Synthesis of 2-oxophosphorindolines: Via the copper-catalyzed intramolecular aromatic C-H insertion of diazophosphonamidates

Article abstract of DOI:10.1039/c6ra10555f

An efficient synthetic method for 2-ethoxy-2-oxophosphorindolines, benzo-γ-phospholactams, has been successfully achieved through the copper-catalyzed intramolecular aromatic C-H insertion of diazophosphonamidates with up to 97% yield. The current method has advantages of mild and clean conditions, and an inexpensive catalyst.

Full text of DOI:10.1039/c6ra10555f

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DOI: 10.1039/C6RA10555F
Journal Name
ARTICLE
Synthesis of 2-oxophosphorindolines via the copper-catalyzed
intramolecular aromatic C-H insertion of
diazophosphonamidates †
Received 00th January 20xx,
Accepted 00th January 20xx
Peipei Huanga and Jiaxi Xua*
DOI: 10.1039/x0xx00000x
An efficient synthetic method for 2-ethoxy-2-oxophosphorindolines, benzo-γ-phospholactams, has been successfully
achieved through the copper-catalyzed intramolecular aromatic C-H insertion of diazophosphonamidates with up to 97% yield.
The current method has following advantages of mild and clean conditions, and inexpensive catalyst.
www.rsc.org/
induced
cyclization
of
dimethyl
2-(N-
Introduction
methylamino)benzoylphosphonate and trimethyl phosphate
under heating and subsequently Steven-type rearrangement.
Notably, both the methods of Swan and Griffiths suffer from
Organophosphorus compounds have attracted increasing
attention because of their extensive application in various fields
such as pesticides, peptidic mimetics, pharmaceuticals,
homogeneous catalysis, and chiral ligands.1 In contrast to more
studies proceeded on lactams and sultams, their analogue
phospholactams,2 as members of organophosphorus
compounds, which are potential stocks for importantly
biological compounds, have been paid less attention. Compared
with diverse synthetic methods for lactams3 and sultams,4 only
limited methods have been reported for the synthesis of
phospholactams.2b-e,5
extreme conditions and limited substrates.
have been widely applied in organic chemistry.9 The transition
metal-catalyzed intramolecular aromatic C-H insertions of
-Diazo compounds
-
diazo compounds are useful methods to construct benzocyclic
compounds.10 Herein, we present our convenient and efficient
synthesis of 3-benzoyl-2-ethoxy-2-oxophosphorindolines,
benzo-γ-phospholactams, from ethyl N-aryl-1-diazo-2-oxo-2-
phenylethylphosphonamidates under the catalysis of
inexpensive copper salts.
Indole and indoline derivatives are importantly biological
compounds and extensively exist in natural products.6 2-
Oxophosphorindolines are phosphorus analogues of indolin-2-
ones. To the best of our knowledge, very limited synthetic
approaches toward 2-oxophosphorindolines have been
reported.7,8 The first synthesis of 2-oxophosphorindolines was
introduced by Swan’s group,7 involving thermal cyclization
through
intramolecular
aminolysis
of
(2-
aminophenyl)methylphosphinates or the zwitterionic inner
salts of the corresponding amino phosphinic acids, and
condensation of inner salts of the amino phosphinic acids with
DCC (N,N’-dicyclohexylcarbodiimide) as coupling reagent
(Scheme 1, eqn. 1). Both 2-oxophosphorindolines and 2-
thioxophosphorindolines were obtained in moderate yields.
Griffiths’ group provided another strategy toward 2-
oxophosphorindoline, only one example of 1,3-dimethyl-2-
methoxy-3-dimethoxyphosphoryl-2-oxophosphorindoline
separated by HPLC without reported yield,8 involving carbene-
Scheme
1.
Synthetic
approaches
toward
2-
oxophosphorindolines.
a.State Key Laboratory of Chemical Resource Engineering, Department of Organic
Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing
100029, P. R. China. E-mail: jxxu@mail.buct.edu.cn; Fax: +86 10 64435565
† Electronic Supplementary Information (ESI) available: [1H and 13C NMR spectra of
Results and discussion
products 1, 2, and 3]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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We initiated our investigation by examining intramolecular C-
insertion of ethyl 1-diazo-N-methyl-2-oxo-2,N-
View Article Online
DOI: 10.1039/C6RA10555F
H
diphenylethylphosphonamidate (1a) (Table 1), which was
prepared from the Arbuzov reaction of 2-bromo-1-
phenylethanone and triethyl phosphite11 followed by
chlorination with oxalyl chloride,12 treatment with N-
methylaniline, and diazo transformation with
acetamidobenzenesulfonyl azide (p-ABSA) in the presence of
triethylamine (TEA) (Scheme 2). Delightly,
p-
diazophosphonamidate 1a was exhausted after refluxing in
toluene for 0.5 h with 10 mol% Cu(acac)2 as catalyst under N2
atmosphere,
affording
the
desired
product
2-
oxophosphorindoline 2a in 40% yield (Table 1, entry 1). The
reaction could be accomplished under air in higher to 78% yield
of the desired product (Table 1, entry 2). Either change solvent
from toluene to dichloromethane (DCM) or decrease of the
catalyst amount resulted in decrease of the product yield (Table
1, entries 3 and 4). The rhodium catalysts, such as Rh2(oct)2
(dirodium
(bis[rhodium(α,α,α
tetraoctanoate)
and
Rh2(esp)2
Scheme
phenylethylphosphonamidates
2.
Synthesis
of
ethyl
N-alkyl-N-aryl-1-diazo-2-oxo-2-
′
,α′-tetramethyl-1,3-benzenedipropionic
acid)]), were also able to catalyze the reaction to afford the
product in 56% and 78% yields, respectively (Table 1, entries 5
and 6). Other cupric catalysts (Table 1, entries 710), such as
Table 1. Optimization of conditions [a]
.
Cu(OAc)2·H 2O, CuCl2·2H2O, CuSO4·5H2O, and Cu(NO3)2·3H2O,
were also evaluated and inexpensive CuSO4·5H2O and
Cu(OAc)2·H 2O showed similar activities as Cu(acac)2 and
Rh2(esp)2 (Table 1, entries 2, 6, 7, and 9). The cuprous catalysts
CuI and CuBr catalyzed the reaction well, leading to the
formation of the desired product 2a in 67% and 75% yields,
respectively (Table 1, entries 11 and 12). The inexpensive
catalyst CuSO4·5H2O was further optimized. The product yield
decreased slightly, but with long reaction time, when the
solvent was changed into 1,2-dichloroethane (DCE) or DCM
(Table 1, entries 13 and 14). The yield dropped obviously when
the catalyst was reduced to 5 mol% (Table 1, entry 15). However,
the yield dropped suddenly when lengthening reaction time
(Table 1, entry 16), revealing that the product was destroyed
possibly under refluxing for long time. Strangely, anhydrous
CuSO4 showed lower activity than CuSO4·5H2O (Table 1, entry
17), indicating that the reaction was not sensitive to water.
Because water was applied as green solvent in the
Cu(NO3)2·3H2O-catalyzed carbene insertion reaction of
diazoacetamides,8 the treatment of diazophosphonamidate 1a
with Cu(NO3)2·3H2O in water was performed, but very poor
yield was obtained (Table 1, entry 18). Finally, although most
copper salts are efficient catalysts for the reaction, the best
conditions for the intramolecular C-H insertion of the
diazophosphonamidate 1a was acquired, 10 mol% CuSO4·5H2O
as catalyst in toluene at reflux for 0.5 h (Table 1, entry 9). The
product 2a was isolated as a pair of interconvertible and
inseparable diastereomers with different diastereomeric ratios
in different trials. The ratio achieved approximate 1:1 after
standing for a period of time (see ESI, Figure S1). We believed
that cis-product 2a was first generated in the aromatic C-H
Yield (%)[b]
Entry
Cat (mol%)
Solvent
Time (h)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Cu(acac)2 (10)
Cu(acac)2 (10)
Cu(acac)2 (10)
Cu(acac)2 (2)
Rh2(oct)2 (2)
Rh2(esp)2 (2)
PhMe
PhMe
DCM
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
DCE
0.5
0.5
15
40
78
68
70
56
78
76
62
77
72
67
75
74
76
70
33
57
25
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
24
0.5
8
0.5
0.5
Cu(OAc)2·H 2O (10)
CuCl2·2H2O (10)
CuSO4·5H2O (10)
Cu(NO3)2·3H2O (10)
CuI (10)
CuBr (10)
CuSO4·5H2O (10)
CuSO4·5H2O (10)
CuSO4·5H2O (5)
CuSO4·5H2O (10)
CuSO4 (10)
DCM
PhMe
PhMe
PhMe
H2O
Cu(NO3)2·3H2O (10)
[a] All reactions were conducted on a 0.5 mmol scale in 10
mL of solvent
[b] Yields were calculated from the H NMR spectra of the
crude reaction mixtures.
.
1
We initiated our investigation by examining intramolecular C-
H
insertion
of
ethyl
1-diazo-N-methyl-2-oxo-2,N-
insertion and it converted into a mixture of cis- and tran- diphenylethylphosphonamidate (1a) (Table 1), which was
isomeric product due to the existence of the acidic proton prepared fromthe Arbuzov reaction of 2-bromo-1-
between the carbonyl and phosphonamidate group.13
phenylethanone and triethyl phosphite9 followed by
2 | J. Name., 2012, 00, 1-3
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chlorination with oxalyl chloride,10 treatment with N- conditions (Table 2). A series of 2-oxophosphorindoline
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methylaniline, and diazo transformation with p- derivatives 2 were obtained from diazophosphonamidates .
DOI: 10.1039/C6RA101555F
acetamidobenzenesulfonyl azide (p-ABSA) in the presence of
triethylamine (TEA). Delightly, diazophosphonamidate 1a was Table 2. Substrate cope of intramolecular C-H insertion of
exhausted after refluxing in toluene for 0.5 hr with 10 mol% diazophosphonamidates.a
Cu(acac)2 as catalyst under N2 atmosphere, affording the
desired product 2-oxophosphorindoline 2a in 40% yield (Table
1, entry 1). The reaction could be accomplished under air in
higher to 78% yield of the desired product (Table 1, entry 2).
Either change solvent from toluene to dichloromethane (DCM)
or decrease of the catalyst amount resulted in decrease of the
-----------------------------------------------------------------------------------
product yield (Table 1, entries 3 and 4). The rhodium catalysts,
such as Rh2(oct)2 (dirodium tetraoctanoate) and Rh2(esp)2
(bis[rhodium(α,α,α
′,α′-tetramethyl-1,3-benzenedipropionic
acid)]), were also able to catalyze the reaction to afford the
product in 56% and 78% yields, respectively (Table 1, entries 5
and 6). Other cupric catalysts (Table 1, entries 710), such as
Cu(OAc)2·H 2O, CuCl2·2H2O, CuSO4·5H2O, and Cu(NO3)2·3H2O,
were also evaluated and inexpensive CuSO4·5H2O and
Cu(OAc)2·H 2O showed similar activities as Cu(acac)2 and
Rh2(esp)2 (Table 1, entries 2, 6, 7, and 9). The cuprous catalysts
CuI and CuBr catalyzed the reaction well, leading to the
formation of the desired product 2a in 67% and 75% yields,
respectively (Table 1, entries 11 and 12). The inexpensive
catalyst CuSO4·5H2O was further optimized. The product yield
decreased slightly, but with long reaction time, when the
solvent was changed into 1,2-dichloroethane (DCE) or DCM
(Table 1, entries 13 and 14). The yield dropped obviously when
the catalyst was reduced to 5 mol% (Table 1, entry 15). However,
the yield dropped suddenly when lengthening reaction time
(Table 1, entry 16), revealing that the product was destroyed
possibly under refluxing for long time. Strangely, anhydrous
CuSO4 showed lower activity than CuSO4·5H2O (Table 1, entry
17), indicating that the reaction was not sensitive to water.
Because water was applied as green solvent in the
Cu(NO3)2·3H2O-catalyzed carbene insertion reaction of
diazoacetamides,8 the treatment of diazophosphonamidate 1a
with Cu(NO3)2·3H2O in water was performed, but very poor
yield was obtained (Table 1, entry 18). Finally, although most
copper salts are efficient catalysts for the reaction, the best
conditions for the intramolecular C-H insertion of the
diazophosphonamidate was acquired, 10 mol% CuSO4·5H2O as
catalyst in toluene at reflux for 0.5 h (Table 1, entry 9).The
product 2a was isolated as a pair of interconvertible and
inseparable diastereomers with different diastereomeric ratios
in different trials. The ratio achieved approximate 1:1 after
standing for a period of time (see ESI, Figure S1). We believed
that cis-product 2a was first generated in the aromatic C-H
insertion and it converted into a mixture of cis- and tran-
isomeric product due to the existence of the acidic proton
between the carbonyl and phosphonamidate group.11
[a] Yields were obtained by chromatography on silica gel.
The results indicated that diazophosphonamidates 1b and 1c
with n-propyl and benzyl instead of methyl at the N atom also
performed excellently, affording products 2b and 2c in 73% and
62% yields, respectively, without aliphatic C-H insertion product
observed. Diazophosphonamidates 1d-j with para-substituents,
either electron-donating or weakly withdrawing, on their N-
phenyl group gave rise to the corresponding products 2d-j in
relatively lower yields than the unsubstituted substrates 1a and
1b, respectively. The influence of substituted positions on the
N-phenyl ring was further studied. Diazophosphonamidate 1k
with N-2-methylphenyl at the N atom produced the desired 2-
oxophosphorindoline 2k in low 45% yield due to steric
hindrance. However, diazophosphonamidates 1l and 1m with
N-3-methylphenyl at the N atom yielded two regioisomeric
