D
M.-X. Cheng et al.
Letter
Synlett
OH
P
O
OEt
HP(OEt)2
OEt
O
DDQ
H
H
N
OEt
N
Ph
P
N
Ph
OEt
Br
Br
Br
OH
OH
Ph
4a
Cl
Cl
CN
CN
1a
3a
Scheme 6 Plausible reaction mechanism for the coupling reaction
1a (3 mmol), 2a (5.4 mmol), and DDQ (1.2 equiv) in toluene
at 80 °C for 48 hours gave the corresponding product 3a in
82% yield (Scheme 5, eq 1). Moreover, to our delight, the
target product 3a was obtained in high yield when we used
Chichester, 2000. (c) Vovk, A. I.; Mischenko, I. M.; Tanchuk, V. Y.;
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M. I.; Medved, T. Y. Dokl. Akad. Nauk SSSR 1952, 83, 689.
(8) For transition-metal-catalyzed oxidative phosphonylations of
tertiary amines, see: (a) Baslé, O.; Li, C. Chem. Commun. 2009,
4124. (b) Han, W.; Ofial, A. R. Chem. Commun. 2009, 6023.
(c) Xie, J.; Li, H.; Xue, Q.; Cheng, Y.; Zhu, C. Adv. Synth. Catal.
2012, 354, 1646. (d) Patil, M. R.; Dedhia, N. P.; Kapdi, A. R.;
Kumar, A. V. J. Org. Chem. 2018, 83, 4477. (e) Alagiri, K.; Devadig,
P.; Prabhu, K. R. Tetrahedron Lett. 2012, 53, 1456. (f) Han, W.;
Mayer, P.; Ofial, A. R. Adv. Synth. Catal. 2010, 352, 1667. (g) Liu,
Y.; Wang, C.; Xue, D.; Xiao, M.; Li, C.; Xiao, J. Chem. Eur. J. 2017,
23, 3051. (h) Lin, B.; Shi, S.; Lin, R.; Cui, Y.; Fang, M.; Tang, G.;
Zhao, Y. J. Org. Chem. 2018, 83, 6754. (i) Cai, J.; Liu, Y.; Jiang, Y.;
Yang, Y. Phosphorus, Sulfur Silicon Relat. Elem. 2017, 192, 1068.
(j) Dhineshkumar, J.; Lamani, M.; Alagiri, K.; Prabhu, K. R. Org.
Lett. 2013, 15, 1092.
(9) For visible-light catalytic oxidative phosphonylations of tertiary
amines, see: (a) Rueping, M.; Zhu, S.-Q.; Koenigs, R. M. Chem.
Commun. 2011, 47, 8679. (b) Yoo, W.-J.; Kobayashi, S. Green
Chem. 2014, 16, 2438. (c) Hari, D. P.; König, B. Org. Lett. 2011, 13,
3852. (d) Xue, Q.; Xie, J.; Jin, H.; Cheng, Y.; Zhu, C. Org. Biomol.
Chem. 2013, 11, 1606. (e) Gandy, M. N.; Raston, C. L.; Stubbs, K.
A. Chem. Commun. 2015, 51, 11041. (f) Wang, X.-Z.; Meng, Q.-Y.;
Zhong, J.-J.; Gao, X.-W.; Lei, T.; Zhao, L.-M.; Li, Z.-J.; Chen, B.;
Tung, C.-H.; Wu, L.-Z. Chem. Commun. 2015, 51, 11256. (g) Niu,
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the
(1E,2E)-N-(4-bromophenyl)-3-phenylprop-2-en-1-
imine (4a) and diethyl phosphite (2a) as starting materials
(Scheme 5, eq 2). This result indicates that allylimine 4a
might be the reaction intermediate.
On the basis of our experimental results and previous
reports,11 we propose the mechanism for the DDQ-mediate
CDC reaction of allylamines with dialkyl phosphonates
shown Scheme 6. Initially, allylimine 4a might be generated
in situ from allylamine 1a under oxidative conditions. Next,
diethyl phosphite isomerizes to the active trivalent phos-
phorus compound. Finally, the active trivalent phosphorus
compound attacks allylimine 4a to afford the target product 3a.
In summary, we have developed a novel DDQ-mediated
simple method for the CDC reaction of secondary amines
with dialkyl phosphonates to give α-aminophospho-
nates.12,13 The reaction proceeded efficiently without in-
volving visible light or transition-metal catalysts. This prac-
tical protocol provides a convenient and efficient approach
to biologically important α-aminophosphonates. Further
investigations on transition-metal-free catalytic reactions
are in progress.
Funding Information
Financial support from the Project of Science and Technology of
Henan Province (No. 162102310448).()
Supporting Information
Supporting information for this article is available online at
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References and Notes
(1) (a) Beers, S. A.; Schwender, C. F.; Loughney, D. A.; Malloy, E.;
Demarest, K.; Jordan, J. Bioorg. Med. Chem. 1996, 4, 1693.
(b) Aminophosphonic and Aminophosphinic Acids: Chemistry and
Biological Activity; Kukhar, V. P.; Hudson, H. R., Ed.; Wiley:
(10) For metal-free catalytic oxidative phosphonylations of tertiary
amines, see: (a) Alagiri, K.; Devadig, P.; Prabhu, K. R. Chem. Eur. J.
2012, 18, 5160. (b) Dhineshkumar, J.; Samaddar, P.; Prabhu, K.
R. ACS Omega 2017, 2, 4885. (c) Huo, C.; Xie, H.; Wu, M.; Jia, X.;
Wang, X.; Chen, F.; Tang, J. Chem. Eur. J. 2015, 21, 5723.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E