the application of decarbox-
ylative 1,3-dipolar cycloaddition routes to the spiro-(indole-3,30-
pyrrolizine)-2-one skeleton8a there has been substantial activity in
this area8bei but to our knowledge the 5-iodo derivatives 12a,b and
13a,b have not been reported (see Experimental).
1.2. Cascades employing allene gas and N,O-protected
hydroxylamines 2
Scheme 2.
Although using an excess of O-substituted hydroxylamine 1 was
sufficient to prevent the formation of the five-component product 6
(Scheme 2), it is wasteful and requires the excess reagent to be
separated from the product. An alternative strategy employing the
N,O-protected 2 was studied under the standard conditions as for
Table 1 except that N,O-protected hydroxylamine 2 (1.05 mol equiv)
was employed (Table 2). Both iodo and bromo substrates gave the
desired products in good to excellent yield demonstrating that the
cascade tolerates both electron withdrawing and electron donating
aryl/heteroaryl substrates (e.g., Table 2, entry 1).
Table 1
Three-component Scheme 2 processes employing 1a
Entry
1
Aryl halide
Product
Yieldb (%)
74
Reactions of N-Boc-O-benzylhydroxylamine 2 with 10,11, and 12
gave better yields than similar reactions with O-benzylhydroxyl-
amine whereas the heterocyclic bromides 9 and 10 gave similar
yields with both 1 and 2.
In one instance we compared the overall two-step yield of 14 via
26a followed by removal of the Boc group (Scheme 3). The latter two
steps route gave 14 (90%) compared to 74% via the direct reaction
with O-benzylhydroxylamine. The greater reactivity of N-Boc-O-
benzylhydroxylamine 2 compared to 1 was emphasised by the re-
action of the former with phenyl triflate to afford 26a in 80% yield at
higher temperature (110 ꢀC) over 84 h (Table 2, entry 10).
2
3
90
67
4
5
86
85
1.3. Cascades employing allene gas and N,O-diBoc-
hydroxylamine 3
The reaction of commercially available N,O-diBoc-hydroxyl-
amine 3 with the iodobenzenes 21a,f and h gave the expected
products 36aec using the same conditions as before (Scheme 4).
6
70
1.4. Cascades employing allene gas and N-
benzyloxyformamide 4 as nucleophile
N-Benzyloxyformamide, which exhibits dynamic 1H NMR
spectra due to restricted rotation about the amide bond9 was
reacted with an aryl and a heteroaryl iodide (Table 3) under our
standard conditions. The iodides 21c and 8 gave the expected
products 37 and 38 in excellent yield (Table 3).
7
70
1.5. Reactions employing 1,1-dimethylallene and O-
benzylhydroxylamine 1 as nucleophile
a
Reactions were carried out for 16 h at 80 ꢀC in DMF under 1 atm of allene gas
and in the presence of O-benzylhydroxylamine 1 (2e3 mol equiv), Pd2dba3 (2.5 mol
%), TFP (10 mol %), K2CO3 (2 mol equiv).
b
Mono- or 1,1-disubstituted allenes can give rise to both syn and
Isolated yield.
anti-
terminus giving rise to three possible products (Scheme 5). Gen-
erally the anti- -allyl complex is favoured because of the steric
clash between the R and Ar groups in the syn- -allyl.
Several aryl iodides and a heterocyclic bromide were reacted
with 1,1-dimethylallene (5 mol equiv) and O-benzylhydroxylamine
using the standard catalyst system in DMF at 80 ꢀC to generate the
corresponding allylic hydroxylamines regiospecifically (Table 4). In
p-allyl complexes each of which can be attacked at either
p
produced allyl hydroxylamine 18 in 85% yield (Table 1, entry 5). Aryl
bromides are generally less reactive than aryl iodides in palladium
catalysed reactions. However, the more reactive 3-bromopyridine 9
and 5-bromopyrimidine 10 gave the expected products 16 and 17 in
good yield under the standard conditions (Table 1, entries 3 and 4)
whilst the sterically demanding spirocycles 12b and 13b were con-
verted into 19 and 20 in good yield (Table 1, entries 6 and 7). In
contrast, phenyl triflate was significantly less reactive and under
more forcing conditions (DMF, 110 ꢀC, 85 h) gave the known two
component O-benzyl-N-phenylhydroxylamine product (61%).7
p
all cases nucleophilic attack on the p-allyl species 39 occurs at the
most substituted site (Scheme 6) in accord with Trost’s suggestion
that when nucleophilic attack occurs at the most substituted ter-
minus of the
p-allyl unit, electronic rather steric effects dominate
regioselectivity.10

E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
3105
Table 2
Three-component Scheme 3 processes employing 2a
Entry
Aryl halide
Product
Yieldb (%)
1
94e97
Scheme 3. (i) See footnote a (Table 2); (ii) 10% TFA (5 mol equiv), CH2Cl2, rt, 16 h.
2
3
92
96
Scheme 4. (i) Conditions as for Table 2.
4
85e88
Table 3
Cascade process involving N-benzyloxyformamide 4a
Entry
Aryl halide
Product
Yieldb (%)
1
93
92
5
6
87
64
2
a
All reactions were conducted in a Schlenk tube, with allene (1 atm), nucleophile
(1.05 mol equiv), Pd2dba3 (2.5 mol %), TFP (10 mol %) and K2CO3 (2 mol equiv) in
DMF at 80 ꢀC for 16 h.
b
Isolated yield.
7
8
81
94
9
87
Scheme 5.
10
80c
3. Experimental
3.1. General
a
Reactions were carried out for 16 h at 80 ꢀC in DMF under 1 atm of allene gas
using N-Boc-O-benzylhydroxylamine 2 (2e3 mol equiv), Pd2dba3 (2.5 mol %), TFP
(10 mol %), K2CO3 (2 mol equiv).
b
Isolated yield.
Reaction carried out at 110 ꢀC for 84 h.
c
Melting points were determined on a Reichert hot-stage appa-
ratus and are uncorrected. 1H Nuclear magnetic resonance spectra
were recorded at 300 MHz on a Bruker DPX 300 instrument or at
500 MHz on a Bruker DRX 500 instrument. 13C Nuclear magnetic
resonance spectra were recorded at 75 MHz on a Bruker DPX 300
instrument. Deuterochloroform was used as solvent unless stated
2. Conclusion
The application of catalytic cascade chemistry to the assembly of
a diverse array of protected hydroxylamines and formamides pro-
ceeds in good to excellent yields.
otherwise, and chemical shifts are given in parts per million (
d)
down field from tetramethylsilane. 1H spectra are referenced to

3106
E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
Table 4
evaporated in vacuo. The residue was purified by flash chroma-
tography eluting with 1:1 v/v ether/ethyl acetate.
Reaction of 1,1-dimethylallene with 1 and aryl/heteroaryl halidesa
Entry
1
Aryl halide
Product
Yieldb (%)
83
3.2.1.1. Methyl 5-iodo-2-oxo-1,10,2,20,500,60,70,7a0-octahydro-spiro
[indole-3,30-pyrrolizine]-20-carboxylate (12a). The product crystal-
lized from ether as colourless prisms (1.69 g, 82%); mp 143e144 ꢀC;
1H NMR
d
: 1.56 (m, 1H, 70-HA), 1.91 (m, 2H, 2ꢁ60-H), 2.06e2.13 (m,
2H, 70-HB and 10-HA), 2.37e2.46 (m, 2H, 50-HA and 10-HB), 2.62 (m,
1H, 50-HB), 3.29 (s, 3H, CH3O), 3.84 (dd, 1H, J 6.5 and 12.5 Hz, 200-H),
4.05 (m, 1H, 7a0-H), 6.73 (m, 1H, ArH), 7.38 (s, 1H, ArH) and 7.57 (d,
1H, J 8.5 Hz, ArH). Found: C, 46.40; H, 4.35; N, 6.90; I, 30.80.
C16H17IN2O3 requires: C, 46.62; H, 4.16; N, 6.80; I, 30.79%. m/z (%)
412 (Mþ, 57), 384 (51), 353 (28), 326 (100), 298 (12), 169 (13), 129
(15) and 83 (74).
