indoles to furnish 2-(1H-indol-3-yl)-2-iminocarbonyls and
2
7
-(1H-indol-3-yl)-2-oxocarbonyls selectively. To the best of
a,b
Table 1. Screening for Optimal Reaction Conditions
our knowledge, transition-metal-catalyzed R-phosphonation
of secondary amines leading to imidoylphosphonates has not
been reported. Compounds containing the imidoylphospho-
nate structure are very important units in organic synthesis
8
and metalÀligand design.
cat.
(mol %)
oxidant
(equiv)
product
(%)
c
Scheme 1. CÀP Bond Formation Adjacent to a Nitrogen Atom
entry
1
solvent
CH Cl
toluene
ClCH CH
2a:3a
Cu(OAc)
2
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
2
2
58
1:1
3
H
2
O (10)
2
3
4
5
6
7
8
9
Cu(OAc)
2
trace
30
3
3
3
3
3
3
3
3
3
3
3
3
3
3
H
2
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
Cu(OAc)
O (15)
Cu(OAc)
O (5)
Cu(OAc)
O (10)
Cu(OAc)
O (10)
CuCl (10)
2
2
2
Cl
10:1
H
2
d
2
DMSO
MeCN
61
>99:1
>99:1
1:1
H
2
2
82
H
2
2
K
2
S
2
O
8
(2.0) MeCN
39
H
2
Our initial study began with 1-phenyl-2-(phenylamino)-
ethanone (1a) and diphenylphosphine oxide in the pre-
sence of 10 mol % Cu(OAc) H O and 2.0 equiv of TBHP
2
(t-BuO)
(2.0)
2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
trace
55
H
2
2
TBHP (1.5)
6:1
>99:1
>99:1
1:1
2
3
2
H
2
in CH Cl under an argon atmosphere (Table 1, entry 1).
2
2
2
TBHP (2.5)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
79
To our delight, the reaction occurred, but the product was
obtained with a mixture of 2-(diphenylphosphoryl)-1-phe-
nyl-2-(phenylimino)ethanone (2a) and 2-(diphenylpho-
sphoryl)-1-phenyl-2-(phenylamino)ethanone (3a), and the
ratio of 2a/3a was 1:1. Encouraged by this result, our
further optimization of the reaction conditions focused on
producing a single product. The reaction underwent
H
2
e
1O
2
71
H
2
f
11
2
83
H
2
1
1
1
1
2
3
4
5
2
82
35:1
H
2
2
83
50:1
H
2
g
2
85
>99:1
>99:1
H
2
(
4) For Cu-catalyzed reactions, see: (a) Li, Z.; Li, C.-J. J. Am. Chem.
Soc. 2004, 126, 11810. (b) Li, Z.; Li, C.-J. J. Am. Chem. Soc. 2005, 127,
672. (c) Li, Z.; Li, C.-J. Eur. J. Org. Chem. 2005, 3173. (d) Li, Z.;
h
2
84
H
2
3
MacLeod, P. D.; Li, C.-J. Tetrahedron: Asymmetry 2006, 17, 590. (e)
Basle, O.; Li, C.-J. Green Chem. 2007, 9, 1047. (f) Basle, O.; Borduas, N.;
Dubois, P.; Chapuzet, J. M.; Chan, T. H.; Lessard, J.; Li, C.-J. Chem.-
Eur. J 2010, 16, 8162. (g) Shen, Y.; Tan, Z.; Chen, D.; Feng, X.; Li, M.;
Guo, C.-C.; Zhu, C. Tetrahedron 2009, 65, 158. (h) Yang, F.; Li, J.; Xie,
J.; Huang, Z.-Z. Org. Lett. 2010, 12, 5214. (i) Huang, L.; Niu, T.; Wu, J.;
Zhang, Y. J. Org. Chem. 2011, 76, 1759. (j) Sureshkumar, D.; Sud, A.;
Klussmann, M. Synlett 2009, 1558. (k) Boess, E.; Schmitz, C.; Kluss-
mann, M. J. Am. Chem. Soc. 2012, 134, 5317. (l) Boess, E.; Sureshkumar,
D.; Sud, A.; Wirtz, C.; Far ꢀe s, C.; Klussmann, M. J. Am. Chem. Soc.
16
17
18
MeCN
MeCN
MeCN
MeCN
34
78
49
43
6:1
17:1
>99:1
>99:1
Cu(OAc)
CuI (10)
2
(10) TBHP (2.0)
TBHP (2.0)
(10) TBHP (2.0)
19
Cu(OTf)
2
a
2
Reaction conditions: 1a (0.2 mmol), H(O)PPh (0.3 mmol), catalyst
(
10 mol %) TBHP (5À6 M in decane), and solvent (2.0 mL) under Ar for
31 e f
b
c
31
d
1
6 h at 30 °C. Isolated yields. Determined by P NMR. 3a was not
2
detectable by P NMR. 1.2 equiv of H(O)PPh . 2.0 equiv of H(O)-
PPh . MeCN (3 mL). MeCN (4 mL).
