Me3P-catalyzed addition of hydrogen phosphoryl compounds P(O)H to electron-deficient alkenes: 1 to 1 vs 1 to 2 adducts

Article abstract of DOI:10.1016/j.tet.2017.10.070

Trimethyl phosphine was used as an efficient catalyst for the addition of P(O)-H compounds to electron-deficient alkenes. The addition reactions were generally conducted using a catalytic amount of Me₃P under mild reaction conditions. Both 1 to 1 and 1 to 2 adducts were obtained.

Full text of DOI:10.1016/j.tet.2017.10.070

Accepted Manuscript
Me P-catalyzed addition of hydrogen phosphoryl compounds P(O)H to electron-
3
deficient alkenes: 1 to 1 vs 1 to 2 adducts
Tian-Zeng Huang, Tieqiao Chen, Yuta Saga, Li-Biao Han
PII:
S0040-4020(17)31116-X
10.1016/j.tet.2017.10.070
TET 29073
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 October 2017
Revised Date: 26 October 2017
Accepted Date: 27 October 2017
Please cite this article as: Huang T-Z, Chen T, Saga Y, Han L-B, Me P-catalyzed addition of hydrogen
3
phosphoryl compounds P(O)H to electron-deficient alkenes: 1 to 1 vs 1 to 2 adducts, Tetrahedron
(2017), doi: 10.1016/j.tet.2017.10.070.
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Me3P-catalyzed addition of hydrogen
phosphoryl compounds P(O)H to electron-
deficient alkenes: 1 to 1 vs 1 to 2 adducts
Leave this area blank for abstract info.
Tian-Zeng Huang,a,c Tieqiao Chen,b,c* Yuta Saga,c Li-Biao Hana,c*
aDivision of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-
8571, Japan
bCollege of Materials and Chemical Engineering, Hainan University, Haikou, China
cNational Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568, Japan

1
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Tetrahedron
journal homepage: www.elsevier.com
Me3P-catalyzed addition of hydrogen phosphoryl compounds P(O)H to electron-
deficient alkenes: 1 to 1 vs 1 to 2 adducts
Tian-Zeng Huanga,c, Tieqiao Chenb,c,*, Yuta Sagac, and Li-Biao Hana,c,
aDivision of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
bCollege of Materials and Chemical Engineering, Hainan University, Haikou, China
cNational Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Trimethyl phosphine was used as an efficient catalyst for the addition of P(O)-H compounds to
electron-deficient alkenes. The addition reactions were generally conducted using a catalytic
amount of Me3P under mild reaction conditions. Both 1 to 1 and 1 to 2 adducts were obtained.
2009 Elsevier Ltd. All rights reserved
.
Available online
Keywords:
Addition
Alkenes
Me3P catalysis
P(O)-H compounds
Organophosphorus compounds
1. Introduction
using Me3P as a catalyst, compared with other catalysts such as
the metal-catalysts,5 is the easy purification of the resulted
products because the Me3P catalyst (and the corresponding
phosphine oxide Me3P(O)) can be easily removed under vacuum
from the products.
It is well-known that, as insecticides and herbicides,
organophosphoryl compounds bearing a phosphoryl group P(O)
play an important role in agrochemistry.1 Phosphorus compounds
are also very useful starting materials in organic synthesis (the
Horner-Wadsworth-Emmons reaction, for example) and ligands
for transition metal catalysts.2 Therefore, the development of new
methods for their preparation is of current concern.
A further study on the synthetic potential of this Me3P-
catalyzed addition by changing the vinylphosphoryl compounds
to other CH2=CHEWG (α, β-unsaturated esters and nitriles etc.),
interestingly revealed that, in addition to the expected 1 to 1 (one
molecule P(O)H with one molecule olefin) adduct 1, a novel 1 to
2 (one molecule P(O)H with two molecules olefin) adduct 1’ was
also generated (eq 3). Noteworthy is that such an adduct 1’ has
only been recognized as a trace amount of by-products of such
addition reactions of P(O)H to an electron-deficient alkene.9a, 9d
Here below we report the details.
The nucleophilic addition of a hydrogen phosphonate to an
electron-deficient alkene is a simple method for the preparation
of phosphonates (eq 1). This reaction has been carried out in the
presence of bases,3 Lewis acids,4 transition metals,5 microwaves,6
and radical initiators such as AIBN.7
Recently, we and others reported that phosphine can
efficiently catalyze the addition of a variety of hydrogen
phosphoryl compounds to electron-deficient alkenes to produce
the corresponding phosphoryl compounds in high yields (eq 2).8,9
Enantiomerically pure P(O)-H starting chemicals also could be
used in this reaction to give the corresponding phosphoryl
compounds with retention of configuration at the phosphorus
center. In addition to its high efficiency, the primary advantage
———
e-mail: libiao-han@aist.go.jp

2
Tetrahedron
ACCEPTED MANUSCRIPT
2. Results and discussion
acrylonitrile only has a tiny effect on the reaction (entries 5 and
6). On the other hand, the reaction temperature can affect the
ratio of the two products 1/1’. Thus, the selectivity to 1’
constantly increased as the reaction temperature decreased
(entries 7-10). The reaction also progressed rapidly in toluene,
CH2Cl2 and EtOAc (entries 11-13). However, only low yields of
the products were obtained in DMF, DMSO and acetone (entries
14-16). On the other hand, no addition products were observed
when the reaction was conducted in EtOH. Surprisingly, however,
1 was selectively generated in a high yield when t-BuOH was
used as the solvent (entry 18).
To a mixture of (MeO)2P(O)H (1.0 mmol) and acrylonitrile
(2.0 mmol) in THF (1.0 mL) was added Me3P (0.05 mmol, 1.0
mol/L in THF) at 0 C. The cooling ice bath was then removed
o
and the solution was stirred at room temperature for 1 h. GC
analysis showed that 97% (MeO)2P(O)H was consumed and the
adduct 1 (1 to 1 adduct) by the addition of one molecule
(MeO)2P(O)H to one molecule acrylonitrile and 1’ (1 to 2
adduct) by the addition of one molecule (MeO)2P(O)H to two
molecules acrylonitrile were generated in 69% and 28% yields,
respectively (eq 4).10
Next, in order to clarify the scope and limitations of this
reaction, the additions of a variety of P(O)H compounds to
electron-deficient alkenes under this optimized reaction condition
(entry 18) were carried out. As shown in Table 2, all the dialkyl
phosphites tested could produce the corresponding products in
good yields with excellent selectivity to the 1 to 1 adduct 1
Although the formation of the 1 to 1 adduct 1 is somewhat a
result within prediction, as mentioned above, the formation of the
1 to 2 adduct 1’ was rather unexpected, i.e. it seems this is the
first time to reveal its formation in such addition reactions of
P(O)H compounds.3-7 In order to selectively obtain the two
adducts, the reaction conditions were subsequently optimized.
(Table
phenylphosphinate
2,
products
and
1-5).
secondary
H-phosphinate
phosphine
isopropyl
oxide
diphenylphosphine oxide were also applicable to this reaction,
generating the corresponding 1 to 1 adducts in high yield with
high selectivity (products 6, 7). The electron-deficient methyl
acrylate and tert-butyl acrylate were found as reactive as
acrylonitrile to react with dimethyl phosphite, furnishing the
expected products 1 in high yields (products 8, 9). The steric
bulky methacrylonitrile and methyl methacrylate also worked
well under the present reaction conditions and the desired
products were given in high yields (products 10, 11).
