Palladium-catalysed aminocarbonylation of iodoarenes and iodoalkenes with aminophosphonate as N-nucleophile

Article abstract of DOI:10.1016/j.tet.2008.06.096

The high-yielding synthesis of novel N-acyl phosphonates with unprecedented structure was carried out by a homogeneous carbonylation reaction under mild reaction conditions. The palladium-catalysed aminocarbonylation of iodoalkenes (1-iodo-cyclohexene, 1-iodo-4-tert-butyl-cyclohexene, 1-iodo-2-methyl-cyclohexene and α-iodostyrene) with diethyl α-aminobenzyl-phosphonate as N-nucleophile resulted in the exclusive formation of carboxamides. The same reaction with iodoaromatics (iodobenzene, 2-iodothiophene) provided the corresponding carboxamide in high yields and some 2-keto-carboxamides as side products due to single and double carbon monoxide insertion, respectively.

Full text of DOI:10.1016/j.tet.2008.06.096

Tetrahedron 64 (2008) 8726–8730
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalysed aminocarbonylation of iodoarenes and iodoalkenes
with aminophosphonate as N-nucleophile
*
´
´
´
´
Attila Takacs, Andrea Petz, Laszlo Kollar
Department of Inorganic Chemistry, University of Pe´cs, H-7624 Pe´cs, P.O. Box 266, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 April 2008
Received in revised form 9 June 2008
Accepted 26 June 2008
Available online 28 June 2008
The high-yielding synthesis of novel N-acyl phosphonates with unprecedented structure was carried out
by a homogeneous carbonylation reaction under mild reaction conditions. The palladium-catalysed
aminocarbonylation of iodoalkenes (1-iodo-cyclohexene, 1-iodo-4-tert-butyl-cyclohexene, 1-iodo-2-
methyl-cyclohexene and a-iodostyrene) with diethyl a-aminobenzyl-phosphonate as N-nucleophile re-
sulted in the exclusive formation of carboxamides. The same reaction with iodoaromatics (iodobenzene,
2-iodothiophene) provided the corresponding carboxamide in high yields and some 2-keto-carbox-
amides as side products due to single and double carbon monoxide insertion, respectively.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Iodoaromatics
Iodoalkenes
Aminocarbonylation
Carbon monoxide
Palladium
Alkyl phosphonate
1. Introduction
further interesting application of alkyl phosphonates is the forma-
tion of coatings on magnetic nanoparticles.9
Alkyl/aryl phosphonates have a wide application in organic and
bioorganic chemistry. Due to their biological activity, they are used
as bioregulators, herbicides and antimalarial agents.1 Phosphonate
derivatives have gained an important role even in catalysis. Their
catalytic application can be divided into two major groups: (i)
immobilised silica catalysts are modified by various transition
metal phosphonates and (ii) transition metal complexes, used as
homogeneous catalysts, contain phosphorus ligands bearing a
phosphonate moiety.