products 2la and 2lb, and 2ma and 2mb in high yields of 97%
and 86%, respectively, with indistinguishable ratios because of
the existence of two pairs of diastereomers in their product
mixtures. Diazophosphonamidates 1n and 1o with sterically
bulkyl isopropyl and tert-butyl groups on their N-phenyl group
also yielded the corresponding 2-oxophosphorindolines 2n and
2oin 65% and 71% yields, respectively. With respect to
diazophosphonamidate 1p with the N-naphth-2-yl group, it
administered the desired product 2p in 69% yield
regiospecifically at the sterically less β-position of the naphthyl
group. Thus, it is reasonable to rationalize the regioisomers 2la
and 2ma as major products in the reactions of 1l and 1m due to
steric hindrance. Diazophosphonamidate 1q derived from
After optimization of the reaction conditions, various
diazophosphonamidates
procedures for the preparation of 1a. The substrate scope of the
intramolecular aromatic C-H insertion of
diazophosphonamidates was investigated with the optimized
1 were prepared followed the
1
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tetrahydroquinoline generated the corresponding 2-oxo-2- mechanism for the CuSO4•5H2O-catalyzed transfoVrmiewaAtritoicnle oOnfliαne-
phosphorindoline 2q in 79% yield under the optimized diazo-β-oxo-N-phenylethanesulfonamidesDO1I: 10t.o10339-/Cbe6RnAz1o0y5l5-52F-
conditions.
To verify
oxophosphorindolines, after several attempts, suitable single the catalysis of Cu catalyst and heating, affording the Cu-
crystals for X-ray diffraction analysis were obtained from a carbenoids , which subsequently undergo an intramolecular
ethoxy-2-oxo-2-phosphorindolines
2
is proposed in Scheme 3.
the
stereostructure
of
prepared
2- Firstly, α-diazo-β-oxoethanesulfonamides
1
release N2 under
A
solution of freshly prepared 2-oxo-2-phosphorindoline 2q in aromatic electrophilic addition through their zwitterionic
ethyl acetate. The X-ray diffraction analysis results indicate that intermediates from their less bulky side to generate cyclized
the freshly prepared 2-oxo-2-phosphorindoline 2q is cis- intermediates
B
. The intermediates
After an orbital symmetry allowed suprafacial
H[1,5] sigmatropic shift and releasing of the Cu catalyst,
zwitterionic enolic intermediates are generated and further
resonate into the final products cis-3-benzoyl-2-oxo-2-
phosphorindolines cis- The products cis- are
B can tautomerize into
product as assumed (CCDC 1483899)(Figure 1).
intermediates C.
D
2
.
2
thermodynamically unstable and can further epimerize into
their more thermodynamically stable form, trans-3-benzoyl-2-
oxo-2-phosphorindolines trans-2, in the presence of acidic
substances, even weak acidic chloroform and water. For
example, trans-product is more stable in energy than the
corresponding cis-product by 2.4 kcal/mol for product 2a 13
.
Conclusions
In summary, an efficient synthesis of 1-alkyl-3-benzoyl-2-
ethoxy-2-oxophosphorindolines that are not accessible by
previous methods has been successfully achieved via the
copper-catalyzed intramolecular aromatic C-H insertion of
diazophosphonamidates. The current method is featured with
mild and clean conditions, inexpensive catalyst, and simple
operations.
Figure 1. Stereostructure of freshly prepared 2-oxophosphorindoline 2q
Experimental
General information
Dichloromethane and 1,2-dichloroethane were refluxed over
CaH2 and freshly distilled prior to use. Toluene was refluxed
over Na with benzophenone as an indicator and freshly distilled
prior to use. Melting points were obtained on a Yanaco MP-500
1
melting point apparatus and are uncorrected. H, 13C, 31P, and
19F NMR spectra were recorded on a Bruker 400 MHz
spectrometer in CDCl3 with TMS as an internal standard, 85%
phosphoric acid and boron trifluoride etherate as external
standards, respectively, and the chemical shifts (δ) are reported
in parts per million (ppm). The IR spectra (KBr pellets, v [cm−1])
were taken on a Nicolet 5700 FTIR spectrometer. HRMS
measurements were carried out on an Agilent LC/MSD TOF
mass spectrometer. TLC separations were performed on silica
gel GF254 plates, and the plates were visualized under UV light.
The ratios of the regiomers, if there were, were determined by
1H NMR analyses of reaction mixtures via the integrals of the
protons on the C3 atom in the γ-phospholactam ring.
Scheme 3. Proposed mechanism for the formation of cis-2-
oxophosphorindolines and their epimerization
Preparation of diethyl 2-oxo-2-phenylethylphosphonate11 (4)
Bromoacetophenone (75 mmol, 14.94 g) and triethylphosphite
(75 mmol, 12.45 g) were mixed and refluxed for 4 h. The
resulting crude brown oil was purified on silica gel column (EA:
Similarly as the Cu(NO3)2•3H2O-catalyzed transformation of α-
diazo-β-ketoanilides to 3-alkylideneoxindoles,10c a plausible
4 | J. Name., 2012, 00, 1-3
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PE = 1: 3, v/v) to yield the pure phosphonate
(13.11 g, 68% yield).
4
as a yellow oil 8.2 Hz, 1H), 4.61 (dd, J = 15.2, 8.8 Hz, 1H), 4.26 – V4ie.1w5Ar(timcle,O1nHlin)e,
DOI: 10.1039/C6RA10555F
4.02 – 3.91 (m, 1H), 3.68 (dd, J = 20.8, 14.0 Hz, 1H), 3.55 (dd, J =
20.8, 14.0 Hz, 1H), 1.20 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
General procedure for the synthesis of ethyl N-alkyl-N-aryl-2-oxo-
2-phenylethylphosphonamidates 3
CDCl3) δ 192.9 (d, JC-P = 5.8 Hz), 141.6 (d, JC-P = 4.4 Hz), 138.4 (d,
JC-P = 2.8 Hz), 136.9 (d, JC-P = 2.1 Hz), 133.4, 129.2, 129.0, 128.5,
128.2, 128.21, 127.1, 127.0 (d, JC-P = 3.1 Hz), 125.8 (d, JC-P = 1.4
To a mixed solution of phosphonate
4 (8 mmol, 2.05 g) and 2
Hz), 60.9 (d, JC-P = 6.7 Hz), 53.7 (d, JC-P = 5.1 Hz), 39.0 (d, JC-P
=
drops of DMF in 8 mL of DCM was added oxalyl chloride (24
mmol, 3.05 g, 2.03 mL), and the mixture was stirred for 16 h at
room temperature. After removal of solvent and low-boiling
residues under reduced pressure, phosphonic chloride was
obtained without any purification.12 The crude phosphonic
chloride was dissolved in 10 mL of DCM. To the solution was
added a mixed solution of secondary amine (8 mmol) and TEA
(8 mmol, 809.5 mg) in 10 mL of DCM. After stirred for another
2 h at room temperature, the mixture was washed with 10 mL
of water and the organic phase was dried over anhydrous
sodium sulfate. After removal of solvent under reduced
pressure, the residual oil was purified on silica gel column (EA:
118.8 Hz), 16.0 (d, JC-P = 7.1 Hz). 31P NMR (162 MHz, CDCl3) δ
22.1. IR (KBr, cm-1): 1678, 1274 (P=O). HRMS (ESI) calcd for
C23H25NO3P+ [M+H+] 394.1567, found 394.1575.
Ethyl
N-methyl-N-(4-methoxyphenyl)-2-oxo-2-
phenylethylphosphonamidate (3d)
Yellow oil, 1.7 g, 61% yield, Rf = 0.28 (PE:EA = 1:1, v/v). 1H NMR
(400 MHz, CDCl3) δ 8.03 – 7.97 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H),
7.44 (t, J = 7.7 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.9 Hz,
2H), 4.26 – 4.15 (m, 1H), 4.10 – 3.99 (m, 1H), 3.77 (s, 3H), 3.68
(dd, J = 21.3, 13.8 Hz, 1H), 3.56 (dd, J = 21.2, 13.8 Hz, 1H), 3.11
(d, J = 8.5 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 192.9 (d, JC-P = 5.7 Hz), 157.1, 136.8 (d, JC-P = 1.7 Hz),
136.5 (d, JC-P = 4.3 Hz), 133.3, 129.0, 128.4, 126.5 (d, JC-P = 3.0
Hz), 114.4, 60.5 (d, JC-P = 6.7 Hz), 55.3, 38.8 (d, JC-P = 117.2 Hz),
37.8 (d, JC-P = 5.6 Hz), 16.0 (d, JC-P = 7.0 Hz). 31P NMR (162 MHz,
CDCl3) δ 22.6. IR (KBr, cm-1): 1676, 1274 (P=O). HRMS (ESI) calcd
for C18H23NO4P+ [M+H+] 348.1359, found 348.1366.
PE = 1: 3, v/v) to yield the pure phosphonamidate 3.
Ethyl N-methyl-2-oxo-2,N-diphenylethylphosphonamidate (3a)
Yellow oil, 3.98 g (20 mmol scale), 63% yield, Rf = 0.40 (PE:EA =
1:1, v/v). 1H NMR (400 MHz, CDCl3) δ 8.00 – 7.96 (m, 2H), 7.58 –
7.52 (m, 1H), 7.47 – 7.40 (m, 2H), 7.35 – 7.27 (m, 4H), 7.15 –
7.08 (m, 1H), 4.27 – 4.16 (m, 1H), 4.07 – 3.99 (m, 1H), 3.71 (dd,
J = 21.4, 14.0 Hz, 1H), 3.60 (dd, J = 21.2, 14.4 Hz, 1H), 3.17 (d, J
= 8.4 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3)
Ethyl
N-benzyl-N-(4-methoxyphenyl)-2-oxo-2-
phenylethylphosphonamidate (3e)
δ 192.6 (d, JC-P = 5.7 Hz), 143.8 (d, JC-P = 4.6 Hz), 136.8 (d, JC-P
=
1.7 Hz), 133.4, 129.1, 129.0, 128.5, 124.3, 123.2 (d, JC-P = 3.4 Hz),
60.7 (d, JC-P = 6.7 Hz), 38.8 (d, JC-P = 117.8 Hz), 36.7 (d, JC-P = 4.8
Hz), 16.0 (d, JC-P = 7.0 Hz). 31P NMR (162 MHz, CDCl3) δ 22.4. IR
(KBr, cm-1): 1676, 1273 (P=O). HRMS (ESI) calcd for C17H21NO3P+
[M+H+] 318.1254, found 318.1258.
Yellow oil, 1.13 g, 33% yield, Rf = 0.48 (PE:EA = 1:1, v/v). 1H NMR
(400 MHz, CDCl3) δ 8.05 – 7.98 (m, 2H), 7.60 – 7.53 (m, 1H), 7.49
– 7.42 (m, 2H), 7.25 – 7.16 (m, 5H), 7.10 (d, J = 8.0 Hz, 2H), 6.77
(d, J = 8.8 Hz, 2H), 4.82 (dd, J = 14.8, 7.7 Hz, 1H), 4.47 (dd, J =
14.8, 8.7 Hz, 1H), 4.25 – 4.13 (m, 1H), 4.02 – 3.91 (m, 1H), 3.75
(s, 3H), 3.67 (dd, J = 21.0, 13.9 Hz, 1H), 3.50 (dd, J = 21.1, 13.9
Hz, 1H), 1.21 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
193.1 (d, JC-P = 5.7 Hz), 157.9 (d, JC-P = 1.2 Hz), 138.4 (d, JC-P = 2.9
Hz), 137.0 (d, JC-P = 2.0 Hz), 133.9 (d, JC-P = 4.2 Hz), 133.4, 129.6
(d, JC-P = 2.8 Hz), 129.0, 128.6, 128.5, 128.2, 127.1, 114.4, 60.8
(d, JC-P = 6.6 Hz), 55.3, 54.6 (d, JC-P = 5.8 Hz), 38.9 (d, JC-P = 118.9
Hz), 16.1 (d, JC-P = 7.1 Hz). 31P NMR (162 MHz, CDCl3) δ 22.5. IR
(KBr, cm-1): 1677, 1275 (P=O). HRMS (ESI) calcd for C24H27NO4P+
[M+H+] 424.1672, found 424.1682.
Ethyl 2-oxo-2,N-diphenyl-N-propylethylphosphonamidate (3b)
1
Yellow oil, 1 g, 36% yield, Rf = 0.52 (PE:EA = 1:1, v/v). H NMR
(400 MHz, CDCl3) δ 8.02 – 7.96 (m, 2H), 7.58 – 7.51 (m, 1H), 7.48
– 7.40 (m, 2H), 7.36 – 7.28 (m, 4H), 7.22 – 7.15 (m, 1H), 4.27 –
4.14 (m, 1H), 4.14 – 4.00 (m, 1H), 3.69 – 3.47 (m, 3H), 3.47 –
3.36 (m, 1H), 1.52 – 1.37 (m, 2H), 1.25 (t, J = 7.0 Hz, 3H), 0.84 (t,
J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 192.9 (d, JC-P = 5.9
Hz), 141.5 (d, JC-P = 4.2 Hz), 136.9 (d, JC-P = 1.8 Hz), 133.3, 129.2
(d, JC-P = 1.1 Hz), 129.0, 128.4, 127.2 (d, JC-P = 3.1 Hz), 125.8 (d,
JC-P = 1.4 Hz), 60.6 (d, JC-P = 6.7 Hz), 51.2 (d, JC-P = 4.4 Hz), 39.1 (d,
JC-P = 117.9 Hz), 22.2 (d, JC-P = 2.5 Hz), 16.1 (d, JC-P = 7.1 Hz), 11.0.
31P NMR (162 MHz, CDCl3) δ 22.1. IR (KBr, cm-1): 1677, 1274
(P=O). HRMS (ESI) calcd for C19H25NO3P+ [M+H+] 346.1567,
found 346.1575.
Ethyl
N-methyl-N-(4-methylphenyl)-2-oxo-2-
phenylethylphosphonamidate (3f)
Yellow oil, 1.79 g, 67% yield, Rf = 0.47 (PE:EA = 1:1, v/v). 1H NMR
(400 MHz, CDCl3) δ 8.01 – 7.95 (m, 2H), 7.58 – 7.52 (m, 1H), 7.46
– 7.40 (m, 2H), 7.18 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H),
4.26 – 4.12 (m, 1H), 4.11 – 3.97 (m, 1H), 3.68 (dd, J = 21.3, 13.9
Hz, 1H), 3.59 (dd, J = 21.2, 13.9 Hz, 1H), 3.14 (d, J = 8.5 Hz, 3H),
2.30 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
192.7 (d, JC-P = 5.7 Hz), 141.1 (d, JC-P = 4.5 Hz), 136.8 (d, JC-P = 1.7
Hz), 134.3, 133.3, 129.7, 129.0, 128.4, 123.8 (d, JC-P = 3.3 Hz),
60.6 (d, JC-P = 6.7 Hz), 38.7 (d, JC-P = 117.6 Hz), 37.0 (d, JC-P = 5.1
Ethyl N-benzyl-2-oxo-2,N-phenylethylphosphonamidate (3c)
1
Yellow oil, 429 mg, 14% yield, Rf = 0.64 (PE:EA = 1:1, v/v). H
NMR (400 MHz, CDCl3) δ 8.02 – 7.97 (m, 2H), 7.59 – 7.52 (m, 1H),
7.45 (t, J = 7.6 Hz, 2H), 7.29 – 7.08 (m, 10H), 4.92 (dd, J = 15.2,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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ARTICLE
Journal Name
Hz), 20.7, 16.0 (d, JC-P = 7.0 Hz). 31P NMR (162 MHz, CDCl3) δ 22.1. 4.09 – 3.99 (m, 1H), 3.73 (dd, J = 21.4, 14.0 Hz, 1H)V,ie3w.5A9rtic(ldedO,nlJin=e
IR (KBr, cm-1): 1678, 1273 (P=O). HRMS (ESI) calcd for 21.2, 14.0 Hz, 1H), 3.14 (d, J = 8.4 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H).
DOI: 10.1039/C6RA10555F
C18H23NO3P+ [M+H+] 332.1410, found 332.1417.
13C NMR (101 MHz, CDCl3) δ 192.5 (d, JC-P = 5.7 Hz), 142.5 (d, JC-
= 4.8 Hz), 136.7 (d, JC-P = 1.7 Hz), 133.6, 129.7, 129.1, 129.0,
P
Ethyl
N-benzyl-N-(4-methylphenyl)-2-oxo-2- 128.6, 124.5 (d, JC-P = 3.4 Hz), 60.9 (d, JC-P = 6.7 Hz), 38.7 (d, JC-P
phenylethylphosphonamidate (3g)
= 117.7 Hz), 36.7 (d, JC-P = 4.7 Hz), 16.1 (d, JC-P = 6.9 Hz). 31P NMR
(162 MHz, CDCl3) δ 22.2. IR (KBr, cm-1): 1678, 1272 (P=O). HRMS
Yellow oil, 950 mg, 29% yield, Rf = 0.48 (PE:EA = 1:1, v/v). H (ESI) calcd for C17H20ClNO3P+ [M+H+] 352.0864, found 352.0872.
1
NMR (400 MHz, CDCl3) δ 8.03 – 7.96 (m, 2H), 7.59 – 7.52 (m, 1H),
7.48 – 7.41 (m, 2H), 7.25 – 7.15 (m, 5H), 7.09 (d, J = 8.1 Hz, 2H), Ethyl
N-(4-fluorophenyl)-N-methyl-2-oxo-2-
7.05 (d, J = 8.5 Hz, 2H), 4.88 (dd, J = 15.1, 8.1 Hz, 1H), 4.55 (dd, J phenylethylphosphonamidate (3j)
= 15.1, 8.8 Hz, 1H), 4.27 – 4.13 (m, 1H), 4.03 – 3.90 (m, 1H), 3.66
(dd, J = 20.9, 14.0 Hz, 1H), 3.53 (dd, J = 21.1, 14.0 Hz, 1H), 2.27 Yellow oil, 1.97 g, 73% yield, Rf = 0.34 (PE:EA = 1:1, v/v). 1H NMR
(s, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 193.0 (400 MHz, CDCl3) δ 8.02 – 7.96 (m, 2H), 7.60 – 7.53 (m, 1H), 7.49
(d, JC-P = 5.8 Hz), 138.8 (d, JC-P = 4.2 Hz), 138.5 (d, JC-P = 2.9 Hz), – 7.42 (m, 2H), 7.29 – 7.22 (m, 2H), 7.02 – 6.94 (m, 2H), 4.27 –
