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Fig. 2 ORTEP drawing of 4c with 30% thermal ellipsoids. Hydrogen
atoms are omitted for clarity. Selected bond lengths [Å]: C2–C3 1.533(6),
C1–N1 1.423(5), C1–N2 1.247(5), C1–N3 1.427(6), C2–N1 1.365(6),
C3–N3 1.366(6), C2–O1 1.199(5), C3–O2 1.211(5), C13–Br1 1.910(4).
the NiPr group on the ring around the CvN double bond
(Fig. 2).
The mechanism for AlMe3-catalyzed formation of acyclic
guanidine A was reported in ref. 16b. As shown in Table 2, one
acyl group in acyl dichloride is attacked by a lone electron pair
of the CvN double bond in A, leading to the formation of B by
the elimination of Et3N·HCl. Then B undergoes intramolecularly
nucleophilic attack of the lone electron pair of the CvN double
bond towards the other acyl group to provide the unsymmetric
cyclic guanidine 4 with the second elimination of Et3N·HCl.
7 (a) D. C. D. Butler, G. A. Inman and H. Alper, J. Org. Chem., 2000, 65,
5887; (b) J.-O. Baeg, C. Bensimon and H. Alper, J. Am. Chem. Soc.,
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J. Streuff, C. H. Hövelmann and A. Núñez, Angew. Chem., Int. Ed.,
2007, 46, 7125.
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(b) D. S. Ermolat’ev, J. B. Bariwal, H. P. L. Steenackers, S. C. J. De
Keersmaecker and E. V. Van der Eychen, Angew. Chem., Int. Ed., 2010,
49, 9465; (c) X. Wang, S. Dixon, N. Yao, M. J. Kurth and K. S. Lam,
Tetrahedron Lett., 2005, 46, 5747.
10 A two-step three-component synthesis from amines, carbodiimides and
acyl dichlorides forming cyclic guanidines was mentioned, in which only
three examples were characterized by melting point and elemental analy-
sis without any NMR data, see: G. Zinner and R. Vollrath, Chem. Ber.,
1970, 103, 766.
11 Selected reviews of carbodiimide chemistry: (a) M. Nishiura and
Z. Hou, Bull. Chem. Soc. Jpn., 2010, 83, 595; (b) T. Suzuki,
W.-X. Zhang, M. Nishiura and Z. Hou, J. Synth. Org. Chem., Jpn., 2009,
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Conclusions
In summary, the metal-free one-pot sequential coupling of
various amines, carbodiimides and acyl dichlorides has been
achieved for the first time, which provides a simple and general
route to cyclic di-oxoguanidines via an unexpected 2,2-dichloro-
imidazolidindione intermediate. Acyl dichlorides serve not only
as the third component but also as the activator of carbodiimides.
This result is quite different from the AlMe3-catalyzed sequential
reaction from the same substrates leading to the isomeric for-
mation of cyclic di-oxoguanidines. Further research on appli-
cation of these di-oxoguanidines is ongoing.
Acknowledgements
12 Selected examples of addition of nucleophiles to carbodiimides:
(a) Y. Wang, W.-X. Zhang, Z. Wang and Z. Xi, Angew. Chem., Int. Ed.,
2011, 50, 8122; (b) D. Li, Y. Wang, W.-X. Zhang, S. Zhang, J. Guang
and Z. Xi, Organometallics, 2011, 30, 5278; (c) W.-X. Zhang,
M. Nishiura, T. Mashiko and Z. Hou, Chem.–Eur. J., 2008, 14, 2167;
(d) X. Xu, J. Gao, D. Cheng, J. Li, G. Qiang and H. Guo, Adv. Synth.
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Chem. Soc., 2005, 127, 16788.
13 Selected examples of cycloaddition of carbodiimides: (a) F. Wang,
S. Cai, Q. Liao and C. Xi, J. Org. Chem., 2011, 76, 3174; (b) G. Shen
and W. Bao, Adv. Synth. Catal., 2010, 352, 981; (c) R. T. Yu and
T. Rovis, J. Am. Chem. Soc., 2008, 130, 3262; (d) A. Volonterio and
M. Zanda, Org. Lett., 2007, 9, 841; (e) T. Saito, K. Sugizaki, T. Otani
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H. Guo and J. Yan, Org. Lett., 2007, 9, 1585; (g) H. Li, J. L. Petersen
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D. Rodríguez and J.-P. Steffen, Angew. Chem., Int. Ed., 2000, 39, 2152.
14 For examples of rearrangement of carbodiimides, see: (a) Y. Wang,
Y. Chi, W.-X. Zhang and Z. Xi, J. Am. Chem. Soc., 2012, 134, 2926;
(b) C. Wentrup, Acc. Chem. Res., 2011, 44, 393; (c) D. Kvaskoff,
M. Vosswinkel and C. Wentrup, J. Am. Chem. Soc., 2011, 133, 5413;
This work was supported by the Natural Science Foundation of
China, and the “973” program from National Basic Research
Program of China (2011CB808601).
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