2.1. Selective generation of 1.
As a model reaction, we started our optimization by
conducting the addition of dimethyl phosphite to acrylonitrile in
the presence of Me3P catalyst (Table 1). The addition reaction at
room temperature in MeCN took place rapidly to produce 98%
total yield of 1/1’ with a ratio of 1/1’ = 70/30 (Table 1, entry 1) in
an hour. Stirring the reaction mixture for a longer time (8 h) did
not give difference in yields and ratios of the products, which
indicates that both 1 and 1’, once formed, are stable under current
conditions (entry 2). The reaction could also be carried out using
less Me3P (1 mol%), albeit the yield of the adducts slightly
Table 2. Selective 1 to 1 addition of a P(O)H compound to an
electron-deficient alkene.a
Table 1. Reaction condition optimization for the selective
generation of 1.a
Entry
1
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
THF
THF
THF
Toluene
CH2Cl2
EtOAc
DMF
DMSO
Acetone
EtOH
Total yield of 1 and 1’ (%)
Ratio of 1/1’
70/30
70/30
68/32
76/24
69/31
70/30
71/29
67/33
60/40
57/43
81/19
89/11
73/27
56/44
50/50
81/19
0/0
98
97
65
54
96
97
97
93
84
81
95
83
83
34
32
38
0
2b
3c
4d
5e
6f
7
aReaction conditions: phosphite (1.0 mmol), alkene (2.0 mmol), Me3P (0.05
8g
mmol), t-BuOH (1.0 mL), 25 oC, 1 h. bIsolated yield.
9h
10i
11
12
13
14
15
16
17
18
2.2. Attempted selective generation of 1’
Since the 1 to 1 addition product 1 was successfully generated
selectively, we turned our attention to the selective generation of
1’. As described in Table 1, the selective generation of 1’ was not
achieved under the conditions of Table 1. Therefore, we decided
to further optimize the conditions in order to selectively obtain 1’
(Table 3). The addition also took place readily with methyl
acrylate (entries 1 and 2). Similar to acrylnitrile, when 1.0
equivalence was used, 52% yield of the adducts with a ratio of
1/1’ = 60/40 was obtained (entry 1). With 2.0 equivalents of
methyl acrylate, 96% yield of the adducts was obtained, albeit the
ratio of the adducts changed little (1/1’ = 58/42) (entry 2). The
addition also took place smoothly with the bulky diisopropyl
phosphosite to give 88% yield of the adducts with 65/35
selectivity (entry 3). In addition to Me3P, the reaction could also
t-BuOH
97
96/4
aReaction conditions: to a solution of dimethyl phosphite (1.0 mmol) and
acrylonitrile (2.0 mmol) in solvent (1.0 mL) was added Me3P (0.05 mmol, 1.0
mol/L in THF) at 0 C. The reaction mixture was stirred at 25 oC for 1 h.
o
Yield was determined by GC. b8 h. cMe3P (0.01 mmol). d1.0 mmol
acrylonitrile was used. e3.0 mmol acrylonitrile was used. f4.0 mmol
acrylonitrile was used. g at 0 oC. h at -40 oC. i at -60 oC.
decreased (entry 3). Similarly, when 1.0 mmol acrylonitrile was
used, a moderate yield of the adduct 54% (entry 4) was obtained.
Interestingly, however, compared to entry 1, the use of more

3
be catalyzed efficiently by other trialkyl phosphines Et3P, n-Bu3P
and even the very bulky t-Bu3P and Cy3P (entries 4-7).
Dimethylphenylphosphine also well catalyzed the addition (entry
8). However, the bulky dicyclohexylphenylphoshine only gave a
low yield of the products under similar conditions (entry 9). The
catalytic activity of diphenylmethylphosphine was also low
(entry 10), while triarylphosphines like Ph3P, (p-MeC6H4)3P, (p-
MeO-C6H4)3P all could not catalyze the addition reaction (entries
11-13). When we used triethylamine (pKb = 3.2), which is a
stronger base than triethylphosphine (pKb = 5.4),11 as catalyst
under similar conditions, the addition failed (entry 14), showing
that basicity is important but is not the only factor for a catalyst.
Very interestingly, however, with a combination of these inactive
phosphine and Et3N, the addition could also take place (entries 15
and 16). Thus, the combination of (p-MeOC6H4)3P gave 16%
yield of the adducts (entry 15), and the combination of Cy2PhP
with Et3N gave 42% yield of the adducts (entry 16). As expected,
the triarylphsophine having an amino group (p-Me2NC6H4)3P
could also catalyze the reaction (entry 17). However, despite
such an extensive study on the reaction, the selective formation
of 1’ has not been found yet.
Table 4. Scope and limitations of the Me3P-catalyzed reaction
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between P(O)H compounds with an electron-deficient alkenes.a
Table 3. Reaction condition optimization for the selective
generation of 1’. a
Yield
(%)b
52
96
88
92
86
84
72
85
12
8
Ratio
(1/1’)c
60/40
58/42
65/35
70/30
70/30
70/30
66/34
70/30
60/40
50/50
-
Entry
R1
R2
Cat.
1d,e
2e
MeO
MeO
i-PrO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
COOMe
COOMe
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
Me3P
Me3P
Me3P
Et3P
n-Bu3P
3e
4f
5f
6f
t-Bu3P
Cy3P
7f
8f
Me2PhP
Cy2PhP
MePh2P
Ph3P
(p-MePh)3P
(p-MeOPh)3P
Et3N
9f
10f
11f
12f
13f
14f
0
0
0
0
-
-
-
CN
(p-MeOPh)3P,
Et3N
Cy2PhP, Et3N
(p-
15f
16f
17f
MeO
MeO
MeO
CN
CN
CN
16
42
58
46/54
52/48
58/42
Me2NPh)3P
aReaction conditions: phosphine (1.0 mmol), alkene (2 mmol), catalyst (0.05
o
b
c
mmol), solvent (1.0 mL), 25 C, 1 h. Total GC yield of 1 and 1’. Ratio of
1/1’ GC yield. d1 mmol alkene was used. eTHF as solvent. fMeCN as solvent.
As summarized in Table 4, in addition to (MeO)2P(O)H, other
dialkylphosphites (RO)2P(O)H (R = Et, n-Bu, i-Pr, PhCH2) also
reacted readily to give the products in high yields (Table 4,
products 2-5 and 2’-5’). Not limited to dialkyl phosphite,
isopropyl phenylphosphinate (products
6
and 6’), and
diphenylphosphine oxide (products 7 and 7’) could also be used
as the substrates to give the corresponding adducts in high yields.
In addition to acrylonitrile, satisfactory results were also
obtained in the reaction of (MeO)2P(O)H with several acrylates
such as methyl acrylate (products 8 and 8’), tert-butyl acrylate
(products 9 and 9’), methyl acrylonitrile (products 10 and 10’),
and methyl methacrylate (products 11 and 11’), in 73% to 95%
yields. Good results were also obtained with isopropyl
phenylphosphinate and methyl acrylate (products 12 and 12’).
