A base-mediated three-component coupling reaction for the synthesis of phosphorohydrazones

Article abstract of DOI:10.1016/j.tet.2013.09.077

A simple and efficient three-component coupling reaction for the synthesis of phosphorohydrazones was developed. Both aldehydes and ketones participated in the reaction to afford the corresponding phosphorohydrazones in moderate-to-good yields. Moreover, a novel P-N ligand was synthesized by this method, which can act as a fluorescent sensor for iron ion.

Full text of DOI:10.1016/j.tet.2013.09.077

Accepted Manuscript
A base-mediated three-component coupling reaction for the synthesis of
phosphorohydrazones
Jun Wen, Liang Dong, Liang Yang, Tao Jiang, Sheng Hu, Tong-Zai Yang, Xiao-Lin
Wang
PII:
S0040-4020(13)01499-3
10.1016/j.tet.2013.09.077
TET 24852
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 11 June 2013
Revised Date: 14 September 2013
Accepted Date: 18 September 2013
Please cite this article as: Wen J, Dong L, Yang L, Jiang T, Hu S, Yang T-Z, Wang X-L, A base-
mediated three-component coupling reaction for the synthesis of phosphorohydrazones, Tetrahedron
(2013), doi: 10.1016/j.tet.2013.09.077.
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ACCEPTED MANUSCRIPT
Graphical Abstract
A base-mediated three-component coupling reaction for the synthesis
of phosphorohydrazones
Jun Wen, Liang Dong, Liang Yang, Tao Jiang, Sheng Hu, Tong-Zai Yang, Xiao-Lin Wang*
Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang
621900, Sichuan Province, China
1

ACCEPTED MANUSCRIPT
A base-mediated three-component coupling reaction for the synthesis
of phosphorohydrazones
Jun Wen, Liang Dong, Liang Yang, Tao Jiang, Sheng Hu, Tong-Zai Yang, Xiao-Lin Wang*
Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang
6
21900, Sichuan Province, China
Tel & Fax: + 86 816 2484289; E-mail: xlwang@caep.ac.cn
Abstract: A simple and efficient three-component coupling reaction for the synthesis of
phosphorohydrazones was developed. Both aldehydes and ketones participated in the reaction to
afford the corresponding phosphorohydrazones in moderate-to-good yields. Moreover, a novel
P–N ligand was synthesized by this method, which can act as a fluorescent sensor for iron ion.
Key Words: phosphorohydrazones, three-component, P–N ligand, fluorescent sensor
1
. Introduction
Heteroatom compounds containing P–N bonds are well known to be chemically
1
stable and hence are widely used in catalysis , metal extraction, bio-organic
2
chemistry , and so on. Further, highly efficient methods for synthesizing these
3
compounds have been reported . In particular, phosphorohydrazones possess a
diverse range of bioactivities such as antitumor, antibacterial, and antiangiogenic
4
5
activity and are valuable intermediates for building blocks in natural products .
However, there are very few reported methods for the synthesis of
phosphorohydrazones. The Atherton–Todd reaction (Scheme 1) is used as a major
6
strategy for the synthesis of phosphorohydrazones , but a mixed product is often
obtained because of the presence of two N–H bonds in the hydrazine group.
7
Condensation of phosphorohydrazidates with carbonyl compounds and conjugate
8
addition of dialkyl phosphites with diazenes can also afford phosphorohydrazones ,
2

ACCEPTED MANUSCRIPT
but the practical applicability of these methods is severely restricted because of the
need for special substrate sources.
Sulfonylhydrazones are valuable intermediates for organic synthesis; they are used
as an in situ source of diazo compounds in many types of transition-metal-catalyzed
9
reactions . Nevertheless, such heavy metals are toxic and contamination of the final
product by the metal catalysts is undesirable, which calls for the development of
transition-metal-free reactions. We have recently reported an effective method for the
synthesis of pyrazoles by the one-pot condensation of α,β-unsaturated carbonyl
10
compounds with tosylhydrazide in the absence of any transition-metal catalyst
.
Herein, we report a base-mediated three-component coupling reaction of dialkyl
phosphites, tosylhydrazide, and carbonyl compounds (Scheme 1) that affords a wide
variety of substituted phosphorohydrazones in moderate-to-good yields.
Scheme 1. Methods for the preparation of phosphorohydrazones
2
. Results and discussion
For the initial optimization of the reaction conditions, the condensation of
benzaldehyde 1a, tosylhydrazide 3, and diethyl phosphite 2a was selected as a model
3