137.0 (d, JC-P = 2.0 Hz), 135.8 (d, JC-P = 1.3 Hz), 133.34, 129.9, 4.15 (m, 1H), 4.13 – 3.99 (m, 1H), 3.71 (dd, J = 21.4, 13.9 Hz, 1H),
129.0, 128.4, 128.3, 128.2, 127.3 (d, JC-P = 3.0 Hz), 127.1, 60.8 (d, 3.58 (dd, J = 21.3, 13.9 Hz, 1H), 3.12 (d, J = 8.5 Hz, 3H), 1.30 (t, J
JC-P = 6.7 Hz), 54.0 (d, JC-P = 5.4 Hz), 38.9 (d, JC-P = 118.9 Hz), 20.8 , = 7.0 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 192.7 (d, JC-P = 5.7 Hz),
16.0 (d, JC-P = 7.1 Hz). 31P NMR (162 MHz, CDCl3) δ 22.4. IR (KBr, 156.0 (d, JC-F = 245.4 Hz), 139.8 (dd, JC-F = 4.5, JC-P = 3.1 Hz), 136.7
cm-1): 1677, 1274 (P=O). HRMS (ESI) calcd for C24H27NO3P+ (d, JC-P = 1.6 Hz), 133.5, 129.0, 128.5, 126.1 (dd, JC-P = 8.2, JC-F
[M+H+] 408.1723, found 408.1734.
3.1 Hz), 115.8 (d, JC-F = 22.3 Hz), 60.7 (d, JC-P = 6.7 Hz), 38.7 (d, JC-
= 117.3 Hz), 37.4 (d, JC-P = 5.0 Hz), 16.0 (d, JC-P = 6.9 Hz). 19
=
F
P
Ethyl
N-(4-bromophenyl)-N-methyl-2-oxo-2- NMR (376 MHz, CDCl3) δ -117.8 (d, J = 1.5 Hz). 31P NMR (162
phenylethylphosphonamidate (3h)
MHz, CDCl3) δ 22.3. IR (KBr, cm-1): 1676, 1275 (P=O). HRMS (ESI)
calcd for C17H20FNO3P+ [M+H+] 336.1159, found 336.1171.
Yellow oil, 565 mg, 18% yield, Rf = 0.26 (PE:EA = 1:1, v/v). Two
1
rotamers exist, rotamers A:B = 1.00:0.30. H NMR (400 MHz, Ethyl
N-methyl-N-(2-methylphenyl)-2-oxo-2-
CDCl3) δ 8.00 – 7.94 (rotamers A and B, m, 4H), 7.59 – 7.52 phenylethylphosphonamidate (3k)
(rotamers A and B, m, 2H), 7.47 – 7.41 (rotamers A and B, m,
1
4H), 7.40 – 7.36 (rotamers A and B, m, 3H), 7.32 – 7.29 (rotamers Yellow oil, 379 mg, 14 % yield, Rf = 0.21 (PE:EA = 1:1, v/v). H
A and B, m, 2H), 7.19 – 7.14 (rotamers A and B, m, 3H), 4.27 – NMR (400 MHz, CDCl3) δ 8.11 – 8.02 (m, 2H), 7.62 – 7.56 (m, 1H),
4.15 (rotamers A and B, m, 2H), 4.09 – 3.97 (rotamers A and B, 7.47 (t, J = 7.6 Hz, 2H), 7.37 – 7.33 (m, 1H), 7.26 – 7.15 (m, 3H),
m, 2H), 3.79 – 3.54 (rotamers A and B, m, 4H), 3.17 (rotamer B, 4.26 – 4.14 (m, 1H), 4.13 – 4.02 (m, 1H), 3.77 (dd, J = 21.4, 13.4
d, J = 8.4 Hz, 3H), 3.13 (rotamer A, d, J = 8.4 Hz, 3H), 1.33 – 1.25 Hz, 1H), 3.62 (dd, J = 21.4, 13.4 Hz, 1H), 3.02 (d, J = 9.0 Hz, 3H),
(rotamers A and B, m, 6H). 13C NMR (101 MHz, CDCl3) δ 192.6 2.37 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
(rotamer B, d, JC-P = 5.9 Hz), 192.4 (rotamer A, d, JC-P = 5.7 Hz), 193.0 (d, JC-P = 6.2 Hz), 142.1 (d, JC-P = 3.3 Hz), 137.1 (d, JC-P = 3.7
143.8 (rotamer B, d, JC-P = 4.6 Hz), 142.9 (rotamer A, d, JC-P = 4.8 Hz), 136.9, 133.4, 131.4, 129.2, 128.9 (d, JC-P = 1.9 Hz), 128.5,
Hz), 136.8 (rotamer B, d, JC-P = 1.6 Hz), 136.6 (rotamer A, d, JC-P 127.3 (d, JC-P = 1.3 Hz), 127.1 (d, JC-P = 1.2 Hz), 61.2 (d, JC-P = 6.7
= 1.8 Hz), 133.5 (rotamer A), 133.4 (rotamer B), 132.0 (rotamer Hz), 39.8 (d, JC-P = 115.1 Hz), 37.7 (d, JC-P = 5.3 Hz), 18.1, 16.1 (d,
A), 129.1 (rotamer B), 128.9 (rotamer B), 128.91 (rotamer A), JC-P = 6.8 Hz). 31P NMR (162 MHz, CDCl3) δ 21.7. IR (KBr, cm-1):
128.5 (rotamer A), 128.4 (rotamer B), 124.6 (rotamer A, d, JC-P
=
1677, 1272 (P=O). HRMS (ESI) calcd for C18H23NO3P+ [M+H+]
3.4 Hz), 124.3 (rotamer B), 123.1 (rotamer B, d, JC-P = 3.4 Hz), 332.1410, found 332.1419.
117.3 (rotamer A), 60.8 (rotamer A, d, JC-P = 6.7 Hz), 60.7
(rotamer B, d, JC-P = 6.7 Hz), 38.7 (rotamer B, d, JC-P = 118.3 Hz), Ethyl
N-benzyl-N-(3-methylphenyl)-2-oxo-2-
38.6 (rotamer A, d, JC-P = 117.7 Hz), 36.7 (rotamer B, d, JC-P = 4.8 phenylethylphosphonamidate (3l)
Hz), 36.5 (rotamer A, d, JC-P = 4.7 Hz), 16.1 (rotamer B, d, JC-P
=
7.6 Hz), 16.0 (rotamer A, d, JC-P = 6.9 Hz). 31P NMR (162 MHz, Yellow oil, 543 mg, 17% yield, Rf = 0.55 (PE:EA = 1:1, v/v). H
CDCl3) δ 22.4 (rotamer B), 22.2 (rotamer A). IR (KBr, cm-1): 1678, NMR (400 MHz, CDCl3) δ 8.02 – 7.96 (m, 2H), 7.58 – 7.51 (m, 1H),
1272 (P=O). HRMS (ESI) calcd for C17H20BrNO3P+ [M+H+] 7.44 (t, J = 7.6 Hz, 2H), 7.25 – 7.16 (m, 5H), 7.13 (t, J = 7.7 Hz,
1
396.0359, found 396.0358.
1H), 7.05 – 6.98 (m, 2H), 6.94 (d, J = 7.5 Hz, 1H), 4.90 (dd, J =
15.3, 8.3 Hz, 1H), 4.60 (dd, J = 15.2, 9.0 Hz, 1H), 4.25 – 4.13 (m,
Ethyl
N-(4-chlorophenyl)-N-methyl-2-oxo-2- 1H), 4.02 – 3.89 (m, 1H), 3.66 (dd, J = 21.2, 14 Hz, 1H), 3.56 (dd,
phenylethylphosphonamidate (3i)
J = 21.2, 14 Hz, 1H), 2.26 (s, 3H), 1.20 (t, J = 7.0 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 192.9 (d, JC-P = 5.9 Hz), 141.5 (d, JC-P = 4.3 Hz),
1
Yellow oil, 670 mg, 24% yield, Rf = 0.31 (PE:EA = 1:1, v/v). H 139.0, 138.5 (d, JC-P = 2.7 Hz), 136.9 (d, JC-P = 2.1 Hz), 133.3, 128.9,
NMR (400 MHz, CDCl3) δ 7.99 – 7.94 (m, 2H), 7.60 – 7.54 (m, 1H), 128.9, 128.4, 128.2, 128.1, 127.6 (d, JC-P = 3.1 Hz), 127.0, 126.6
7.45 (t, J = 7.7 Hz, 2H), 7.28 – 7.19 (m, 4H), 4.27 – 4.17 (m, 1H), (d, JC-P = 1.3 Hz), 124.0 (d, JC-P = 3.1 Hz), 60.9 (d, JC-P = 6.7 Hz),
6 | J. Name., 2012, 00, 1-3
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Journal Name ARTICLE
53.7 (d, JC-P = 5.1 Hz), 39.0 (d, JC-P = 118.7 Hz), 21.3, 16.0 (d, JC-P Yellow oil, 1.7 g, 58% yield, Rf = 0.27 (PE:EA = 1:1, Vvie/wv)A.rt1icHleNOnMlinRe
= 7.1 Hz). 31P NMR (162 MHz, CDCl3) δ 22.3.IR (KBr, cm-1): 1677, (400 MHz, CDCl3) δ 7.89 – 7.83 (m, 2H), 7.71 – 7.62 (m, 3H), 7.54
DOI: 10.1039/C6RA10555F
1274 (P=O). HRMS (ESI) calcd for C24H27NO3P+ [M+H+] 408.1723, (s, 1H), 7.45 – 7.39 (m, 2H), 7.38 – 7.26 (m, 4H), 3.65 (dd, J =
found 408.1733.
21.3, 14.0 Hz, 1H), 3.56 (dd, J = 21.1, 14.0 Hz, 1H), 3.17 (d, J =
8.4 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
Ethyl
N-methyl-N-(3-methylphenyl)-2-oxo-2- 192.5 (d, JC-P = 5.8 Hz), 141.3 (d, JC-P = 4.5 Hz), 136.7 (d, JC-P = 1.8
phenylethylphosphonamidate (3m)
Hz), 133.7, 133.3, 130.5, 128.8, 128.8, 128.4, 127.3, 126.2, 125.1,
122.8 (d, JC-P = 2.8 Hz), 120.1 (d, JC-P = 4.2 Hz), 60.8 (d, JC-P = 6.7
Yellow oil, 1.23 g, 46% yield, Rf = 0.34 (PE:EA = 1:1, v/v). 1H NMR Hz), 38.7 (d, JC-P = 117.6 Hz), 36.8 (d, JC-P = 4.7 Hz), 16.0 (d, JC-P
=
(400 MHz, CDCl3) δ 8.03 – 7.93 (m, 2H), 7.55 (t, J = 7.2 Hz, 1H), 6.9 Hz). 31P NMR (162 MHz, CDCl3) δ 22.6. IR (KBr, cm-1): 1677,
7.44 (t, J = 7.7 Hz, 2H), 7.19 (t, J = 7.7 Hz, 1H), 7.12 – 7.06 (m, 1274 (P=O). HRMS (ESI) calcd for C21H23NO3P+ [M+H+] 368.1410,
2H), 6.92 (d, J = 7.4 Hz, 1H), 4.26 – 4.15 (m, 1H), 4.09 – 3.98 (m, found 368.1420.
1H), 3.69 (dd, J = 21.6, 13.8 Hz, 1H), 3.62 (dd, J = 21.2, 13.6 Hz,
1H), 3.15 (d, J = 8.4 Hz, 3H), 2.32 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). Ethyl
(3,4-dihydroquinolin-1(2H)-yl)(2-oxo-2-
13C NMR (101 MHz, CDCl3) δ 192.6 (d, JC-P = 5.8 Hz), 143.7 (d, JC- phenylethyl)phosphinate (3q)
= 4.6 Hz), 139.0, 136.8 (d, JC-P = 1.6 Hz), 133.4, 129.0, 128.9,
P
128.5, 125.2, 124.0 (d, JC-P = 3.5 Hz), 120.4 (d, JC-P = 3.3 Hz), 60.6 Yellow oil, 1.48 g, 54% yield, Rf = 0.29 (PE:EA = 1:1, v/v). 1H NMR
(d, JC-P = 6.7 Hz), 38.8 (d, JC-P = 117.7 Hz), 36.8 (d, JC-P = 4.8 Hz), (400 MHz, CDCl3) δ 7.97 – 7.88 (m, 2H), 7.57 – 7.50 (m, 1H), 7.46
21.5, 16.0 (d, JC-P = 7.0 Hz). 31P NMR (162 MHz, CDCl3) δ 22.4. IR – 7.37 (m, 3H), 7.16 – 7.04 (m, 2H), 6.97 – 6.89 (m, 1H), 4.23 –
(KBr, cm-1): 1677, 1275 (P=O). HRMS (ESI) calcd for C18H23NO3P+ 4.13 (m, 1H), 4.04 – 3.93 (m, 1H), 3.90 – 3.80 (m, 1H), 3.73 (d, J
[M+H+] 332.1410, found 332.1419.
= 21.2 Hz, 2H), 3.48 – 3.39 (m, 1H), 2.85 – 2.70 (m, 2H), 1.92 –
1.75 (m, 2H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3)
Ethyl
N-(4-isopropylphenyl)-N-methyl-2-oxo-2- δ 192.0 (d, JC-P = 5.9 Hz), 139.3 (d, JC-P = 4.7 Hz), 136.7 (d, JC-P
=
1.4 Hz), 133.3, 130.1, 128.9, 128.4, 127.4 (d, JC-P = 6.7 Hz), 126.4,
122.0, 119.0 (d, JC-P = 1.5 Hz), 60.6 (d, JC-P = 6.8 Hz), 44.5 (d, JC-P
phenylethylphosphonamidate (3n)
Yellow oil, 1.31 g, 45% yield, Rf = 0.27 (PE:EA = 1:1, v/v). 1H NMR = 2.9 Hz), 38.6 (d, JC-P = 117.5 Hz), 27.3, 22.7 (d, JC-P = 2.5 Hz),
(400 MHz, CDCl3) δ 8.00 – 7.95 (m, 2H), 7.58 – 7.51 (m, 1H), 7.43 15.9 (d, JC-P = 7.1 Hz). 31P NMR (162 MHz, CDCl3) δ 21.8. IR (KBr,
(t, J = 7.6 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), cm-1): 1678, 1275 (P=O). HRMS (ESI) calcd for C19H23NO3P+
4.26 – 3.96 (m, 2H), 3.69 (dd, J = 21.2, 11.2 Hz, 1H), 3.61 (dd, J = [M+H+] 344.1410, found 344.1420.
21.2, 11.2 Hz, 1H), 3.15 (d, J = 8.4 Hz, 3H), 2.87 (hept, J = 6.9 Hz,
1H), 1.28 (t, J = 7.1 Hz, 3H), 1.22 (d, J = 6.9 Hz, 6H). 13C NMR (101 General procedure for the synthesis of ethyl N-alkyl- N-aryl-1-
MHz, CDCl3) δ 192.7 (d, JC-P = 5.8 Hz), 145.1, 141.4 (d, JC-P = 4.5 diazo-2-oxo-2-phenylethylphosphonamidates 1
Hz), 136.9 (d, JC-P = 1.8 Hz), 133.4, 129.0, 128.5, 127.1, 123.6 (d,
JC-P = 3.4 Hz), 60.6 (d, JC-P = 6.7 Hz), 38.8 (d, JC-P = 117.5 Hz), 37.0 The corresponding phosphonamidate 3 (1 mmol) was dissolved
(d, JC-P = 5.0 Hz), 33.4, 23.9, 16.0 (d, JC-P = 7.0 Hz). 31P NMR (162 in 5 mL of dry MeCN with p-acetamidobenzenesulfonyl azide
MHz, CDCl3) δ 22.6. IR (KBr, cm-1): 1677, 1273 (P=O). HRMS (ESI) (1.02 mmol, 245.04 mg). The resulting solution was cooled to 0
calcd for C20H27NO3P+ [M+H+] 360.1723, found 360.1714.
oC. Et3N (1.5 mmol, 151.67 mg, 0.22 mL) was added, and the
reaction mixture was warmed up to room temperature and
Ethyl
N-[4-(tert-butyl)phenyl]-N-methyl-2-oxo-2- stirred for 15 h. The volatiles were evaporated under reduced
phenylethylphosphonamidate (3o)
pressure to yield the crude product that was purified on silica
gel column (EA: PE = 1: 3, v/v) to yield the pure product
1
.
Yellow oil, 1.06 g, 36% yield, Rf = 0.42 (PE:EA = 1:1, v/v). 1H NMR
(400 MHz, CDCl3) δ 8.01 – 7.95 (m, 2H), 7.59 – 7.52 (m, 1H), 7.47 Ethyl
1-diazo-N-methyl
-2-oxo-2,N-
– 7.41 (m, 2H), 7.32 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), diphenylethylphosphonamidate (1a)
4.26 – 4.13 (m, 1H), 4.13 – 3.98 (m, 1H), 3.69 (dd, J = 21.2, 10 Hz,
1H), 3.61 (dd, J = 21.2, 10 Hz, 1H), 3.16 (d, J = 8.5 Hz, 3H), 1.30 – Yellow oil, 1.35 g (5 mmol scale), 79% yield, Rf = 0.41 (PE:EA =
1.26 (m, 12H). 13C NMR (101 MHz, CDCl3) δ 192.75 (d, JC-P = 5.8 1:1, v/v). 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.45 (m, 3H), 7.42 –
Hz), 147.25 , 141.06 (d, JC-P = 4.5 Hz), 136.92 , 133.38 , 129.03 , 7.35 (m, 2H), 7.30 – 7.26 (m, 2H), 7.14 – 7.08 (m, 3H), 4.34 –
128.49 , 126.04 , 122.98 (d, JC-P = 3.4 Hz), 60.62 (d, JC-P = 6.7 Hz), 4.22 (m, 2H), 3.16 (d, J = 9.0 Hz, 3H), 1.40 (t, J = 7.1 Hz, 3H). 13
38.85 (d, JC-P = 117.6 Hz), 36.83 (d, JC-P = 5.0 Hz), 34.26 , 31.33 , NMR (101 MHz, CDCl3) δ 188.0 (d, JC-P = 10.5 Hz), 143.2 (d, JC-P
C
=
16.07 (d, JC-P = 7.0 Hz). 31P NMR (162 MHz, CDCl3) δ 22.6. IR (KBr, 5.5 Hz), 137.1 (d, JC-P = 2.6 Hz), 132.1, 129.0, 128.5, 127.2, 124.7
cm-1): 1678, 1272 (P=O). HRMS (ESI) calcd for C21H29NO3P+ (d, JC-P = 1.2 Hz), 123.1 (d, JC-P = 4.0 Hz), 62.2 (d, JC-P = 5.6 Hz),
[M+H+] 374.1880, found 380.1871.
37.2 (d, JC-P = 4.9 Hz), 16.1 (d, JC-P = 6.8 Hz). IR (KBr, cm-1): 2102,
1631, 1274 (P=O). HRMS (ESI) calcd for C17H19N3O3P+ [M+H+]
Ethyl
N-methyl-N-(naphthalen-2-yl)-2-oxo-2- 344.1159, found 344.1164.
phenylethylphosphonamidate (3p)
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Ethyl
Journal Name
1-diazo-2-oxo-2,N-diphenyl-N- 128.4, 128.2, 127.4, 127.2, 114.3, 62.1 (d, JC-P = 5.8 Hz), 55.3,
View Article Online
31
propylethylphenylphosphonamidate (1b)
55.2 (d, JC-P = 6.0 Hz), 16.1 (d, JC-P = 6.9 HzD).OI:P10N.1M03R9/C(166R2A1M05H55zF,
CDCl3) δ 13.2. IR (KBr, cm-1): 2101, 1654, 1276 (P=O). HRMS (ESI)
Yellow oil, 255 mg, 69% yield, Rf = 0.62 (PE:EA = 1:1, v/v). H calcd for C24H25N3O4P+ [M+H+] 450.1577, found 450.1576.
1
NMR (400 MHz, CDCl3) δ 7.57 – 7.47 (m, 3H), 7.44 – 7.37 (m, 2H),
7.32 – 7.27 (m, 2H), 7.21 – 7.15 (m, 1H), 7.10 (d, J = 8.3 Hz, 2H), Ethyl
1-diazo-N-methyl-N-(4-methylphenyl)-2-oxo-2-
4.36 – 4.22 (m, 2H), 3.70 – 3.59 (m, 1H), 3.49 – 3.38 (m, 1H), phenylethylphosphonamidate (1f)
1.48 – 1.36 (m, 5H), 0.85 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz,
1
CDCl3) δ 188.1 (d, JC-P = 9.9 Hz), 140.9 (d, JC-P = 5.1 Hz), 137.1 (d, Yellow oil, 301 mg, 84% yield, Rf = 0.41 (PE:EA = 1:1, v/v). H
JC-P = 2.8 Hz), 132.1, 129.1 (d, JC-P = 1.0 Hz), 128.5, 127.4, 126.8 NMR (400 MHz, CDCl3) δ 7.55 – 7.47 (m, 3H), 7.42 – 7.37 (m, 2H),
(d, JC-P = 3.6 Hz), 126.1 (d, JC-P = 1.4 Hz), 62.0 (d, JC-P = 5.8 Hz), 7.07 (d, J = 8.2 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 4.33 – 4.21 (m,
51.9 (d, JC-P = 4.5 Hz), 22.3 (d, JC-P = 2.4 Hz), 16.1 (d, JC-P = 6.9 Hz), 2H), 3.13 (d, J = 9.1 Hz, 3H), 2.30 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H).
11.0. 31P NMR (162 MHz, CDCl3) δ 12.9. IR (KBr, cm-1): 2101, 13C NMR (101 MHz, CDCl3) δ 188.1 (d, JC-P = 10.4 Hz), 140.5 (d,
1629, 1275 (P=O). HRMS (ESI) calcd for C19H23N3O3P+ [M+H+] JC-P = 5.4 Hz), 137.1 (d, JC-P = 2.4 Hz), 134.7 (d, JC-P = 1.2 Hz), 132.1,
372.1472, found 372.1482.
129.6, 128.4, 127.3, 123.5 (d, JC-P = 3.9 Hz), 62.0 (d, JC-P = 5.7 Hz),
37.6 (d, JC-P = 5.2 Hz), 20.7, 16.1 (d, JC-P = 6.7 Hz). 31P NMR (162
Ethyl
N-benzyl-1-diazo-2-oxo-2,N- MHz, CDCl3) δ 13.2. IR (KBr, cm-1): 2101, 1632, 1274 (P=O).
diphenylethylphosphonamidate (1c)
HRMS (ESI) calcd for C18H21N3O3P+ [M+H+] 358.1315, found
358.1324.
Yellow oil, 206 mg (0.57 mmol scale), 86% yield, Rf = 0.63 (PE:EA