2
3
90
76
3.2.1.2. Methyl 5-iodo-2-oxo-1,10,2,50,60,70,80,8a0-octahydro-20H-
spiro[indole-3,30-indolizine]-20-carboxylate (13a). Prepared by gen-
eral procedure A but with 1.2 mol equiv of methyl acrylate and
heating for 120 h. The product crystallized from 2:1 v/v petroleum
ether/ethyl acetate as colourless plates (1.38 g, 65%); mp
47 (n¼1)
64 (n¼2)
4
156e159 ꢀC; 1H NMR
d
: 1.21e1.31 (m, 3H, 2ꢁ80-H and 60-HA), 1.50
(m, 1H, 60-HB), 1.72e1.75 (m, 1H, 70-HA), 1.90e1.93 (m, 1H, 70-HB),
2.09e2.20 (m, 2H, 2ꢁ10-H), 2.34e2.39 (m, 2H, 2ꢁ50-H), 3.16e3.19
(m, 1H, 8a0-H), 3.26 (s, 3H, OCH3), 3.37 (dd, 1H, J 8.0 and 10.0 Hz, 20-
H), 6.60e6.63 (m, 1H, ArH), 7.41 (s, 1H, ArH), 7.52 (dd, 1H, J 1.5 and
5
76
a
8.0 Hz, ArH); 13C NMR
d: 24.1, 26.0, 32.1, 34.2, 46.0, 51.6, 51.9, 60.0,
All reactions were conducted in
a Schlenk tube, with 1,1-dimethylallene
(5 mol equiv), O-benzylhydroxylamine (2e3 mol equiv), Pd2dba3 (2.5 mol %), TFP
73.0, 85.4,111.7,132.2,134.4, 138.1,172.2. Found: C, 48.10; H, 4.50; N,
6.40; I, 29.70. C17H19IN2O3 requires: C, 47.90; H, 4.49; N, 6.27; I,
29.77%. m/z (%): 426 (Mþ, 33), 398 (22), 339 (100), 300 (53), 272
(56), 271 (94), 256 (25) and 241 (30).
(10 mol %) and K2CO3 (2 mol equiv) in DMF at 80 ꢀC for 16 h.
b
Isolated yield.
3.2.2. Boc protection (procedure B). The cycloadduct (2 mmol), di-
tert-butyl dicarbonate (3 mmol) and triethylamine (3 mmol) were
combined in dichloromethane (20 mL) and stirred at reflux for
30 h. The mixture was concentrated in vacuo and the residue pu-
rified by flash chromatography eluting with 1:1 v/v petroleum
ether/ether.
Scheme 6.
3.2.2.1. 1-tert-Butyl 20-methyl 5-iodo-2-oxo-10,20,50,60,70,7a0-hex-
ahydrospiro[indole-3,30-pyrrolizine]-1,20-(2H)-dicarboxylate
(12b). The product crystallized as colourless prisms from ether
tetramethylsilane and 13C spectra are referenced to deutero-
chloroform. Assignments of 1H signals were made with the aid of
2D COSY spectra where necessary. Assignments of 13C signals were
made with the aid of DEPT or APT spectra. Coupling constants are
reported to the nearest 0.5 Hz. Microanalyses were obtained using
a Carlo Erba Elemental Analyser MOD 1106 instrument. Infrared
spectra were recorded either neat (for liquids) or as Nujol mulls (for
solids) on a Phillips PU 9706 using KBr discs. Mass spectra were
recorded on a V.G.-AutoSpec spectrometer using electron impact
(EI) operating at 70 eV or fast atom bombardment (FAB), as speci-
fied. Accurate molecular weights were determined on the AutoSpec
using perfluorokerosene as internal standard. Flash column chro-
matography was performed on silica gel 60 (Merk 230e400 mesh).
Ether refers to diethyl ether and petroleum ether refers to the
fraction with boiling point 40e60 ꢀC. All reagents and solvents
were purified according to procedures given in Purification of
Laboratory Chemicals, 6th ed., Armarego, W. and Chai, C. L. L.,
ButterwortheHeinemann, 2009.
(993 mg, 97%); mp 120e121 ꢀC; 1H NMR : 1.60 (m, 1H, 70-HA), 1.63
d
(s, 9H, 3ꢁCH3), 1.94 (m, 2H, 2ꢁ60-H), 2.02e2.10 (m, 2H, 70-HB and
10-HA), 2.36e2.48 (m, 2H, 50-HA and 10-HB), 2.60 (m, 1H, 50-HB), 3.29
(s, 3H, CH3O), 3.87 (dd, 1H, J 6.5 and 12.5 Hz, 20-H), 4.05 (m, 1H,
NCH), 6.80 (m, 1H, ArH), 7.40 (s, 1H, ArH), 7.61 (d, 1H, J 8.5 Hz, ArH).
Found: C, 49.25; H, 5.10; N, 5.35; I, 24.90. C21H25IN2O5 requires: C,
49.23; H, 4.92; N, 5.47; I, 24.77%. m/z (%) 512 (Mþ, 47), 484 (35), 428
(36), 412 (71), 384 (43), 369 (45), 353 (38), 326 (100), 284 (12), 169
(15) and 83 (92).
3.2.2.2. 1-tert-Butyl 20-methyl 5-iodo-2-oxo-10,50,60,70,80,8a0-hex-
ahydro-20H-spiro[indole-3,30-indolizine]-1,20(2H)-dicarboxylate
(13b). The product was obtained as a colourless amorphous solid
from petroleum ether/ether (989 mg, 94%); mp 120e122 ꢀC; 1H
NMR
d
: 1.20e1.38 (m, 3H, 2ꢁ80-H and 60-HA), 1.50 (m, 1H, 60-HB),
1.64 (s, 9H, 3ꢁCH3), 1.72e1.77 (m, 1H, 70-HA), 1.90e1.93 (m, 1H,
70-HB), 2.05e2.26 (m, 2H, 2ꢁ10-H), 2.30e2.39 (m, 2H, 50-H),
3.13e3.19 (m, 1H, 8a0-H), 3.24 (s, 3H, OCH3), 3.36 (dd, 1H, J 8.0
and 10.0 Hz, 20-H), 7.44 (d, 1H, J 1.0 Hz, ArH), 7.60 (m, 2H, ArH);
3.2. General procedure for the two-step synthesis of
spirocycles 12b and 13b via 1,3-dipolar cycloaddition and N-
Boc protection
13C NMR
d: 13.5, 24.0, 25.9, 28.4, 32.2, 34.0, 45.8, 51.9, 52.6, 60.0,
72.5, 77.6, 85.1, 88.1, 116.8, 130.6, 133.9, 138.5, 140.4, 149.3, 171.7,
176.2. Found: C, 50.00; H, 5.15; N, 5.20; I, 24.05. C22H27IN2O5
requires: C, 50.20; H, 5.17; N, 5.32; I, 24.11%. m/z (%): 526 (Mþ,
18), 498 (23), 442 (28), 426 (40), 397 (77), 339 (74), 213 (20), 97
(100) and 41 (96).
3.2.1. Cycloaddition (procedure A). A solution of 5-iodoisatin
(5 mmol), proline or pipecolinic acid (1 mol equiv) and methyl ac-
rylate (1 mol equiv) in acetonitrile (100 mL) was heated under
reflux for 16 h. The solution was cooled, filtered and the solvent

E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
3107
3.2.3. General procedure for reactions using allene gas (procedure
C). Nucleophile (1e3 mol equiv), tris-(dibenzylideneacetone)
1,3-dimethyluracil (1.01 g, 3.80 mmol), O-benzylhydroxylamine
(1.43 g, 11.66 mmol) and allene gas (1 atm) in DMF (30 mL). Puri-
fication by column chromatography eluting with 3:1 v/v petroleum
ether/ethyl acetate afforded the product as a pale orange oil
dipalladium (2.5 mol %), tris-(2-furyl)phosphine (10 mol %) and
potassium carbonate (2 mol equiv) were added to a solution of the
aryl halide (1 mmol) in dry dimethylformamide (10 mL) in
a Schlenk tube. The reaction mixture was then degassed using the
freeze, pump, thaw (F.P.T.) technique (one cycle). Allene gas was
then introduced at the required pressure (1 atm) and the Schlenk
tube contents stirred and heated at 80 ꢀC for 16 h. After cooling and
venting, DCM (20 mL) was added and the mixture filtered to
remove inorganic salts. The filtrate was concentrated in vacuo and
the residue was purified by column chromatography.
(973 mg, 85%); 1H NMR
d
: 3.33 and 3.34 (s, 6H, 2ꢁNCH3), 3.85 (s,
2H, NCH2), 4.66 (s, 2H, OCH2), 5.30 and 5.56 (s, 2ꢁ1H, ]CH2), 5.64
(br s, 1H, NH), 7.20e7.36 (m, 6H, 5ꢁArH and ]CHN); 13C NMR
d:
28.4, 37.5, 56.7, 76.2, 113.6, 119.2, 128.2, 128.7, 128.8, 138.5, 138.6,
141.1, 151.7, 162.6. Found: C, 63.80; H, 6.35; N, 13.70. C16H19N3O3
requires: C, 63.77; H, 6.36; N,13.94%. m/z (%): 301 (Mþ,18), 283 (10),
210 (14), 194 (38), 180 (51), 165 (10), 109 (15), 91 (100), 77 (18), 51
(16) and 42 (42).