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reaction system. The results are listed in Table 1. When the reaction was carried out in
N,N-dimethylformamide (DMF) with K CO as the base, the desired product 4a was
2
3
isolated in 46% yield (entry 1). A similar yield was obtained in the reaction carried
out with K PO as the base (entry 2). Other bases such as NaOH, Cs CO , and
3
4
2
3
MeONa (entries 3–5), however, gave only trace amounts of the desired product, and
no product was detected in the absence of the base (entry 6). These results implied
that the presence of a base is crucial for the success of the reaction. Screening of
solvents (entries 7–10) revealed that 1,4-dioxane was the most suitable for the
reaction, affording the desired product in 76% yield. Screening of base amounts on a
2 3
small scale (entries 8, 11–13) indicated that 3 equiv of K CO was the optimal amount
for the reaction, in which case 76% product yield was obtained (entry 8). Increasing
the reaction temperature dramatically increased the product yield, with 60 °C being
the optimal temperature. Higher temperatures were unfavorable because of the greater
amount of by-products formed (entries 14–16).
a
Table 1 Optimization of reaction conditions
o
b
Entry
Base
Base amount (equiv.)
Solvent
DMF
Temp ( C)
Yield (%)
1
2
3
4
5
6
7
8
9
K CO3
2
3
3
3
3
3
-
60
60
60
60
60
60
60
60
60
60
46
K PO4
3
DMF
41
NaOH
DMF
trace
trace
trace
NR
Cs
2
CO
3
DMF
MeONa
-
DMF
DMF
K
2
CO
CO
CO
CO
3
3
3
3
3
3
3
3
DMSO
1,4-dioxane
toluene
EtOH
trace
76
K
2
K
2
23
1
0
K
2
11
4

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1
1
1
1
1
1
1
2
3
4
5
6
K
2
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
1
1.5
2
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
60
60
60
r.t.
40
80
14
22
51
NR
25
66
K
2
K
2
K
2
3
K
2
3
K
2
3
a
Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol)), 3 (0.625 mmol), base (3.0 equiv), solvent
b
(
2 mL), 24 h, in air. Isolated yield.
Under the optimized conditions, we next evaluated the substrate scope by extending
the reaction to various carbonyl compounds. The results of the coupling reactions of
diethyl phosphite, tosylhydrazide, and carbonyl compounds mediated by a base are
summarized in Table 2. Benzaldehydes with electron-rich and electron-deficient
substituents afforded the corresponding phosphorohydrazones 4a–g in
moderate-to-good yields. The results indicated that benzaldehydes with
electron-withdrawing substituents can give the corresponding products in better yields.
The sterically hindered 2-bromobenzaldehyde did not affect the result and gave the
desired product 4g in 71% yield. A heteroarene carbaldehyde such as
thiophene-3-carbaldehyde also gave the desired product 4h in 70% yield. When
acetophenone was used as the substrate under the optimized conditions, the product 4i
was obtained but in poor yield (35%). Therefore, we optimized the reaction conditions,
including the type of base and temperature, and obtained 4i in fairly good (68%) yield
o
when the reaction was performed at 80 C using K PO as the base. Under these
3
4
conditions, substituted acetophenone and benzophenone could afford the
corresponding phosphorohydrazones 4j–l in moderate yields.
Table 2. Base-mediated three-component coupling of diethyl phosphite, tosylhydrazide, and
a
carbonyl compounds
5

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H
H
O
H
O
O
N
N
N
N
P
N
P
N
P
O
O
O
O
O
O
N
O2N
HO
4
a 76%
4b 57%
4
c 66%
H
N
H
O
O
H
O
N
N
N
P
N
P
N
P
O
O
O
O
O
O
Br
NC
4
d 75%
4e 73%
4f 40%
H
N
H
N
O
O
H
N
O
N
P
N
P
N
P
O
O
O
O
O
S
O
Br
4i 35%, 68% c
4
g 71%
4h 70%
Ph
H
O
H
N
O
N
N
P
N
P
O
O
O
O
j 53% c
4k 66% c
4
Br Ph
Ph
H
H
O
O
N
N
N
P
N P
O
O
O
O
H CO
3
l 50% c
4m 47% c
4
a
Reaction conditions: 1 (0.5 mmol), 2a (0.75 mmol)), 3 (0.625 mmol), K
2
CO
3
(3.0 equiv),
o
b
c
o
1
,4-dioxane (2 mL), 60 C, 24 h, in air. Isolated yield. K
PO
3 4
(3.0 equiv), 80 C.
Reactions employing various dialkyl phosphites with substituted benzaldehydes
and tosylhydrazide were also investigated; the results are summarized in Table 3.
H-phosphite diesters bearing different alkyl groups could react smoothly under the
optimized reaction conditions to afford the products 5. Di-t-butyl phosphite gave the
corresponding product 5d in relatively lower yield (55%) than that with the other
dialkyl phosphites, probably because of the steric effect. Dibenzyl or diallyl phosphite,
too, gave the desired products 5e and 5f in 72% and 43% yields, respectively.
6

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Table 3.
K CO -mediated three-component coupling reactions of dialkyl phosphites,
2
3
a
tosylhydrazide, and carbonyl compounds
a
Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol)), 3 (0.625 mmol), K CO (3.0 equiv),
2
3
o
b
1
,4-dioxane (2 mL), 60 C, 24 h, in air. Isolated yield.
We speculated that the reaction started with the condensation of tosylhydrazide
with the carbonyl compound to form the tosylhydrazone, Base will deprotonate the
11
proton of -NHTs and then kick out Tosyl group to form the diazo compound
.
Thereafter, the intermediate diazo compound was trapped by a dialkyl phosphate to
give the final product. The main byproduct is N,N'-dialkenylhydrazine, which is
12
formed via self-coupling of the diazo compound (Scheme 2) .
Scheme 2. Proposed mechanism for the reaction.
7