1
= 1:1, v/v). H NMR (400 MHz, CDCl3) δ 7.52 (t, J = 7.5 Hz, 3H), Ethyl
N-benzyl-N-(4-methylphenyl)-1-diazo-2-oxo-2-
7.46 – 7.39 (m, 2H), 7.25 – 7.15 (m, 7H), 7.15 – 7.09 (m, 1H), phenylethylphosphonamidate (1g)
7.06 (d, J = 8.3 Hz, 2H), 4.91 (dd, J = 15.5, 9.1 Hz, 1H), 4.67 (dd, J
= 15.5, 9.2 Hz, 1H), 4.35 – 4.14 (m, 2H), 1.34 (t, J = 7.1 Hz, 3H). Yellow oil, 220 mg (0.77 mmol scale), 66% yield, Rf = 0.62 (PE:EA
13C NMR (101 MHz, CDCl3) δ 188.1 (d, JC-P = 9.6 Hz), 141.0 (d, JC- = 1:1, v/v). 1H NMR (400 MHz, CDCl3) δ 7.60 – 7.50 (m, 3H), 7.47
P = 5.2 Hz), 138.2 (d, JC-P = 3.1 Hz), 137.0 (d, JC-P = 3.3 Hz), 132.2, – 7.41 (m, 2H), 7.25 – 7.14 (m, 5H), 7.00 (d, J = 8.3 Hz, 2H), 6.91
129.1, 128.5, 128.2, 128.1, 127.3, 127.1, 126.7 (d, JC-P = 3.6 Hz), (d, J = 7.6 Hz, 2H), 4.86 (dd, J = 15.4, 9.0 Hz, 1H), 4.60 (dd, J =
126.1 (d, JC-P = 1.4 Hz), 62.3 (d, JC-P = 5.8 Hz), 54.4 (d, JC-P = 5.2 15.3, 9.2 Hz, 1H), 4.34 – 4.23 (m, 1H), 4.23 – 4.12 (m, 1H), 2.26
Hz), 16.0 (d, JC-P = 6.9 Hz). 31P NMR (162 MHz, CDCl3) δ 13.1. IR (s, 3H), 1.34 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 188.2
(KBr, cm-1): 2102, 1630, 1275 (P=O). HRMS (ESI) calcd for (d, JC-P = 9.7 Hz), 138.3 (d, JC-P = 3.1 Hz), 138.1 (d, JC-P = 5.0 Hz),
C23H23N3O3P+ [M+H+] 420.1472, found 420.1482.
137.1 (d, JC-P = 3.2 Hz), 136.0 (d, JC-P = 1.6 Hz), 132.2, 129.8, 128.5,
128.2, 127.4, 127.1, 126.9 (d, JC-P = 3.5 Hz), 62.2 (d, JC-P = 5.8 Hz),
Ethyl
phenylethylphosphonamidate (1d)
1-diazo-N-(4-methoxyphenyl)-N-methyl-2-oxo-2- 54.6 (d, JC-P = 5.6 Hz), 20.9, 16.1 (d, JC-P = 6.9 Hz). 31P NMR (162
MHz, CDCl3) δ 13.1. IR (KBr, cm-1): 2101, 1630, 1275 (P=O).
HRMS (ESI) calcd for C24H25N3O3P+ [M+H+] 434.1628, found
1
Yellow oil, 128 mg, 34% yield, Rf = 0.28 (PE:EA = 1:1, v/v). H 434.1636.
NMR (400 MHz, CDCl3) δ 7.59 – 7.46 (m, 3H), 7.46 – 7.38 (m, 2H),
7.05 (d, J = 8.3 Hz, 2H), 6.80 (d, J = 8.9 Hz, 2H), 4.33 – 4.22 (m, Ethyl
N-(4-bromophenyl)-1-diazo-N-methyl-2-oxo-2-
2H), 3.77 (s, 3H), 3.13 (d, J = 9.2 Hz, 3H), 1.39 (t, J = 7.1 Hz, 3H). phenylethylphosphonamidate (1h)
13C NMR (101 MHz, CDCl3) δ 188.1 (d, JC-P = 10.0 Hz), 157.2,
137.1 (d, JC-P = 2.8 Hz), 135.9 (d, JC-P = 5.2 Hz), 132.1, 128.5, 127.3, Yellow oil, 378 mg, 90% yield, Rf = 0.38 (PE:EA = 1:1, v/v). Two
126.0 (d, JC-P = 3.6 Hz), 114.3, 62.0 (d, JC-P = 5.8 Hz), 55.3, 38.2 (d, rotamers exist, rotamers A:B = 1.00:0.27. 1H NMR (400 MHz,
JC-P = 5.8 Hz), 16.1 (d, JC-P = 6.8 Hz). 31P NMR (162 MHz, CDCl3) δ CDCl3) δ 7.53 – 7.47 (rotamers A and B, m, 6H), 7.43 – 7.35
13.4. IR (KBr, cm-1): 2101, 1631, 1275 (P=O). HRMS (ESI) calcd (rotamers A and B, m, 8H), 7.30 – 7.25 (rotamer B, m, 1H), 7.14
for C18H21N3O4P+ [M+H+] 374.1264, found 374.1266.
– 7.08 (rotamer B, m, 1H), 7.04 – 6.98 (rotamer A, m, 2H), 4.34
– 4.23 (rotamers A and B, m, 4H), 3.16 (rotamer B, d, J = 3.0 Hz,
Ethyl
N-benzyl-1-diazo-N-(4-methoxyphenyl)-2-oxo-2- 3H), 3.13 (rotamer A, d, J = 3.0 Hz, 3H), 1.40 (rotamer A, t, J =
phenylethylphosphonamidate (1e)
7.2 Hz, 3H), 1.398 (rotamer B, t, J = 7.2 Hz, 3H). 13C NMR (101
MHz, CDCl3) δ 187.8 (rotamer A, d, JC-P = 10.2 Hz), 142.4
1
Yellow oil, 328 mg, 73% yield, Rf = 0.50 (PE:EA = 1:1, v/v). H (rotamer A, d, JC-P = 5.8 Hz), 136.9 (rotamer A,), 132.3 (rotamer
NMR (400 MHz, CDCl3) δ 7.62 – 7.58 (m, 2H), 7.57 – 7.50 (m, 1H), A,), 132.1 (rotamer B,), 132.0 (rotamer A,), 129.0 (rotamer B,),
7.48 – 7.42 (m, 2H), 7.26 – 7.16 (m, 5H), 6.95 – 6.92 (m, 2H), 128.6 (rotamer A,), 128.5 (rotamer B,), 127.2 (rotamer B,),
6.73 (d, J = 8.9 Hz, 2H), 4.82 (dd, J = 15.1, 8.7 Hz, 1H), 4.58 (dd, J 127.21 (rotamer A,), 124.7 (rotamer B,), 124.6 (rotamer A, d, JC-
= 15.1, 8.9 Hz, 1H), 4.34 – 4.24 (m, 1H), 4.24 – 4.13 (m, 1H), 3.73 P = 4.0 Hz), 123.0 (rotamer B, d, JC-P = 4.1 Hz), 117.8 (rotamer A,),
(s, 3H), 1.34 (t, J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 188.2, 62.4 (rotamer A, d, JC-P = 5.7 Hz), 62.2 (rotamer B, d, JC-P = 5.9
158.0 (d, JC-P = 1.5 Hz), 138.3 (d, JC-P = 3.3 Hz), 137.1 (d, JC-P = 3.3 Hz), 37.2 (rotamer B, d, JC-P = 4.6 Hz), 37.2 (rotamer A, d, JC-P
=
Hz), 133.3 (d, JC-P = 5.0 Hz), 132.2, 129.0 (d, JC-P = 3.3 Hz), 128.6, 4.7 Hz), 16.1 (rotamer A, d, JC-P = 6.7 Hz). 31P NMR (162 MHz,
8 | J. Name., 2012, 00, 1-3
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CDCl3) δ 13.2 (rotamer B), 13.0 (rotamer A). IR (KBr, cm-1): 2102, (m, 2H), 2.21 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
View Article Online
1631, 1272 (P=O). HRMS (ESI) calcd for C17H18BrN3O3P+ [M+H+] CDCl3) δ 188.2 (d, JC-P = 9.9 Hz), 140.9 (d, J = 5.0 Hz), 138.9 (d,
DOI: 10.1039/C6RA10555F
C-P
422.0264, found 422.0266.
JC-P = 0.9 Hz), 138.4 (d, JC-P = 2.9 Hz), 137.2 (d, JC-P = 3.0 Hz), 132.2,
128.8, 128.5, 128.2, 128.1, 127.4, 127.3, 127.1, 127.0 (d, JC-P
=
Ethyl
N-(4-chlorophenyl)-1-diazo-N-methyl-2-oxo-2- 1.3 Hz), 123.9 (d, JC-P = 3.5 Hz), 62.2 (d, JC-P = 5.7 Hz), 54.4 (d, JC-
phenylethylphosphonamidate (1i)
P = 5.2 Hz), 21.3, 16.1 (d, C-PJ = 7.0 Hz). 31P NMR (162 MHz, CDCl3)
δ 13.1. IR (KBr, cm-1): 2101, 1630, 1275 (P=O). HRMS (ESI) calcd
Yellow oil, 267 mg, 71% yield, Rf = 0.41 (PE:EA = 1:1, v/v). H for C24H25N3O3P+ [M+H+] 434.1628, found 434.1639.
1
NMR (400 MHz, CDCl3) δ 7.54 – 7.48 (m, 3H), 7.43 – 7.37 (m, 2H),
7.23 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 4.35 – 4.23 (m, Ethyl
1-diazo-N-methyl-N-(3-methylphenyl)-2-oxo-2-
2H), 3.13 (d, J = 9.0 Hz, 3H), 1.40 (t, J = 7.1 Hz, 3H). 13C NMR (101 phenylethylphosphonamidate (1m)
MHz, CDCl3) δ 187.9 (d, JC-P = 10.2 Hz), 141.9 (d, JC-P = 5.7 Hz),
1
136.9 (d, JC-P = 2.7 Hz), 132.3, 130.1 (d, JC-P = 1.3 Hz), 129.0, 128.6, Yellow oil, 249 mg, 70% yield, Rf = 0.38 (PE:EA = 1:1, v/v). H
127.2, 124.4 (d, JC-P = 4.0 Hz), 62.4 (d, JC-P = 5.7 Hz), 37.3 (d, JC-P NMR (400 MHz, CDCl3) δ 7.53 – 7.46 (m, 3H), 7.43 – 7.36 (m, 2H),
= 4.8 Hz), 16.1 (d, JC-P = 6.6 Hz). 31P NMR (162 MHz, CDCl3) δ 13.1. 7.15 (t, J = 7.8 Hz, 1H), 6.93 (d, J = 7.7 Hz, 2H), 6.83 (s, 1H), 4.34
IR (KBr, cm-1): 2103, 1631, 1272 (P=O). HRMS (ESI) calcd for – 4.22 (m, 2H), 3.13 (d, J = 9.1 Hz, 3H), 2.28 (s, 3H), 1.40 (t, J =
C17H18ClN3O3P+ [M+H+] 378.0769, found 378.0782.
7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 188.1 (d, JC-P = 10.5 Hz),
143.1 (d, JC-P = 5.5 Hz), 138.9, 137.1 (d, JC-P = 2.2 Hz), 132.1,
Ethyl
1-diazo-N-(4-fluorophenyl)-N-methyl-2-oxo-2- 128.8 , 128.4, 127.3, 125.6, 123.9 (d, JC-P = 4.2 Hz), 120.3 (d, JC-P
phenylethylphosphonamidate (1j)
= 3.8 Hz), 62.1 (d, JC-P = 5.8 Hz), 37.3 (d, JC-P = 5.0 Hz), 21.4, 16.1
(d, JC-P = 6.8 Hz). 31P NMR (162 MHz, CDCl3) δ 13.2. IR (KBr, cm-
Yellow oil, 205 mg, 57% yield, Rf = 0.34 (PE:EA = 1:1, v/v). H 1): 2101, 1632, 1285 (P=O). HRMS (ESI) calcd for C18H21N3O3P+
NMR (400 MHz, CDCl3) δ 7.55 – 7.49 (m, 3H), 7.44 – 7.39 (m, 2H), [M+H+] 358.1315, found 358.1316.
7.14 – 7.07 (m, 2H), 7.00 – 6.93 (m, 2H), 4.34 – 4.22 (m, 2H),
1
3.15 (d, J = 9.0 Hz, 3H), 1.40 (t, J = 7.0 Hz, 3H). 13C NMR (101 Ethyl
1-diazo-N-(4-isopropylphenyl)-N-methyl-2-oxo-2-
MHz, CDCl3) δ 188.0 (d, JC-P = 9.7 Hz), 160.1 (d, JC-F = 244.3 Hz), phenylethylphosphonamidate (1n)
139.2 (dd, JC-F = 5.5, JC-P = 2.8 Hz), 137.0 (d, JC-P = 3.0 Hz), 132.3,
128.6, 127.2, 125.8 (dd, JC-P = 8.3, JC-F = 3.7 Hz), 115.8 (d, JC-F
=
Yellow oil, 270 mg, 74% yield, Rf = 0.46 (PE:EA = 1:1, v/v). 1H
22.2 Hz), 62.3 (d, JC-P = 5.7 Hz), 37.9 (d, JC-P = 5.2 Hz), 16.1 (d, JC- NMR (400 MHz, CDCl3) δ 7.51 – 7.43 (m, 3H), 7.37 (t, J = 7.6 Hz,
P = 6.7 Hz). 19F NMR (376 MHz, CDCl3) δ -117.2 (d, J = 2.3 Hz). 31
P
2H), 7.12 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 8.2 Hz, 2H), 4.35 – 4.20
NMR (162 MHz, CDCl3) δ 13.5. IR (KBr, cm-1): 2103, 1632, 1275 (m, 2H), 3.15 (d, J = 9.0 Hz, 3H), 2.86 (hept, J = 7.0 Hz, 1H), 1.39
(P=O). HRMS (ESI) calcd for C17H18FN3O3P+ [M+H+] 362.1064, (t, J = 7.1 Hz, 3H), 1.22 (d, J = 6.9 Hz, 6H). 13C NMR (101 MHz,
found 362.1072.
CDCl3) δ 188.2 (d, JC-P = 10.2 Hz), 145.5, 140.8 (d, JC-P = 5.3 Hz),
137.2 (d, JC-P = 2.8 Hz), 132.0, 128.4, 127.2, 127.0, 123.4 (d, JC-P
Ethyl
1-diazo-N-methyl-N-(2-methylphenyl)-2-oxo-2- = 4.0 Hz), 62.0 (d, JC-P = 5.8 Hz), 37.5 (d, JC-P = 5.0 Hz), 33.5, 23.9
phenylethylphosphonamidate (1k)
(d, JC-P = 1.7 Hz), 16.1 (d, JC-P = 6.6 Hz). IR (KBr, cm-1): 2100, 1633,
1273 (P=O). HRMS (ESI) calcd for C20H25N3O3P+ [M+H+] 386.1628,
Yellow oil, 167 mg (0.59 mmol scale), 79% yield, Rf = 0.38 (PE:EA found 386.1619.
= 1:1, v/v).1H NMR (400 MHz, CDCl3) δ 7.63 – 7.59 (m, 2H), 7.57
– 7.52 (m, 1H), 7.49 – 7.43 (m, 2H), 7.26 – 7.13 (m, 4H), 4.28 – Ethyl
N-[4-(tert-butyl)phenyl]-1-diazo-N-methyl-2-oxo-2-
4.18 (m, 2H), 3.13 (d, J = 9.6 Hz, 3H), 2.36 (s, 3H), 1.36 (t, J = 7.0 phenylethylphosphonamidate (1q)
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 188.2 (d, JC-P = 8.0 Hz),
141.5 (d, JC-P = 4.4 Hz), 137.5 (d, JC-P = 3.3 Hz), 137.2 (d, JC-P = 4.3 Yellow oil, 270 mg, 80% yield, Rf = 0.46 (PE:EA = 1:1, v/v). 1H
Hz), 132.3, 131.4, 128.8, 128.7, 127.5 (d, JC-P = 1.5 Hz), 127.3, NMR (400 MHz, CDCl3) δ 7.51 – 7.42 (m, 3H), 7.40 – 7.34 (m, 2H),
127.0 (d, JC-P = 1.4 Hz), 62.6 (d, JC-P = 5.7 Hz), 38.6 (d, JC-P = 5.7 7.28 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.2 Hz, 2H), 4.35 – 4.20 (m,
Hz), 17.9, 16.1 (d, JC-P = 7.0 Hz). 31P NMR (162 MHz, CDCl3) δ 13.2. 2H), 3.15 (d, J = 9.0 Hz, 3H), 1.39 (t, J = 7.0 Hz, 3H), 1.29 (s, 9H).
IR (KBr, cm-1): 2101. 1630. 1275 (P=O). HRMS (ESI) calcd for 13C NMR (101 MHz, CDCl3) δ 188.2 (d, JC-P = 10.2 Hz), 147.7,
C18H21N3O3P+ [M+H+] 358.1315, found 358.1321.
140.5 (d, JC-P = 5.4 Hz), 137.2 (d, JC-P = 2.7 Hz), 132.0, 128.4, 127.2,
125.9, 122.8 (d, JC-P = 4.0 Hz), 62.0 (d, JC-P = 5.7 Hz), 37.3 (d, JC-P
Ethyl
N-benzyl-N-(3-methylphenyl)-1-diazo-2-oxo-2- = 5.1 Hz), 34.3, 31.3, 16.1 (d, JC-P = 6.7 Hz). 31P NMR (162 MHz,
phenylethylphosphonamidate (1l)
CDCl3) δ 13.5. IR (KBr, cm-1): 2100, 1632, 1273 (P=O). HRMS (ESI)
calcd for C21H27N3O3P+ [M+H+] 400.1785, found 400.1777.
Yellow oil, 315 mg (0.89 mmol scale), 81% yield, Rf = 0.68 (PE:EA
= 1:1, v/v). 1H NMR (400 MHz, CDCl3) δ 7.59 – 7.50 (m, 3H), 7.48 Ethyl
1-diazo-N-methyl-N-(naphthalen-2-yl)-2-oxo-2-
– 7.40 (m, 2H), 7.25 – 7.14 (m, 5H), 7.09 (t, J = 7.8 Hz, 1H), 6.94 phenylethylphosphonamidate (1p)
(d, J = 7.5 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.81 (s, 1H), 4.88 (dd,
J = 15.5, 9.3 Hz, 1H), 4.63 (dd, J = 15.5, 9.5 Hz, 1H), 4.33 – 4.12
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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1
Yellow oil, 309 mg, 79% yield, Rf = 0.38 (PE:EA = 1:1, v/v). H CDCl3) δ 191.5 (trans-isomer, d, JC-P = 4.7 Hz), 192.2 (cis-isomer,
View Article Online
DOI: 10.1039/C6RA10555F
NMR (400 MHz, CDCl3) δ 7.80 – 7.73 (m, 2H), 7.70 (d, J = 7.7 Hz, d, JC-P = 3.2 Hz), 145.1 (cis-isomer, d, JC-P = 26.4 Hz), 144.7 (trans-
1H), 7.49 – 7.41 (m, 6H), 7.37 – 7.31 (m, 3H), 4.40 – 4.28 (m, 2H), isomer), 136.7 (cis-isomer), 136.67 (trans-isomer), 134.1 (trans-
3.25 (d, J = 9.0 Hz, 3H), 1.43 (t, J = 7.0 Hz, 3H).13C NMR (101 MHz, isomer), 133.7 (cis-isomer), 129.4 (cis-isomer), 129.2 (trans-
CDCl3) δ 188.0 (d, JC-P = 10.5 Hz), 140.7 (d, JC-P = 5.4 Hz), 137.1 (d, isomer), 129.1 (cis-isomer), 128.8 (cis-isomer), 128.7 (trans-
JC-P = 2.2 Hz), 133.6, 132.1, 130.8, 128.8, 128.5, 128.4, 127.5, isomer), 128.2 (trans-isomer, d, JC-P = 13.3 Hz), 127.5 (cis-isomer,
127.3, 126.4, 125.4, 122.6 (d, JC-P = 3.3 Hz), 120.6 (d, JC-P = 4.8 d, JC-P = 13.7 Hz), 121.9 (cis-isomer, d, JC-P = 4.3 Hz), 120.8 (trans-
Hz), 62.3 (d, JC-P = 5.8 Hz), 37.5 (d, JC-P = 4.9 Hz), 16.1 (d, JC-P = 6.7 isomer, d, JC-P = 4.9 Hz), 120.7 (cis-isomer, d, JC-P = 1.3 Hz), 120.6
Hz). 31P NMR (162 MHz, CDCl3) δ 13.3. IR (KBr, cm-1): 2102, 1631, (trans-isomer), 108.9 (cis-isomer, d, JC-P = 11.5 Hz), 108.4 (trans-
1276 (P=O). HRMS (ESI) calcd for C21H21N3O3P+ [M+H+] 394.1315, isomer, d, JC-P = 11.6 Hz), 64.2 (trans-isomer, d, JC-P = 7.2 Hz),
found 394.1324.
63.3 (cis-isomer, d, JC-P = 6.9 Hz), 48.7 (trans-isomer, d, JC-P
102.8 Hz), 48.1 (cis-isomer, d, JC-P = 106.0 Hz), 27.4 (cis-isomer,
(1-diazo-2-oxo-2-phenylethyl)(3,4-dihydroquinolin- d, JC-P = 1.9 Hz), 27.1 (trans-isomer, d, JC-P = 1.9 Hz), 16.7 (cis-
1(2H)-yl)phosphinate (1q)
isomer, d, JC-P = 5.8 Hz) 16.1 (trans-isomer, d, JC-P = 5.9 Hz). 31
NMR (162 MHz, CDCl3) δ 39.1 (cis-isomer), 38.6 (trans-isomer).
=
Ethyl
P
Yellow oil, 242 mg, 66% yield, Rf = 0.41 (PE:EA = 1:1, v/v). H IR (KBr, cm-1): 1679, 1633, 1278 (P=O), 1236 (P=O). HRMS (ESI)
NMR (400 MHz, CDCl3) δ 7.49 – 7.41 (m, 3H), 7.39 – 7.32 (m, 2H), calcd for C17H19NO3P+ [M+H+] 316.1097, found 316.1106.
7.30 (d, J = 8.2 Hz, 1H), 7.16 – 7.10 (m, 1H), 7.00 (d, J = 7.5 Hz,
1
1H), 6.92 (t, J = 7.3 Hz, 1H), 4.33 – 4.15 (m, 2H), 3.78 – 3.69 (m, 3-Benzoyl-2-ethoxy-2-oxo-1-propylphosphorindoline (2b)
1H), 3.64 – 3.55 (m, 1H), 2.71 – 2.61 (m, 1H), 2.61 – 2.53 (m, 1H),
1.86 – 1.66 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, Colorless crystals, 102 mg (0.41 mmol scale), 73% yield, m.p.
CDCl3) δ 187.8 (d, JC-P = 10.6 Hz), 138.5 (d, JC-P = 5.5 Hz), 137.2 (d, 145