3.2.3.1. O-Benzyl-N-(2-phenyl-allyl)-hydroxylamine (14). Prepared
by procedure C from iodobenzene (0.24 mL, 2.10 mmol), O-benzyl-
hydroxylamine (753 mg, 6.11 mmol) and allene gas (1 atm) in
DMF (20 mL). Purification by flash column chromatography eluting
with 9:1 v/v petroleum ether/ether afforded the product as a col-
3.2.3.6. 1-tert-Butyl 20-methyl 5-(1-{[(benzyloxy)amino]methyl}-
vinyl)-2-oxo-10,20,50,60,70,7a0-hexahydrospiro[indole-3,30-pyrrolizine]-
1,20(2H)-dicarboxylate (19). Prepared by procedure C from 12b
(553 mg, 1.08 mmol), O-benzylhydroxylamine (345 mg, 2.80 mmol)
and allene gas (1 atm) in DMF (10 mL). Purification by flash column
chromatography eluting with 3:1 v/v petroleum ether/ethyl acetate
afforded the product as a thick pale yellow oil (417 mg, 70%); 1H
ourless oil (371 mg, 74%); 1H NMR
d
: 3.94 (s, 2H, NCH2), 4.67 (s, 2H,
OCH2), 5.29 and 5.47 (2ꢁs, 2ꢁ1H, ]CH2), 5.62 (br s, 1H, NH),
7.21e7.44 (m, 10H, ArH); 13C NMR
: 56.6, 76.5, 116.0, 126.6,
d
NMR
d
: 1.55 (m, 1H, 70-HA), 1.62 (s, 9H, OC(CH3)3), 1.84 (m, 2H, 2ꢁ60-
128.1, 128.2, 128.7, 128.8, 128.8, 138.3, 139.8, 144.3. Found: C, 80.05;
H, 7.00; N, 5.75. C16H17NO requires: C, 80.30; H, 7.16; N, 5.85%. m/z (%):
240 (100, Mþ1).
H), 2.04 (m, 1H, 70-HB), 2.13 (m, 1H, 10-HA), 2.39e2.42 (m, 2H, 50-HA
and 10-HB), 2.55 (m,1H, 50-HB), 3.17 (s, 3H, CH3O), 3.88 (dd,1H, J 13.0
and 7.0 Hz, 20-H), 3.93 (s, 2H, ONHCH2), 4.05 (m, 1H, 7a0-H), 4.68 (s,
2H, OCH2), 5.30 and 5.45 (2ꢁs, 2ꢁ1H, ]CH2), 5.65 (br s, 1H, NH),
7.28e7.45 (m, 7H, ArH), 7.89 (d, 1H, J 8.5 Hz, ArH). Found: C, 67.95;
H, 6.70; N, 7.80. C31H37N3O6 requires: C, 67.99; H, 6.81; N, 7.67%. m/z
(%) 547 (Mþ, 6), 461 (9), 447 (6), 361 (41), 298 (57), 266 (31) and
91 (100).
3.2.3.2. O-Benzyl-N-(2-thiophen-2-yl-allyl)-hydroxylamine
(15). Prepared by procedure C from 2-iodothiophene (442 mg,
2.10 mmol), O-benzylhydroxylamine (753 mg, 6.11 mmol) and
allene gas (1 atm) in DMF (20 mL). Purification by flash column
chromatography eluting with 9:1 v/v petroleum ether/ether affor-
ded the product as a colourless oil (465 mg, 90%); 1H NMR
d: 3.90 (s,
3.2.3.7. 1-tert-Butyl 20-methyl 5-(1-{[(benzyloxy)amino]methyl}-
vinyl)-2-oxo-10,50,60,70,80,8a0-hexahydro-20H-spiro[indole-3,30-in-
2H, NCH2), 4.71 (s, 2H, OCH2), 5.20 and 5.54 (2ꢁs, 2ꢁ1H, ]CH2),
5.71 (br s, 1H, NH), 6.95e6.98 (m, 1H, ArH), 7.06e7.08 (m, 1H, ArH),
7.18e7.20 (m, 1H, ArH), 7.28e7.36 (m, 5H, ArH). Found: C, 68.25; H,
6.05; N, 5.60; S,13.10. C14H15NOS requires: C, 68.54; H, 6.16; N, 5.71;
S, 13.07%. m/z (%): 246 (Mþ1).
dolizine]-1,20(2H)-dicarboxylate (20). Prepared by procedure
C
from 13b (556 mg, 1.06 mmol), O-benzylhydroxylamine (341 mg,
2.77 mmol) and allene gas (1 atm) in DMF (10 mL). Purification by
flash column chromatography eluting with 3:1 v/v petroleum
ether/ether afforded the product as a thick colourless oil (416 mg,
3.2.3.3. O-Benzyl-N-(2-pyridin-3-yl-allyl)-hydroxylamine
(16). Prepared by procedure C from 3-bromopyridine (248 mg,
1.57 mmol), O-benzylhydroxylamine (583 mg, 4.74 mmol) and
allene gas (1 atm) in DMF (15 mL). Purification by flash column
chromatography eluting with 3:1 v/v petroleum ether/ethyl acetate
70%); 1H NMR
d
1.15e1.30 (m, 3H, 2ꢁ80-H and 60-HA), 1.45 (m, 1H,
60-HB), 1.65 (s, 9H, 3ꢁCH3), 1.73 (m, 1H, 70-HA), 1.89e1.92 (m, 1H, 70-
HB), 2.10e2.20 (m, 2H, 2ꢁ10-H), 2.28 (m, 2H, 2ꢁ50-H), 3.09 (s, 3H,
OCH3), 3.21 (m,1H, 8a0-H), 3.38 (dd,1H, J 10.0 and 8.5 Hz, 20-H), 3.94
(s, 2H, ONHCH2), 4.68 (s, 2H, OCH2), 5.28 and 5.47 (2ꢁs, 2ꢁ1H, ]
CH2), 5.65 (br s, 1H, NH), 7.27e7.39 (m, 7H, ArH), 7.74 (d, 1H, J
8.5 Hz, ArH). Found: C, 68.70; H, 7.15; N, 7.40. C32H39N3O6 requires:
C, 68.43; H, 7.00; N, 7.48%. m/z (%): 562 (Mþ1, 7), 456 (7), 341 (7),
212 (28), 172 (69), 126 (45), 98 (100) and 84 (53).
afforded the product as a pale yellow oil (254 mg, 67%); 1H NMR
d:
3.93 (s, 2H, NCH2), 4.65 (s, 2H, OCH2), 5.40 and 5.53 (2ꢁs, 2ꢁ1H, ]
CH2), 5.60 (br s, 1H, NH), 7.21e7.37 (m, 6H, ArH), 7.70 (m, 1H, ArH),
8.51 (dd, 1H, J 5.0 and 1.5 Hz, ArH), 8.71 (dd, 1H, J 2.5 and 1.0 Hz,
ArH); 13C NMR
d: 56.4, 76.7, 117.7, 123.5, 128.2 128.8, 128.9, 133.9
3.2.3.8. tert-Butylbenzyloxy(2-phenyl-2-propenyl)carbamate(26a).
135.5, 138.1, 141.7, 148.1, 149.2. Found: C, 74.70; H, 6.75; N, 11.80.
C15H16N2O requires: C, 74.97; H, 6.71; N, 11.66%. m/z (%): 240 (Mþ,
52), 209 (93), 195 (11), 145 (15), 131 (23), 117 (41), 104 (43), 91 (100)
and 77 (49).
(a) Prepared by procedure C from iodobenzene (225 mg,1.11 mmol),
N-Boc-O-benzylhydroxylamine (272 mg, 1.22 mmol) and allene
gas (1 atm) in DMF (10 mL). Purification by flash column chro-
matography eluting with 9:1 v/v petroleum ether/ether afforded
the product as colourless oil (357 mg, 95%).
3.2.3.4. O-Benzyl-N-(2-pyrimidin-5-yl-allyl)-hydroxylamine
(17). Prepared by procedure C from 5-bromopyrimidine (231 mg,
1.45 mmol), O-benzylhydroxylamine (508 mg, 4.13 mmol) and
allene gas (1 atm) in DMF (15 mL). Purification by flash column
chromatography eluting with 1:1 v/v petroleum ether/ethyl acetate
(b) Prepared by procedureC from phenyl triflate (99 mg, 0.44 mmol),
N-Boc-O-benzylhydroxylamine (105 mg, 0.45 mmol), allene gas
(1 atm), potassium carbonate (140 mg,1.01 mmol) and a catalytic
system comprising tris-(dibenzylideneacetone)dipalladium
(11 mg, 2.7 mol %) and tris-(2-furyl)phosphine (11 mg, 11 mol %)
in DMF (5 mL) at 110 ꢀC for 84 h. Purification by flash column
chromatography eluting with 9:1 v/v petroleum ether/ether
afforded the product as a colourless oil (311 mg, 89%); 1H NMR
d:
3.92 (s, 2H, NCH2), 4.61 (s, 2H, OCH2), 5.46 and 5.60 (2ꢁs, 2ꢁ1H, ]
CH2), 7.24e7.40 (m, 5H, ArH), 8.81 (s, 2H, ArH), 9.13 (s, 1H, ArH).
