An efficient aerobic oxidative phosphonation of a-amino C[sbnd]H bonds over CoNiFe hydrotalcite

Article abstract of DOI:10.1016/j.tetlet.2019.151121

An efficient and convenient heterogeneous catalytic procedure has been developed for the phosphonation of a-amino C[sbnd]H bonds with various dialkyl phosphites and diarylphosphine oxides using molecular oxygen as a sustainable oxidant over CoNiFe hydrota

Full text of DOI:10.1016/j.tetlet.2019.151121

Tetrahedron Letters 60 (2019) 151121
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Tetrahedron Letters
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An efficient aerobic oxidative phosphonation of a-amino CAH bonds
over CoNiFe hydrotalcite
a
a
a
a
Zhenzhen Xia a, Lizhen Qin a,b, Weiyou Zhou a, , Hui Wang , Binxun Yu , Zhonghua Sun , Junfeng Qian ,
⇑
Mingyang He a,
⇑
a Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, China
b School of Chemical and Environmental Engineering, Jiangsu University of Technology, Changzhou 213001, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 July 2019
Revised 2 September 2019
Accepted 6 September 2019
Available online 7 September 2019
An efficient and convenient heterogeneous catalytic procedure has been developed for the phosphona-
tion of a-amino CAH bonds with various dialkyl phosphites and diarylphosphine oxides using molecular
oxygen as a sustainable oxidant over CoNiFe hydrotalcite. The catalytic system could tolerate various
tetrahydroquinoline derivatives, and the corresponding a-amino phosphonic compounds could be
obtained in good to excellent yields. Synergistic effect might exist in the oxidative phosphonation under
the catalysis of CoNiFe hydrotalcite.
Keywords:
Phosphonation
Ó 2019 Elsevier Ltd. All rights reserved.
CAH activation
CoNiFe hydrotalcite
Cross-dehydrogenative coupling
Introduction
a-phosphonation of N-aryl tetrahydroisoquinolines, heterogeneous
catalytic procedure has been rarely reported. Therefore, develop-
a-Amino phosphonic compounds and their derivatives are valu-
able precursors of a multitude of biologically active molecules
[1,2]. Kabachnik-Field reaction and Pudovik reaction, using aldehy-
des or imines as the raw materials, are the traditional methods to
synthesis these compounds. In the recent years, cross-dehydro-
genative coupling (CDC) reaction has attracted considerable atten-
tion and a number of notable advances have been achieved. CDC
reaction provides a more efficient protocol in the formation of
CAP bonds, because CDC reactions do not require prefunctionaliza-
tion of the starting material. Actually, various catalytic systems
based on Au complexes [3], cobalt salts [4,5], iron salts [6,7], cop-
per salts [8], MoO3 [9], antimony(V) anions [10] and some metal-
free systems [11–13], have been developed for the a-phosphona-
tion of tertiary amines using CDC reactions. However, peroxide as
the oxidant or additives are always required in most of the sys-
tems. Dhineshkumar et al. have reported that the reaction could
proceed without any catalyst using air as the oxidant, but even
long reaction time was required with moderate yield for the cou-
pling product [14]. Other than these reports, the CDC reaction
has also been performed under electro- or photo-catalyzed sys-
tems [15–20]. Although tremendous progress has been made for
ment of a more environmentally benign and efficient heteroge-
neous system originated from available materials for oxidative a-
amino CAH phosphonation is highly desirable.
Layered double hydroxides (LDHs) with the hydrotalcite struc-
ture consisted of M2+ and M3+ cations in the brucite layer, and
anions in the interlayer [21,22], has a great application potential
in catalysis for its adjustability of composition and physicochemi-
cal properties. Actually, the hydrotalcite-like compounds have
been investigated in various reactions, and efficient catalytic per-
formance has been observed [23–27]. In this study, hydrotalcites
has been studied as a new catalytic system for the aerobic oxida-
tive CDC for the synthesis of
additives in the present research. And an efficient and convenient
method for the -amino CAH phosphonation with various dialkyl
a-aminophosphonates without any
a
phosphites as well as diarylphosphine oxides has been developed.