147 oC. Rf = 0.43 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
1
JC-P = 2.3 Hz), 132.0, 129.8, 128.4, 128.1 (d, JC-P = 7.3 Hz), 127.2, = 1.00:0.00. H NMR (400 MHz, CDCl3) δ 8.04 – 7.94 (m, 2H),
126.2, 122.3, 119.1 (d, JC-P = 2.5 Hz), 62.0 (d, JC-P = 5.8 Hz), 45.2 7.59 (t, J = 7.4 Hz, 1H), 7.51 – 7.45 (m, 2H), 7.31 – 7.23 (m, 1H),
(d, JC-P = 2.9 Hz), 27.2, 22.2 (d, JC-P = 3.1 Hz), 16.0 (d, JC-P = 6.8 Hz). 7.04 (d, J = 7.3 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 8.0 Hz,
31P NMR (162 MHz, CDCl3) δ 11.4. IR (KBr, cm-1): 2101, 1633, 1H), 4.97 (d, J = 20.7 Hz, 1H), 4.27 – 4.09 (m, 2H), 3.53 – 3.32 (m,
1283 (P=O). HRMS (ESI) calcd for C19H21N3O3P+ [M+H+] 370.1315, 2H), 1.86 – 1.69 (m, 2H), 1.38 (t, J = 7.1 Hz, 3H), 0.99 (t, J = 7.4
found 370.1325.
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 192.2 (d, JC-P = 3.2 Hz),
144.5 (d, JC-P = 26.7 Hz), 136.7, 133.5, 129.2, 128.8, 128.7, 127.6
General procedure for the synthesis of 1-alkyl-3-benzoyl-2- (d, JC-P = 13.8 Hz), 122.1 (d, JC-P = 4.3 Hz), 120.4, 109.4 (d, JC-P
ethoxy-2-oxophosphorindolines 2 11.7 Hz), 63.0 (d, JC-P = 6.8 Hz), 48.3 (d, JC-P = 105.0 Hz), 43.4,
21.4, 16.6 (d, JC-P = 6.1 Hz), 11.3. 31P NMR (162 MHz, CDCl3) δ
To a suspension of CuSO4·5H2O (0.05 mmol, 12.5 mg) in 10 mL 38.5 (cis isomer), 38.1 (trans-isomer). IR (KBr, cm-1): 1680, 1231
of toluene was added the corresponding diazo compound
(0.5 (P=O). HRMS (ESI) calcd for C19H23NO3P+ [M+H+] 344.1410,
=
1
mmol), and the mixture was refluxed for 0.5 h. The volatiles found 344.1414.
were removed under reduced pressure and the crude reaction
mixture was purified on silica gel column (PE : EA = 3 :1, v/v) to 3-Benzoyl-1-benzyl-2-ethoxy-2-oxophosphorindoline (2c)
afford the desired product
2.
Colorless crystals, 60 mg (0.24 mmol scale), 62% yield, m.p.
3-Benzoyl-2-ethoxy-1-methyl-2-oxophosphorindoline (2a)
166

