also been used as an effective nitrogen source for direct
aromatic and heteroaromatic CꢀH amination via a similar
catalytic process.8
transformations to form CꢀC10 and CꢀX (X = O, N,
B)11ꢀ13 bonds. In 2011, the groups of Antonchick,12a
Chang,12b and DeBoef12c independently realized transition-
metal-free CꢀN bond formation between ordinary arenes
and amides or sulfonamides using PhI(OAc)2 as an oxidant.
At the same time, Nachtsheim’s group achieved a similar
transformation between benzoxazoles and amines using
iodide as the catalyst under oxidative conditions.12d
As a continuation of our own interest in transition-
metal-free transformations,10c,13a,13c we conceived that
the reactions between electrophilic R1R2Nþ synthons
and nucleophilic organoboron compounds might not re-
quire transition metal catalysts. Herein we report a novel
and convenient strategy to construct C(sp2)ꢀN bonds
by using arylboroxines and O-benzoyl hydroxylamines as
coupling partners in the presence of only base (K2CO3)
(Scheme 1, path D).
Scheme 1. C(sp2)ꢀN Bond Formation
Organoboron compounds are generally more stable
and less toxic over other organometallic reagents. It is
thus highly desirable to develop a C(sp2)ꢀN bond forming
reaction based on organoboron reagents. In 2008, Lei
et al. reported a Cu-catalyzed amination of phenylboronic
acid derivatives with N-chloro-N-arylacetamide.7g Very
recently, groups of Miura and Lalic independently disclosed
Cu-catalyzed cross-coupling reactions of arylboronates
with N,N-dialkyl-O-acylhydroxylamine derivatives.7h,i This
significant progress have made it possible to prepare bromo-
and iodo-substituted dialkyl anilines directly.9
However, the above-described methods, although very
powerful, all require transition metals such as palladium,
nickel, and copper and in many cases the corresponding
ligands as catalysts, which make these methods expensive
and environmentally less friendly. Recently, great progress
has been made in the development of transition-metal-free
Table 1. Electrophilic Amination with Boron Compoundsa
entry
1, X
2, PhꢀB (equiv)
base
yield (%)b
1
2
3
4
5
6
7
8
9e
1a, OBz
1a, OBz
1b, OAc
1c, Cl
2a, PhBin (3)c
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K3PO4
none
none
42
2b, PhB(OH)2 (2)
2b, PhB(OH)2 (2)
2b, PhB(OH)2 (2)
2b, PhB(OH)2 (2)
2b, PhB(OH)2 (2)
2b, PhB(OH)2 (2)
2c, (PhBO)3 (1)
2c, (PhBO)3 (1)
18
traced
30
1a, OBz
1a, OBz
1a, OBz
1a, OBz
1a, OBz
26
21
K2CO3
K2CO3
71
91
a Reaction conditions if not otherwise noted: 1 (0.6 mmol) and 2 in
dioxane (3 mL) were heated for 8 h. b Yields of isolated product. c Bin:
pinacolato. d Detected by GC-MS. e The solution of 1a (0.6 mmol) in
dioxane (1 mL) was added to the solution containing 2c and K2CO3 in
dioxane (2 mL) via syringe pump for 20 h, and then the reaction was
carried out for an additional 4 h at the same temperature.
(8) (a) Kawano, T.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem.
Soc. 2010, 132, 6900. (b) Yoo, E. J.; Ma, S.; Mei, T.-S.; Chan, K. S. L.;
Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 7652.
(9) For relevant halogen-compatible CꢀN formations based on
palladium catalysts, see: (a) Thu, H.-Y.; Yu, W.-Y.; Che, C.-M.
J. Am. Chem. Soc. 2006, 128, 9048. (b) Jordan-Hore, A. A.; Johansson,
C. C. C.; Gulias, M.; Beck, E. M.; Gaunt, M. J. J. Am. Chem. Soc. 2008,
130, 16184. (c) Mei, T.-S.; Wang, X.; Yu, J.-Q. J. Am. Chem. Soc. 2009,
131, 10806. (d) Xiao, B.; Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am.
Chem. Soc. 2011, 133, 1466.