To initiate our study, the reaction of N-phenyltetrahydroiso-
quinoline 1a with dimethyl phosphite 2a was chosen as a model
reaction. Various LDHs have been prepared via coprecipitation
method, and the hydrotalcite structure can be confirmed by XRD
analysis (Fig. S1). Under the selected reaction conditions, these
prepared catalysts have been screened in the CDC reaction
(Table S1). It can be observed that although most of the catalysts
could provide excellent conversion of the substrate, the selectivity
of the CDC product was not satisfactory. The highest selectivity of
the corresponding product was observed in the case of CoNiFe-LDH
⇑
Corresponding authors.
E-mail addresses: zhouwy426@126.com (W. Zhou), hemy_cczu@126.com
(M. He).
https://doi.org/10.1016/j.tetlet.2019.151121
0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.

2
Z. Xia et al. / Tetrahedron Letters 60 (2019) 151121
with an acceptable conversion. Therefore, CoNiFe-LDH was
selected as the catalyst for the further optimization of the reaction
conditions (Table 1). Various solvents were initially evaluated in
the coupling reaction (entries 1–7). It was notable that when diox-
ane, methanol or H2O was used as the solvent, acceptable conver-
sion of the starting material 1a could be obtained. However, only a
small amount of desired product 3aa formed under methanol,
which might be due to the fact that enamine nucleophilic attack
was significantly slower than over-oxidative amide (4) formation
in methanol. The results in Table 1 show that the highest conver-
sion of 1a could be observed under the solvent dioxane with mod-
erate polarity (entry 2), also with the highest selectivity to the
corresponding product. For the reaction temperature (entries 8–9),
decreasing the temperature to 60 °C resulted in a reduced conver-
sion of 1a with similar selectivity of 3aa. However, quite lower
selectivity of the product was obtained in the case of 100 °C, which
was mainly due to the formation of the overoxidation product 2-
phenyl-3,4-dihydroisoquinolin-1(2H)-one (4). Decreasing the ratio
of 2a/1a could lead to an increasement of the selectivity of 3aa
(entry 10), while the conversion changed slightly. And 4 equivalent
of 2a gave the highest selectivity (entry 11). Under the selected
conditions, prolonging the reaction time from 18 h to 22 h could
markedly improve the conversion of the substrate with excellent
selectivity (entry 12). However, when the reaction time was fur-
ther prolonged to 26 h, only slight improvement for the conversion
could be obtained with a little decreasement of the selectivity
(entry 12). The recyclability of the CoNiFe-LDH catalyst was also
investigated under the optimized conditions (entries 13–14). The
results indicated that only slight decreasement of the catalytic
activity could be observed with no change of the selectivity in
the third recycle. The XRD pattern for the recycled catalyst in
Fig. S2 suggests that the dedecreasement might be due to the
partly collapse of the hydrotalcite structure. Summary, an conve-
nient and efficient catalytic system has been developed for the
CDC reaction between N-phenyltetrahydroisoquinoline and
dimethyl phosphite, and excellent conversion and selectivity could
be obtained under mild reaction conditions.
With the optimized reaction conditions established, the scope
of this protocol was investigated in the CDC reaction under analo-
gous reaction conditions (Table 2). Firstly, a variety of N-phenylte-
trahydroquinolin derivatives were subjected to the oxidative CAP
coupling reaction and they could afford the desired products in
good to excellent isolated yields (entries 1–10). It is important to
point out that electron-donating as well as electron-withdrawing
groups on the aromatic rings were compatible in the aerobic oxida-
tive CAP coupling reaction (entries 2–3 and entries 6–8). They
could uniformly provide the corresponding products in a little
longer reaction times. Subsequently, different dialkyl phosphites
were examined. To our delight, the reaction could also proceed
smoothly to furnish the CAP coupling products in good yields,
although prolonging reaction time were required (entries 11–12).