ACCEPTED MANUSCRIPT
Phosphorohydrazones may find application in coordination chemistry and metal
extraction as well. Thus, to expand the practical utility of this synthetic method, we
applied the coupling reaction to the preparation of a novel 1,1'-bi-2-naphthol
(BINOL) ligand 7. As depicted in Scheme 3, 7 was prepared in 53% yield by the
reaction of binaphthalene dialdehyde 6 with tosylhydrazide and diisopropyl phosphite
under the optimized conditions. The fluorescence spectra of 7 in DMF exhibited a
broad emission peak, with λmax at 408 nm (Figure 1). We then tested the fluorescence
response of 7 toward a series of metal ions. As shown in this figure, the
2
+
fluorescence of 7 was clearly quenched upon the addition of 10 equiv of Fe , while
+
+
2+
2+
2+
2+
2+
3+
the addition of other metal ions such as K , Na , Ca , Mg , Co , Cu , Mn , Al ,
2
+
2+
and Zn had no influence on the fluorescence. Fluorescence titration with Fe ions in
varying concentrations was performed. As shown in Figure 2, the addition of
2+
increasing concentrations of Fe ions led to a gradual diminished intensity, and the
2+
fluorescence of compound 7 was essentially quenched by 15 equiv of Fe ions. In
3
+
addition, Fe has the same phenomenon of fluorescence quenching when add it to the
solution of compound 7. This result indicated the formation of a well-defined
complex between 7 and iron ion, thus confirming the potential application of 7 as a
fluorescent sensor for iron ion detection, which has received great attention because
13
of the simplicity of operation as well as high selectivity and sensitivity .
Scheme 3. Preparation of binol-based P-N ligand 7.
8

ACCEPTED MANUSCRIPT
-5
Figure 1: Fluorescence response of 7 (2.0 × 10 M in DMF) toward various (10 equiv) metal ions
(
λexc = 300 nm, slits: 5 nm/5 nm).
+
+
2+
2+
3
2
2
2
2
2
1
1
1
1
1
00
80
60
40
20
00
80
60
40
20
00
7 only, K , Na , Ca , Mg ,
2+
2+
2+
3+
2+
Co , Cu , Mn , Al , Zn
80
60
40
20
0
2+
Fe
350
400
450
Wavelength (nm)
-5
2+
Figure 2: Fluorescence titration of 7 (2.0 × 10 M in DMF) with Fe (λexc = 300 nm, slits: 5 nm/5
nm)
9

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7
7
7
7
7
7
2
2
1
1
50
00
50
00
2+
+1 equiv Fe
2
+
+2 equiv Fe
+3 equiv Fe
+5 equiv Fe
2
+
2+
2
+
+10 equiv Fe
2
+
7+15 equiv Fe
50
0
350
400
450
500
550
Wavelength (nm)
3
. Conclusion
In conclusion, we have developed a simple and efficient method—a base-mediated
three-component coupling reaction of dialkyl phosphites, tosylhydrazide, and
carbonyl compounds—for the synthesis of phosphorohydrazones. Both aldehydes and
ketones participated in the reaction to afford the corresponding phosphorohydrazones
in moderate-to-good yields. Moreover, a novel P–N ligand that can act as a
fluorescent sensor for iron ion was synthesized by this method; further studies to
explore the properties of this ligand are underway. The developed reaction is expected
to be a powerful tool for the synthesis of compounds containing P–N bonds.
4
. Experimental
4
.1 General
1
13
H-NMR, C-NMR spectra were measured on a Bruker AM400 NMR spectrometer (400 MHz
as solvent and recorded in ppm relative to internal
tetramethylsilane standard. ESI-MS spectral data were recorded on a Finnigan LCQDECA mass
or 100MHz, respectively) with CDCl
3
10

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spectrometer. Fluorescence spectra were recorded in the front face mode at 298 K. Unless
otherwise noted, all reagents were obtained from commercial suppliers and used without further
purification. Solvents were freshly distilled prior to use.
4
.2 General procedure for the preparation of phosphorohydrazones.
A Schlenk tube with a magnetic stirring bar was charged with aldehyde or ketone (0.5 mmol, 1
equiv), sulfonylhydrazide (0.625 mmol, 1.25 equiv), dialkyl phosphites (0.75 mmol, 1.5 equiv),
o
base (1.5 mmol, 3 equiv), and 1,4-dioxane (2 mL). The reaction vessel was placed in a 60 C oil
bath, and then stirred at this temperature for 10 h. The reaction mixture was then allowed to cool
to ambient temperature, and diluted with 20 mL of ethyl acetate, and washed with brine (15 mL)
2 4
and water (15 mL). The organic layer was dried over anhydrous Na SO . After concentrated in
vacuo, the crude product was purified by column chromatography. The identity and purity of the
1
13
known product was confirmed by H-NMR, C-NMR and ESI-MS.
1
4
a: colorless oil; H-NMR (400 MHz, CDCl
3
), 8.57-8.49 (d, J = 28.8 Hz, 1H), 7.86 (s, 1H),
1
3
7
.63-7.60 (m, 2H), 7.36-7.34 (m, 3H), 4.24-4.18 (m, 4H), 1.39-1.35 (m, 6H); C-NMR (100
), 144.97, 144.77, 134.60, 129.30, 128.55, 126.69, 63.49, 63.43, 16.20, 16.13;
P-NMR (400 MHz, CDCl ), 1.91; HRMS (ESI): Calcd for: C11H18N2O3P, 257.1055. Found:
MHz, CDCl
3
31
3
-
1
2
4
5
7
57.1048. IR (KBr, cm ): 3136, 2988, 2936, 1480, 1251, 1059, 1022, 985, 844, 755, 689, 560,
70.
1
b: colorless oil; H-NMR (400 MHz, CDCl
3
), 8.61-8.53 (d, J = 28.8 Hz, 1H), 7.86 (s, 1H),
1
3
.63-7.59 (m, 2H), 7.38-7.31 (m, 3H), 4.76-4.70 (m, 2H), 1.40-1.32 (m, 12H); C-NMR (100
), 144.29, 144.10, 134.86, 129.11, 128.53, 126.58, 72.08, 72.02, 23.89, 23.85, 23.64,
3.59; P-NMR (400 MHz, CDCl ), 0.08; HRMS (ESI): Calcd for: C13H22N2O3P, 285.1368.
Found: 285.1372. IR (KBr, cm ): 3430, 3185, 2981, 2932, 1604, 1470, 1384, 1240, 992, 885, 834,
61, 700, 553, 480, 427.
MHz, CDCl
3
31
2
3
-1
7
Acknowledgments
This work was financially supported by China Postdoctoral Science Foundation Grant (No.
2012M521716), Training Program of the Major Research Plan of the National Natural Science
Foundation of China (Nos. 91026022).
11