Diphenyl phosphine oxide also served well to react with acrylates,
producing the products in high yields (products 13-16 and 13’-
16’). It is worth noting that under the reaction conditions, the 1 to
aReaction conditions: P(O)-H compounds (1.0 mmol), alkene (2.0 mmol)
Me3P (0.05 mmol), THF (1.0 mL), 25 C, 1 h. The yields in the table were
isolated yields.
o
1 adduct 11 and 16 were obtained selectively (products 11 and
16). Methyl vinylketone also could be used as the substrate to
give the 1 to 1 adduct 17 and 18 predominantly. The two adducts
could be separated and isolated in pure form by conventional
techniques. All these compounds we obtained have been fully

4
Tetrahedron
characterized spectroscopically as shown in the experimental
addition of (MeO)2P(O)H to CH2=CHCN is proposed (Scheme 2).
ACCEPTED MANUSCRIPT
section.
Dimethylphosphite and trimethylphosphine may generate an
intermediate I. This intermediate I adds to acrylonitrile, perhaps
via an intermediate II, to give the 1 to 1 adduct 1. On the other
hand, intermediate II may add to another molecule acrylonitrile
to generated III which, via a subsequent protonation, will give
the 1 to 2 adduct 1’. 1 to 1 adduct 1 was major product when t-
BuOH as solvent since t-BuOH provides the proton which can
2.3. Mechanistic study.
To gain some insights into the reaction mechanism, a series of
control experiments were carried out (Scheme 1). It was known
that
acrylonitrile
could
dimerize
to
produce
2-
methyleneglutaronitrile 19.12 Therefore, it was first thought that
the addition of P(O)-H compounds to acrylonitrile should give
the 1 to 1 adduct 1, while the addition to 19 should give the 1 to 2
adduct 1’ (eq. 5). Indeed, a separate experiment using 19
confirmed that the addition did occur to produce 1’ (eq. 6).
However, as described below, this reaction path, although could
not be completely excluded out, should not be the major path for
the formation of 1’ under the reaction conditions.
quickly quench the intermediate II. Although the addition of
Me3P to acrylonitrile generating a zwitterionic species IV is also
a long-proposed reasonable reaction, however, apparently, this is
a dead path for the catalytic addition of (MeO)2P(O)H to
acrylonitrile as shown in eq.s 7-9.
3. Conclusion
In conclusion, we have disclosed a simple Me3P-catalyzed
addition of hydrogen phosphoryl compounds P(O)H to electron-
deficient alkenes to give the very useful functional phosphoryl
compounds. The reaction produced not only the 1 to 1 adduct 1
but also 1 to 2 adduct 1’. The generation of the 1 to 1 adduct 1
was selective. Although a selective generation of 1’ was not
achieved, this adduct could be isolated via conventional
techniques. The workup of the reaction mixture is very simple
compared with other methods since the catalyst can be easily
removed from the product under vacuum.
Scheme 1. Control experiments
4. Experimental section
General information: All materials were purchased and used
1
without further purification. H NMR spectra were recorded on
JEOL JNM-ECS400 (400 MHz) FT NMR in CDCl3 with Me4Si
as an internal standard. 13C NMR spectra were taken on JEOL
JNM-ECS400 (100 MHz) FT NMR system in CDCl3. 31P NMR
spectra were taken on JEOL JNM-ECX400 (162 MHz) FT NMR
system in CDCl3 with 85% H3PO4 solution as an external
standard. HPLC (recycle GPC) method for isolation was
performed on JAPAN ANALYTICAL INDUSTRY LC-908 with
JAIGEL-1H (polystyrene-based column). High resolution mass
spectra were obtained on JEOL JMS700 at Kyoto-Nara
Firstly, under the reaction conditions in the absence of
(MeO)2P(O)H, the dimerization product 19 from acrylonitrile in
THF and t-BuOH, was obtained in only 5% and 10% yield,
respectively (eq.s 7 and 8). Very surprisingly, the addition almost
did not take place when (MeO)2P(O)H was subsequently added
to the mixtures. On the other hand, by the addition of another 5
mol% Me3P, the addition took place rapidly to give the adducts
in high yields (eq. 8). Therefore, it can be safely concluded that
the combination of CH2=CHCN with Me3P can significantly
deactivate the catalytic activity of Me3P in the addition of
(MeO)2P(O)H to CH2=CHCN. However, interestingly, such a
deactivation of the catalyst Me3P was not observed with the
combination of (MeO)2P(O)H with Me3P, because the addition
still took place readily when CH2=CHCN was subsequently
added to the mixture of (MeO)2P(O)H with Me3P (eq 9).
Advanced
Nanotechnology
Network.
Caution:
trimethylphosphine has toxicity and high volatility. When
trimethylphosphine is manipulated, ventilate the bench carefully.
General procedure for Me3P catalyzed addition of P(O)-H
compounds to electron-deficient alkenes: A glass schlenk tube
was charged with P(O)-H compounds (1.0 mmol), electron-
deficient alkenes (1.0 mmol) and 1.0 mL solvent. After the tube
was cooled in an ice-water bath, Me3P (1.0 mol/L in THF, 0.05
mL) was injected with a syringe. After stirring for 5 minutes, the
ice bath was removed. The reaction mixture was warmed up to
room temperature and stirred for 1 h. The solvent and PMe3 was
removed under reduce pressure. The crude product was purified
by GPC to get the analytically pure samples.
Scheme 2. A plausible mechanism for the Me3P-catalyzed
addition of (MeO)2P(O)H to acrylonitrile.
4.1. Dimethyl (2-cyanoethyl)phosphonate (1). Colorless oil; δH
(400 MHz, CDCl3) 3.54 (6H, d, J 11.2 Hz), 2.40 (2H, td, J 8.0 Hz,
J 15.2 Hz), 1.87 (2H, td, J 8.0 Hz, J 18.0 Hz); δC (100 MHz,
CDCl3) 117.96 (d, J 16.2 Hz), 52.23 (d, J 6.7 Hz), 21.03 (d, J
144.8 Hz), 10.84 (d, J 3.8 Hz); δP (162 MHz, CDCl3) 29.48. This
compound is known.13
4.2. Dimethyl (2,4-dicyanobutyl)phosphonate (1’). Colorless oil;
δH (400 MHz, CDCl3) 3.74 (6H, d, J 11.2 Hz, d, J 10.8 Hz),
3.06~3.03 (1H, m), 2.76~2.46 (2H, m), 2.20~1.94 (2H, m); δC
(100 MHz, CDCl3) 119.04 (d, J 11.4 Hz), 117.70, 52.89 (d, J 6.6
Hz), 52.82 (d, J 8.6 Hz), 28.58 (d, J 10.5 Hz), 27.79 (d, J 143.9
Hz), 25.40 (d, J 3.8 Hz), 14.99; δP (162 MHz, CDCl3) 27.54.
Although a detailed mechanism is not clear, on the basis of the
above results, a simplified mechanism for the Me3P-catalyzed

5
HRMS (ESI) Calcd for [M+H]+ C8H14N2O3P: 217.0742, Found:
217.0729.
J 2.9 Hz), 15.12; δP (162 MHz, CDCl3) 25.88. HRMS (ESI)
ACCEPTED MANUSCRIPT
Calcd for [M+H]+ C20H22N2O3P: 369.1368, Found: 369.1387.