Intriguingly, long-chain phosphites were also very effective in
the catalytic system and could give good results (entry 12). The rel-
atively decreased yield for diisopropyl phosphite than dimethyl
phosphite and dibutyl phosphite might be due to the steric hin-
drance effect.
To further illustrate the generality of our protocol,
diphenylphosphine was also introduced into the reaction. It was
also found that the substituents on aromatic rings hardly affected
the oxidative CAP coupling reaction. All the tertiary amines 1d-g
and 1i could be coupled with diphenylphosphine 2d readily to
afford the desired product in good yields (entries 13–18). It should
Table 1
Optimization of the reaction conditions for the CDC reaction between N-phenyltetrahydroisoquinoline and dimethyl phosphite.
Entry
Solvent
Temp./ °C
2a/1a
Conv.a/%
Sel.a/%
1
2
3
4
5
6
7
8
Acetonitrile
Dioxane
Trifluorotoluene
Methanol
Mesitylene
H2O
80
80
80
80
80
80
80
60
100
80
80
80
80
80
80
6
6
6
6
6
6
6
6
6
2
4
4
4
4
4
14
73
17
42
17
52
23
45
77
67
74
92
94
90
88
57
90
57
46
57
87
87
87
11
95
98
98
96
97
96
DMF
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
9
10
11
12b
13c
14b,d
15b,e
Reaction conditions: N-phenyltetrahydroquinoline 0.5 mmol, dimethyl phosphite 3 mmol, CoNiFe-LDH 0.2 g, solvent 2 mL, 18 h, O2 atmosphere.
a
Based on the 1H NMR analysis; selectivity of 3aa.
22 h.
26 h.
Second recycle.
b
c
d
e
Third recycle.

Z. Xia et al. / Tetrahedron Letters 60 (2019) 151121
3
Table 2
Catalytic CDC reaction between N-phenyltetrahydroisoquinoline derivatives and various dialkyl phosphites or diarylphosphine oxides over CoNiFe-LDH.
Entry
1
1
2
3
Time/h
22
Yielda/%
81
2
2a
32
67
3
4
2a
2a
32
28
61
76
5
6
7
2a
2a
2a
30
30
30
73
74
78
8
9
2a
2a
30
26
67
80
10
11
2a
28
36
59
1a
51
(continued on next page)

4
Z. Xia et al. / Tetrahedron Letters 60 (2019) 151121
Table 2 (continued)
Entry
1
2
3
Time/h
Yielda/%
12
13
1a
1a
36
24
86
61
14
15
1d
1e
2d
2d
25
27
55
54
16
17
1f
2d
2d
26
26
56
62
1g
18
1i
2d
28
36
Reaction conditions: 1 0.5 mmol, 2 3 mmol, CoNiFe-LDH 0.2 g, dioxane 2 mL, 80 °C, O2 atmosphere.
a
Isolated yield.
be noted that the yields were basically lower than the case of
dimethyl phosphite, implying the existence of steric effect.