Found: C, 69.70; H, 6.35; N, 17.15. C14H15N3O requires: C, 69.69; H,
6.27; N, 17.41%. m/z (%): 241 (Mþ, 29), 210 (72), 165 (20), 105 (18), 91
(100), 77 (35), 65 (50) and 51 (53).
afforded the product as a colourless oil (120 mg, 80%); 1H NMR
d:
1.48 (s, 9H, 3ꢁCH3), 4.49(s, 2H, NCH2), 4.68 (s, 2H, OCH2), 5.31and
5.52 (2ꢁs, 2ꢁ1H, ]CH2), 7.26e7.50 (m, 10H, ArH); 13C NMR
d:
28.6, 54.3, 77.6, 81.9, 116.0, 126.8, 128.2, 128.7, 128.8, 128.9, 129.8,
135.9, 139.3, 143.6, 156.8. Found: C, 74.00; H, 7.50; N, 3.85.
3.2.3.5. 5-[1-(Benzyloxy)amino-methyl-vinyl]-1,3-dimethyl-1H-
pyrimidine-2,4-dione (18). Prepared by procedure C from 5-iodo-

3108
E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
C21H25NO3 requires: C, 74.31; H, 7.42; N, 4.13%. m/z (%) 339 (Mþ,
<1), 266 (<1), 239 (<1), 206 (20), 193 (8), 91 (100), 57 (80).
ArH), 8.32e8.34 (m, 1H, ArH). Found: C, 65.80; H, 6.40; N, 7.05.
C21H24N2O5 requires: C, 65.61; H, 6.29; N, 7.29%.
3.2.3.14. tert-Butyl benzyloxy[2-(2-nitro-phenyl)-2-propenyl]car-
bamate (26g). Prepared by procedure C from 2-iodonitrobenzene
(365 mg, 1.47 mmol), N-Boc-O-benzylhydroxylamine (345 mg,
1.54 mmol) and allene gas (1 atm) in DMF (15 mL). Purification by
flash column chromatography eluting with 9:1 v/v petroleum
ether/ether afforded the product as a pale yellow oil (428 mg, 94%);
3.2.3.9. tert-Butyl benzyloxy[2-(2-methoxy-phenyl)-2-propenyl]
carbamate (26b). Prepared by procedure C from 2-iodoanisole
(315 mg, 1.35 mmol), N-Boc-O-benzylhydroxylamine (308 mg,
1.38 mmol) and allene gas (1 atm) in DMF (10 mL). Purification by
flash column chromatography eluting with 9:1 v/v petroleum
ether/ether afforded the product as a colourless oil (475 mg, 95%);
1H NMR
d: 1.31 (s, 9H, 3ꢁCH3), 4.32 (s, 2H, NCH2), 4.82 (s, 2H,
1H NMR
d
: 1.40 (s, 9H, 3ꢁCH3), 3.80 (s, 3H, OCH3), 4.43 (s, 2H,
OCH2), 5.08 and 5.33 (2ꢁs, 2ꢁ1H, ]CH2), 7.33e7.45 (m, 7H, ArH),
7.51e7.54 (m, 1H, ArH), 7.97e8.00 (m, 1H, ArH). Found: C, 65.75; H,
6.55; N, 7.15. C21H24N2O5 requires: C, 65.61; H, 6.29; N, 7.29%. m/z
(%): 383 (Mꢂ1, <1), 369 (13), 285 (40) and 91 (100).
NCH2), 4.74 (s, 2H, OCH2), 5.22 and 5.33 (2ꢁs, 2ꢁ1H, ]CH2),
6.84e6.94 (m, 2H, ArH), 7.20e7.36 (m, 7H, ArH). Found: C, 71.75; H,
7.40; N, 3.75. C22H27NO4 requires: C, 71.52; H, 7.37; N, 3.79%. m/z (%)
370 (Mþ1, 9), 314 (39), 270 (77), 91 (100).
3.2.3.15. tert-Butyl benzyloxy[2-(thiophen-2-yl)-2-propenyl]car-
bamate (27). Prepared by procedure C from 2-iodothiophene
(298 mg, 1.41 mmol), N-Boc-O-benzylhydroxylamine (340 mg,
1.52 mmol) and allene gas (1 atm) in DMF (15 mL). Purification by
flash column chromatography eluting with 9:1 v/v petroleum
ether/ether afforded the product as a colourless oil (451 mg, 92%);
3.2.3.10. tert-Butyl benzyloxy(2-(4-acetylphenyl)-2-propenyl)car-
bamate (26c). Prepared by procedure C from 4-iodoacetophenone
(467 mg, 1.99 mmol), N-Boc-O-benzylhydroxylamine (468 mg,
2.09 mmol) and allene gas (1 atm) in DMF (20 mL). Purification by
flash column chromatography eluting with 5:1 v/v petroleum
ether/ether afforded the product as a colourless oil (725 mg, 96%);
1H NMR
d
: 1.51 (s, 9H, 3ꢁCH3), 4.43 (s, 2H, NCH2), 4.74 (s, 2H,
1H NMR
d
: 1.49 (s, 9H, 3ꢁCH3), 2.60 (s, 3H, ArC(O)CH3), 4.50 (s, 2H,
OCH2), 5.21 and 5.58 (2ꢁs, 2ꢁ1H, ]CH2), 6.98 (dd, 1H, J 5.0 and
3.5 Hz, thiophene H), 7.15 (dd, 1H, J 1.0 and 3.5 Hz, thiophene H),
7.18 (dd, 1H, J 5.0 and 1.0 Hz, thiophene H), 7.30e7.31 (m, 5H,
NCH2), 4.67 (s, 2H, OCH2), 5.42 and 5.63 (2ꢁs, 2ꢁ1H, ]CH2),
7.26e7.31 (m, 5H, ArH), 7.56e7.59 (m, 2H, ArH), 7.92e7.95 (m, 2H,
ArH); 13C NMR
d: 27.0, 28.6, 54.1, 77.6, 82.2, 118.1, 126.9, 128.7, 128.9,
ArH); 13C NMR
d: 28.7, 54.3, 77.8, 82.1, 114.7, 124.7, 125.0 127.9,
129.7,135.8, 136.7, 142.9, 143.9,156.7,198.0. Found: C, 72.25; H, 7.10;
N, 3.80. C23H27NO4 requires: C, 72.42; H, 7.13; N, 3.67%. m/z (%) 380
(Mþ1, 2), 326 (21), 282 (21), 161 (7), 91 (100), 57 (44).
128.8, 128.9, 129.8 135.9, 137.2, 143.1, 156.7. Found: C, 66.25; H,
6.90; N, 3.80, S, 9.15. C19H23NO3S requires: C, 66.06; H, 6.71; N,
4.05, S, 9.28%. m/z (%): 363 (Mþ18, 35), 346 (8, Mþ1), 307 (100)
and 246 (15).
3.2.3.11. Methyl 4-(1-{[(benzyloxy)(tert-butoxycarbonyl)amino]
methyl}vinyl)benzoate (26d). Prepared by procedure C from 4-
iodobenzoic acid methyl ester (317 mg, 1.21 mmol), N-Boc-O-ben-
zylhydroxylamine (298 mg, 1.33 mmol) and allene gas (1 atm) in
DMF (10 mL). Purification by flash column chromatography eluting
with 20:20:1 v/v/v petroleum ether/DCM/ether afforded the
3.2.3.16. tert-Butyl benzyloxy[2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropydimidin-5-yl)prop-2-enyl]carbamate (28). Prepared by
procedure C from 5-iodo-1,3-dimethyluracil (268 mg, 1.01 mmol),
N-Boc-O-benzylhydroxylamine (236 mg, 1.06 mmol) and allene gas
(1 atm) in DMF (10 mL). Purification by flash column chromatog-
raphy eluting with 3:1 v/v petroleum ether/ethyl acetate afforded
product as a colourless oil (469 mg, 97%); 1H NMR
d: 1.48 (s, 9H,
the product as a pale yellow oil (402 mg, 96%); 1H NMR
d: 1.47 (s,
3ꢁCH3), 3.92 (s, 3H, OCH3), 4.50 (s, 2H, NCH2), 4.66 (s, 2H, OCH2),
5.41 and 5.61 (2ꢁs, 2ꢁ1H, ]CH2), 7.26e8.02 (m, 9H, ArH). Found: C,
69.50; H, 6.90; N, 3.60. C23H27NO5 requires: C, 69.50; H, 6.85; N,
3.52%. m/z (%): 398 (Mþ1, <1), 388 (<1), 369 (<1), 342 (28), 310
(12), 298 (29) and 91 (100).
9H, 3ꢁCH3), 3.34 and 3.36 (s, 6H, 2ꢁNCH3), 4.38 (s, 2H, NCH2), 4.75
(s, 2H, OCH2), 5.34 and 5.74 (2ꢁs, 2ꢁ1H, ]CH2), 7.32e7.34 (m, 6H,
5ꢁArH and 1ꢁ]CHN). Found: C, 62.60; H, 6.90; N, 10.20.
C21H27N3O5 requires: C, 62.83; H, 6.78; N, 10.47%. m/z (%): 419
(Mþ18, 7), 402 (44, Mþ1), 302 (100), 239 (40), 222 (50), 196 (38)
and 181 (74).