4.3. Diethyl (2-cyanoethyl)phosphonate (2). Colorless oil; δH
(400 MHz, CDCl3) 4.13~4.05 (4H, m), 2.63~2.55 (2H, m),
2.08~1.99 (2H, m), 1.30 (6H, td, J 1.6 Hz, J 7.6 Hz,); δC (100
MHz, CDCl3) 118.37 (d, J 18.1 Hz), 62.34 (d, J 6.7 Hz), 22.844
(d, J 144.8 Hz), 16.41 (d, J 5.7 Hz), 11.59 (d, J 3.8 Hz); δP (162
MHz, CDCl3) 26.62. This compound is known.13
4.11. Isopropyl (2-cyanoethyl)(phenyl)phosphinate (6). Colorless
oil; δH (400 MHz, CDCl3) 7.66~7.61 (2H, m), 7.45~7.41 (1H, m),
7.37~7.33 (2H, m), 4.46~4.34 (1H, m), 2.56~2.33 (2H, m),
2.17~1.92 (2H, m), 1.24 (3H, d, J 6.0 Hz), 1.03 (3H, d, J 6.4 Hz);
δC (100 MHz, CDCl3) 132.52 (d, J 1.9 Hz), 131.30 (d, J 10.4 Hz),
130.29 (d, J 126.8 Hz), 128.55 (d, J 12.4 Hz), 118.21 (d, J 18.1
Hz), 70.28 (d, J 6.6 Hz), 26.41 (d, J 101.0 Hz), 24.14 (d, J 2.8
Hz), 23.55 (d, J 4.8 Hz), 10.31, δP (162 MHz, CDCl3) 38.70.
HRMS (ESI) Calcd for [M+H]+ C12H17NO2P: 238.0996, Found:
238.0994.
4.4. Diethyl (2,4-dicyanobutyl)phosphonate (2’). Colorless oil; δH
(400 MHz, CDCl3) 4.17~4.09 (4H, m), 3.13~3.03 (1H, m),
2.67~2.50 (2H, m), 2.22~2.12 (2H, m), 2.08~1.94 (2H, m), 1.33
(6H, t, J 7.2 Hz); δC (100 MHz, CDCl3) 119.17 (d, J 11.5 Hz),
117.63, 62.59 (d, J 6.7 Hz), 62.56 (d, J 6.7 Hz), 28.91 (d, J 11.5
Hz), 28.70 (d, J 123.0 Hz), 25.67 (d, J 3.8 Hz), 16.37 (d, J 4.8
Hz), 15.15; δP (162 MHz, CDCl3): δ (ppm) 24.63. HRMS (ESI)
Calcd for [M+H]+ C10H18N2O3P: 245.1055, Found: 245.1079.
4.12. Isopropyl (2,4-dicyanobutyl)(phenyl)phosphinate (6’).
Colorless oil; δH (400 MHz, CDCl3) 7.76~7.71 (2H, m),
7.57~7.52 (1H, m), 7.49~7.44 (2H, m), 4.55~4.45 (1H, m),
3.29~3.16 (0.6H, m), 3.03~2.92 (0.4H, m), 2.62~2.45 (2H, m),
2.38~1.91 (4H, m,), 1.36 (3H, d, J 6.4 Hz, d, J 6.4 Hz), 1.13 (3H,
d, J 6.0 Hz, d, J 6.4 Hz); δC (100 MHz, CDCl3) 133.01 (d, J 2.8
Hz), 132.91 (d, J 1.9 Hz), 131.63 (d, J 9.5 Hz), 131.51 (d, J 10.5
Hz), 131.04 (d, J 127.8 Hz), 130.31 (d, J 127.7 Hz), 128.92 (d, J
12.4 Hz), 128.86 (d, J 12.4 Hz), 119.33 (d, J 11.6 Hz), 119.14 (d,
J 12.4 Hz), 117.65, 70.98 (d, J 5.7 Hz), 70.95 (d, J 5.8 Hz), 32.76
(d, J 100.1 Hz), 32.39 (d, J 100.0 Hz), 28.85 (d, J 7.6 Hz), 28.56
(d, J 6.7 Hz), 24.96 (d, J 6.7 Hz), 24.89 (d, J 3.8 Hz), 24.43 (d, J
2.9 Hz), 24.35 (d, J 2.8 Hz), 23.77 (d, J 2.8 Hz), 23.73 (d, J 2.9
Hz), 15.07, 14.97; δP (162 MHz, CDCl3) 37.68 (s), 37.01. HRMS
(ESI) Calcd for [M+H]+ C15H20N2O2P: 291.1262, Found:
291.1226.
4.5. Diisopropyl (2-cyanoethyl)phosphonate (3). Colorless oil; δH
(400 MHz, CDCl3) 4.71~4.63 (2H, m), 2.60~2.52 (2H, m),
2.03~1.94 (2H, m), 1.29 (12 H, dd, J 3.2 Hz, J 6.4 Hz); δC (100
MHz, CDCl3) 118.49 (d, J 19.1 Hz), 71.09 (m, J 6.7 Hz), 23.95
(d, J 3.8 Hz), 23.89 (d, J 136.3 Hz), 11.68 (d, J 3.9 Hz); δP (162
MHz, CDCl3) 24.33. HRMS (ESI) Calcd for [M+H]+ C9H19NO3P:
220.1102, Found: 220.111.
4.6. Diisopropyl (2,4-dicyanobutyl)phosphonate (3’). Colorless
oil; δH (400 MHz, CDCl3) 4.77~4.67 (2H, m), 3.12~3.02 (1H, m),
2.67~2.50 (2H, m), 2.25~1.88 (4H, m), 1.33 (12H, dd, J 2.0 Hz, J
6.0 Hz); δC (100 MHz, CDCl3) 119.32 (d, J 12.4 Hz), 117.64,
71.59 (d, J 6.7 Hz), 71.52 (d, J 6.6 Hz), 30.08 (d, J 129.6 Hz),
28.70 (d, J 6.7 Hz), 25.83 (d, J 3.8 Hz), 23.98 (d, J 3.8 Hz), 15.17;
δP (162 MHz, CDCl3): δ (ppm) 22.39. HRMS (ESI) Calcd for
[M+H]+ C12H22N2O3P: 273.1368, Found: 273.1389.
4.13. 3-(diphenylphosphoryl)propanenitrile (7). White solid; δH
(400 MHz, CDCl3) 7.74~7.69 (4H, m), 7.58~7.47 (6H, m),
2.67~2.56 (4H, m); δC (100 MHz, CDCl3) 132.57 (d, J 2.8 Hz),
131.48 (d, J 101.1 Hz), 130.80 (d, J 9.5 Hz), 129.11 (d, J 11.4
Hz), 118.64 (d, J 18.1 Hz), 26.63 (d, J 69.6 Hz), 10.47; δP (162
MHz, CDCl3) 30.04. This compound is known.14
4.7. Dibutyl (2-cyanoethyl)phosphonate (4). Colorless oil; δH
(400 MHz, CDCl3) 4.07~3.95 (4H, m), 2.61~2.54 (2H, m),
2.08~1.99(2H, m), 1.65~1.58 (4H, m), 1.40~1.31 (4H, m), 0.89
(6H, t, J 7.2 Hz); δC (100 MHz, CDCl3) 118.33 (d, J 18.1 Hz),
65.99 (d, J 6.7 Hz), 32.42 (d, J 5.7Hz), 22.66 (d, J 144.8 Hz),
18.63, 13.48, 11.56 (d, J 3.8 Hz); δP (162 MHz, CDCl3) 26.62.
HRMS (ESI) Calcd for [M+H]+ C11H23NO3P: 248.1415, Found:
248.1435.
4.14.
2-((diphenylphosphoryl)methyl)pentanedinitrile
(7’).