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Supplementary data
Detailed experimental procedures and compound characterization. Supplementary data
related to this article can be found in the online version.
References and notes
1
.
(a) Agbossou, F.; Carpentier, J. F.; Hapiot, F.; Suisse, I.; Mortreux, A. Coordin. Chem. Rev.
1998, 178-180, 1615-1645; (b) Agbossou, F.; Suisse, I. Coordin. Chem. Rev. 2003, 242,
145-158.
2
.
(a) Sladek, N. E. Pharm. Ther. 1988, 37, 301-355; (b) Ludeman, S. M. Curr. Pharm. Des.
999, 5, 627-643; (c) Colvin, O. M. Curr. Pharm. Des. 1999, 5, 555-560.
1
3
4
.
.
Ly, T. Q.; Woollins, J. D. Coord. Chem. Rev., 1998, 176, 451-481.
(a) Nawrot-Modeanka, J.; Ochocki, J.; Graczyk, J., Pharmazie, 2004, 59, 731-732; (b)
Nawrot-Modeanka, J.; Nawrot, E., Acta Pol. Pharm., 2007, 63, 429-434; (c) Michalska, M.;
Pajak, W.; Kolodziejska, J.; Lazarenkow, A.; Nawrot-Modeanka, J., Acta Biochim. Pol., 2008,
55, 612-617.
5
6
.
.
Mitsunobu, O. Synthesis, 1981, 1-28.
(a) Harger, M. J. P.; Smith, A. J. Chem. Soc., Perkin Trans. 1, 1985, 2651-2656; (b)
Wadsworth Jr. W. S.; Emmons, W. D. J. Org. Chem. 1967, 32, 1279-1285.
(a) Koziara, A.; Turski, K.; Zwieraak, A. Synthesis, 1986, 298-301, (b) Fox, J. L.; Chen, C. H.;
Luss, H. R., J. Org. Chem. 1986, 51, 3551-3553.
7
.
8
9
.
.
Jiang, Z.; Zhang, Y.; Ye, W.; Tan, C. H. Tetrahedron Lett. 2007, 48, 51-54.
(a) Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org. Chem. 2005, 1479-1492; (b)
Lee, Y. T. ; Chung, Y. K., J. Org. Chem., 2008, 73, 4698-4701; (c) Li, G.; Ding, Z.; Xu, B.,
Org. Lett., 2012, 14, 5338-5341.
10. Wen, J.; Fu, Y.; Zhang, R. Y.; Zhang, J.; Chen, S. Y.; Yu, X. Q., Tetrahedron, 2011, 67,
9618-9621.
1
1
1
1. Creary, X., Org. Synth. 1986, 64, 207.
2. Sha, Q.; Wei, Y., Tetrahedron, 2013, 69, 3829-3835.
3. Sahoo, S. K.; Sharma, D.; Bera, R. K.; Crisponi, G.; Callan, J. F., Chem. Soc. Rev., 2012, 41,
7195–7227.
12

