a broad spectrum of tertiary amines and sulfonyl azides
employing a CuCl/CCl4 system.
Table 1. Synthesis of 3a under Various Conditionsa
Carbon tetrachloride was frequently used as a solvent.
Except the Appel reaction which involved PPh3/CCl4-
promoted the transformation of an alcohol into an alkyl
chloride,9 carbon tetrachloride was rarely used as a reactant
since it is normally very stable.10 Due to the inherent
similarity in tertiary phosphine and tertiary amine in several
aspects, we speculate that the chemical interaction or reaction
might occur between CCl4 and tertiary amine. We first
examined the reaction between 10 mmol of triethylamine
and CCl4 each. As expected, a considerable amount of white
water-soluble solid identified as Et3N·HCl was generated after
several hours under room temperature and chloroform could
be detected by GC-MS from the reaction system (see the
Supporting Information). According to these results, we guess
N,N-diethylethenamine may be produced. Based on our and
others’ previous works,7,8 1 mmol of TsN3, with the
expectation of capturing the in situ formed N,N-diethyleth-
enamine, was added to the mixture of 2 mmol of triethy-
lamine and 4 mL of CCl4. To our delight, sulfonyl amidine
3a was indeed obtained albeit in 53% yield even in the
absence of any catalyst. This prompted us to undertake
further experiments to find effective conditions for the
synthesis of the sulfonyl amidine derivatives.
entry
solvent
THF
cat.
time (h) yieldb (%)
1
2
3
4
5
6
36
36
15
36
36
36
36
36
10
13
14
14
15
13
12
15
41
38
51
48
18
34
38
63
71
72
59
47
54
69
52
62
CH3CN
CH2Cl2
CHCl3
diethyl ether
toluene
dioxane
CCl4
CCl4
CCl4
CCl4
CCl4
7
8c
9c
CuCl
10c
11c
12c
13c
14c
15c
16c
Cu(NO3)2·3H2O
CuBr
CuI
Cu
CCl4
CCl4
CCl4
CCl4
CuSO4
Cu(OAc)2
CuBr2
a p-Toluenesulfonyl azide (1 mmol), triethylamine (3 mmol), and CCl4
(1.3 mmol) in solvent (4 mL) under room temperature in the presence/
absence of 0.2-0.3% equiv of copper catalyst until otherwise noted.
b Isolated yields based on TsN3. c CCl4 (4 mL) was used as the solvent and
reactant.
The optimization of the reaction conditions for the
formation of 3a was done by screening several solvents and
copper catalysts. The results are summarized in Table 1. As
can be seen, even in the absence of a catalyst, the reaction
could proceed smoothly in all of the solvents examined and
the desired product can be obtained in low to moderate yields
at room temperature in 15-36 h (entries 1-7). In compari-
son, the result obtained by use of CCl4 both as the solvent
and reagent was better (entry 8). Interestingly, it was found
that the reaction time can be shortened by adding a catalytic
amount of copper sources in CCl4. Several copper catalysts
such as CuCl, CuBr, CuI, CuSO4, Cu(OAc)2, CuBr2,
Cu(NO3)2·3H2O, and copper powder were tested (entries
9-16). CuCl and Cu(NO3)2·3H2O gave the best results. Thus,
the standard reaction condition was established as using
0.2-0.3 mol % of CuCl relative to sulfonyl azides, 3 equiv
of triethylamine, and CCl4 as both the solvent and reactant.
Table 2. CuCl-Catalyzed Synthesis of Sulfonyl Amidine
Derivatives from Acylic Tertiary amines and Sulfonyl Azidesa
entry
R1
R2; R3; R4
yieldb (%)
1
2
3
4
5
6
4-CH3C6H4 (1a)
4-CH3OC6H4 (1b)
Ph (1c)
4-ClC6H4 (1d)
3-NO2C6H4 (1e)
4-PriC6H4 (1f)
H; Et; Et (2a)
H; Et; Et (2a)
H; Et; Et (2a)
H; Et; Et (2a)
H; Et; Et (2a)
H; Et; Et (2a)
3a; 71
3b; 66
3c; 73
3d; 62
3e; 67
3f; 74
7
8
9
4-CH3C6H4CH2 (1 g) H; Et; Et (2a)
2-naphthyl (1 h) H; Et; Et (2a)
2,4,6-(CH3)3C6H2 (1i) H; Et; Et (2a)
3g; 61
3h; 65
3i; 61
(6) (a) Li, Z.; Yu, R.; Li, H. Angew. Chem., Int. Ed. 2008, 47, 7497. (b)
Li, Z.; Li, H.; Guo, X.; Cao, L.; Yu, R.; Li, H.; Pan, S. Org. Lett. 2008, 10,
803. (c) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130,
9254. (d) Cheng, D.; Bao, W. J. Org. Chem. 2008, 73, 6881. (e) Cheng,
D.; Bao, W. AdV. Synth. Catal. 2008, 350, 1263. (f) Murahashi, S.-I.; Nakae,
T.; Terai, H.; Komiya, N. J. Am. Chem. Soc. 2008, 130, 11005. (g) Niu,
M.; Yin, Z.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2008, 73, 3961. (h)
Liu, X.; Zhang, Y.; Wang, L.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem.
2008, 73, 6207. (i) Zhang, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Org. Lett. 2007,
9, 3813. (j) Li, Z.; Bohle, D. S.; Li, C.-J. Proc. Natl. Acad. Sci. U.S.A
2006, 103, 8928. (k) Doye, S. Angew. Chem., Int. Ed. 2001, 40, 3351. (l)
Murahashi, S.-I. Pure Appl. Chem. 1992, 64, 403.
10
11c
12d
13
14
15e
CH3(CH2)3 (1j)
H; Et; Et (2a)
Et; Bu; Bu (2b)
H; Me; Et (2c)
H; Pri; Pri (2d)
H; Et; c-hexyl (2e) 3n; 65
H; Et; Ph (2f) 3o; 34
3j; 84
1a
1a
1a
1a
1a
3k; 66
3l:3a; 46:15
3m; 76
a Sulfonyl azide (1 mmol), tertiary amine (3 mmol), CuCl (0.2-0.3%
mmol), CCl4 (4 mL) under room temperature until otherwise noted (see
the Supporting Information). b Isolated yields based on the sulfonyl azides.
c 2b (4 mmol), 70 °C. d 2c (6 mmol). e 70 °C, 30 h, K2CO3 (1 mmol).
(7) (a) Xu, X.; Li, X. Org. Lett. 2009, 11, 1027. (b) Xu, X.; Li, X.; Ma,
L.; Ye, N.; Weng, B. J. Am. Chem. Soc. 2008, 130, 14048. (c) Liu, N.;
Tang, B.; Chen, Y.; He, L. Eur. J. Org. Chem. 2009, 2059.
(8) Wang, S.; Wang, Z.; Zheng, X. Chem. Commun. 2009, 7372.
(9) Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
(10) (a) Falck, J. R.; Li, D. R.; Bejot, R.; Mioskowski, C. Tetrahedron
Lett. 2006, 47, 5111. (b) Ochiai, M.; Sueda, T. Tetrahedron Lett. 2004, 45,
3557. (c) Tanaka, H.; Yamashita, S.; Yamanoue, M.; Torii, S. J. Org. Chem.
1989, 54, 444.
As shown in Table 2, various substituted sulfonyl azides
and acylic tertiary amines were investigated to expand the
scope and generality of this reaction system. Aromatic
898
Org. Lett., Vol. 12, No. 5, 2010