Colorless oil; δH (400 MHz, CDCl3) 7.79~7.70 (4H, m),
7.61~7.47 (6H, m), 3.20~3.11 (1H, m), 2.78~2.70 (1H, m),
2.63~2.44 (3H, m), 2.37~2.29 (1H, m), 2.08~1.98 (1H, m); δC
(100 MHz, CDCl3) 132.79 (d, J 2.8 Hz), 132.66 (d, J 2.9 Hz),
132.48 (d, J 101.9 Hz), 131.03 (d, J 9.5 Hz), 130.83 (d, J 100.0
Hz), 130.53 (d, J 9.5 Hz), 129.23 (d, J 12.4 Hz), 129.17 (d, J 12.4
Hz), 119.28 (d, J 11.4 Hz), 117.61, 32.48 (d, J 67.7 Hz), 28.97 (d,
J 4.8 Hz), 25.16 (d, J 1.9 Hz), 15.24; δP (162 MHz, CDCl3) 28.72.
HRMS (ESI) Calcd for [M+H]+ C18H17N2OP: 308.1078, Found:
308.1080.
4.8. Dibutyl (2,4-dicyanobutyl)phosphonate (4’). Colorless oil; δH
(400 MHz, CDCl3) 4.12~4.00 (4H, m), 3.13~3.02(1H, m),
2.67~2.50 (2H, m), 2.23~2.13 (2H, m), 2.08~1.94 (2H, m),
1.69~1.62 (4H, m), 1.43~1.34 (4H, m), 0.92 (6H, t, J 7.2 Hz); δC
(100 MHz, CDCl3) 119.20 (d, J 12.4 Hz), 117.58, 66.36 (d, J 6.7
Hz), 66.34 (d, J 6.7 Hz), 32.49 (d, J 5.8 Hz), 32.47 (d, J 5.8 Hz),
28.89 (d, J 143.9 Hz), 28.86 (d, J 9.5 Hz), 25.75 (d, J 3.8 Hz),
18.71, 15.22, 13.57; δP (162 MHz, CDCl3) 24.65. HRMS (ESI)
Calcd for [M+H]+ C14H26N2O3P: 301.1681, Found: 301.1663.
4.15. Methyl 3-(dimethoxyphosphoryl)propanoate (8). Colorless
oil; δH (400 MHz, CDCl3) 3.67 (9H, d, J 10.4 Hz, s), 2.57~2.50
(2H, m), 2.07~1.99 (2H, m); δC (100 MHz, CDCl3) 172.41 (d, J
18.1 Hz), 52.48 (d, J 6.7 Hz), 51.99, 27.17 (d, J 3.8 Hz), 20.69 (d,
J 143.9 Hz); δP (162 MHz, CDCl3) 33.39. HRMS (ESI) Calcd for
[M+H]+ C6H14O5P: 197.0578, Found: 197.0554. This compound
is known.13
4.9. Dibenzyl (2-cyanoethyl)phosphonate (5). Colorless oil; δH
(400 MHz, CDCl3) 7.38~7.24 (10H, m), 5.08~4.92 (4H, m),
2.52~2.45 (2H, m), 2.05~1.94 (2H, m); δC (100 MHz, CDCl3)
135.70 (d, J 5.7 Hz), 128.81 (d, J 6.7 Hz), 128.21, 118.25 (d, J
19.1 Hz), 67.95 (d, J 6.6 Hz), 23.38 (d, J 144.0 Hz), 11.42 (d, J
2.8 Hz); δP (162 MHz, CDCl3): δ (ppm) 27.82. HRMS (ESI)
Calcd for [M+H]+ C17H19NO3P: 316.1102, Found: 316.1136.
4.16. Dimethyl 2-((dimethoxyphosphoryl)methyl)pentanedioate
(8’). Colorless oil; δH (400 MHz, CDCl3) 3.69~3.62 (12 H, m),
2.80~2.70 (1H, m), 2.31~2.15 (3H, m), 1.96~1.77 (3H, m); δC
(100 MHz, CDCl3) 174.33 (d, J 8.6 Hz), 172.79, 52.55 (d, J 6.6
Hz), 52.46 (d, J 6.7 Hz), 52.05, 51.69, 39.05 (d, J 3.8 Hz), 31.19,
28.42 (d, J 12.4 Hz), 27.65 (d, J 142.0 Hz); δP (162 MHz, CDCl3)
31.77. HRMS (ESI) Calcd for [M+H]+ C10H20O7P: 283.0946,
Found: 283.0927.
4.10. Dibenzyl (2,4-dicyanobutyl)phosphonate (5’). Colorless oil;
δH (400 MHz, CDCl3) 7.35 (10H, b), 5.10~4.92 (4H, m),
3.00~2.89 (1H, m), 2.55~2.36 (2H, m), 2.17~2.00 (2H, m),
1.96~1.85 (2H, m); δC (100 MHz, CDCl3) 135.57 (d, J 5.7 Hz),
135.51 (d, J 4.7 Hz), 128.96, 128.92, 128.84, 128.80, 128.45,
128.37, 119.08 (d, J 12.4 Hz), 117.52, 68.31 (d, J 6.6 Hz), 68.20
(d, J 6.7 Hz), 29.53 (d, J 143.9 Hz), 28.68 (d, J 8.6 Hz), 25.59 (d,
4.17.
tert-butyl
3-(dimethoxyphosphoryl)propanoate
(9).
Colorless oil; δH (400 MHz, CDCl3) 3.69 (6H, d, J 10.8 Hz),
2.48~2.41 (2H, m,), 2.03~1.94 (2H, m), 1.39 (9H, s); δC (100

6
Tetrahedron
MHz, CDCl3) 171.08 (d, J 18.1 Hz), 80.90, 52.38 (d, J 6.7 Hz),
23.82 (d, J 4.8 Hz); δP (162 MHz, CDCl3) 40.71, 40.29. HRMS
ACCEPTED MANUSCRIPT
28.41 (d, J 3.8 Hz), 27.94, 20.68 (d, J 143.0 Hz); δP (162 MHz,
CDCl3) 33.99. HRMS (ESI) Calcd for [M+H]+ C9H20O5P:
239.1048, Found: 239.1076.
(ESI) Calcd for [M+H]+ C17H26O6P: 357.1467, Found: 357.1477.
4.24. Methyl 3-(diphenylphosphoryl)propanoate (13). Colorless
oil; δH (400 MHz, CDCl3) 7.86~7.63 (4H, m), 7.45~7.36 (6H, m),
3.53 (3H, s), 2.59~2.47 (4H, m); δC (100 MHz, CDCl3) 172.63 (d,
J 16.2 Hz), 132.51 (d, J 99.1 Hz)， 131.82 (d, J 2.8 Hz), 130.63
(d, J 9.6 Hz), 128.63 (d, J 11.5 Hz), 51.84, 26.11 (d, J 1.9 Hz),
25.24 (d, J 72.9 Hz); δP (162 MHz, CDCl3) 32.02. This
compound is known.15
4.18.
Di-tert-butyl
2-
((dimethoxyphosphoryl)methyl)pentanedioate (9’). Colorless oil;
δH (400 MHz, CDCl3) 3.69 (6 H, d, J 2.4 Hz, d, J 3.2 Hz),
2.67~2.57 (1H, m), 2.25~2.13 (3H, m), 1.86~1.69 (3H, m), 1.42
(18H, s, s); δC (100 MHz, CDCl3) 169.14 (d, J 7.6 Hz), 167.75,
77.05, 76.41, 48.38 (d, J 6.7 Hz), 48.28 (d, J 6.7 Hz), 35.80 (d, J
2.9 Hz), 28.60, 25.01 (d, J 13.3 Hz), 24.00, 23.93, 23.44 (d, J
142.0 Hz); δP (162 MHz, CDCl3) 32.55. HRMS (ESI) Calcd for
[M+H]+ C16H32O7P: 367.1885, Found: 367.1886.