As for the heterogeneous catalytic application, a range of
heterogeneous metal alkyl phosphonate modified silica catalysts
have been developed for oxidations. Vanadyl and cobalt(II) alkyl
phosphonate modified silicas were used for the oxidation of sul-
fides2 and allylic alcohols.3,4 Cerium(IV) alkyl phosphonate modified
silica proved to be an efficient catalyst for the oxidation of alcohols
to ketones or carboxylic acids.5 Zirconium phosphonate films con-
taining manganese(III) porphyrines are efficient catalysts towards
the epoxidation of cyclooctene.6 Titanium phosphonates supported
on palladium7 and immobilised titanium phosphonates8 are used as
catalysts for the hydrogenation of acetophenone and for the enan-
tioselective addition of diethylzinc to benzaldehyde, respectively. A
On the other hand, the coordination chemistry of phosphonated
phosphanes (primarily triphenylphosphine derivatives) with pal-
ladium(II) and platinum(II) was investigated in detail.10 These
highly water soluble ligands were exploited in rhodium-catalysed
hydroformylation11,12 and in carbonylation of benzyl chloride
towards phenylacetic acid.13 The heterobidentate (hemilabile)
phosphonate–phosphane ligands were used successfully in
methanol carbonylation.14,15 Bulky triphenylphosphines possessing
the PO(OEt)2 moiety were used as ligands in platinum-catalysed
hydroformylation in the presence of tin(II) chloride.16
Alkyl phosphonates have been coupled to the para position of
a pincer-ligand via Suzuki coupling.17 It was proved that diphenyl
methylphosphonate can be formed by reductive elimination from
a Pd(II) intermediate possessing methyl and P(O)(OPh)2 moieties.18
The replacement of a carboxylic group by an organophosphorus
moiety allows the resulting compounds to be bound to enzymes
that transfer substrates possessing a carboxylic functionality, and
this way may act as ‘false’ substrates. Phosphonates, acting as far-
nesyltransferase inhibitors, are promising antimalarial agents.19
Other type of inhibitors can be found among the phosphonates, e.g.,
b
-carboxamido-phosphonates were found as potent inhibitors of
glycerol phosphate dehydratase.20 The potential biological impor-
tance of our target compounds also prompted us to investigate the
possibility of their high-yielding synthesis.
The work presented here describes the functionalisation of
aminoalkyl phosphonates on their amino functionality, in order to
* Corresponding author.
E-mail address: kollar@ttk.pte.hu (L. Kollar).
´
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.096

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A. Takacs et al. / Tetrahedron 64 (2008) 8726–8730
8727
synthesise novel N-acyl phosphonates with unprecedented struc-
ture. From another point of view, palladium-catalysed amino-
carbonylation of iodoaromatics and iodoalkenes was applied to the
coupling of a phosphonate moiety to an aryl/alkenyl fragment.
insertion is due to the difficulty in forming the corresponding
carbamoyl ligand. The insertion of carbon monoxide into the pal-
ladium–N bond (i.e., into palladiumdsterically highly bulky amido
ligand) is unfavoured.
Even the effect of the carbon monoxide pressure on carbox-
amide (1a) yield shows an optimum. Practically no product
formation can be detected either at low (less than 10 bar) or high
(ca. higher than 55 bar) carbon monoxide pressure (entries 1–5).
A similar phenomenon was already observed in the amino-
carbonylation of iodoferrocene.23
2. Results and discussion
Iodoaromatics and iodoalkenes like iodobenzene (1), 2-iodo-
thiophene (2), 1-iodo-cyclohexene (3), 4-tert-butyl-1-iodo-cyclo-
hexene (4), 2-methyl-1-iodo-1-cyclohexene (5) and 10-iodostyrene
(6) were reacted with carbon monoxide and racemic diethyl
a
-
The aminocarbonylation of 3, 4 and 6 proceeds with excellent
conversion and high isolated yields (entries 7, 8 and 10) at atmo-
spheric carbon monoxide pressure. Much lower reactivity was
observed with 5, possessing a methyl group adjacent to the iodo
substituents, under the same reaction conditions (entry 9).
The formation of the above products can be rationalised on the
basis of the following simplified reaction mechanism (Scheme 2).
The oxidative addition of the iodoaryl/iodoalkenyl bond of the
substrate to palladium(0) complexes (PdLn, where L stands for tri-
phenylphosphine and solvent donor ligands), formed in situ from
palladium(II)-acetate and triphenylphosphine, resulted in the cor-
responding palladium-aryl/alkenyl catalytic intermediate (A). It is
followed by carbon monoxide activation yielding a complex with
terminal carbonyl ligand (B) and its insertion into palladium-aryl/
alkenyl bond results in the corresponding palladium-acyl complex
(C). This catalytic intermediate could react further in two ways. (i)
The aminolysis of C by primary or secondary amine affords the
corresponding amide as major product. The elimination of the
hydrogen iodide by triethylamine provides the ‘starting’ palla-
dium(0) complex. (ii) The activation of the amine as an amido
complex (D) is followed by carbon monoxide activation resulting as
a carbonyl complex, which undergoes carbon monoxide insertion
into the palladium-nitrogen bond resulting in a carbamoyl complex
(E). The corresponding ketocarboxamides are formed from the
latter intermediate by reductive elimination.