167 oC. Rf = 0.33 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
1
= 1.00:0.00. H NMR (400 MHz, CDCl3) δ 8.06 – 7.99 (m, 2H),
Colorless crystals, 127 mg (0.5 mmol scale), 77% yield, m.p. 7.64 – 7.57 (m, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.43 (d, J = 7.4 Hz,
148

149 oC. Rf = 0.38 (PE:EA = 1:1, v/v). cis-isome:trans-isomer 2H), 7.34 (t, J = 7.4 Hz, 2H), 7.29 – 7.24 (m, 1H), 7.14 (t, J = 7.8
1
= 1.00:0.43. H NMR (400 MHz, CDCl3) δ 8.30 – 8.21 (trans- Hz, 1H), 7.06 (d, J = 7.4 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.57 (d, J
isomer, m, 2H), 8.05 – 7.92 (cis-isomer, m, 2H), 7.66 (trans- = 8.0 Hz, 1H), 5.10 (d, J = 20.9 Hz, 1H), 4.69 (d, J = 9.6 Hz, 2H),
isomer, t, J = 7.4 Hz, 1H), 7.62 – 7.58 (cis-isomer, m, 1H), 7.57 4.26 – 4.04 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
(trans-isomer, t, J = 7.7 Hz, 2H), 7.49 (cis-isomer, t, J = 7.7 Hz, CDCl3) δ 192.1 (d, JC-P = 3.1 Hz), 144.3 (d, JC-P = 26.7 Hz), 136.7,
2H), 7.27 (trans-isomer, d, J = 5.7 Hz, 1H), 7.31 (cis-isomer, d, J 136.6 (d, JC-P = 2.1 Hz), 133.6, 129.2, 128.8, 128.76, 128.7, 127.5,
= 7.8 Hz, 1H), 7.12 (trans-isomer, d, J = 7.3 Hz, 1H), 7.04 (cis- 127.4, 127.0, 121.9 (d, JC-P = 4.3 Hz), 120.8, 110.3 (d, JC-P = 11.6
isomer, d, J = 7.4 Hz, 1H), 6.95 (trans-isomer, t, J = 7.6 Hz, 1H), Hz), 63.3 (d, JC-P = 6.9 Hz), 48.4 (d, JC-P = 106.3 Hz), 45.4 (d, JC-P
=
6.90 (cis-isomer, t, J = 7.5 Hz, 1H), 6.72 (cis-isomer, d, J = 8.0 Hz, 2.3 Hz), 16.6 (d, JC-P = 6.0 Hz). 31P NMR (162 MHz, CDCl3) δ 38.8
1H), 6.69 (trans-isomer, d, J = 8.0 Hz, 1H), 5.25 (trans-isomer, d, (cis-isomer), 38.1 (trans-isomer). IR (KBr, cm-1): 1688, 1274
J = 23.7 Hz, 1H), 5.02 (cis-isomer, d, J = 20.9 Hz, 1H), 4.26 – 4.13 (P=O). HRMS (ESI) calcd for C23H22KNO3P+ [M+K+] 430.0969,
(cis-isomer, m, 2H), 3.95 – 3.83 (trans-isomer, m, 1H), 3.61 – found 430.0961.
3.49 (trans-isomer, m, 1H), 3.04 (cis-isomer, d, J = 8.7 Hz, 3H),
3.00 (trans-isomer, d, J = 8.8 Hz, 3H), 1.38 (cis-isomer, t, J = 7.1 3-Benzoyl-2-ethoxy-5-methoxy-1-methyl-2-
Hz, 3H).0.96 (trans-isomer, t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, oxophosphorindoline (2d)
10 | J. Name., 2012, 00, 1-3
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Journal Name ARTICLE
Colorless crystals, 81 mg (0.53 mmol scale), 47% yield, m.p.
View Article Online
o
DOI: 10.1039/C6RA10555F
Colorless crystals, 53 mg (0.25 mmol scale), 60% yield, m.p. 161
179

163 C. Rf = 0.23 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
1

181 oC. Rf = 0.17 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer = 1.00:0.00. H NMR (400 MHz, CDCl3) δ 8.03 – 7.97 (m, 2H),
1
= 1.00:0.19. H NMR (400 MHz, CDCl3) δ 8.28 – 8.23 (trans- 7.62 – 7.56 (m, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.09 (d, J = 8.0 Hz,
isomer, m, 2H), 8.03 – 7.97 (cis-isomer, m, 2H), 7.69 – 7.64 1H), 6.87 (s, 1H), 6.62 (d, J = 8.1 Hz, 1H), 4.98 (d, J = 20.7 Hz, 1H),
(trans-isomer, m, 1H), 7.63 – 7.58 (cis-isomer, m, 1H), 7.58 – 4.22 – 4.12 (m, 2H), 3.02 (d, J = 8.8 Hz, 3H), 2.25 (s, 3H), 1.37 (t,
7.55 (trans-isomer, m, 2H), 7.49 (cis-isomer, t, J = 7.7 Hz, 2H), J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 192.3 (d, JC-P = 3.1
6.89 – 6.82 (cis-isomer and trans-isomer, m, 2H), 6.76 – 6.74 Hz), 142.7 (d, JC-P = 26.2 Hz), 136.7, 133.5, 130.0 (d, JC-P = 1.3 Hz),
(trans-isomer, m, 1H), 6.67 (cis-isomer, d, J = 2.4 Hz, 1H), 6.64 129.7, 128.7, 128.7, 128.0 (d, JC-P = 13.5 Hz), 121.7 (d, JC-P = 4.3
(cis-isomer, d, J = 8.7 Hz, 1H), 6.61 (trans-isomer, d, J = 8.7 Hz, Hz), 108.7 (d, JC-P = 11.2 Hz), 63.0 (d, JC-P = 6.9 Hz), 48.1 (d, JC-P
1H), 5.24 (trans-isomer, d, J = 23.5 Hz, 1H), 4.98 (cis-isomer, d, J 106.0 Hz), 27.4 (d, JC-P = 1.9 Hz), 20.7, 16.6 (d, JC-P = 5.9 Hz). 31
=
P
= 20.7 Hz, 1H), 4.23 – 4.12 (cis-isomer, m, 2H), 3.91 – 3.82 (trans- NMR (162 MHz, CDCl3) δ 39.2 (cis-isomer), 38.8 (trans-isomer).
isomer, m, 1H), 3.76 (trans-isomer, s, 3H), 3.72 (cis-isomer, s, IR (KBr, cm-1): 1679, 1274 (P=O), 1248 (P=O). HRMS (ESI) calcd
3H), 3.59 – 3.50 (trans-isomer, m, 1H), 3.02 (cis-isomer, d, J = for C18H21NO3P+ [M+H+] 330.1254, found 330.1265.
8.9 Hz, 3H), 2.98 (trans-isomer, d, J = 9.0 Hz, 3H), 1.37 (cis-
isomer, t, J = 7.1 Hz, 3H), 0.96 (trans-isomer, t, J = 7.0 Hz, 3H). 3-Benzoyl-1-benzyl-2-ethoxy-5-methyl-2-
13C NMR (101 MHz, CDCl3) δ 192.1 (cis-isomer, d, J = 3.0 Hz), oxophosphorindoline (2g)
191.4 (trans-isomer, d, J = 5.2 Hz), 154.1 (trans-isomer, d, JC-P
=
1.9 Hz), 138.9 (cis-isomer, d, JC-P = 26.3 Hz), 136.6 (cis-isomer), Colorless crystals, 75 mg (0.32 mmol scale), 57% yield, m.p.
136.59 (trans-isomer), 134.0 (trans-isomer), 133.6 (cis-isomer), 188

190 oC. Rf = 0.50 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
1
129.0 (trans-isomer), 128.8 (cis-isomer), 128.7 (cis-isomer), = 1.00:0.18. H NMR (400 MHz, CDCl3) δ 8.32 – 8.25 (trans-
128.69 (trans-isomer), 122.8 (cis-isomer, d, JC-P = 4.5 Hz), 114.7 isomer, m, 2H), 8.03 (cis-isomer, d, J = 7.4 Hz, 2H), 7.69 – 7.62
(trans-isomer, d, J = 13.4 Hz), 114.3 (cis-isomer), 114.2 (cis- (trans-isomer, m, 1H), 7.65 – 7.54 (cis-isomer and trans-isomer,
isomer, d, JC-P = 13.9 Hz), 109.4 (cis-isomer, d, JC-P = 10.8 Hz), m, 3H), 7.50 (cis-isomer, t, J = 7.7 Hz, 2H), 7.44 – 7.39 (cis-isomer
108.9 (trans-isomer, d, J = 11.1 Hz), 64.0 (trans-isomer, d, J = 7.1 and trans-isomer, m, 4H), 7.36 – 7.30 (cis-isomer and trans-
Hz), 63.0 (cis-isomer, d, JC-P = 7.0 Hz), 55.8 (trans-isomer), 55.7 isomer, m, 4H), 7.29 – 7.22 (cis-isomer and trans-isomer, m, 2H),
(cis-isomer), 49.1 (trans-isomer, d, J = 103.9), 48.5 (cis-isomer, 6.97 – 6.90 (cis-isomer and trans-isomer, m, 3H), 6.89 (cis-
d, JC-P = 106.3 Hz), 27.7 (cis-isomer, d, JC-P = 1.8 Hz), 27.3 (trans- isomer, s, 1H), 6.46 (cis-isomer, d, J = 8.1 Hz, 1H), 6.42 (trans-
isomer, d, J = 1.6 Hz), 16.6 (cis-isomer, d, JC-P = 5.8 Hz) 16.0 isomer, d, J = 8.1 Hz, 1H), 5.32 (trans-isomer, d, J = 26 Hz, 1H),
(trans-isomer, d, J = 6.0 Hz). 31P NMR (162 MHz, CDCl3) δ 39.1 5.07 (cis-isomer, d, J = 20.7 Hz, 1H), 4.67 (cis-isomer, d, J = 9.6
(cis-isomer), 38.6 (trans-isomer). IR (KBr, cm-1): 1675, 1631, Hz, 2H), 4.62 (trans-isomer, d, J = 10.6 Hz, 2H), 4.24 – 4.03 (cis-
1255 (P=O), 1233 (P=O). HRMS (ESI) calcd for C18H21NO4P+ isomer, m, 2H), 3.88 – 3.76 (trans-isomer, m, 1H), 3.59 – 3.47
[M+H+] 346.1203, found 346.1213.
(trans-isomer, m, 1H), 2.25 (trans-isomer, s, 3H), 2.21 (cis-
isomer, s, 3H), 1.32 (cis-isomer, t, J = 7.0 Hz, 3H), 0.88 (trans-
isomer, t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 192.3 (cis-
isomer, d, JC-P = 3.1 Hz), 141.9 (cis-isomer, d, JC-P = 26.7 Hz),
136.74 (trans-isomer), 136.7 (cis-isomer, d, JC-P = 2.4 Hz), 134.0
3-Benzoyl-1-benzyl-2-ethoxy-5-methoxy-2-
oxophosphorindoline (2e)
Colorless srystals, 101 mg (0.49 mmol scale), 49% yield, m.p. (trans-isomer), 133.6 (cis-isomer), 130.2 (cis-isomer), 129.6 (cis-
168
172 oC. Rf = 0.40 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer isomer), 129.4 (trans-isomer), 129.0 (trans-isomer), 128.8 (cis-