4.25. Dimethyl 2-((diphenylphosphoryl)methyl)pentanedioate
(13’). Colorless oil; δH (400 MHz, CDCl3) 7.69~7.64 (4H, m),
7.46~7.36 (6H, m), 3.53 (3H, s), 3.35 (3H, s), 2.91~2.72 (2H, m),
2.32~2.21 (3H, m), 1.97~1.92 (2H, m); δC (100 MHz, CDCl3)
174.32 (d, J 6.7 Hz), 172.63, 133.51 (d, J 99.2 Hz), 132.34 (d, J
98.1 Hz), 131.77 (d, J 3.8 Hz), 131.73 (d, J 2.8 Hz), 130.94 (d, J
9.5 Hz), 130.48 (d, J 8.6 Hz), 128.63 (d, J 11.5 Hz), 128.48 (d, J
12.4 Hz), 51.73, 51.51, 38.16 (d, J 2.9 Hz), 32.11 (d, J 70.5 Hz),
31.18, 29.90 (d, J 9.5 Hz); δP (162 MHz, CDCl3) 30.11. This
compound is known.16
4.19. Dimethyl (2-cyanopropyl)phosphonate (10). Colorless oil;
δH (400 MHz, CDCl3) 3.72~3.68(6H, d, J 10.8 Hz, d, J 11.2 Hz),
2.99~2.87 (1H, m), 2.16~2.05 (1H, m), 1.93~1.83 (1H, m),
1.39~1.37 (3H, d, J 7.2 Hz, d, J 6.0 Hz); δC (100 MHz, CDCl3)
121.56 (d, J 12.4 Hz), 52.72 (d, J 6.7 Hz), 52.59 (d, J 6.6 Hz),
29.97 (d, J 142.9 Hz), 20.39 (d, J 3.8 Hz), 19.28 (d, J 9.5 Hz); δP
(162 MHz, CDCl3) 28.65. HRMS (ESI) Calcd for [M+H]+
C6H13NO3P: 178.0633, Found: 178.0646.
4.26.
tert-butyl
3-(diphenylphosphoryl)propanoate
(14).
Colorless oil; δH (400 MHz, CDCl3) 7.74~7.69 (4H, m),
7.51~7.42 (6H, m), 2.57~2.47 (4H, m), 1.36 (9H, s); δC (100
MHz, CDCl3) 171.61 (d, J 17.2 Hz), 132.85 (d, J 101.9 Hz),
131.85, 130.79 (d, J 8.6 Hz), 128.73 (d, J 11.4 Hz), 81.02, 27.97,
27.43 (d, J 1.9 Hz), 25.36 (d, J 72.5 Hz); δP (162 MHz, CDCl3)
32.35. This compound is known.17
4. 20. Dimethyl (2,4-dicyano-2-methylpentyl)phosphonate (10’).
Colorless oil; δH (400 MHz, CDCl3) 3.76 ~3.72 (6H, m),
2.88~2.80 (1H, m), 2.31~1.98 (4H, m), 1.63~1.59 (3H, s, s,),
1.41~1.39 (3H, d, J 7.2 Hz, d, J 6.8 Hz,); δC (100 MHz, CDCl3)
122.24, 122.13, 121.98 (d, J 11.4 Hz), 121.80 (d, J 11.4 Hz),
52.91 (d, J 6.6 Hz), 52.84 (d, J 7.7 Hz), 52.71 (d, J 5.7 Hz), 43.11
(d, J 7.7 Hz), 42.93 (d, J 7.7 Hz), 36.09 (d, J 142.9 Hz), 33.78 (d,
J 142.0 Hz), 33.37 (d, J 2.9 Hz), 33.07 (d, J 2.9 Hz), 26.28 (d, J
5.7 Hz), 25.20 (d, J 7.6 Hz), 22.09 (d, J 26.6 Hz), 19.59 (d, J 16.2
Hz); δP (162 MHz, CDCl3) 26.48. HRMS (ESI) Calcd for
[M+H]+ C10H18N2O3P: 245.1055, Found: 245.1067.
4.27.
5-((diphenylphosphoryl)methyl)-2,2,10,10-
tetramethylundecane-4,8-dione (14’). Colorless oil; δH (400 MHz,
CDCl3) 7.72~7.64 (4 H, m), 7.45~7.36 (6H, m), 3.55 (3H, d),
3.43 (3H, d). 2.83~2.76 (1H, m), 2.51~2.41 (2H, m), 2.30~2.24
(1H, m), 2.16~2.05 (1H, m), 1.24 (3H, d), 1.02 (3H, d); δC (100
MHz, CDCl3) 169.33 (d, J 6.7 Hz), 167.74, 129.91 (d, J 101.1
Hz), 128.90 (d， J= 98.2 H)， 127.67， 127.02 (d, J 9.5 Hz),
126.60 (d, J 8.6 Hz), 124.63 (d, J 8.6 Hz), 124.51 (d, J 8.6 Hz),
77.05, 76.26, 34.90, 28.74, 27.81 (d, J 70.5 Hz), 25.48 (d, J 8.6
Hz), 23.97, 23.83; δP (162 MHz, CDCl3) 30.62. HRMS (ESI)
Calcd for [M]+ C26H35O5P: 458.2222, Found:458.2246.
4.21. Methyl 3-(dimethoxyphosphoryl)-2-methylpropanoate (11).
Colorless oil; δH (400 MHz, CDCl3) 3.68~3.64 (9H, m),
2.84~2.72 (1H, m), 2.28~2.18 (1H, m), 1.81~1.70 (1H, m), 1.25
(3H, d, J 8.0 Hz); δC (100 MHz, CDCl3) 175.58 (d, J 12.4 Hz),
52.36 (d, J 4.8 Hz), 52.00, 34.30 (d, J 2.9 Hz), 28.95 (d, J 141.1
Hz), 18.67 (d, J 9.6 Hz); δP (162 MHz, CDCl3) 32.55. HRMS
(ESI) Calcd for [M+H]+ C7H16O5P: 211.0735, Found: 211.0764.
4.28.
3-(diphenylphosphoryl)-2-methylpropanenitrile
(15).
Colorless oil; δH (400 MHz, CDCl3) 7.74~7.66 (4H, m),
7.50~7.38 (6H, m), 3.10~3.05 (1H, m), 2.73~2.65 (1H, m),
2.46~2.37 (1H, m), 1.36 (3H, d, J 7.6 Hz); δC (100 MHz, CDCl3)
132.86 (d, J 100.0 Hz), 132.23 (d, J 2.9 Hz), 132.10 (d, J 2.9 Hz),
131.46 (d, J 100.0 Hz), 130.76 (d, J 9.5 Hz), 130.34 (d, J 9.6 Hz),
128.79 (d, J 11.4 Hz), 121.76 (d, J 12.4 Hz), 34.09 (d, J 68.6 Hz),
19.63 (d, J 1.9 Hz), 19.51 (d, J 5.7 Hz); δP (162 MHz, CDCl3)
28.79. HRMS (ESI) Calcd for [M]+ C11H16NOP: 269.0969,
Found: 269.0947.