aminobenzyl-phosphonate (Scheme 1). A widely applied palla-
dium(0) catalyst formed in situ from palladium acetate and
triphenylphosphine was used also in this case.21 The corresponding
carboxamides (1a–6a) were formed with high chemoselectivity
and isolated in moderate to good yields. Ketocarboxamide forma-
tion, due to double carbon monoxide insertion, was observed only
with iodoaromatics (iodobenzene (1) and iodothiophene (2)) as
substrate resulting in 1b and 2b in traces (less than 5% in all cases)
and in 14% yield, respectively. No ketocarboxamides were detected
in case of the iodoalkenes (3–6).
It is known from previous studies that by the amino-
carbonylation of iodoaromatics, carried out with simple amines or
amines with ester functionality (amino acid esters), the keto-
carboxamide formation is highly favoured.22 Especially under
increased carbon monoxide pressure, high selectivities towards
double carbon monoxide insertion were observed. Surprisingly, the
application of an N-nucleophile with a phosphonate functionality
(diethyl
carboxamide selectivity, which reflects the high influence of the
phosphonate group bound to the -carbon. This fact might be due
a-aminobenzyl-phosphonate) resulted in low keto-
a
to the coordination of the phosphonate group to the palladium(0)
intermediates, modifying its structure favouring mono-
carbonylation. Furthermore, from mechanistic aspects (vide infra)
it seems to be obvious that the lack of double carbon monoxide
NHCH(Ph)P(O)(OEt)2
I
O
O
NHCH(Ph)P(O)(OEt)2
O
1
1a
1b
O
2
NHCH(Ph)P(O)(OEt)2
2a
I
NHCH(Ph)P(O)(OEt)2
2b
S
I
S
S
O
O
H
P(O)(OEt)2
H2N
+
O
O
NHCH(Ph)P(O)(OEt)2
CO
3
3a
Pd(OAc)2 / PPh3
I
NHCH(Ph)P(O)(OEt)2
4
4a
O
I
NHCH(Ph)P(O)(OEt)2
5
5a
NHCH(Ph)P(O)(OEt)2
I
O
6
6a
Scheme 1. Aminocarbonylation of iodoaromatics and iodoalkenes 1–6 with diethyl a-aminobenzyl-phosphonate.

´
8728
A. Takacs et al. / Tetrahedron 64 (2008) 8726–8730
1b
O
O
NHCH(Ph)P(O)(OEt)2
E
1a
1
O
O
PdLn-2
O
Et3NHI
NHCH(Ph)P(O)(OEt)2
CO
O
I
NHCH(Ph)P(O)(OEt)2
PdLn
Et3N
H2NCH(Ph)P(O)(OEt)2
D
PdLn-2NHCH(Ph)P(O)(OEt)2
C
A
Ln-2IPd
O
Ln-2IPd
Et3NHI
CO
Et3N
H2NCH(Ph)P(O)(OEt)2
B
Ln-2I(CO)Pd
Scheme 2. A simplified reaction mechanism for the aminocarbonylation with diethyl a-aminobenzyl-phosphonate as N-nucleophile.
Table 1
3. Conclusions
Aminocarbonylation of iodoaromatics and iodoalkenes with diethyl
phosphonate as amine nucleophilea
a-aminobenzyl-
The palladium-catalysed aminocarbonylation of various
iodoaromatics and iodoalkenes towards the corresponding car-
boxamides was carried out in high isolated yields. This way, novel
substituted phosphonates with N-acyl groups were obtained. The
highly selective formation of carboxamides to ketocarboxamides
can be explained by favoured single carbon monoxide insertion
relative to double CO insertion. The reaction tolerates structural
variation of the iodo-substrate. The high chemoselectivity and the
easy work-up of the reaction mixtures make these reactions of
synthetic importance.