= 1.00:0.00. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.4 Hz, 2H), isomer), 128.71 (trans-isomer), 128.7 (cis-isomer), 128.6 (cis-
7.60 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.41 (d, J = 7.4 Hz, isomer), 128.1 (cis-isomer), 128.0 (cis-isomer), 127.4 (trans-
2H), 7.34 (t, J = 7.5 Hz, 2H), 7.29 – 7.22 (m, 1H), 6.71 – 6.65 (m, isomer), 127.3 (cis-isomer), 127.0 (cis-isomer), 126.99 (trans-
2H), 6.47 (d, J = 8.3 Hz, 1H), 5.07 (d, J = 20.6 Hz, 1H), 4.69 – 4.63 isomer), 121.9 (cis-isomer, d, JC-P = 4.0 Hz), 110.2 (cis-isomer, d,
(m, 2H), 4.26 – 4.04 (m, 2H), 3.67 (s, 3H), 1.33 (t, J = 7.0 Hz, 3H). JC-P = 11.2 Hz), 109.7 (trans-isomer, d, JC-P = 11.7 Hz). 64.1 (trans-
13C NMR (101 MHz, CDCl3) δ 192.0 (d, JC-P = 3.1 Hz), 154.1 (d, JC- isomer, d, JC-P = 7.2 Hz), 63.1 (cis-isomer, d, JC-P = 6.9 Hz), 48.9
P = 1.9 Hz), 138.0 (d, JC-P = 26.8 Hz), 136.8 (d, JC-P = 2.4 Hz), 136.7, (trans-isomer, d, JC-P = 113.0 Hz), 48.4 (cis-isomer, d, JC-P = 106.4
133.6, 128.8, 128.7, 128.6, 127.3, 127.0, 123.0 (d, JC-P = 4.3 Hz), Hz), 45.4 (cis-isomer, d, JC-P = 2.3 Hz), 45.2 (trans-isomer), 20.8
114.2, 114.1 (d, JC-P = 14.0 Hz), 111.0 (d, JC-P = 10.9 Hz), 63.1 (d, (trans-isomer), 20.7 (cis-isomer), 15.9 (trans-isomer, d, JC-P = 6.0
JC-P = 6.9 Hz), 55.6, 48.8 (d, JC-P = 106.6 Hz), 45.6 (d, JC-P = 2.2 Hz), Hz). 16.5 (cis-isomer, d, JC-P = 6.2 Hz). 31P NMR (162 MHz, CDCl3)
16.6 (d, JC-P = 6.1 Hz). 31P NMR (162 MHz, CDCl3) δ 38.8 (cis- δ 38.9 (cis-isomer), 38.3 (trans-isomer). IR (KBr, cm-1): 1678,
isomer), 38.2 (trans-isomer). IR (KBr, cm-1): 1676, 1278 (P=O), 1229 (P=O). HRMS (ESI) calcd for C24H25NO3P+ [M+H+] 406.1567,
1245 (P=O). HRMS (ESI) calcd for C24H25NO4P+ [M+H+] 422.1516, found 406.1578.
found 422.1528.
3-Benzoyl-5-bromo-2-ethoxy-1-methyl-2-
3-Benzoyl-2-ethoxy-1,5-dimethyl-2-oxophosphorindoline (2f)
oxophosphorindoline (2h)
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
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ARTICLE
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Colorless crystals, 110 mg (0.52 mmol scale), 54% yield, m.p. 1690, 1630, 1267 (P=O), 1240 (P=O). HRMS (ESI) calcd for
View Article Online
+
+
162
166 oC. Rf = 0.22 (PE:EA = 1:1, v/v). Two pairs of C17H18ClNO3P [M+H ] 350.0707, found 350.0714.
DOI: 10.1039/C6RA10555F
diastereomeric rotamers exist. Their stereostructures cannot be
identified. 1H NMR (400 MHz, CDCl3) δ 8.29 – 8.20 (m, 4H), 8.04 3-Benzoyl-2-ethoxy-5-fluoro-1-methyl-2-
– 7.96 (m, 4H), 7.72 – 7.60 (m, 4H), 7.63 – 7.54 (m, 4H), 7.56 – oxophosphorindoline (2j)
7.46 (m, 4H), 7.45 – 7.37 (m, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.30 –
7.23 (m, 2H), 7.21 – 7.15 (m, 2H), 7.16 – 7.09 (m, 1H), 7.00 – Colorless crystals, 55 mg (0.38 mmol scale), 43% yield, m.p.
6.93 (m, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.5 Hz, 1H), 6.60 162
163 oC. Rf = 0.17 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
– 6.53 (m, 1H), 5.25 (d, J = 23.6 Hz, 1H), 5.23 (d, J = 23.4 Hz, 1H), = 1.00:0.18. 1H NMR (400 MHz, CDCl3) δ 8.28 – 8.21 (cis-isomer,
5.02 (d, J = 20.8 Hz, 1H), 5.01 (d, J = 20.8 Hz, 1H), 4.27 – 4.14 (m, m, 2H), 8.04 – 7.96 (trans-isomer, m, 2H), 7.72 – 7.59 (trans-
4H), 3.94 – 3.81 (m, 2H), 3.61 – 3.47 (m, 2H), 3.04 (d, J = 8.8 Hz, isomer- and cis-isomer, m, 2H), 7.58 (cis-isomer, t, J = 7.6 Hz,
3H), 3.01 (d, J = 11.6 Hz, 3H), 3.00 (d, J = 13.2 Hz, 3H), 2.98 (d, J 2H), 7.51 (trans-isomer, t, J = 7.8 Hz, 2H), 7.05 – 6.97 (trans-
= 8.7 Hz, 3H), 1.42 – 1.37 (m, 6H), 0.99 – 0.93 (m, 6H). 13C NMR isomer and cis-isomer, m, 2H), 6.93 – 6.88 (cis-isomer, m, 1H),
(101 MHz, CDCl3) δ 190.7 (d, JC-P = 4.7 Hz), 143.9 (d, JC-P = 26.5 6.85 – 6.81 (trans-isomer, m, 1H), 6.66 – 6.63 (trans-isomer, m,
Hz), 136.6, 136.5, 134.2, 134.0, 133.9, 132.1, 131.9, 131.0 (d, JC- 1H), 6.63 – 6.58 (cis-isomer, m, 1H), 5.23 (cis-isomer, d, J = 23.5
P = 13.4 Hz), 130.3 (d, JC-P = 13.9 Hz), 129.1, 129.0, 128.8, 128.6, Hz, 1H), 5.01 (trans-isomer, d, J = 20.9 Hz, 1H), 4.25 – 4.16
128.0, 122.6 (d, JC-P = 5.4 Hz), 120.5, 112.5 (d, JC-P = 2.0 Hz), 110.3 (trans-isomer, m, 2H), 3.96 – 3.81 (cis-isomer, m, 1H), 3.61 –
(d, JC-P = 10.9 Hz), 109.9 (d, JC-P = 11.1 Hz), 108.4 (d, JC-P = 11.7 3.46 (cis-isomer, m, 1H), 3.02 (trans-isomer, d, J = 8.7 Hz, 3H),
Hz), 64.3 (d, JC-P = 7.2 Hz), 64.1 (d, JC-P = 7.5 Hz), 63.4 (d, JC-P = 7.1 2.99 (cis-isomer, d, J = 8.8 Hz, 3H), 1.39 (trans-isomer, t, J = 7.0
Hz), 49.7 (d, JC-P = 102.5 Hz), 48.5 (d, JC-P = 102.8 Hz), 47.6 (d, JC- Hz, 3H), 0.96 (cis-isomer, t, J = 7.0 Hz, 3H). 13C NMR (101 MHz,
= 100.1 Hz), 27.5 (d, JC-P = 1.9 Hz), 27.1 (d, JC-P = 1.9 Hz), 27.0 CDCl3) δ 190.9 (cis-isomer, d, JC-P = 4.6 Hz), 157.2 (cis-isomer, dd,
P
(d, JC-P = 2.0 Hz), 16.6 (d, JC-P = 5.8 Hz), 16.0 (d, JC-P = 5.8 Hz). 31
P
JC-F = 238.8, 1.9 Hz), 141.0 (cis-isomer, dd, JC-P = 26.6, JC-F = 2.0
NMR (162 MHz, CDCl3) δ 39.0, 38.5, 38.3, 37.9. IR (KBr, cm-1): Hz), 136.4 (cis-isomer), 134.2 (cis-isomer), 129.1 (cis-isomer),
1690, 1659, 1267 (P=O), 1244 (P=O). HRMS (ESI) calcd for 128.7 (cis-isomer), 122.0 (cis-isomer, dd, JC-F = 8.5, JC-P = 5.4 Hz),
C17H18BrNO3P+ [M+H+] 394.0202, found 394.0209.
115.9 (cis-isomer, dd, JC-F = 24.7, JC-P = 13.4 Hz), 115.5 (cis-isomer,
d, JC-F = 22.9 Hz), 108.8 (cis-isomer, dd, JC-P = 10.8 Hz, JC-F = 8.1
Hz), 64.2 (cis-isomer, d, JC-P = 7.3 Hz), 63.4 (trans-isomer, d, JC-P
= 6.9 Hz), 48.9 (cis-isomer, d, JC-P = 105.2 Hz), 48.3 (trans-isomer,
d, JC-P = 110.6 Hz), 27.7 (trans-isomer, d, JC-P = 2.2 Hz), 27.3 (cis-
3-Benzoyl-5-chloro-2-ethoxy-1-methyl-2-
oxophosphorindoline (2i)
Colorless crystals, 101 mg (0.45 mmol scale), 63% yield, m.p. isomer, d, JC-P = 1.8 Hz), 16.7 (trans-isomer, d, JC-P = 6.0 Hz), 16.0
172
175 oC. Rf = 0.19 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer (cis-isomer, d, JC-P = 5.8 Hz). 19F NMR (376 MHz, CDCl3) δ -122.7

= 1.00:0.18. 1H NMR (400 MHz, CDCl3) δ 8.27 – 8.20 (cis-isomer, (trans-isomer), -122.8 (cis-isomer). 31P NMR (162 MHz, CDCl3) δ
m, 2H), 8.04 – 7.96 (trans-isomer, m, 2H), 7.72 – 7.62 (trans- 38.8 (trans-isomer), 38.4 (cis-isomer). IR (KBr, cm-1): 1689, 1659,
isomer and cis-isomer, m, 2H), 7.58 (cis-isomer, t, J = 7.6 Hz, 2H), 1264 (P=O), 1230 (P=O). HRMS (ESI) calcd for C17H18FNO3P+
7.54 – 7.48 (trans-isomer, m, 2H), 7.30 – 7.22 (trans-isomer and [M+H+] 334.1003, found 334.1008.
cis-isomer, m, 2H), 7.16 – 7.10 (cis-isomer, m, 1H), 7.07 – 7.02
(trans-isomer, m, 1H), 6.64 (trans-isomer, d, J = 8.6 Hz, 1H), 6.61 3-Benzoyl-2-ethoxy-1,7-dimethyl-2-oxophosphorindoline (2k)
(cis-isomer, d, J = 8.5 Hz, 1H), 5.22 (cis-isomer, d, J = 23.4 Hz, 1H),
5.01 (trans-isomer, d, J = 20.7 Hz, 1H), 4.27 – 4.14 (trans-isomer, Colorless crystals, 44 mg (0.30 mmol scale), 45% yield, m.p.
m, 2H), 3.95 – 3.83 (cis-isomer, m, 1H), 3.62 – 3.47 (cis-isomer, 124

126 oC. Rf = 0.31 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
1
m, 1H), 3.02 (trans-isomer, d, J = 8.7 Hz, 3H), 2.98 (cis-isomer, d, = 1.00:0.78. H NMR (400 MHz, CDCl3) δ 8.28 – 8.21 (trans-
J = 8.7 Hz, 3H), 1.39 (trans-isomer, t, J = 7.1 Hz, 3H), 0.96 (cis- isomer, m, 2H), 8.05 (cis-isomer, m, J = 7.1, 1.4 Hz, 2H), 7.69 –
isomer, t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 190.7 (cis- 7.47 (cis-isomer and trans-isomer, m, 6H), 7.13 – 7.02 (cis-
isomer, d, JC-P = 4.6 Hz), 143.4 (cis-isomer, d, JC-P = 26.5 Hz), 136.5 isomer and trans-isomer, m, 2H), 6.97 (trans-isomer, d, J = 7.4
(trans-isomer), 136.3 (cis-isomer), 134.2 (cis-isomer), 133.8 Hz, 1H), 6.96 – 6.87 (cis-isomer and trans-isomer, m, 3H), 5.27
(trans-isomer), 129.2 (trans-isomer), 129.1 (cis-isomer), 129.0 (trans-isomer, d, J = 23.0 Hz, 1H), 4.95 (cis-isomer, d, J = 19.8 Hz,
(cis-isomer), 128.8 (trans-isomer), 128.7 (cis-isomer), 128.3 (cis- 1H), 4.24 – 4.06 (cis-isomer, m, 2H), 3.99 – 3.84 (trans-isomer,
isomer, d, JC-P = 13.4 Hz), 127.6 (trans-isomer, d, JC-P = 13.8 Hz), m, 1H), 3.70 (trans-isomer, m, J = 9.8, 7.1 Hz, 1H), 3.28 (trans-
125.4 (cis-isomer, d, JC-P = 2.0 Hz), 122.2 (cis-isomer, d, JC-P = 5.4 isomer, d, J = 9.2 Hz, 3H), 3.24 (cis-isomer, d, J = 9.5 Hz, 3H), 2.48
Hz), 109.8 (trans-isomer, d, JC-P = 10.9 Hz), 109.4 (cis-isomer, d, (trans-isomer, s, 3H), 2.45 (cis-isomer, s, 3H), 1.32 (cis-isomer, t,
JC-P = 11.1 Hz), 64.3 (cis-isomer, d, JC-P = 7.2 Hz), 63.4 (trans- J = 7.1 Hz, 3H), 1.00 (trans-isomer, t, J = 7.1 Hz, 3H). 13C NMR
isomer, d, JC-P = 7.0 Hz), 48.5 (cis-isomer, d, JC-P = 103.6 Hz), 47.8 (101 MHz, CDCl3) δ 192.55 (cis-isomer, d, J = 2.6 Hz), 191.77
(trans-isomer, d, JC-P = 106.4 Hz), 27.5 (trans-isomer, d, JC-P = 1.9 (trans-isomer, d, J = 5.3 Hz), 144.79 (cis-isomer, d, J = 22.9 Hz),
Hz),27.2 (trans-isomer, d, JC-P = 1.8 Hz), 16.6 (trans-isomer, d, JC- 143.68 (trans-isomer, d, J = 24.3 Hz), 136.85 (trans-isomer),
P = 5.8 Hz) 16.0 (cis-isomer, d, JC-P = 5.7 Hz). 31P NMR (162 MHz, 136.51 (cis-isomer), 133.85 (trans-isomer), 133.59 (cis-isomer),
CDCl3) δ 38.1 (trans-isomer), 37.7 (cis-isomer). IR (KBr, cm-1): 132.64 (trans-isomer), 132.41 (cis-isomer), 128.94 (trans-
isomer), 128.90 (cis-isomer), 128.76 (cis-isomer), 128.65 (trans-
12 | J. Name., 2012, 00, 1-3
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isomer), 126.31 (trans-isomer, d, J = 3.4 Hz), 126.17 (cis-isomer, 1H), 6.92 (d, J = 7.6 Hz, 1H), 6.77 (d, J = 7.5 Hz, 1HV),ie6w.A7rt6icl–e O6n.l7in0e
d, J = 13.5 Hz), 125.56 (trans-isomer, d, J = 12.1 Hz), 124.91 (cis- (m, 2H), 6.58 (d, J = 7.9 Hz, 1H), 6.55 (s, 1HD),O6I:.5101.1(0s3, 91/HC)6,R5A.120155(5dF,
isomer, d, J = 14.2 Hz), 123.47 (trans-isomer, d, J = 4.5 Hz), JC-P = 23.7 Hz, 1H), 4.96 (d, J = 20.9 Hz, 1H), 4.94 (d, J = 21.2 Hz,
123.14 (cis-isomer, d, J = 12.4 Hz), 122.86 (cis-isomer), 121.82 1H), 4.25 – 4.12 (m, 4H), 3.92 – 3.82 (m, 1H), 3.60 – 3.48 (m, 1H),
(trans-isomer), 63.44 (trans-isomer, d, J = 7.3 Hz), 61.91 (cis- 3.03 (d, JH-P = 8.7 Hz, 1H), 2.99 (d, J = 8.8 Hz, 1H), 2.98 (d, J = 8.8
isomer, d, J = 7.2 Hz), 49.0 (trans-isomer, d, J = 101.1 Hz), 48.11 Hz, 1H), 2.36 (s, 3H) ×2, 2.02 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H) ×2,
(cis-isomer, d, J = 106.0 Hz), 34.02 (cis-isomer, d, J = 3.3 Hz), 0.96 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 192.3 (d, JC-
32.49 (trans-isomer, d, J = 3.0 Hz), 19.70 (trans-isomer), 19.32 P = 3.1 Hz), 145.0 (d, JC-P = 26.3 Hz), 139.8, 139.6, 136.9, 136.7,
(cis-isomer), 16.38 (cis-isomer, d, J = 6.1 Hz), 15.98 (trans- 133.9, 133.5, 129.2, 129.0, 128.8, 128.7, 128.5, 127.1 (d, JC-P
isomer, d, J = 5.9 Hz). 31P NMR (162 MHz, CDCl3) δ 39.9 (cis- 13.4 Hz), 122.4, 121.3, 118.8 (d, JC-P = 4.3 Hz), 109.7 (d, JC-P = 11.3
isomer), 38.5 (trans-isomer).IR (KBr, cm-1): 1687, 1251 (P=O). Hz), 106.4 (d, JC-P = 11.5 Hz), 63.1 (d, JC-P = 6.9 Hz), 47.8 (d, JC-P
=
=
HRMS (ESI) calcd for C18H21NO3P+ [M+H+] 330.1254, found 105.7 Hz), 27.5 (d, JC-P = 2.1 Hz), 27.4 (d, JC-P = 2.0 Hz), 21.9, 19.2,
330.1264.
16.6 (d, JC-P = 5.8 Hz). 31P NMR (162 MHz, CDCl3) δ 39.6, 39.2,
39.1, 38.2. IR (KBr, cm-1): 1683, 1613, 1279 (P=O), 1241 (P=O).
3-benzoyl-1-benzyl-2-ethoxy-6-methyl-2- HRMS (ESI) calcd for C18H21NO3P+ [M+H+] 330.1254, found
Mixture
of
oxophosphorindoline (2la) and 3-benzoyl-1-benzyl-2-ethoxy- 330.1263.
4-methyl-2-oxophosphorindoline (2lb)
3-Benzoyl-2-ethoxy-5-isopropyl-1-methyl-2-
mixture of two pairs of regioisomeric oxophosphorindoline (2n)
diastereomers with indistinguishable ratio. Colorless crystals,
Isolated as
a
182 mg (0.46 mmol scale), 97% yield, m.p. 165