3.2.3.12. tert-Butyl benzyloxy[2-(4-nitro-phenyl)-2-propenyl]car-
bamate (26e). Prepared by procedure C from 4-iodonitrobenzene
(307 mg, 1.23 mmol), N-Boc-O-benzylhydroxylamine (304 mg,
1.36 mmol) and allene gas (1 atm) in DMF. Purification by flash
column chromatography eluting with 9:1 v/v petroleum ether/
ether afforded the product as a pale yellow oil (460 mg, 96%); 1H
3.2.3.17. 1-tert-Butyl 20-methyl 5-(1-{[(benzyloxy)(tert-butox-
ycarbonyl)amino]methyl}vinyl)-2-oxo-10,20,50,60,70,7a0-hexahydrospiro
[indole-3,30-pyrrolizine]-1,20(2H)-dicarboxylate (29). Prepared by
procedure C from 12 (1.123 g, 2.19 mmol), N-Boc-O-benzylhydrox-
ylamine (500 mg, 2.23 mmol), allene gas (1 atm), potassium
carbonate (335 mg, 2.43 mmol), tris-(dibenzylideneacetone) dipal-
ladium (51 mg, 2.5 mol %) and tris-(2-furyl)phosphine (64 mg,
12 mol %). Purification by flash column chromatography eluting
with 9:1 v/v petroleum ether/ether afforded the product as a col-
NMR
5.49 and 5.66 (2ꢁs, 2ꢁ1H, ]CH2), 7.28e7.34 (m, 5H, ArH),
7.60e7.63 (m, 2H, ArH), 8.17e8.21 (m, 2H, ArH); 13C NMR
: 28.6,
d
: 1.48 (s, 9H, 3ꢁCH3), 4.50 (s, 2H, NCH2), 4.67 (s, 2H, OCH2),
d
53.8, 77.6, 82.4, 119.7, 124.0, 127.6, 128.8, 129.0, 129.4 129.7, 130.9,
135.7, 142.2, 145.7, 147.7, 156.7. Found: C, 65.90; H, 6.35; N, 7.35.
C21H24N2O5 requires: C, 65.61; H, 6.29; N, 7.29%. m/z (%): 383 (Mþ1,
<1), 329 (24), 285 (8), 235 (12) and 91 (100).
ourless glass (1.25 g, 88%); 1H NMR
d
: 1.53 (s, 9H, 3ꢁCH3), 1.60 (m,
1H, 70-HA), 1.65 (s, 9H, 3ꢁCH3), 1.84 (m, 2H, 2ꢁ60-H), 2.05 (m, 1H, 70-
HB), 2.17 (m, 1H,10-HA), 2.35e2.41 (m, 2H, 50-HA and 10-HB), 2.55 (m,
1H, 50-HB), 3.15 (s, 3H, CH3O), 3.89 (dd, 1H, J 13.0 and 7.0 Hz, 20-H),
4.05 (m, 1H, 7a0-H), 4.44e4.68 (m, 4H, ONHCH2 and OCH2), 5.34 and
5.57 (2ꢁs, 2ꢁ1H, ]CH2), 7.26e7.31 (m, 6H, ArH), 7.50e7.54 (m, 1H,
3.2.3.13. tert-Butyl benzyloxy[2-(3-nitro-phenyl)-2-propenyl]car-
bamate (26f). Prepared by procedure C from 3-iodonitrobenzene
(365 mg, 1.47 mmol), N-Boc-O-benzylhydroxylamine (336 mg,
1.51 mmol) and allene gas (1 atm) in DMF (15 mL). Purification by
flash column chromatography eluting with 9:1 v/v petroleum
ether/ether afforded the product as a pale yellow oil (536 mg, 94%);
ArH), 7.92 (d, 1H, J 8.5 Hz, ArH); 13C NMR
d: 28.4, 28.7, 28.9, 32.8,
33.8, 47.6, 51.8, 54.5, 57.7, 65.6, 72.8, 82.2, 84.8, 115.5, 116.3, 123.4,
125.8,127.7, 128.7, 128.9, 129.6,134.7, 135.8, 140.3,142.2,149.7, 157.2,
170.6, 178.0. Found: C, 66.55; H, 7.10; N, 6.30. C36H45N3O8 requires:
C, 66.75; H, 7.00; N, 6.49%. m/z (%): 648 (Mþ1, 22), 620 (5), 461 (14),
325 (11), 298 (23), 91 (95) and 57 (100).
1H NMR
d
: 1.49 (s, 9H, 3ꢁCH3), 4.50 (s, 2H, NCH2), 4.69 (s, 2H,
OCH2), 5.30 and 5.45 (2ꢁs, 2ꢁ1H, ]CH2), 7.30e7.34 (m, 5H, ArH),
7.48e7.53 (m, 1H, ArH), 7.78e7.81 (m, 1H, ArH), 8.13e8.17 (m, 1H,

E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
3109
3.2.3.18. 1-tert-Butyl 20-methyl 5-(1-{[(benzyloxy)(tert-butox-
ycarbonyl)amino]methyl}vinyl)-2-oxo-10,50,60,70,80,8a0-hexahydro-20H-
spiro[indole-3,30-indolizine]-1,20(2H)-dicarboxylate (30). Prepared by
procedure C from 13 (553 mg, 1.05 mmol), N-Boc-O-benzylhydrox-
ylamine (240 mg, 1.07 mmol), allene gas (1 atm), potassium car-
bonate (253 mg, 1.83 mmol), tris-(dibenzylideneacetone)dipalladium
(28 mg, 3 mol %) and tris-(2-furyl)phosphine (31 mg, 12 mol %). Pu-
rification by flash column chromatography eluting with 9:1 v/v pe-
troleum ether/ether afforded the product as a colourless glass
and tris-(2-furyl)phosphine (26 mg, 11 mol %). Purification by flash
column chromatography eluting with 9:1 v/v petroleum ether/ether
afforded the product as a colourless oil (399 mg, 94%); 1H NMR
d: 1.49
(s, 9H, 3ꢁCH3), 4.53 (s, 2H, NCH2), 4.70 (s, 2H, OCH2), 5.34 and 5.60 (s,
2ꢁ1H, ]CH2), 7.31e7.37 (m, 8H, ArH), 7.41e7.50 (m, 2H, ArH),
7.58e7.62 (m, 4H, ArH). Found: C, 77.90; H, 7.15; N, 3.15. C27H29NO3
requires: C, 78.04; H, 7.03; N, 3.37%. m/z (%): 415 (Mþ, <1), 282 (45),
269 (7), 206 (74), 178 (83), 152 (48), 105 (17) and 57 (100).
(592 mg, 85%); 1H NMR
d
: 1.20e1.30 (m, 3H, 2ꢁ80-H and 60-HA), 1.43
3.2.3.23. tert-Butyl benzyloxy(2-cyclohex-1-en-1-ylprop-2-enyl)
carbamate (35). Prepared from cyclohex-1-enyl triflate (79 mg,
0.34 mmol), N-Boc-O-benzylhydroxylamine (81 mg, 0.36 mmol),
allene gas (1 atm), caesium carbonate (225 mg, 0.69 mmol), tris-
(dibenzylideneacetone) dipalladium (8 mg, 2.5 mol %) and tris-(2-
furyl)phosphine (8 mg, 10 mol %). in DMF (5 mL) at 105 ꢀC for
96 h. Purification by flash column chromatography eluting with
15:1 v/v petroleum ether/ether afforded the product as a colourless
(m, 1H, 60-HB), 1.50 (s, 9H, 3ꢁCH3), 1.65 (s, 9H, 3ꢁCH3), 1.70 (m, 1H,
70-HA), 1.90e1.93 (m, 1H, 70-HB), 2.15e2.25 (m, 2H, 2ꢁ10-H), 2.30 (m,
2H, 2ꢁ50-H), 3.09 (s, 3H OCH3), 3.21 (m, 1H, 8a0-H), 3.39 (dd, 1H, J 10
and 8.5 Hz, 20-H), 4.46 (s, 2H, ONHCH2), 4.68 (2ꢁd, 2H, J 19.5 Hz,
OCH2), 5.29 and 5.52 (2ꢁs, 2ꢁ1H, ]CH2), 7.30e7.76 (m, 8H, ArH);
HRMS: 662.3430; C37H47N3O8þH requires: 662.3441. m/z (%) 661
(Mþ, <1), 633 (5), 561 (40), 533 (48), 476 (10), 403 (12), 370 (12), 339
(28), 312 (75), 279 (31), 253 (82), 91 (100), 57 (80).
oil (103 mg, 87%); 1H NMR
d
: 1.47 (s, 9H, 3ꢁCH3), 1.58e1.69 (m, 4H,
cyclohexene 2ꢁCH2), 2.10e2.29 (m, 4H, cyclohexene 2ꢁCH2), 4.28
(s, 2H, NCH2), 4.77 (s, 2H, OCH2), 5.04 and 5.16 (2ꢁs, 2ꢁ1H, C]CH2),
3.2.3.19. tert-Butyl benzyloxy(2-pyrimidin-5-ylprop-2-enyl)car-
bamate (31). Prepared by procedure C from 5-bromopyrimidine
(209 mg, 1.31 mmol), N-Boc-O-benzylhydroxylamine (310 mg,
1.38 mmol), allene gas (1 atm), potassium carbonate (219 mg,
1.58 mol), tris-(dibenzylideneacetone)dipalladium (33 mg, 2.8 mol
%) and tris-(2-furyl)phosphine (36 mg, 12 mol %). Purification by
flash column chromatography eluting with 4:1 v/v petroleum
ether/ethyl acetate afforded the product as a pale yellow oil
5.98 (m, 1H, cyclohexene ]CH), 7.32e7.40 (m, 5H, ArH); 13C NMR
d:
22.5, 23.2, 26.2, 26.4, 28.7, 53.0, 77.5, 81.6, 112.5, 125.9, 128.7, 128.8,
129.8, 129.9, 134.7, 136.0, 143.2, 156.7. Found: C, 73.40; H, 8.25; N,
3.80. C21H29NO3 requires: C, 73.44; H, 8.51; N, 4.08%. m/z (%): 361
(Mþ18, 13), 344 (30, Mþ1), 305 (100), 288 (62), 244 (43), 136 (68)
and 91 (48).