ACCEPTED MANUSCRIPT
A base-mediated three-component coupling reaction for the synthesis
of phosphorohydrazones
Jun Wen, Liang Dong, Liang Yang, Tao Jiang, Sheng Hu, Tong-Zai Yang, Xiao-Lin Wang*
Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang
6
21900, Sichuan Province, China
General information.
1
13
H-NMR, C-NMR spectra were measured on a Bruker AM400 NMR spectrometer (400 MHz or
00MHz, respectively) with CDCl as solvent and recorded in ppm relative to internal
1
3
tetramethylsilane standard. ESI-MS spectral data were recorded on a Finnigan LCQDECA mass
spectrometer. Fluorescence spectra were recorded in the front face mode at 298 K. Unless
otherwise noted, all reagents were obtained from commercial suppliers and used without further
purification. Solvents were freshly distilled prior to use.
General procedure for the phosphorohydrazones.
A Schlenk tube with a magnetic stirring bar was charged with aldehyde or ketone (0.5 mmol, 1
equiv), sulfonylhydrazide (0.625 mmol, 1.25 equiv), dialkyl phosphites (0.75 mmol, 1.5 equiv),
o
base (1.5 mmol, 3 equiv), and 1,4-dioxane (2 mL). The reaction vessel was placed in a 60 C oil
bath, and then stirred at this temperature for 10 h. The reaction mixture was then allowed to cool
to ambient temperature, and diluted with 20 mL of ethyl acetate, and washed with brine (15 mL)
2 4
and water (15 mL). The organic layer was dried over anhydrous Na SO . After concentrated in
vacuo, the crude product was purified by column chromatography. The identity and purity of the
1
13
known product was confirmed by H-NMR, C-NMR and ESI-MS.
Spectroscopic data of products
1
diethyl (2-benzylidenehydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl ), 8.57-8.49
3
(
d, J = 28.8 Hz, 1H), 7.86 (s, 1H), 7.63-7.60 (m, 2H), 7.36-7.34 (m, 3H), 4.24-4.18 (m, 4H),
1
3
1
.39-1.35 (m, 6H); C-NMR (100 MHz, CDCl
3
), 144.97, 144.77, 134.60, 129.30, 128.55, 126.69,
3
1
6
3.49, 63.43, 16.20, 16.13; P-NMR (400 MHz, CDCl ), 1.91; HRMS (ESI): m/z = 257.1028
3
+
-1
[
M+H] ; IR (KBr, cm ): 3136, 2988, 2936, 1480, 1251, 1059, 1022, 985, 844, 755, 689, 560, 470.
1
diethyl (2-(4-(dimethylamino)benzylidene)hydrazinyl)Phosphite, white crystal; H-NMR (400
3
MHz, CDCl ), 7.72-7.70 (d, J = 8.0 Hz, 2H), 7.50-7.47 (d, J = 8.8 Hz, 2H), 6.69-6.66 (m, 2H),

ACCEPTED MANUSCRIPT
1
3
4
1
2
1
.23-4.16 (m, 4H), 2.98 (s, 6H), 1.38-1.34 (m, 6H); C-NMR (100 MHz, CDCl
3
), 151.21, 145.58,
3
1
45.39, 127.99, 122.58, 111.86, 63.28, 63.23, 40.29, 16.22, 16.15; P-NMR (400 MHz, CDCl ),
3
+
-1
.23; HRMS (ESI): m/z = 300.1465 [M+H] . IR (KBr, cm ): 3137, 2828, 1875, 1610, 1534, 1480,
362, 1236, 1170, 1030, 856, 810, 548, 466.
1
diethyl (2-(4-nitrobenzylidene)hydrazinyl)Phosphite, yellow oil; H-NMR (400 MHz, CDCl
3
),
9
2
1
.20-9.13 (d, J = 29.2 Hz, 1H), 8.20-8.19 (d, J = 8.4 Hz, 1H), 7.93 (s, 1H), 7.76-7.73 (d, J = 8.4 Hz,
13
H), 4.24-4.17 (m, 4H), 1.39-1.35 (m, 6H); C-NMR (100 MHz, CDCl
3
), 147.88, 142.42, 142.22,
3
1
40.73, 127.08, 123.95, 63.80, 63.75, 16.18, 16.11; P-NMR (400 MHz, CDCl ), 0.89; HRMS
3
+
-1
(
ESI): m/z = 302.0925 [M+H] . IR (KBr, cm ): 3426, 3109, 2990, 2937, 2450, 2200, 1933, 1652,
589, 1513, 1340, 1245, 1172, 1036, 980, 865, 747, 684, 575.
1
1
diethyl (2-(4-bromobenzylidene)hydrazinyl)Phosphite, yellow oil; H-NMR (400 MHz, CDCl ),
3
8
6
1
.88-8.80 (d, J = 28.8 Hz, 1H), 7.83 (s, 1H), 7.50-7.48 (m, 4H), 4.24-4.17 (m, 4H), 1.39-1.35 (m,
13
H); C-NMR (100 MHz, CDCl
3
), 143.77, 143.58, 133.62, 131.73, 128.06, 123.28, 63.52, 63.47,
3
1
+
6.16, 16.10; P-NMR (400 MHz, CDCl
3
), 1.32; HRMS (ESI): m/z = 335.0159 [M+H] . IR (KBr,
-
1
cm ): 3431, 3143, 2981, 2924, 1600, 1480, 1400, 1237, 1156, 1030, 986, 820, 750, 570, 518.
1
diethyl (2-(4-cyanobenzylidene)hydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl ),
3
9
2
1
.04-8.96 (d, J = 29.2 Hz, 1H), 7.88 (s, 1H), 7.72-7.70 (d, J = 8.0 Hz, 2H) 7.65-7.63 (d, J = 8.0 Hz,
13
H), 4.25-4.18 (m, 4H), 1.40-1.36 (m, 6H); C-NMR (100 MHz, CDCl
3
), 142.76, 142.56, 138.88,
31
32.39, 126.95, 118.71, 112.31, 63.74, 63.68, 16.19, 16.12; P-NMR (400 MHz, CDCl ), 1.07;
3
+
-1
HRMS (ESI): m/z = 282.1033 [M+H] . IR (KBr, cm ): 3422, 3131, 2936, 2220, 1594, 1480, 1240,
040, 977, 847, 798, 545.
1
1
diethyl (2-(4-hydroxybenzylidene)hydrazinyl)Phosphite, white crystal; H-NMR (400 MHz,
CDCl ), 8.19 (s, 1H), 7.67 (s, 1H), 7.43-7.33 (m, 3H), 6.89-6.87 (d, J = 8.8 Hz, 2H), 4.22-4.16 (m,
H), 1.36-1.32 (m, 6H); C-NMR (100 MHz, CDCl
3
1
3
4
3
), 158.30, 145.65, 145.46, 128.42, 126.10,
31
1
2
1
15.78, 63.85, 63.79, 16.16, 16.10; P-NMR (400 MHz, CDCl ), 1.61; HRMS (ESI): m/z =
3
+
-1
73.1021 [M+H] . IR (KBr, cm ): 3280, 3170, 2910, 2586, 2452, 1600, 1507, 1453, 1370, 1200,
020, 833, 797, 752, 563, 527, 455.
1
diethyl (2-(2-bromobenzylidene)hydrazinyl)Phosphite, white crystal; H-NMR (400 MHz,