These results suggest that a radical pathway is probable involved
in the a-phosphonation of N-aryl tetrahydroisoquinolines. On the
basis of the obtained and reported results [3,8,9,11], a plausible
mechanism is described in Scheme 1. We believe that N-aryl
tetrahydroisoquinoline (1a) is oxidized to iminium ion intermedi-
ate (5) under the catalysis of CoNiFe-LDH. Subsequently, the inter-
mediate reacts nucleophilic phosphite species to furnish the
desired coupling product 3aa (Scheme 1). To verify the possible
catalytic active site, the catalytic performance of various Co-, Ni-
and Fe-containing hydrotalcites have been compared and the
results can be found in Table S1. CoAl, CoFe, CoGa and MgFe hydro-
talcites gave excellent conversion of N-phenyltetrahydroquinoline
with moderate selectivity to the coupling product (Table S1,
entries 8–11), implying that Co or Fe might be able to activate
the substrate. On the other hand, Ni-containing samples exhibited
relatively low activity and good selectivity (Table S1, entries
To validate the reaction mechanism, some controlled experi-
ments have been performed and the results are summarized in
Table 3. Quite lower conversion and selectivity of the correspond-
ing phosphonation product was observed (entry 2) in the absence
of catalyst, indicating the catalytic function of CoNiFe-LDH. When
the reaction was performed under N2 or air atmosphere, only very
low conversion could be obtained, but with moderate to good
selectivity of the corresponding product (entries 3 and 4), suggest-
ing that the molecular oxygen is essential for the activation of the
substrate. Introduction of two equivalent of 2,6-di-tert-butyl-4-
methylphenol (BHT) into the reaction resulted in only a 20% con-
version (entry 5). Although a 86% conversion could be obtained
in the presence of (2,2,6,6-tetramethylpiperidin-1-yl) oxyl
(TEMPO), the selectivity significantly decreased to 58% (entry 6).

Z. Xia et al. / Tetrahedron Letters 60 (2019) 151121
5
Table 3
The results of some controlled experiments.
Entry
Catalyst
Additive
Conv.a/%
Sel.a/%
1
2
CoNiFe-LDH
–
CoNiFe-LDH
CoNiFe-LDH
CoNiFe-LDH
CoNiFe-LDH
–
–
–
–
92
26
23
46
20
86
98
33
62
88
91
58
3b
4c
5
BHTd
TEMPOd
6
Reaction conditions: 1,2,3,4-tetrahydroquinoline 0.5 mmol, dimethyl phosphite 3 mmol, CoNiFe-LDH 0.2 g, dioxane 2 mL, 22 h, 80 °C, O2 atmosphere.
a
Based on the 1H NMR analysis.
Under the N2 atmosphere.
Under the air atmosphere.
2 Equivalent of substrate.
b
c
d
University, Jiangsu Key Laboratory of Advanced Catalytic Materials
and Technology (BM2012110), Natural Science Foundation of
Jiangsu Province of China (BK20181461).
Appendix A. Supplementary data
Supplementary data (general experimental information, and 1H
and 13C NMR spectral data for all compounds) to this article can be
found online at https://doi.org/10.1016/j.tetlet.2019.151121.
References
[1] L. Albrecht, A. Albrecht, H. Krawczyk, K. Jorgensen, Chem. Eur. J. 16 (2010) 28–
48.
[2] D.P. Zhao, R. Wang, Chem. Soc. Rev. 41 (2012) 2095–2108.
[3] J. Xie, H.M. Li, Q.C. Xue, Y.X. Cheng, C.J. Zhu, Adv. Synth. Catal. 354 (2012)
1646–1650.
[4] R.P. Mahendra, P.D. Noopur, R.K. Anant, J. Org. Chem. 83 (2018) 4477–4490.
[5] B.Z. Lin, S.S. Shi, R.C. Lin, Y.Q. Cui, M.J. Fang, G. Tang, Y.F. Zhao, J. Org. Chem. 83
(2018) 6754–6761.
[6] B. Olivier, J.L. Chao, Chem. Commun. 40 (2009) 4124–4126.
[7] A. Kaliyamoorthy, D. Kandikere, R.P. Pradeep, Tetrahedron Lett. 53 (2012)
1456–1459.
Scheme 1. A possible reaction path for the a-phosphonation of N-phenyltetrahy-
droisoquinolines over CoNiFe-LDH.
[8] T. Arata, Y. Woo, K. Shu, Adv. Synth. Catal. 355 (2013) 269–273.
[9] A. Kaliyamoorthy, D. Pradeep, R.P. Kandikere, Chem. Eur. J. 18 (2012) 5160–
5164.