We started our investigation by using R1R2Nþ synthons
1aꢀc to react with organoboron compounds 2 (Table 1).
The reaction of O-benzoyl hydroxylamine 1a with pinacol
boronate 2a failed to generate the expected product 3a
(Table 1, entry 1), while with PhB(OH)2 2b the reaction
did afford the 4-phenylmorpholine 3a, albeit in low yield
(Table 1, entry 2). The reaction withmorpholino acetate 1b
and 4-chloromorpholine 1c led to a reduced yield due to
(10) For selected examples, see: (a) Yoshimitsu, T.; Arano, Y.;
Nagaoka, H. J. Am. Chem. Soc. 2005, 127, 11610. (b) Dohi, T.; Ito,
M.; Morimoto, K.; Iwata, M.; Kita, Y. Angew. Chem., Int. Ed. 2008, 47,
1301. (c) Peng, C.; Zhang, W.; Yan, G.; Wang, J. Org. Lett. 2009, 11,
ꢀ
ꢀ
1667. (d) Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Nat.
Chem. 2009, 1, 494. (e) Sun, C.; Li, H.; Yu, D.; Yu, M.; Zhou, X.; Lu, X.;
Huang, K.; Zheng, S.; Li, B.; Shi, Z. Nat. Chem. 2010, 2, 1044. (f) Liu,
W.; Cao, H.; Zhang, H.; Zhang, H.; Chung, K. H.; He, C.; Wang, H.;
Kwong, F. Y.; Lei, A. J. Am. Chem. Soc. 2010, 132, 16737. (g)
Shirakawa, E.; Itoh, K.; Higashino, T.; Hayashi, T. J. Am. Chem. Soc.
2010, 132, 15537. (h) Shirakawa, E.; Zhang, X.; Hayashi, T. Angew.
Chem., Int. Ed. 2011, 50, 4671. (i) Sun, C.; Gu, Y.; Wang, B.; Shi, Z.
Chem.;Eur. J. 2011, 17, 10844. (j) Ito, K.; Tamashima, H.; Iwasawa,
N.; Kusama, H. J. Am. Chem. Soc. 2011, 133, 3716.
(12) For selected examples of CꢀN bond formation, see: (a)
Antonchick, A. P.; Samanta, R.; Kulikov, K.; Lategahn, J. Angew.
Chem., Int. Ed. 2011, 50, 8605. (b) Kim, H. J.; Kim, J.; Cho, S. H.;
Chang, S. J. Am. Chem. Soc. 2011, 133, 16382. (c) Kantak, A. A.;
Potavathri, S.; Barham, R. A.; Romano, K. M.; DeBoef, B. J. Am.
Chem. Soc. 2011, 133, 19960. (d) Froehr, T.; Sindlinger, C. P.; Kloeckner,
U.; Finkbeiner, P.; Nachtsheim, B. J. Org. Lett. 2011, 13, 3754.
(11) For selected examples of CꢀO bond formation, see: (a) Schmidt,
V. A.; Alexanian, E. J. Angew. Chem., Int. Ed. 2010, 49, 4491. (b)
ꢀ
ꢀ
Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Angew. Chem.,
Int. Ed. 2010, 49, 4993. (c) Zhao, J.; Zhao, Y.; Fu, H. Angew. Chem., Int.
Ed. 2011, 50, 3769. (d) Schmidt, V. A.; Alexanian, E. J. J. Am. Chem.
Soc. 2011, 133, 11402. (e) Giglio, B. C.; Schmidt, V. A.; Alexanian, E. J.
J. Am. Chem. Soc. 2011, 133, 13320.
(13) For selected examples of CꢀB bond formation, see: (a) Mo, F.;
Jiang, Y.; Qiu, D.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2010, 49,
ꢀ
ꢀ
184. (b) Bonet, A.; Gulyas, H.; Fernandez, E. Angew. Chem., Int. Ed.
2010, 49, 5130. (c) Li, H.; Wang, L.; Zhang, Y.; Wang, J. Angew. Chem.,
Int. Ed. 2012, 51, 2943.
B
Org. Lett., Vol. XX, No. XX, XXXX