ACCEPTED MANUSCRIPT
CDCl
3
),8.73-8.66 (d, J = 28.8 Hz, 1H), 8.24 (s, 1H), 7.91-7.88 (m, 1H), 7.51-7.49 (d, J = 8.0 Hz,
1
6
1
3
7
H), 7.27-7.26 (d, J = 2.0 Hz, 1H), 7.16-7.15 (d, J = 2.0 Hz, 1H), 4.21-4.18 (m, 4H), 1.38-1.34 (m,
13
H); C-NMR (100 MHz, CDCl
3
), 143.85, 143.65, 133.50, 132.93, 130.42, 127.43, 127.35,
31
23.38, 63.47, 63.41, 16.22, 16.16; P-NMR (400 MHz, CDCl
3
), 1.12; HRMS (ESI): m/z =
+
-1
37.0155 [M+H] . IR (KBr, cm ): 3450, 3120, 2930, 1590, 1460, 1246, 1093, 1025, 977, 850,
60, 572, 545, 473.
1
diethyl (2-(thiophen-3-ylmethylene)hydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz,
3
CDCl ), 8.46-8.38 (d, J = 28.0 Hz, 1H), 7.90 (s, 1H), 7.44-7.39 (m, 2H), 7.28-7.27 (m, 1H),
1
3
4
1
.22-4.15 (m, 4H), 1.38-1.33 (m, 6H); C-NMR (100 MHz, CDCl
3
), 140.47, 140.28, 137.74,
31
26.24, 125.12, 125.08, 63.44, 63.38, 16.19, 16.12; P-NMR (400 MHz, CDCl ), 1.78; HRMS
3
+
-1
(
ESI): m/z = 263.0625 [M+H] . IR (KBr, cm ): 3341, 3060, 2981, 2930, 1630, 1460, 1390, 1230,
165, 1040, 960, 860, 806, 713, 608, 560.
1
1
diethyl (2-(1-phenylethylidene)hydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl ),
3
7
4
1
.71-7.69 (d, J = 5.2 Hz, 2H), 7.38-7.33 (m, 3H), 7.21-7.17 (d, J = 18.0 Hz, 1H), 4.23-4.19 (m,
1
3
H), 2.19 (s, 3H), 1.38-1.35 (m, 6H); C-NMR (100 MHz, CDCl
3
), 148.33, 148.16, 138.43,
31
28.69, 128.29, 125.92, 63.49, 63.44, 16.23, 16.16, 12.29; P-NMR (400 MHz, CDCl ), 1.29;
3
+
-1
HRMS (ESI): m/z = 271.1192 [M+H] . IR (KBr, cm ): 3359, 2981, 2657, 2406, 1969, 1606, 1440,
390, 1360, 1205, 1040, 960, 820, 750, 690, 550.
1
1
diethyl (2-(1-(p-tolyl)ethylidene)hydrazinyl)Phosphite, white crystal; H-NMR (400 MHz, CDCl ),
3
7
4
1
.60-7.58 (d, J = 8.0 Hz, 2H), 7.17-7.15 (d, J = 8.0 Hz, 2H), 6.94-6.87 (d, J = 26.8 Hz, 1H),
1
3
.24-4.16 (m, 4H), 2.36 (s, 3H), 2.16 (s, 3H), 1.38-1.34 (m, 6H); C-NMR (100 MHz, CDCl
3
),
48.24, 148.06, 138.75, 135.57, 129.01, 125.85, 63.50, 63.44, 21.22, 16.23, 16.16, 12.07;
3
1
+
-1
3
P-NMR (400 MHz, CDCl ), 1.83; HRMS (ESI): m/z = 285.1357 [M+H] . IR (KBr, cm ): 3458,
3110, 2980, 2918, 2807, 1615, 1486, 1240, 1025, 986, 850, 806, 560, 523, 450.
1
diethyl (2-(diphenylmethylene)hydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl ),
3
7
4
1
.57-7.50 (m, 5H), 7.32-7.31 (m, 3H), 7.25-7.23 (m, 2H), 6.64-6.56 (d, J = 29.2 Hz, 1H),
1
3
.24-4.18 (m, 4H), 1.41-1.37 (m, 6H); C-NMR (100 MHz, CDCl
3
), 151.67, 151.50, 137.25,
31
31.64, 129.85, 129.74, 129.10, 128.53, 128.22, 127.07, 63.53, 63.47, 16.25, 16.19; P-NMR
+
-1
(
400 MHz, CDCl
3
), 1.28; HRMS (ESI): m/z = 333.1346 [M+H] . IR (KBr, cm ): 3664, 3420,
3
175, 3140, 2980, 1640, 1568, 1483, 1446, 1250, 1165, 1030, 896, 774, 688, 517.