[10] H.L. Wang, X.C. Li, F. Wu, Tetrahedron Lett. 53 (2012) 681–683.
[11] W. Han, A.R. Ofial, Chem. Commun. 41 (2009) 6023–6025.
[12] B. Lin, G.Z. Lu, R.C. Lin, Y.Q. Cui, Y. Liu, G. Tang, Y.F. Zhao, Synlett 29 (2018)
2697–2700.
[13] W. Han, P. May, A.R. Ofial, Adv. Synth. Catal. 352 (2010) 1667–1676.
[14] J. Dhineshkumar, P. Samaddar, K.R. Prabhu, ACS Omega 2 (2017) 4885–4893.
[15] Q.C. Xue, J. Xie, H.M. Jin, Y.X. Cheng, Org. Biomol. Chem. 11 (2013) 1606–1609.
[16] J. Woo, K. Shu, Green Chem. 16 (2014) 2438–2442.
[17] W.P. To, Y.J. Liu, T.C. Lau, C.M. Che, Chem. Eur. J. 19 (2013) 5654–5664.
[18] K. Chen, Y. Cheng, Y.Z. Chang, E.Q. Li, Tetrahedron 74 (2018) 483–489.
[19] P.H. Li, G.W. Wang, X.J. Zhu, L. Wang, Tetrahedron 75 (2019) 3448–3455.
[20] Y. Yuan, J. Qiao, Y.M. Cao, J.M. Tang, M.Q. Wang, G.J. Ke, Y.C. Lu, X. Liu, A.W. Lei,
Chem. Commun. 55 (2019) 4230–4233.
[21] B.M. Choudhary, M.L. Kantam, A. Rahman, C.V. Reddy, K.K. Rao, Angew. Chem.
Int. Ed. Engl. 40 (2001) 763–766.
[22] T. Kawabata, Y. Shinozuka, Y. Ohishi, T. Shishido, K. Takaki, K. Takehira, J. Mol.
Catal. A: Chem. 236 (2005) 206–215.
[23] Z. Wang, P. Fongarland, G.Z. Lu, N. Essayem, J. Catal. 318 (2014) 108–118.
[24] D.P. Debecker, E.M. Gaigneaux, G. Busca, Chem. Eur. J. 15 (2009) 3920–3935.
[25] G.F. Fan, F. Li, D.G. Evans, X. Duan, Chem. Soc. Rev. 43 (2014) 7040–7066.
[26] W.Y. Zhou, Q.Y. Tao, J.G. Pan, J. Liu, J.F. Qian, M.Y. He, Q. Chen, J. Mol. Catal. A:
Chem. 425 (2016) 255–265.
12–13), suggesting that the presence of Ni in the structure might
benefit to the coupling reaction. Therefore, synergistic effect might
exist in the aerobic oxidative phosphonation of a-amino CAH
bonds over CoNiFe hydrotalcite. In addition, it is also well known
that nucleophilic phosphite 2a is an equivalent to phosphonate
2e in the reaction [8], and CoNiFe-LDH catalyst might also play a
role in the phosphate/phosphite equilibrium by facilitating the
deprotonation of the former and subsequently accelerate the rate
of the reaction.
In summary, a convenient heterogeneous catalytic system for
the a-phosphonation of N-aryl tetrahydroisoquinolines over CoN-
iFe hydrotalcite has been developed. Various substrates could be
tolerated by the present protocol. Moreover, the safe, convenient
and environmentally benign process makes it very practical. Fur-
ther studies on catalytic mechanism for the aerobic oxidative
CAH activation and the application of the protocol to other nucle-
ophiles are under way in our laboratory.
Acknowledgment
[27] W.Y. Zhou, Q.Y. Tao, F.A. Sun, X.B. Cao, J.F. Qian, Q. Chen, J. Catal. 361 (2018) 1–
11.
This work was supported by Advanced Catalysis and Green
Manufacturing Collaborative Innovation Center of Changzhou