Entry Substrate Retention p(CO) Conversion Ratio of the carbonylated products,b
time [h] [bar] [%]
(isolated yields) [%]
Carboxamide
Ketocarboxamide
1
2
3
4
5
6
7
8
9
10
1
1
1
1
1
2
3
4
5
6
20
20
40
40
24
20
20
20
20
23
10
20
20
40
60
40
1
1
40
1
0
55
60
85
3<
>98
>98
>98
50
d
d
96 (1a), (n.d.)
98 (1a), (52)
98 (1a), (72)
n.d.
86 (2a), (76)
100 (3a), (82)
100 (4a), (80)
100 (5a), (43)
100 (6a), (70)
4 (1b)
2 (1b)
2 (1b)
n.d.
14 (2b)
0
0
0
0
4. Experimental
>98
a
Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3, 10 mL DMF;
4.1. General procedures
a
-aminobenzyl-phosphonate/substrate¼1.1/1; 1 mmol substrate: iodobenzene (1),
2-iodothiophene (2), 1-iodo-cyclohexene (3), 4-tert-butyl-1-iodo-cyclohexene (4),
2-methyl-1-iodo-1-cyclohexene (5), 10-iodostyrene (6), reaction temperature: 50 ꢀC.
1H and 13C NMR spectrawere recorded in CDCl3 on a Varian Inova
400 spectrometer at 400.13 MHz and 100.62 MHz, respectively.
b
Determined by GC–MS.
Chemical shifts d are reported in parts per million relative to CHCl3
solution and the atmosphere was changed to carbon monoxide. The
colour changed to dark red. The reaction was conducted for 20 h at
50 ꢀC. Some metallic palladium was formed at the end of the re-
action, which was filtered. A sample of this solution was immedi-
ately analysed by GC–MS. The mixture was then concentrated and
evaporated to dryness in vacuo. The residue was dissolved in
chloroform (20 mL) and washed with water (20 mL). The organic
phase was thoroughly washed twice with 5% HCl (20 mL), saturated
NaHCO3 (20 mL), brine (20 mL), dried over Na2SO4 and concen-
trated to a yellow waxy material or a thick oil. Chromatography
(silica, EtOAc/CHCl3 or EtOAc/CH2Cl2, for exact eluent composition
see characterisation) yielded the desired carboxamides (3a–6a).
(7.26 and 77.00 ppm for 1H and 13C, respectively). Elemental analy-
ses were measured on a 1108 Carlo Erba apparatus. Samples of the
catalytic reactions were analysed with a Hewlett Packard 5830A gas
chromatograph fitted with a capillary column coated with OV-1.
Substrates 1 and 2, as well as diethyl a-aminobenzyl-phospho-
nate were purchased from Aldrich and were used as obtained.
Substrates 3–6 were synthesised in a three-step synthesis accord-
ing to modified conventional synthetic procedures22,24,25 by using
the corresponding keto derivatives as starting materials.
4.2. Aminocarbonylation experiments carried out
at normal pressure
In
0.025 mmol), PPh3 (13.1 mg, 0.05 mmol), substrates (3–6)
(0.5 mmol) and diethyl -aminobenzyl-phosphonate (153.7 mg,
a
typical experiment,
a
solution of Pd(OAc)2 (5.6 mg,
4.3. Aminocarbonylation experiments carried out
at high pressure
a
0.55 mmol) (see Table 1) was dissolved in 10 mL DMF under argon.
Triethylamine (1.0 mL) was added to the homogeneous yellow
The DMF solution of the catalyst precursor and reactants
(amounts given in Section 4.2) was transferred under argon into

´
A. Takacs et al. / Tetrahedron 64 (2008) 8726–8730
8729
a 100 mL stainless steel autoclave. The reaction vessel was pres-
surised to 10–60 bar total pressure with carbon monoxide and the
magnetically stirred mixture was heated in an oil bath at 50 ꢀC for
24 h. The work-up procedure is identical with that given above.