4.22. Methyl 3-(isopropoxy(phenyl)phosphoryl)propanoate (12).
Colorless oil; δH (400 MHz, CDCl3) 7.67~7.62 (2H, m),
7.42~7.31 (3H, m), 4.59~4.34 (1H, m), 3.47 (3H, s), 2.53~2.31
(2H, m), 2.17~1.95 (2H, m), 1.24 (3H, d, J 6.4 Hz), 1.02 (3H, d,
J 6.4 Hz); δC (100 MHz, CDCl3) 172.36 (d, J 17.2 Hz), 132.08 (d,
J 1.9 Hz), 131.45 (d, J 123.9 Hz), 131.41 (d, J 9.5 Hz), 128.38 (d,
J 12.3 Hz), 69.59 (d, J 5.8 Hz), 51.62, 26.38, 25.79 (d, J 102.0
Hz), 24.31 (d, J 2.9 Hz), 23.71 (d, J 4.8 Hz); δP (162 MHz,
CDCl3) 41.79. HRMS (ESI) Calcd for [M+H]+ C13H20O4P:
271.1099, Found: 271.1080.
4.29.
2-((diphenylphosphoryl)methyl)-2,4-
dimethylpentanedinitrile (15’). Colorless oil; δH (400 MHz,
CDCl3) 7.83~7.71 (4H, m), 7.51~7.44 (6H, m), 2.93~2.67 (3H,
m), 2.31~1.96 (2H, m), 1.57 (3H, d, J 2.4 Hz), 1.35 (3H, t, J 7.2
Hz); δC (100 MHz, CDCl3) 133.34 (d, J 101.0 Hz), 133.17,
132.71 (d, J 100.1 Hz), 132.19, 130.77 (8.6 Hz), 130.57 (d, J 8.6
Hz), 130.52 (d, J 3.8 Hz), 130.43 (d, J 2.9 Hz), 128.90 (d, J 11.5
Hz), 128.86 (d, J 11.5 Hz), 122.40 (d, J 11.5 Hz), 121.72 (d, J
11.5 Hz), 121.61 (d, J 8.5 Hz), 43.34 (d, J 4.7 Hz), 43.02 (d, J 3.8
Hz), 39.05 (d, J 67.6 Hz), 37.04 (d, J 67.6 Hz), 34.79 (d, J 3.8
Hz), 34.34 (d, J 3.8 Hz), 26.75 (d, J 4.8 Hz), 25.86 (d, J 5.8 Hz),
22.14 (d, J 18.2 Hz), 19.51 (d, J 17.2 Hz); δP (162 MHz, CDCl3)
26.78, 26.34. HRMS (ESI) Calcd for [M]+ C20H21N2OP:
336.1391, Found: 336.1416.
4.23.
Dimethyl
2-
(12’).
((isopropoxy(phenyl)phosphoryl)methyl)pentanedioate
Colorless oil; δH (400 MHz, CDCl3) 7.74~7.67 (2H, m),
7.49~7.38 (3H, m), 4.48~4.37 (1H, m), 3.56 (6H, d, J 12.4 Hz, d,
J 65.2 Hz), 2.84~2.67 (1H, m), 2.42~2.18 (3H, m), 2.00~1.77
(3H, m), 1.28 (3H, d, J 6.0 Hz, d, J 5.6 Hz), 1.05 (3H, d, J 5.2 Hz,
d, J 6.0 Hz); δC (100 MHz, CDCl3) 174.42 (d, J 6.6 Hz), 174.21
(d, J 7.6 Hz), 172.77, 172.70, 132.20, 132.08 (d, J 124.9 Hz),
131.75 (d, J 10.4 Hz), 131.72 (d, J 123.9 Hz), 131.63 (d, J 10.5
Hz), 128.50 (d, J 12.4 Hz), 128.43 (d, J 12.4 Hz), 69.88 (d, J 6.7
Hz), 69.82 (d, J 6.6 Hz), 51.80, 51.68, 51.54, 38.48, 38.44, 32.86
(d, J 101.0 Hz), 32.65 (d, J 101.1 Hz), 31.16, 28.71 (d, J 12.4 Hz),
28.51 (d, J 11.4 Hz), 24.46 (d, J 2.9 Hz), 24.38 (d, J 2.8 Hz),

7
3. (a) Pudovik, N.; Konovalova, I. V. Synthesis 1979, 81; (b) Enders, D.;
4.30. Methyl 3-(diphenylphosphoryl)-2-methylpropanoate (16).
Colorless oil; δH (400 MHz, CDCl3) 7.75~7.71 (4H, m),
7.50~7.42 (6H, m), 3.47 (3H, s), 3.01~2.82 (2H, m), 2.33~2.25
(1H, m), 1.27 (3H, d, J 6.8 Hz); δC (100 MHz, CDCl3) 175.85 (d,
J 10.5 Hz), 134.00 (d, J 99.1Hz), 132.73 (d, J 98.2 Hz), 131.75,
131.00 (d, J 9.6 Hz), 130.61 (d, J 9.6 Hz), 128.70 (d, J 12.4 Hz),
128.62 (d, J 11.4 ), 51.91, 33.69 (d, J 92.5 Hz), 33.67 (d, J 20.0
Hz), 19.24 (d, J 7.7 Hz); δP (162 MHz, CDCl3) 30.66. This
compound is known.6
ACCEPTED MANUSCRIPT
Saint-Dizier, A.; Lannou, M. I.; Lenzen, A. Eur. J. Org. Chem. 2006, 29.
(c) Miller, R. C.; Bradley, J. S.; Hamilton, L. A. J. Am. Chem. Soc. 1956,
78, 5299. (d) Bodalski, R.; Pietrusiewicz, K. Tetrahedron Lett. 1972, 13,
4209. (e) Simoni, D.; Invidiata, F. P.; Manferdini, M.; Lampronti, I.;
Rondanin, R.; Roberti, M.; Pollini, G. P. Tetrahedron Lett. 1998, 39,
7615.
4. (a) Green, K. Tetrahedron Lett. 1989, 30, 4807. (b) Hindersinn, R. R.;
Ludington, R. S. J. Org. Chem. 1965, 30, 4020.
5. (a) Shulyupin, M. O.; Kazankova, M. A.; Beletskaya, I. P. Org. Lett.
2002, 4, 761. (b) Xu, Q.; Han, L.-B. Org. Lett. 2006, 8, 2099.
4.31. Dimethyl (3-oxobutyl)phosphonate (17). Colorless oil; δH
(400 MHz, CDCl3) 3.69 (6H, d, J 11.2 Hz), 2.72~2.65 (2H, m),
2.13 (3H, s), 2.01~1.92 (2H, m). δC (100 MHz, CDCl3) 205.65 (d,
J 14.3 Hz), 52.43 (d, J 6.7 Hz), 36.11 (d, J 3.8 Hz), 29.60, 18.93
(d, J 14.4 Hz). δP (162 MHz, CDCl3) 34.98. This compound is
known.18
6. Stockland, Jr. R. A.; Taylor, R. I.; Thompson, L. E.; Patel, P. B. Org. Lett.
2005, 7, 851.
7. (a) Semenzin, D.; Etemad-Moghadam, G.; Albouy, D.; Diallo, O.;
Koenig, M. J. Org. Chem. 1997, 62, 2414. (b) Han, L.-B.; Zhao, C.-Q. J.
Org. Chem. 2005, 70, 10121.
4.32.
Dimethyl
(2-acetyl-5-oxohexyl)phosphonate
(17’).