(392 mg, 87%); 1H NMR
d
: 1.49 (s, 9H, 3ꢁCH3), 4.45 (s, 2H, NCH2),
3.2.3.24. tert-Butyl (tert-butoxycarbonyl)oxy(2-phenylprop-2-
enyl)carbamate (36a). Prepared by procedure C from iodo-
4.71 (s, 2H, OCH2), 5.47 and 5.60 (2ꢁs, 2ꢁ1H, ]CH2), 7.28e7.38 (m,
5H, ArH), 8.80 (s, 2H, ArH), 9.13 (s, 1H, ArH). Found: C, 66.55; H,
6.80; N,12.20. C19H23N3O3 requires: C, 66.84; H, 6.79; N,12.31%. m/z
(%): 341 (Mþ, 2), 241 (13), 211 (15), 120 (12), 91 (100) and 57 (90).
benzene (302 mg, 1.48 mmol), N-Boc-O-Boc-hydroxylamine
(364 mg, 1.56 mmol), allene gas (1 atm), potassium carbonate
(247 mg, 1.79 mol), tris-(dibenzylideneacetone) dipalladium
(35 mg, 2.5 mol %) and tris-(2-furyl)phosphine (36 mg, 10 mol %).
Purification by flash column chromatography eluting with 9:1 v/v
petroleum ether/ether afforded the product as a colourless oil
3.2.3.20. tert-Butyl benzyloxy(2-pyridin-3-ylprop-2-enyl)carba-
mate (32). Prepared by procedure
C from 3-bromopyridine
(216 mg, 1.37 mmol), N-Boc-O-Benzylhydroxylamine (322 mg,
1.44 mmol), allene gas (1 atm), potassium carbonate (230 mg,
1.67 mol), tris-(dibenzylideneacetone)dipalladium (33 mg, 2.7 mol
%) and tris-(2-furyl)phosphine (36 mg, 11 mol %). Purification by
flash column chromatography eluting with 4:1 v/v petroleum
ether/ethyl acetate afforded the product as a pale yellow oil
(412 mg, 80%); 1H NMR
OCH2), 5.31 and 5.49 (2ꢁs, 2ꢁ1H, ]CH2), 7.29e7.46 (m, 5H, ArH);
13C NMR
: 27.9, 28.4, 28.7, 54.2, 82.8, 115.7, 126.5, 126.6, 126.8,
d
: 1.46 and 1.47 (s, 18H, 6ꢁCH3), 4.64 (s, 2H,
d
128.2, 128.7, 139.1, 142.5, 152.5 155.0. Found: C, 65.60; H, 7.90; N,
3.90. C19H27NO5 requires: C, 65.31; H, 7.79; N, 4.01%. m/z (%): 349
(Mþ, <1), 193 (5), 177 (18), 159 (32), 130 (94), 103 (100), 91 (27), 77
(56) and 57 (93).
(300 mg, 64%); 1H NMR
d
: 1.48 (s, 9H, 3ꢁCH3), 4.47 (s, 2H, NCH2),
4.69 (s, 2H, OCH2), 5.40 and 5.56 (s, 2ꢁ1H, ]CH2), 7.27e7.33 (m, 6H,
ArH), 7.74 (m, 1H, ArH), 8.53 (dd, 1H, J 5.0 and 1.5 Hz, ArH), 8.73 (dd,
1H, J 2.5 and 1.0 Hz, ArH); HRMS: 341.1865; C20H24N2O3þH re-
quires: 341.1869. m/z (%): 341 (Mþ1, 100), 240 (16).
3.2.3.25. tert-Butyl (tert-butoxycarbonyl)oxy[2-(3-nitrophenyl)
prop-2-enyl]carbamate (36b). Prepared by procedure C from 3-
iodonitrobenzene (287 mg, 1.15 mmol), N-Boc-O-Boc-hydroxyl-
amine (287 mg, 1.23 mmol), allene gas (1 atm), tris-(dibenzylide-
neacetone)dipalladium (26 mg, 2.5 mol %) and tris-(2-furyl)
phosphine (27 mg, 10 mol %) in DMF (10 mL). Purification by flash
column chromatography eluting with 9:1 v/v petroleum ether/
ether afforded the product as a colourless oil (307 mg, 67%); 1H
3.2.3.21. tert-Butyl benzyloxy(2-(2-acetylphenyl)-2-propenyl)car-
bamate (33). Prepared by procedure C from 2-bromoacetophenone
(303 mg, 1.52 mmol), N-Boc-O-benzylhydroxylamine (371 mg,
1.66 mmol), allene gas (1 atm), potassium carbonate (250 mg,
1.81 mol), tris-(dibenzylideneacetone)dipalladium (38 mg, 2.7 mol
%) and tris-(2-furyl)phosphine (41 mg, 11 mol %). Purification by
flash column chromatography eluting with 6:1 v/v petroleum
ether/ether afforded the product as a colourless oil (469 mg, 81%);
NMR
d
: 1.47 (s, 18H, 6ꢁCH3), 4.66 (s, 2H, NCH2), 5.48 and 5.63 (2ꢁs,
2ꢁ1H, ]CH2), 7.48e7.53 (m, 1H, ArH), 7.77e7.78 (m, 1H, ArH),
8.12e8.16 (m, 1H, ArH), 8.31e8.33 (m, 1H, ArH). Found: C, 57.55; H,
6.80; N, 7.15. C19H26N2O7 requires: C, 57.86; H, 6.64; N, 7.10%. m/z
(%): 412 (Mþ18, 100), 312 (27) and 256 (53).
1H NMR
d
: 1.35 (s, 9H, 3ꢁCH3), 2.51 (s, 3H, ArC(O)CH3), 4.32 (s, 2H,
NCH2), 4.79 (s, 2H, OCH2), 5.05 and 5.30 (s, 2ꢁ1H, ]CH2), 7.20e7.62
(m, 9H, ArH). Found: C, 72.15; H, 7.20; N, 3.60. C23H27NO4 requires:
C, 72.42; H, 7.13; N, 3.67%. m/z (%): 382 (Mþ1, 9), 326 (8), 282 (100),
173 (15), 159 (60), 57 (47).
3.2.3.26. Methyl 3-[1-({(tert-butoxycarbonyl)[(tert-butoxycarbonyl)
oxy]amino}methyl)vinyl]benzoate (36c). Prepared by procedure C
from methyl 3-iodobenzoate (275 mg, 1.05 mmol), N-Boc-O-Boc-hy-
droxylamine (260 mg, 1.11 mmol), allene gas (1 atm), potassium
carbonate (205 mg, 1.48 mol), tris-(dibenzylideneacetone)dipalla-
dium (24 mg, 2.5 mol %) and tris-(2-furyl)phosphine (29 mg, 12 mol
%). Purification by flash column chromatography eluting with 9:1 v/v
petroleum ether/ether afforded the product as a colourless oil
3.2.3.22. tert-Butyl benzyloxy[2-(1,10-biphenyl-4-yl)prop-2-enyl]
carbamate (34). Prepared by procedure C from 4-bromobiphenyl
(238 mg, 1.02 mmol), N-Boc-O-benzylhydroxylamine (240 mg,
1.07 mmol), allene gas (1 atm), potassium carbonate (315 mg,
2.28 mol), tris-(dibenzylideneacetone)dipalladium (27 mg, 2.9 mol %)
(264 mg, 62%); 1H NMR
d: 1.47 (s, 18H, 6ꢁCH3), 3.91 (s, 3H, OCH3),

3110
E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
4.64 (s, 2H, NCH2), 5.39 and 5.55 (2ꢁꢁs, 2ꢁ1H, ]CH2), 7.40 (m, 1H,
2.5 mol %) and tris-(2-furyl)phosphine (15 mg, 10 mol %) in DMF
(5 mL). Purification by flash column chromatography eluting with
30:1 v/v petroleum ether/ether afforded the product as a colourless
ArH), 7.65 (m, 1H, ArH), 7.96 (m, 1H, ArH), 8.11 (m, 1H, ArH); 13C NMR
d: 27.9, 28.4, 52.5, 54.1, 78.6, 83.0, 85.2 116.9, 127.8, 128.8, 129.3, 130.7,
131.1, 139.4, 141.8, 152.4, 154.9, 167.3. Found: C, 61.85; H, 7.25; N, 3.35.