OCHaHb), 3.65–3.73 (m, 1H, OCHaHb), 1.55–2.27 (m, 7H,
CHþ3ꢁCH2), 1.25 (t, 7.0 Hz, 3H), 1.06 (t, 7.0 Hz, 3H), 0.88 (s, 9H, tBu).
13C NMR (CDCl3)
d: 167.7, 135.4, 134.4, 132.9, 128.6, 128.0, 127.9, 63.1
(2J(P,C)¼6.9 Hz), 62.9 (2J(P,C)¼6.9 Hz), 50.0 (1J(P,C)¼153.1 Hz), 43.3,
39.2, 32.0, 27.0, 25.7, 23.5, 16.3 (3J(P,C)¼5.4 Hz), 16.1
(3J(P,C)¼5.4 Hz). IR (KBr, (cmꢂ1)): 1664 (CON), 1637 (C]C), 1245
(P]O), 1028 (P–O). MS m/z (rel int. %): 407 (7), 270 (53), 165 (100),
106 (16). Analysis calculated for C22H34NO4P (407.49): C, 64.85; H,
8.41; N, 3.44. Found: C, 64.72; H, 8.23; N, 3.28. Rf (40% EtOAc/CHCl3)
0.61; yellow solid, mp 76–78 ꢀC. Yield: 80%.
4.4. Characterisation of the products
4.4.1. Diethyl N-benzoyl-
a-aminobenzyl-phosphonate (1a)
1H NMR (CDCl3)
d: 7.80–7.84 (m, 2H, Ph-ortho), 7.50–7.53 (m, 2H,
Ph-meta), 7.40–7.43 (m, 1H, Ph-para), 7.25–7.36 (m, 5H, Ph), 5.76
(dd, 9.4, 21.2 Hz, 1H, CH), 4.02–4.15 (m, 2H, 2ꢁ(OCHaHb)), 3.88–3.97
(m, 1H, OCHaHb), 3.66–3.75 (m, 1H, OCHaHb), 1.25 (t, 7.0 Hz, 3H),
4.4.7. Diethyl N-(2-methyl-cyclohexen-1-yl)-a-aminobenzyl-
1.05 (t, 7.0 Hz, 3H). 13C NMR (CDCl3)
d: 166.9, 135.3, 134.0, 131.6,
phosphonate (5a)
128.6, 128.5, 128.4, 128.3, 128.1, 128.0, 127.4, 63.1 (2J(P,C)¼7.0 Hz),
63.3 (2J(P,C)¼7.0 Hz), 51.2 (1J(P,C)¼153.8 Hz), 16.4 (3J(P,C)¼5.9 Hz),
16.1 (3J(P,C)¼5.9 Hz). IR (KBr, (cmꢂ1)): 1654 (CON), 1247 (P]O),
1025 (P–O). MS m/z (rel int. %): 347 (7), 210 (60), 105 (100), 77 (30).
Analysis calculated for C18H22NO4P (347.35): C, 62.24; H, 6.38; N,
4.03. Found: C, 62.10; H, 6.55; N, 3.79. Rf (40% EtOAc/CH2Cl2) 0.42;
off-white solid, mp 87–90 ꢀC. Yield: 72%.
1H NMR (CDCl3)