8. For examples with Me3P: (a) Saga, Y.; Han, D.; Kawaguchi, S.-I.;
Ogawa, A.; Han, L.-B. Tetrahedron Lett. 2015, 56, 5303. (b) Saga, Y.;
Mino, Y.; Kawaguchi, S.-I.; Han, D.; Ogawa, A.; Han, L.-B. Tetrahedron
Asymmetry 2017, 28, 84.
Colorless oil; δH (400 MHz, CDCl3) 3.66~3.62 (6H, m),
2.93~2.83 (1H, m), 2.45~2.29 (2H, m), 2.25~2.14 (4H, m), 2.08
(3H, d), 1.94~1.85 (1H, m), 1.78~1.60 (2H, m). δC (100 MHz,
CDCl3) 209.43 (d, J 5.8 Hz), 207.20, 52.51 (d, J 7.6 Hz), 52.43
(d, J 6.7 Hz), 45.20 (d, J 2.9 Hz), 39.69, 30.05, 29.32, 26.05 (d, J
3.8 Hz), 25.92 (d, J 132.5 Hz). δP (162 MHz, CDCl3) 32.95.
HRMS (ESI) Calcd for [M+H]+ C10H20O5P: 251.1048, Found:
251.1030.
9. For eamples with other phosphines: (a) Kim, S. H., Kim, S. H., Kim, H.
J., Kim, J. N. Bull. Korean Chem. Soc., 2013, 34, 989; (b) Salin, A. V.,
Il’in, A. V., Shamsutdinova, F. G., Fatkhutdinov, A. R., Galkin, V. I.,
Islamov, D. R., Kataeva, O. N., Tetrahedron Lett., 2015, 56, 6282; (c)
Il’in, A. V., Fatkhutdinov, A. R., Salin, A. V., Phosphorus Sulfur Silicon
Relat. Elem. 2016, 186, 1628; (d) Salin, A. V., Il’in, A. V.,
Shamsutdinova, F. G., Fatkhutdinov, A. R., Islamov, D. R., Kataeva, O.
N., Galkin, V. I., Curr. Org. Synthesis, 2016, 13, 132.
4.33. 4-(diphenylphosphoryl)butan-2-one (18). White solid; δH
(400 MHz, CDCl3) 7.69~7.64 (4H, m), 7.48~7.38 (6H, m),
2.73~2.67 (2H, m), 2.51~2.44 (2H, m), 2.05 (3H, s); δC (100
MHz, CDCl3) 206.20 (d, J 13.4 Hz), 132.88, 131.93 (d, J 2.0 Hz),
130.75 (d, J 9.6 Hz), 128.80 (d, J 11.5 Hz), 35.24 (d, J 1.9 Hz),
29.75, 23.68 (d, J 73.4 Hz); δP (162 MHz, CDCl3) 33.11. This
compound is known.19
10. Considering the total yield of 1a and 1a’, other adducts, even generated,
are omittable. 31P NMR spectra of the crude mixture also support this
conclusion.
11. Henderson, W. A.; Streuli, C. A. J. Am. Chem. Soc. 1960, 82, 5791.
12. (a) Yu, L.; Wang, J.; Zhang, X.; Cao, H.; Wang, G.; Ding, K.; Xu, Q.;
Lautens, M. RCS Adv. 2014, 4, 19122; (b) Aroyan, C. E., Dermenci, A.,
Miller, S. J., Tetrahedron, 2009, 65, 4069.
4.34. 3-((diphenylphosphoryl)methyl)heptane-2,6-dione (18’).
Colorless oil; δH (400 MHz, CDCl3) 7.69~7.58 (4H, m), 7.45,
7.33 (6H, m), 2.97~2.79 (2H, m), 2.43~2.24 (2H, m), 2.12~2.04
(1H, m), 1.99 (3H, s), 1.93~1.84 (4H, m), 1.73~1.64 (1H, m); δC
(100 MHz, CDCl3) 209.41 (d, J 4.8 Hz), 207.20, 133.56 (d, J
87.7 Hz), 132.36 (d, J 86.7 Hz), 131.79 (d, J 2.0 Hz), 130.81 (d, J
9.5 Hz), 130.44 (d, J 8.6 Hz), 128.65 (d, J 11.5 Hz), 128.54 (d, J
12.3 Hz), 44.22 (d, J 1.9 Hz), 39.58, 30.25 (d, J 71.4 Hz), 29.81,
28.99, 26.33 (d, J 8.6 Hz); δP (162 MHz, CDCl3) 31.51. HRMS
(ESI) Calcd for [M+H]+ C20H24O3P: 343.1463, Found: 343.1440.
13. Strappaveccia, G.; Bianchi, L.; Ziarelli, S.; Santoro, S.; Lanari, D.; Pizzo,
F.; Vaccaro, L. Org. Biomol. Chem. 2016, 14, 3521.
14. Hirai, T.; Han; L.-B. Org. Lett. 2007, 9, 53.
15. Aoki, H.; Mukaiyama, T. Chem. Lett. 2006, 35, 456.
16. Harsanyi K.; Domany G.; Greiner I.; Forintos H.; Keglevich G.
Heteroatom Chem. 2005, 16, 562.
17. Lamas, M.-C.; Studer, A. Org. Lett. 2011, 13, 2236.
18. Chudasama, V.; Akhbar, A. R.; Bahou, K. A.; Fitzmaurice, R. J.;
4.35. 2-methylenepentanedinitrile (19). Colorless oil; δH (400
MHz, CDCl3) 6.02 (1H, s), 5.91 (1H, s), 2.64~2.56 (4H, m); δC
(100 MHz, CDCl3) 133.38, 119.00, 117.46, 117.09, 30.35, 16.03.
This compound is known.12
Caddick, S. Org. Biomol. Chem., 2013, 11, 7301.
19. Goryunov, E. I.; Matveeva, A. G.; Safiulina, A. M.; Goryunova, I. B.;
Bodrin, G. V.; Brel, V. K. Russ. J. Gen. Chem. 2016, 86, 629.
Acknowledgments
T.H. thanks a scholarship from China Scholarship Council
(CSC) (20153022) through the CGGSOS program.
References and notes
1. (a) Toy, A. D. F.; Walsh, E. N. Phosphorus Chemistry in Everyday
Living, ACS, Washington, DC, 1987. (b) Corbridge, D. E. C.
PhosPhorus: chemistry, biochemistry and technology, CRC Press, Boca
Raton, 6th edn, 2013. (c) Quin, L. D. A Guide to Organophosphorus
Chemistry, Wiley Interscience, New York, 2000. (d) Hendlin, D.;
Stapley, E. O.; Jackson, M.; Wallick, H.; Miller, A. K.; Wolf, F. J.;
Miller, T. W.; Chaiet, L.; Kahan, F. M.; Foltz, E. L.; Woodruff, H. B.;
Mata, J. M.; Hernandez, S.; Mochales, S. Science 1969, 166, 122. (e)
John, F. N-phosphonomethylglycine phytotoxicant compositions. U.S.
Patent 3799758, 1974; (f) Hoerlein, G. Rev. Environ. Contam. Toxicol.
1994, 138, 73.
2. (a) Phosphorus Ligands in Asymmetric Catalysis, A. Bӧrner, ed. Wiley-
VCH, Weinheim, 2008. (b) Tang, W.; Zhang, X. Chem. Rev. 2003, 103,
3029; (c) Grushin, V. V. Chem. Rev. 2004, 104, 1629.