2
g
h
2011, 133, 8106. (m) Xie, J.; Huang, Z.-Z. Angew. Chem., Int. Ed. 2010,
49, 10181. For Ru-catalyzed reactions, see: (n) Murahashi, S.-I.; Nakae,
T.; Terai, H.; Komiya, N. J. Am. Chem. Soc. 2008, 130, 11005. (o) Wu,
W. L.; Su, W. P. J. Am. Chem. Soc. 2011, 133, 11924. (p) Wang, M.-Z.;
Zhou, C.-Y.; Wong, M.-K.; Che, C.-M. Chem.ÀEur. J 2010, 16, 5723.
various solvent screenings before a single product 2a was
acquired in DMSO or MeCN in 61% and 82% yields
(entries 2À5). Furthermore, replacing the TBHP with
other oxidants such as K S O and (t-BuO) resulted in
both lower yields and a lower ratio of 2a/3a (entries6and7).
We also found that a reduction or an increase in the amount
of TBHP resulted in a lower yield or a poor ratio of 2a/3a
(
q) Condie, A. G.; Gonz ꢁa lez-G oꢁ mez, J. C.; Stephenson, C. R. J. J. Am.
Chem. Soc. 2010, 132, 1464. (r) Rueping, M.; Vila, C.; Koenigs, R. M.;
Poscharny, K.; Fabry, D. C. Chem. Commun. 2011, 2360. For
Rh-catalyzed reactions, see: (s) Catino, A. J.; Nichols, J. M.; Nettles,
B. J.; Doyle, M. P. J. Am. Chem. Soc. 2006, 128, 5648. For Fe-catalyzed
reactions, see: (t) Ratnikov, M. O.; Xu, X. F.; Doyle, M. P. J. Am. Chem.
Soc. 2013, 135, 9475. (u) Han, W.; Ofial, A. R. Chem. Commun. 2009,
2
2
8
2
5024. (v) Boess, E.; Sureshkumar, D.; Sud, A.; Wirtz, C.; Fares, C.;
Klussmann, M. J. Am. Chem. Soc. 2011, 133, 8106. (w) Singhal, S.; Jain,
S. L.; Sain, B. Adv. Synth. Catal. 2010, 352, 1338. (x) Ghobrial, M.;
Harhammer, K.; Mihovilovic, M. D.; Schn u€ rch, M. Chem. Commun.
(entries 8 and 9). Remarkably, the equivalent of diphenyl-
phosphine oxide in the reaction is crucial to the ratio of 2a/
2
4
2
010, 8836. (y) Richter, H.; Manche n~ o, O. G. Eur. J. Org. Chem. 2010,
460. (z) Kumaraswamy, G.; Murthy, A. N.; Pitchaiah, A. J. Org. Chem.
010, 75, 3916.
(6) (a) Hu, J.; Zhao, N.; Yang, B.; Wang, G.; Guo, L.-N.; Liang,
Y. M.; Yang, S.-D. Chem.;Eur. J 2011, 17, 5516. (b) Li, Y.-M.; Sun,
M.; Wang, H.-L.; Tian, Q.-P.; Yang, S.-D. Angew. Chem., Int. Ed. 2013,
52, 3972. (c) Sun, M.; Zhang, H.-Y.; Han, Q.; Yang, K.; Yang, S.-D.
Chem.;Eur. J. 2011, 17, 9566. (d) Zhang, H.-Y.; Sun, M.; Ma, Y.-N.;
Tian, Q.-P.; Yang, S.-D. Org. Biomol. Chem. 2012, 10, 9627.
(
5) (a) Alagiri, K.; Devadig, P.; Prabhu, K. R. Tetrahedron Lett.
2
012, 53, 1456. (b) Xie, J.; Li, H.; Xue, Q. C.; Cheng, Y. X.; Zhu, C. J.
Adv. Synth. Catal. 2012, 354, 1646. (c) Hari, D. P.; Konlg, B. Org. Lett.
011, 13, 3852. (d) Basle, O.; Li, C.-J. Chem. Commun. 2009, 4124. (e)
2
Han, W.; Mayer, P.; Ofial, A. R. Adv. Synth. Catal. 2010, 352, 1667.
B
Org. Lett., Vol. XX, No. XX, XXXX