d: 7.42 (d, 7.2 Hz, 2H, Ph-ortho), 7.21–7.35 (m,
3H, Ph), 6.50 (br s, 1H, NH), 5.55 (dd, 9.6, 20.8 Hz, 1H, CH), 4.05–4.16
(m, 2H, 2ꢁ(OCHaHb)), 3.86–3.95 (m, 1H, OCHaHb), 3.65–3.73 (m, 1H,
OCHaHb), 1.73 (s, 3H, ]CCH3), 1.55–2.22 (m, 8H, 4ꢁCH2), 1.25 (t,
7.0 Hz, 3H), 1.06 (t, 7.0 Hz, 3H). 13C NMR (CDCl3)
d: 170.8, 135.7,
135.2, 132.3, 128.6, 128.0, 127.9, 63.1 (2J(P,C)¼7.0 Hz), 62.9
(2J(P,C)¼7.0 Hz), 49.8 (1J(P,C)¼152.7 Hz), 31.4, 26.8, 25.5, 22.1, 20.8,
16.4 (3J(P,C)¼5.6 Hz), 16.1 (3J(P,C)¼5.6 Hz). IR (KBr, (cmꢂ1)): 1651
(CON), 1237 (P]O), 1023 (P–O). MS m/z (rel int. %): 365 (10), 228
(23), 123 (100), 95 (21). Analysis calculated for C19H28NO4P
(365.41): C, 62.45; H, 7.72; N, 3.83. Found: C, 62.32; H, 7.49; N,
3.61. Rf (50% EtOAc/CH2Cl2) 0.49; off-white solid, mp 79–83 ꢀC.
Yield: 43%.
4.4.2. Diethyl N-phenylglyoxyloyl-a-aminobenzyl-
phosphonate (1b)
MS m/z (rel int. %): 375 (3), 270 (10), 238 (32), 105 (100), 77 (35).
4.4.3. Diethyl N-(2-thiophenyl-carbonyl)-a-aminobenzyl-
phosphonate (2a)
1H NMR (CDCl3) 7.65 (dd, 3.7, 1.0 Hz, 1H, Thioph), 7.34 (dd, 4.8,
1.0 Hz, 1H, Thioph), 7.20 (br s, 1H, NH), 7.05 (dd, 3.7, 4.8 Hz, 1H,
Thioph), 5.66 (dd, 1H, 9.3, 21.2 Hz, CH), 4.08–4.20 (m, 2H,
2ꢁ(OCHaHb)), 3.95 (dq, 7.0, 12.0 Hz, OCHaHb), 3.73 (dq, 7.0, 12.0 Hz,
4.4.8. Diethyl N-(1-phenyl-ethen-1-yl-carbonyl)-a-aminobenzyl-
phosphonate (6a)
1H NMR (CDCl3)
d
: 7.20–7.55 (m, 10H, 2ꢁPh), 6.80 (br s, 1H, NH),
6.05 (s, 1H, ]CH), 5.65 (s, 1H, ]CH), 5.60 (dd, 9.4, 20.6 Hz, 1H, CH),
4.00–4.15 (m, 2H, 2ꢁ(OCHaHb)), 3.88–3.96 (m, 1H, OCHaHb), 3.71–
3.80 (m, 1H, OCHaHb), 1.26 (t, 7.0 Hz, 3H), 1.07 (t, 7.0 Hz, 3H). 13C
OCHaHb), 1.30 (t, 7.0 Hz, 3H), 1.09 (t, 7.0 Hz, 3H). 13C NMR (CDCl3)
d:
161.1, 138.2, 135.1, 133.1, 130.6, 63.4 (2J(P,C)¼6.9 Hz), 63.2
(2J(P,C)¼6.9 Hz), 50.6 (1J(P,C)¼154.4 Hz), 16.3 (3J(P,C)¼5.7 Hz), 16.1
(3J(P,C)¼5.7 Hz). IR (KBr, (cmꢂ1)): 1649 (CON), 1228 (P]O), 1029
(P–O). MS m/z (rel int. %): 353 (2), 277 (6), 216 (43),111 (100), 83 (5).
Analysis calculated for C16H20NO4PS (353.37): C, 54.38; H, 5.70; N,
3.96. Found: C, 54.26; H, 5.57; N, 3.74. Rf (30% EtOAc/CHCl3) 0.34;
off-white solid, mp 122–125 ꢀC. Yield: 76%.
NMR (CDCl3) d: 166.8, 144.3, 136.4, 136.2, 132.0, 131.9, 128.6, 128.5,
128.0, 127.9, 122.0, 63.1 (2J(P,C)¼6.9 Hz), 62.9 (2J(P,C)¼6.9 Hz), 50.4
(1J(P,C)¼152.7 Hz), 16.3 (3J(P,C)¼5.7 Hz), 16.1 (3J(P,C)¼5.7 Hz). MS
m/z (rel int. %): 373 (4), 268 (33), 236 (60), 131 (31), 103 (100), 77
(25). Analysis calculated for C20H24NO4P (373.39): C, 64.34; H, 6.48;
N, 3.75. Found: C, 64.22; H, 6.63; N, 3.48. Rf (30% EtOAc/CHCl3) 0.38;
highly viscous oil. Yield: 70%.