C21H29NO7 requires: C, 61.90; H, 7.17; N, 3.44%. m/z (%): 408 (Mþ1).
oil (161 mg, 90%); 1H NMR
d
: 1.33 (s, 6H, 2ꢁCH3), 4.75 (s, 2H, OCH2),
5.34 and 5.39 (2ꢁs, 2ꢁ1H, ]CH2), 5.43 (br s, 1H, NH), 6.97 (dd, 1H, J
5.0 and 3.5 Hz, thiophene H), 7.14 (dd, 1H, J 3.5 and 1.0 Hz, thiophene
H), 7.21 (dd, 1H, J 5.0 and 1.0 Hz, thiophene H), 7.28e7.35 (m, 5H,
3.2.3.27. N-[2-(4-Acetyl-phenyl)-allyl]-N-benzyloxyformamide
(37). Prepared by procedure
C
from 4-iodo-phenyl-ethanone
ArH); 13C NMR
d: 25.41, 61.1, 77.1, 116.8, 125.3, 126.6, 126.8, 128.0,
(244 mg, 1.00 mmol), N-benzyloxyformamide (156 mg, 1.03 mmol),
allene gas (1 atm), tris-(dibenzylideneacetone)dipalladium (23 mg,
2.5 mol %) and tris-(2-furyl)phosphine (23 mg, 10 mol %) in DMF
(10 mL). Purification by flash column chromatography eluting with
2:1 v/v petroleum ether/ethyl acetate afforded the product as a pale
128.6, 128.7, 138.7, 142.7, 147.8. Found: C, 70.35; H, 6.95; N, 5.20; S,
11.80. C16H19NOS requires: C, 70.29; H, 7.00; N, 5.12; S, 11.73%. m/z (%)
273 (Mþ, 1), 258 (10), 242 (32), 164 (72), 151 (34), 97 (42) and
91 (100).
yellow oil (287 mg, 93%); 1H NMR
d
: 2.60 (s, 3H, CH3), 4.30 and 4.67
3.2.4.3. 5-(2-Benzyloxyamino-2-methyl-1-methylene-propyl)-
1,3-dimethyl-1H-pyrimidine-2,4-dione (42). Prepared by procedure
D from 5-iodo-1,3-dimethyluracil (142 mg, 0.53 mmol), O-benzyl-
hydroxylamine (186 mg, 1.51 mmol), 1,1-dimethylallene (0.25 mL,
5 mol equiv), potassium carbonate (152 mg, 1.10 mol), tris-(diben-
zylideneacetone)dipalladium (15 mg, 3 mol %) and tris-(2-furyl)
phosphine (17 mg, 13 mol %) in DMF (5 mL). Purification by flash
column chromatography eluting with 2:1 v/v petroleum ether/ethyl
acetate afforded the product as a pale yellow oil (133 mg, 76%); 1H
(2ꢁbr s, 2ꢁ1H, NCH2), 4.73 and 4.93 (2ꢁbr s, 2ꢁ1H, OCH2), 5.47 and
5.72 (2ꢁs, 2ꢁ1H, ]CH2), 7.13e7.30 (m, 5H, ArH), 7.56 (br s, 2H,
ArH), 7.95 (d, 2H, J 8.5 Hz, ArH), 8.13 (br s,1H, CHO); 13C NMR
d: 27.1,
49.1, 77.6, 78.7, 119.3, 126.8, 129.1, 129.6, 129.8, 137.0, 141.8, 142.7,
163.8, 198.0. Found: C, 73.50; H, 6.20; N, 4.40. C19H19NO3 requires:
C, 73.77; H, 6.19; N, 4.53%. m/z (%): 327 (Mþ18, 85), 310 (13, Mþ1),
221 (100), 178 (72) and 161 (30).
3.2.3.28. N-Benzyloxy-N-(2-thiophen-2-yl-allyl)-formamide
(38). Prepared by procedure C from 2-iodothiophene (218 mg,
1.03 mmol), N-benzyloxyformamide (158 mg, 1.04 mmol), allene
gas (1 atm), tris-(dibenzylideneacetone)dipalladium (24 mg,
2.5 mol %) and tris-(2-furyl)phosphine (24 mg, 10 mol %) in DMF
(10 mL). Purification by flash column chromatography eluting with
2:1 v/v petroleum ether/ether afforded the product as a colourless
NMR
d
: 1.28 (s, 6H, 2ꢁCH3), 3.30 and3.34 (s, 6H, 2ꢁNCH3), 4.71 (s, 2H,
OCH2), 5.14 and 5.48 (2ꢁs, 2ꢁ1H, ]CH2), 5.86 (br s, 1H, NH), 7.15 (s,
1H, ]CHN), 7.27e7.37 (m, 5H, ArH). Found: C, 65.40; H, 7.15; N,12.55.
C18H23N3O3 requires: C, 65.63; H, 7.04; N, 12.76%. m/z (%) 330 (Mþ1,
<1), 315 (<1), 239(<1), 209 (100),193 (36),164 (19),122 (16), 91 (93).
3.2.4.4. 1-tert-Butyl 20-methyl 5-(1-{1-[(benzyloxy)amino]-1-
methylethyl}vinyl)-2-oxo-10,20,50,60,70,7a0-hexahydrospiro[indole-3,30-
pyrrolizine]-1,20(2H)-dicarboxylate (43). Prepared by procedure D
from 12 (349 mg, 0.68 mmol), O-benzylhydroxylamine (240 mg,
1.95 mmol), 1,1-dimethylallene (0.35 mL, 5 mol equiv), potassium
carbonate (172 mg, 1.24 mmol), tris-(dibenzylideneacetone)dipal-
ladium (19 mg, 3 mol %) and tris-(2-furyl)phosphine (22 mg,
14 mol %) in DMF (5 mL). Purification by flash column chromatog-
raphy eluting with 6:1 v/v petroleum ether/ethyl acetate afforded
oil (260 mg, 92%); 1H NMR
d
: 4.20 and 4.57 (2ꢁbr s, 2ꢁ1H, NCH2),
4.76 and 4.92 (2ꢁbr s, 2ꢁ1H, OCH2), 5.24 and 5.63 (2ꢁs, 2ꢁ1H, ]
CH2), 6.99 (dd, 1H, J 5.0 and 3.5 Hz, thiophene H), 7.15e7.32 (m, 7H,
ArH), 8.14 (br s, 1H, CHO); 13C NMR
d: 49.5, 79.2, 115.9, 124.6, 125.5,
125.6, 128.3, 129.1, 129.5, 130.0, 134.8, 136.3, 142.0, 163.9. Found: C,
65.65; H, 5.40; N, 4.90, S, 11.60. C15H15NO2S requires: C, 65.91; H,
5.53; N, 5.12, S, 11.73%.
3.2.4. General procedure for reactions using 1,1-dimethylallene
(procedure D). Nucleophile (1e3 mol equiv), 1,1-dimethylallene
(5 mol equiv), tris-(dibenzylideneacetone)dipalladium (2.5 mol %),
tris-(2-furyl)phosphine (10 mol %) and potassium carbonate
(2 mol equiv) were added to a solution of the aryl halide (1 mmol)
in dry dimethylformamide (10 mL) in a Schlenk tube. The reaction
mixture was then stirred and heated at 80 ꢀC for 16 h. After cooling
and venting, DCM (20 mL) was added and the mixture filtered to
remove inorganic salts. The filtrate was concentrated in vacuo and
the residue was purified by column chromatography.
the product as a pale yellow glass (269 mg, 47%); 1H NMR
d: 1.09
and 1.36 (s, 6H, 2ꢁCH3), 1.61 (m, 1H, 70-HA), 1.64 (s, 9H, 3ꢁCH3), 1.78
(m, 2H, 2ꢁ60-H),1.90 (m, 1H, 70-HB), 2.08 (m,1H,10-HA), 2.27 (m, 1H,
50-HA), 2.41 (m, 1H, 10-HB), 2.55 (m, 1H, 50-HB), 3.15 (s, 3H, CH3O),
3.84 (dd, 1H, J 13.0 and 6.0 Hz, 20-H), 3.97 (m, 1H, 7a0-H), 4.80 (s, 2H,
OCH2), 5.04 and 5.35 (2ꢁs, 2ꢁ1H, ]CH2), 5.58 (br s, 1H, NH),
7.21e7.41 (m, 7H, ArH), 7.86 (d, 1H, J 8.5 Hz, ArH). Found: C, 68.65;
H, 7.40; N, 7.40. C33H41N3O6 requires: C, 68.85; H, 7.18; N, 7.30%. m/z
(%) 575 (Mþ, 7), 489 (12), 460(9), 426 (13), 389 (21), 352 (26), 293
(33), 251 (17), 164 (19), 91 (100), 57 (36).