ACCEPTED MANUSCRIPT
1
diethyl (2-((2-bromophenyl)(phenyl)methylene)hydrazinyl)Phosphite, white crystal; H-NMR
400 MHz, CDCl ), 7.79-7.76 (m, 2H), 7.51-7.47 (m, 3H), 7.41-7.38 (m, 1H), 7.34-7.32 (m, 3H),
.20-7.17 (m, 1H), 6.40-6.34 (d, J = 19.6 Hz, 1H), 4.24-4.20 (m, 4H), 1.40-1.38 (m, 6H);
(
3
7
1
3
C-NMR (100 MHz, CDCl
3
), 149.75, 149.63, 135.90, 133.90, 133.03, 131.45, 130.43, 129.22,
31
1
28.72, 128.41, 126.53, 122.53, 63.70, 63.67, 63.54, 63.51, 16.23, 16.21; P-NMR (400 MHz,
+
-1
3
CDCl ), 0.70; HRMS (ESI): m/z = 411.0457 [M+H] . IR (KBr, cm ): 3430, 3160, 3088, 2980,
2
905, 2860, 1957, 1908, 1811, 1589, 1565, 1430, 1250, 1161, 1027, 978, 890, 775, 690, 545, 470.
1
diethyl (2-((4-methoxyphenyl)(phenyl)methylene)hydrazinyl)Phosphite, colorless oil; H-NMR
400 MHz, CDCl ), 7.52-7.43 (m, 3H), 7.32-7.30 (m, 2H), 7.23-7.16 (m, 2H), 7.07-6.82 (m, 2H),
.70-6.44 (m, 1H), 4.24-4.16 (m, 4H), 3.88-3.80 (d, J = 31.2 Hz, 3H), 1.41-1.36 (m, 6H);
(
3
6
1
3
3
C-NMR (100 MHz, CDCl ), 160.46, 151.62, 151.45, 137.63, 131.88, 130.09, 130.02, 129.78,
1
1
3
8
29.63, 129.01, 128.50, 128.17, 127.15, 123.39, 115.25, 113.59, 63.49, 63.43, 55.44, 55.32, 16.26,
3
1
+
-1
3
6.19; P-NMR (400 MHz, CDCl ), 1.45; HRMS (ESI): m/z = 363.1409 [M+H] . IR (KBr, cm ):
453, 3325, 3155, 2983, 2934, 2910, 2835, 2049, 1658, 1604, 1510, 1400, 1248, 1160, 1030, 967,
91, 837, 776, 703, 542.
1
diisopropyl (2-benzylidenehydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl
3
),
8
2
1
.61-8.53 (d, J = 28.8 Hz, 1H), 7.86 (s, 1H), 7.63-7.59 (m, 2H), 7.38-7.31 (m, 3H), 4.76-4.70 (m,
13
H), 1.40-1.32 (m, 12H); C-NMR (100 MHz, CDCl
3
), 144.29, 144.10, 134.86, 129.11, 128.53,
31
26.58, 72.08, 72.02, 23.89, 23.85, 23.64, 23.59; P-NMR (400 MHz, CDCl ), 0.08; HRMS (ESI):
3
+
-1
m/z = 285.1392 [M+H] . IR (KBr, cm ): 3430, 3185, 2981, 2932, 1604, 1470, 1384, 1240, 992,
85, 834, 761, 700, 553, 480, 427.
8
1
dibutyl (2-benzylidenehydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl
3
), 8.59-8.52
(
d, J = 29.2 Hz, 1H), 7.86 (s, 1H), 7.62-7.59 (m, 2H), 7.36-7.34 (m, 3H), 4.16-4.11 (m, 4H),
13
1
.73-1.65 (m, 4H), 1.48-1.38 (m, 4H), 0.92-0.88 (m, 6H); C-NMR (100 MHz, CDCl
3
), 144.76,
3
1
1
44.56, 134.69, 129.21, 128.52, 126.63, 67.13, 67.07, 32.29, 32.22, 18.70, 13.55; P-NMR (400
+
-1
3
MHz, CDCl ), 1.64; HRMS (ESI): m/z = 313.1699 [M+H] . IR (KBr, cm ): 3400, 3172, 2965,
2
867, 1604, 1474, 1390, 1241, 1033, 860, 762, 700, 554, 453.