4.4.4. Diethyl N-(2-thiophenyl-glyoxyloyl)-a-aminobenzyl-
phosphonate (2b)
MS m/z (rel int. %): 381 (4), 265 (8), 244 (35), 132 (15), 111 (100),
91 (24).
Acknowledgements
The authors thank the Hungarian Research Fund (OTKA
NI61591) and the Joint Project of the European UniondHungarian
National Development Program (GVOP-3.2.1-2004-04-0168/3) for
the financial support and Johnson Matthey for the generous gift of
palladium(II) acetate.
4.4.5. Diethyl N-(cyclohexen-1-yl-carbonyl)-
a
-aminobenzyl-
phosphonate (3a)
1H NMR (CDCl3)
d: 7.42 (d, 7.2 Hz, 2H, Ph-ortho), 7.22–7.33 (m,
3H, Ph), 6.78 (br s, 1H, NH), 6.62 (br s, 1H, ]CH), 5.55 (dd, 9.3,
21.0 Hz, 1H, CH), 4.02–4.15 (m, 2H, 2ꢁ(OCHaHb)), 3.86–3.95 (m, 1H,
OCHaHb), 3.80 (m, 1H, OCHaHb), 2.25 (br s, 2H, CH2), 2.12 (br s, 2H,
CH2), 1.55–1.65 (m, 4H, 2ꢁCH2), 1.25 (t, 7.0 Hz, 3H), 1.05 (t, 7.0 Hz,
References and notes
3H). 13C NMR (CDCl3)
d: 167.7, 135.4, 134.4, 132.9, 128.6, 128.0, 127.9,
1. Toy, D. F. Phosphorus Chemistry in Everyday Living; ACS: Washiongton, DC, 1976.
2. Al-Hashimi, M.; Fisset, E.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett. 2006,
47, 8017–8019.
3. Jurado-Gonzalez, M.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett. 2004, 45,
4465–4468.
4. Jurado-Gonzalez, M.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett. 2003, 44,
4283–4286.
5. Al-Haq, N.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett. 2003, 44, 769–771.
6. Benitez, I. O.; Bujoli, B.; Camus, L. J.; Lee, C. M.; Odobel, F.; Talham, D. R. J. Am.
Chem. Soc. 2002, 124, 4363–4370.
63.3 (2J(P,C)¼6.9 Hz), 62.9 (2J(P,C)¼6.9 Hz), 49.1 (1J(P,C)¼152.7 Hz),
25.3, 24.2, 22.0, 21.4, 16.3 (3J(P,C)¼5.7 Hz), 16.1 (3J(P,C)¼5.7 Hz). IR
(KBr, (cmꢂ1)): 1658 (CON),1632 (C]C),1247 (P]O),1027 (P–O). MS
m/z (rel int. %): 351 (9), 242 (12), 214 (54), 109 (100), 81 (28).
Analysis calculated for C18H26NO4P (351.38): C, 61.53; H, 7.46; N,
3.99. Found: C, 61.40; H, 7.41; N, 3.80. Rf (50% EtOAc/CHCl3) 0.54;
off-white solid, mp 92–95 ꢀC. Yield: 82%.
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1H NMR (CDCl3)
d: 7.40 (d, 7.2 Hz, 2H, Ph-ortho), 7.16–7.26 (m,
3H, Ph), 6.65 (br s, 1H, ]CH), 6.58 (br s, 1H, NH), 5.54 (dd, 9.4,
21.0 Hz, 1H, CH), 4.02–4.15 (m, 2H, 2ꢁ(OCHaHb)), 3.86–3.95 (m, 1H,
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