3.2.4.1. O-Benzyl-N-(1,1-dimethyl-2-phenyl-allyl)-hydroxylamine
3.2.4.5. 1-tert-Butyl 20-methyl 5-(1-{1-[(benzyloxy)amino]-1-
methylethyl}vinyl)-2-oxo-10,50,60,70,80,8a0-hexahydro-20H-spiro[in-
dole-3,30-indolizine]-1,20(2H)-dicarboxylate (44). Prepared by pro-
cedure D from 13 (288 mg, 0.55 mmol), O-benzylhydroxylamine
(220 mg, 1.79 mmol), 1,1-dimethylallene (0.25 mL, 5 mol equiv),
potassium carbonate (118 mg mg, 0.85 mmol), tris-(dibenzylide-
neacetone) dipalladium (13 mg, 2.5 mol %) and tris-(2-furyl)phos-
phine (13 mg, 10 mol %) in DMF (5 mL). Purification by flash column
chromatography eluting with 3:1 v/v petroleum ether/diethyl ether
(40). Prepared by procedure
D from iodobenzene (99 mg,
0.48 mmol), O-benzylhydroxylamine (196 mg, 1.59 mmol), 1,1-
dimethylallene (0.24 mL, 5 mol equiv), tris-(dibenzylideneace-
tone) dipalladium (11 mg, 2.5 mol %) and tris-(2-furyl)phosphine
(11 mg, 10 mol %) in DMF (5 mL). Purification by flash column
chromatography eluting with 19:1 v/v petroleum ether/ether
afforded the product as a colourless oil (108 mg, 83%); 1H NMR
d:
1.26 (s, 6H, 2ꢁCH3), 4.75 (s, 2H, OCH2), 5.02 and 5.34 (2ꢁs, 2ꢁ1H, ]
CH2), 5.45 (br s, 1H, NH), 7.27e7.35 (m, 10H, ArH). Found: C, 80.55;
H, 8.00; N, 5.20. C18H21NO requires: C, 80.86; H, 7.92; N, 5.24%. m/z
(%): 268 (Mþ1).
afforded the product as a colourless glass (207 mg, 64%); 1H NMR
d:
1.16 and 1.31 (s, 6H, 2ꢁCH3), 1.20e1.27 (m, 3H, 2ꢁ80-H and 60-HA),
1.55 (m, 1H, 60-HB), 1.66 (s, 9H, 3ꢁCH3), 1.70 (m, 1H, 70-HA), 1.89 (m,
1H, 70-HB), 2.11e2.17 (m, 2H, 2ꢁ10-H), 2.28e2.36 (m, 2H, 2ꢁ50-H),
3.13 (s, 3H OCH3), 3.18 (m, 1H, 8a0-H), 3.41 (dd, 1H, J 10.5 and 8.0 Hz,
20-H), 4.79 (s, 2H, OCH2), 5.00 and 5.32 (2ꢁs, 2ꢁ1H, ]CH2), 5.50 (br
s, 1H, NH), 7.22e7.42 (m, 7H, ArH), 7.71 (d, 1H, J 8.5 Hz, ArH); 13C
3.2.4.2. O-Benzyl-N-(1,1-dimethyl-2-thiophen-2-yl-allyl)-hydroxyl-
amine (41). Prepared by procedure
D from 2-iodothiophene
(137 mg, 0.65 mmol), O-benzylhydroxylamine (235 mg, 1.92 mmol),
1,1-dimethylallene (0.32 mL, 5 mol equiv), potassium carbonate
(131 mg, 0.95 mol), tris-(dibenzylideneacetone)dipalladium (14 mg,
NMR
d: 24.1, 24.9, 25.1, 26.1, 28.5, 32.2, 34.3, 45.7, 51.7, 52.8, 59.9,
60.9, 72.7, 77.6, 84.7, 113.9, 115.9, 126.0, 127.7, 127.9, 128.6, 128.7,

E.E. Elboray et al. / Tetrahedron 68 (2012) 3103e3111
3111
pp 303e341; (c) Melman, A. In Chemistry of Hydroxylamines, Oximes and Hy-
droxamic Acids; Rappoport, Z., Liebman, J. F., Eds.; Wiley: Chichester, UK, 2009;
pp 117e161; (d) Buncel, E.; Um, I. K. H.; Terrer, F. In Chemistry of Hydroxyl-
amines, Oximes and Hydroxamic Acids; Rappoport, Z., Liebman, J. F., Eds.; Wiley:
Chichester, UK, 2009; pp 817e837; (e) Romine, J. L. Org. Prepn. Procedures 1996,
28, 249e288.
130.5,138.6,139.5,149.6,154.3,172.1,177.6. Found: C, 68.95; H, 7.40;
N, 7.25. C34H43N3O6 requires: C, 69.25; H, 7.35; N, 7.13%. m/z (%) 575
(Mþ, 6), 489 (12), 475 (9), 389 (17), 352 (22), 326 (12), 293 (29), 251
(17), 164 (19), 91 (100).
3. (a) Lantos, I. Chim. Oggi 1995, 13, 39e41; (b) Ganem, B. Chemtracts: Org. Chem.
1990, 3, 363e364; (c) Ashani, Y.; Silman, I. In Chemistry of Hydroxylamines,
Oximes and Hydroxamic Acids; Rappoport, Z., Liebman, J. F., Eds.; Wiley: Chi-
chester, 2009; pp 609e651; (d) Prince, R. C.; George, G. N. Nat. Struct. Biol. 1997,
4, 247e250.
4. (a) Grigg, R.; Kemp, J.; Thompson, N. Tetrahedron Lett. 1978, 2827e2830; (b)
Grigg, G.; Markandu, J.; Surendrakumar, S.; Thornton-Pett, M.; Warnock, W. J.
Tetrahedron 1992, 48, 10399e10422; (c) Grigg, R.; Markandu, J.; Perrior, T.;
Surendrakumar, S.; Warnock, W. J. Tetrahedron 1992, 48, 6929e6952; (d) Grigg,
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Commun. 1993, 372e374.
3.2.4.6. O-Benzyl-N-(1,1-dimethyl-2-pyrimidin-5-yl-allyl)-hydrox-
ylamine (45). Prepared by procedure D from 5-bromopyrimidine
(84 mg, 0.53 mmol), O-benzylhydroxylamine (183 mg, 1.49 mmol),
1,1-dimethylallene (0.25 mL, 5 mol equiv), potassium carbonate
(129 mg, 0.93 mol), tris-(dibenzylideneacetone)dipalladium (19 mg,
3.9 mol %) and tris-(2-furyl)phosphine (22 mg, 18 mol %) in DMF
(5 mL). Purification by flash column chromatography eluting with
5:1 v/v petroleum ether/diethyl ether afforded the product as a col-
ourless oil (131 mg, 81%); 1H NMR
d: 1.29 (s, 6H, 2ꢁCH3), 4.67 (s, 2H,
5. Grigg, R.; Major, J. P.; Martin, F. M.; Whittaker, M. Tetrahedron Lett. 1999, 40,
7709e7771.
OCH2), 5.16 and 5.52 (2ꢁs, 2ꢁ1H, ]CH2), 5.18 (br s, 1H, NH),
7.29e7.37 (m, 5H, ArH), 8.77 (s, 2H, ArH), 9.14 (s, 1H, ArH). Found: C,
71.05; H, 7.20; N, 15.60. C16H19N3O requires: C, 71.35; H, 7.11; N,
15.60%. m/z (%) 270 (Mþ1, 12), 239(73), 91 (100), 51 (15).
6. (a) Grigg, R.; MacLachlan, W. S.; Rasparini, M. Chem. Commun. 2000, 2241e2242;
(b) von Seebach, M.; Grigg, R.; de Meijere, A. Eur. J. Org. Chem. 2002, 3268e3273;
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2005, 44, 7570e7574; (e) Grigg, R.; Inman, M.; Kilner, C.; Koppen, I.; Marchbank,
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Sridharan, V. J. Organomet. Chem. 1999, 576, 65e87.
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Hazra, A.; Paira, P.; Sahu, K. B.; Naskar, S.; Saha, P.; Paira, R.; Mondal, S.; Maity,
A.; Luger, P.; Weber, M.; Mondal, N. B.; Banerjee, S. Tetrahedron Lett. 2010, 51,
1585e1588; (c) Zhao, K.; Zhu, S.-L.; Shi, D.-Q.; Xu, X.-P.; Ji, S.-J. Synthesis 2010,
1793e1803; (d) Prasanna, R.; Purushothaman, S.; Suresh, M.; Raghunathan, R.
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Acknowledgements
We thank the ORS and Leeds University for a Tetley and Lupton
scholarships (to C.G.) and the Egyptian Government for a scholar-
ship (to E.E.E.).
References and notes
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