167 oC. Rf = 0.50 Colorless crystals, 116 mg, 65% yield, m.p. 145

147 oC, Rf = 0.28
1
(PE:EA = 1:1, v/v). H NMR (400 MHz, CDCl3) δ 8.31 – 8.26 (m, (PE:EA = 1:1, v/v). cis-isomer:trans-isomer = 1.00:0.00. 1H NMR
2H), 8.07 – 7.98 (m, 4H), 7.68 – 7.63 (m, 1H), 7.62 – 7.54 (m, 4H), (400 MHz, CDCl3) δ 8.04 – 7.97 (m, 2H), 7.59 (t, J = 7.3 Hz, 1H),
7.52 – 7.46 (m, 4H), 7.52 – 7.46 (m, 3H), 7.45 – 7.39 (m, 5H), 7.49 (t, J = 7.6 Hz, 2H), 7.15 (d, J = 8.1 Hz, 1H), 6.91 (s, 1H), 6.65
7.37 – 7.30 (m, 5H), 7.29 – 7.22 (m, 2H), 7.06 (t, J = 7.8 Hz, 1H), (d, J = 8.1 Hz, 1H), 5.00 (d, J = 20.8 Hz, 1H), 4.24 – 4.13 (m, 2H),
7.02 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 6.74 (d, J = 7.6 3.02 (d, J = 8.8 Hz, 3H), 2.81 (hept, J = 6.9 Hz, 1H), 1.38 (t, J = 7.0
Hz, 1H), 6.70 (d, J = 7.8 Hz, 1H), 6.69 (d, J = 7.6 Hz, 1H), 6.42 (d, Hz, 3H), 1.18 (t, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ
J = 7.8 Hz, 1H), 6.40 (s, 1H), 6.36 (s, 1H), 5.30 (d, J = 23.7 Hz, 1H), 192.4 (d, JC-P = 3.0 Hz), 143.0 (d, JC-P = 26.3 Hz), 141.3 (d, JC-P
=
5.05 (d, J = 20.8 Hz, 1H), 5.03 (d, J = 20.8 Hz, 1H), 4.71 – 4.59 (m, 1.4 Hz), 136.8, 133.5, 128.7, 128.7, 127.1, 125.6 (d, JC-P = 13.6
6H), 4.26 – 3.99 (m, 4H), 3.86 – 3.74 (m, 1H), 3.57 – 3.44 (m, 1H), Hz), 121.7 (d, JC-P = 4.4 Hz), 108.6 (d, JC-P = 11.1 Hz), 63.0 (d, JC-P
2.22 (s, 3H)×2, 2.03 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 = 6.9 Hz), 48.3 (d, JC-P = 105.9 Hz), 33.5, 27.5 (d, JC-P = 2.0 Hz),
Hz, 3H), 0.85 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 24.1 (d, JC-P = 28.1 Hz), 16.6 (d, JC-P = 5.8 Hz). 31P NMR (162 MHz,
192.3 (d, JC-P = 3.2 Hz), 144.3 (d, JC-P = 26.8 Hz), 139.4, 139.2, CDCl3) δ 39.4. IR (KBr, cm-1): 1678, 1243 (P=O). HRMS (ESI) calcd
136.8 (d, JC-P = 2.3 Hz), 136.7 (d, JC-P = 4.9 Hz), 136.5 (d, JC-P = 1.9 for C20H25NO3P+ [M+H+] 372.1723, found 372.1704.
Hz), 134.0, 133.5, 129.1, 129.0, 128.8, 128.76, 128.7, 128.69,
128.6, 128.62, 128.0 (d, JC-P = 13.1 Hz), 127.3, 127.32, 127.2 (d, 3-Benzoyl-5-(tert-butyl)-2-ethoxy-1-methyl-2-
JC-P = 13.6 Hz), 127.0, 126.96, 122.5, 121.6, 121.5, 118.9 (d, JC-P oxophosphorindoline (2o)
= 3.9 Hz), 117.6, 111.0 (d, JC-P = 11.3 Hz), 110.5 (d, JC-P = 11.3 Hz),
108.0 (d, JC-P = 11.6 Hz), 64.0 (d, JC-P = 7.2 Hz), 63.1 (d, JC-P = 6.8 Colorless crystals, 131 mg, 71% yield, m.p. 120
121 oC, Rf = 0.28
Hz), 63.08 (d, JC-P = 6.2 Hz), 48.6 (d, JC-P = 104.3 Hz), 48.1 (d, JC-P (PE:EA = 1:1, v/v). cis-isomer:trans-isomer = 1.00:0.00. 1H NMR
= 106.4 Hz), 45.4 (d, JC-P = 2.5 Hz), 45.3 (d, JC-P = 2.2 Hz), 45.1 (d, (400 MHz, CDCl3) δ 8.02 – 7.98 (m, 2H), 7.63 – 7.56 (m, 1H), 7.49
JC-P = 2.3 Hz), 21.8, 21.81, 19.3, 16.5 (d, JC-P = 6.1 Hz), 16.49 (d, (t, J = 7.6 Hz, 2H), 7.31 (d, J = 8.3 Hz, 1H), 7.06 (s, 1H), 6.66 (d, J
JC-P = 5.4 Hz), 15.9 (d, JC-P = 5.9 Hz). 31P NMR (162 MHz, CDCl3) δ = 8.4 Hz, 1H), 5.01 (d, J = 20.9 Hz, 1H), 4.24 – 4.13 (m, 2H), 3.02
39.4, 38.8, 38.3, 38.0. IR (KBr, cm-1): 1683, 1612, 1279 (P=O), (d, J = 8.7 Hz, 3H), 1.38 (t, J = 7.0 Hz, 3H), 1.24 (s, 9H). 13C NMR
1232 (P=O). HRMS (ESI) calcd for C25H27NO3P+ [M+H+] 406.1567, (101 MHz, CDCl3) δ 192.4 (d, JC-P = 3.1 Hz), 143.6, 142.7 (d, JC-P
=
found 406.1573.
26.2 Hz), 136.8, 133.5, 128.7, 128.69 , 126.0, 124.6 (d, JC-P = 13.6
Hz), 121.4 (d, JC-P = 4.5 Hz), 108.3 (d, JC-P = 11.2 Hz), 63.0 (d, JC-P
Mixture
of
3-benzoyl-2-ethoxy-1,6-dimethyl-2- = 6.9 Hz), 48.4 (d, JC-P = 105.9 Hz), 34.3, 31.4, 27.4 (d, JC-P = 2.0
oxophosphorindoline (2ma) and 3-benzoyl-2-ethoxy-1,4- Hz), 16.6 (d, JC-P = 5.7 Hz). 31P NMR (162 MHz, CDCl3) δ 39.4. IR
dimethyl-2-oxophosphorindoline (2mb)
(KBr, cm-1): 1690, 1261 (P=O). HRMS (ESI) calcd for C21H27NO3P+
[M+H+] 358.1567, found 358.1553.
Isolated as
a mixture of two pairs of regioisomeric
diastereomers with indistinguishable ratio. Colorless crystals, 3-Benzoyl-2-ethoxy-1-methyl-2-oxobenzo[f]
147 mg (0.52 mmol scale), 86% yield, m.p. 155
(PE:EA = 1:1, v/v). H NMR (400 MHz, CDCl3) δ 8.28 – 8.21 (m,

157 oC. Rf = 0.22 phosphorindoline (2p)
1
2H), 8.04 – 7.95 (m, 4H), 7.68 – 7.63 (m, 1H), 7.62 – 7.54 (m, 4H), Colorless crystals, 131 mg (0.52 mmol scale), 69% yield, m.p.
7.52 – 7.44 (m, 4H), 7.21 (t, J = 7.9 Hz, 1H), 7.00 (d, J = 7.6 Hz, 168

172 oC. Rf = 0.19 (PE:EA = 1:1, v/v). cis-isomer:trans-isomer
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 13
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ARTICLE
Journal Name
= 1.00:0.79. 1H NMR (400 MHz, CDCl3) δ 8.31 (cis-isomer, d, J = isomer, d, JC-P = 12.8 Hz), 125.1 (trans-isomer, d, JC-P = 13.1 Hz),
View Article Online
DOI: 10.1039/C6RA10555F
7.4 Hz, 2H), 8.13 – 8.05 (trans-isomer, m, 2H), 7.88 (trans- 120.5 (trans-isomer, d, JC-P = 21.7 Hz), 120.2 (cis-isomer), 120.1
isomer, s, 1H), 7.86 (cis-isomer, s, 1H), 7.79 (trans-isomer, d, J = (cis-isomer), 119.69 (trans-isomer), 119.7 (cis-isomer), 64.0 (cis-
3.6 Hz, 1H), 7.80 – 7.74 (cis-isomer, m, 1H), 7.74 – 7.65 (cis- isomer, d, JC-P = 7.3 Hz), 63.2 (trans-isomer, d, JC-P = 6.9 Hz), 49.0
isomer, m, 1H), 7.65 – 7.56 (trans-isomer and cis-isomer, m, 3H), (cis-isomer, d, JC-P = 103.4 Hz), 48.5 (trans-isomer, d, JC-P = 105.6
7.55 – 7.46 (trans-isomer, m, 2H), 7.38 – 7.29 (trans-isomer, m, Hz), 39.4 (trans-isomer), 39.2 (cis-isomer), 25.1 (trans-isomer),
2H), 7.28 – 7.24 (cis-isomer, m, 2H), 7.23 – 7.21 (trans-isomer, 25.0 (cis-isomer), 21.3 (trans-isomer, d, JC-P = 5.3 Hz), 21.2 (cis-
m, 1H), 7.12 (cis-isomer, d, J = 3.6 Hz, 1H), 7.10 (trans-isomer, d, isomer, d, JC-P = 5.5 Hz), 16.7 (trans-isomer, d, JC-P = 5.9 Hz), 16.1
J = 3.1 Hz, 1H), 7.07 (cis-isomer, d, J = 8.8 Hz, 1H), 5.60 (cis- (cis-isomer, d, JC-P = 5.7 Hz). 31P NMR (162 MHz, CDCl3) δ 38.7
isomer, d, J = 22.6 Hz, 1H), 5.34 (trans-isomer, d, J = 20.8 Hz, 1H), (trans-isomer), 38.1 (cis-isomer). IR (KBr, cm-1): 1693, 1655,
4.30 – 4.15 (trans-isomer, m, 2H), 4.08 – 3.95 (cis-isomer, m, 1H), 1270 (P=O), 1244 (P=O). HRMS (ESI) calcd for C19H21NO3P+
3.69 – 3.54 (cis-isomer, m, 1H), 3.16 (trans-isomer, d, J = 8.8 Hz, [M+H+] 342.1254, found 342.1257.
3H), 3.10 (cis-isomer, d, J = 8.8 Hz, 3H), 1.38 (trans-isomer, t, J =
7.1 Hz, 3H), 1.00 (cis-isomer, t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 192.0 (trans-isomer, d, JC-P = 2.9 Hz), 191.4 (cis-isomer,
Acknowledgements
d, JC-P = 4.3 Hz), 143.6 (trans-isomer, d, JC-P = 26.4 Hz), 143.3 (cis-
isomer, d, JC-P = 28.0 Hz), 136.8 (trans-isomer), 136.6 (cis-
isomer), 134.1 (cis-isomer), 133.6 (trans-isomer), 130.7 (cis-
isomer), 130.6 (trans-isomer), 130.5 (cis-isomer), 129.1 (cis-
isomer), 129.1 (cis-isomer), 128.8 (cis-isomer), 128.7 (cis-
isomer), 128.7 (trans-isomer), 127.6 (trans-isomer), 127.4 (cis-
isomer), 123.2 (trans-isomer), 123.1 (cis-isomer), 122.5 (cis-
isomer), 122.0 (trans-isomer), 114.4 (trans-isomer, d, JC-P = 5.4
Hz), 113.3 (cis-isomer, d, JC-P = 6.3 Hz), 110.7 (trans-isomer, d, JC-
P = 11.3 Hz), 110.2 (cis-isomer, d, JC-P = 11.8 Hz), 64.4 (cis-isomer,
d, JC-P = 6.8 Hz), 63.0 (trans-isomer, d, JC-P = 7.0 Hz), 47.8 (cis-
isomer, d, JC-P = 102.5 Hz), 47.0 (trans-isomer, d, JC-P = 104.7 Hz),
27.8 (trans-isomer, d, JC-P = 2.1 Hz), 27.3 (cis-isomer, d, JC-P = 1.7
Hz), 16.6 (trans-isomer, d, JC-P = 5.9 Hz), 16.1 (cis-isomer, d, JC-P
= 5.8 Hz). 31P NMR (162 MHz, CDCl3) δ 40.5 (trans-isomer), 39.5
(cis-isomer). IR (KBr, cm-1): 1687, 1625, 1278 (P=O), 1251 (P=O).
HRMS (ESI) calcd for C21H21NO3P+ [M+H+] 366.1254, found
366.1261.
This work was supported in part by the National Basic Research
Program of China (No. 2013CB328905), the National Natural
Science Foundation of China (Nos. 21372025 and 21572017).
Notes and references
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Graphic abstract
2-Ethoxy-2-oxophosphorindolines, benzo-γ-phospholactams, were synthesized efficiently with up
to 97% yield through the copper-catalyzed intramolecular aromatic C-H insertion of
diazophosphonamidates.