ACCEPTED MANUSCRIPT
1
di-tert-butyl (2-benzylidenehydrazinyl)Phosphite, white crystal; H-NMR (400 MHz, CDCl
3
),
7
.76 (s, 1H), 7.63-7.60 (m, 2H), 7.58-7.51 (d, J = 28.8 Hz, 1H), 7.38-7.31 (m, 3H), 1.53 (s, 18H);
1
3
C-NMR (100 MHz, CDCl
3
), 143.04, 142.85, 135.09, 128.93, 128.52, 126.55, 82.85, 82.78,
3
1
+
3
0.16, 30.12; P-NMR (400 MHz, CDCl
3
), 0.13; HRMS (ESI): m/z = 313.1671 [M+H] . IR (KBr,
-
1
cm ): 3360, 2962, 2926, 2840, 2356, 1624, 1447, 1374, 1006, 960, 860, 752, 684, 500.
1
diallyl (2-benzylidenehydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl
3
), 8.48-8.40
(
d, J = 28.8 Hz, 1H), 7.84 (s, 1H), 7.62-7.59 (m, 2H), 7.37-7.34 (m, 3H), 6.01-5.94 （m, 2H），
13
5
.42-5.36 (m, 2H), 5.25-5.21 (m, 2H), 4.69-4.63 (m, 4H); C-NMR (100 MHz, CDCl
3
), 145.33,
31
1
45.14, 134.45, 132.68, 132.61, 129.41, 128.57, 126.74, 118.10, 67.95, 67.90; P-NMR (400
+
-1
3
MHz, CDCl ), 1.81; HRMS (ESI): m/z = 281.1050 [M+H] . IR (KBr, cm ): 3430, 3147, 2932,
1
650, 1451, 1225, 1025, 937, 848, 756, 690, 630, 560, 515.
1
dibenzyl (2-(4-bromobenzylidene)hydrazinyl)Phosphite, white crystal; H-NMR (400 MHz,
CDCl ), 8.56-8.48 (d, J = 28.8 Hz, 1H), 7.59 (s, 1H), 7.40-7.37 (m, 2H), 7.31-7.28 (m, 6H),
3
1
3
7
1
.23-7.17 （m, 6H），5.11-5.07 (m, 4H); C-NMR (100 MHz, CDCl
3
), 134.89, 134.82, 132.33,
31
30.68, 127.44, 127.35, 127.11, 126.86, 122.40, 67.99, 67.94; P-NMR (400 MHz, CDCl ), 1.55;
3
+
-1
HRMS (ESI): m/z = 461.0471 [M+H] . IR (KBr, cm ): 3430, 3130, 2930, 1592, 1451, 1397, 1240,
017, 853, 814, 730, 690, 570, 507.
1
1
dibutyl (2-(4-bromobenzylidene)hydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl
3
),
8
1
1
1
1
.55-8.53 (d, J = 10.4 Hz, 1H), 7.79 (s, 1H), 7.47 (m, 4H), 4.15-4.09 (m, 4H), 1.71-1.66 (m, 4H),
1
3
.45-1.39 (m, 4H), 0.92-0.88 (m, 6H); C-NMR (100 MHz, CDCl
3
), 143.53, 143.33, 133.58,
31
31.74, 128.03, 123.29, 67.20, 67.14, 32.26, 32.20, 18.69, 13.55; P-NMR (400 MHz, CDCl ),
3
+
-1
.53; HRMS (ESI): m/z = 391.0746 [M+H] . IR (KBr, cm ): 3427, 3147, 2955, 2827, 2870, 1595,
470, 1390, 1240, 1059, 1035, 822, 730, 570, 515.
1
diallyl (2-(4-bromobenzylidene)hydrazinyl)Phosphite, colorless oil; H-NMR (400 MHz, CDCl
3
),
8
4
.60-8.52 (d, J = 29.2 Hz, 1H), 7.79 (s, 1H), 7.48-7.47 (m, 4H), 5.98-5.93 (m, 2H), 5.40-5.21 (m,
1
3
3
H), 4.65-4.63 (m, 4H); C-NMR (100 MHz, CDCl ), 144.11, 143.91, 133.40, 132.57, 132.50,

ACCEPTED MANUSCRIPT
31
1
31.78, 128.12, 123.46, 118.19, 67.98, 67.93; P-NMR (400 MHz, CDCl
3
), 1.56; HRMS (ESI):
m/z = 361.0146 [M+H] . IR (KBr, cm ): 3453, 3140, 2940, 1653, 1590, 1474, 1240, 1028, 920,
53, 814, 668, 630, 561, 522.
+
-1
8
1
Binol P-N ligand 7, white crystal; H-NMR (400 MHz, CDCl
3
), 8.54 (s, 2H), 8.31 (s, 2H),
7
2
1
2
3
4
.95-7.92 (m, 4H), 7.42-7.40 (m, 2H), 7.27-7.16 (m, 4H), 4.82-4.77 （m, 4H），4.59-4.52 (m, 4H),
13
3
.84 (s, 6H), 1.46-1.38 (m, 24H); C-NMR (100 MHz, CDCl ), 151.92, 141.04, 140.85, 134.27,
30.71, 128.80, 127.70, 127.14, 126.85, 126.05, 125.55, 125.37, 99.79, 56.94, 23.94, 23.92, 23.73,
3
1
+
-1
3
3.70; P-NMR (400 MHz, CDCl ), 0.43; HRMS (ESI): m/z = 787.3158 [M+H] . IR (KBr, cm ):
480, 3130, 2970, 2829, 1604, 1494, 1380, 1354, 1230, 1156, 1121, 1075, 980, 760, 570, 475,
15.

ACCEPTED MANUSCRIPT
1
13
31
H-NMR, C-NMR spectra and P-NMR:

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