3
To elucidate the mechanism of the reaction, several
controlled experiments were carried out under optimal conditions.
As showed in scheme 4, the reaction of 1-phenyl-2-propyn-1-ols
and morpholines in the absence of Ag2CO3 failed to yield the
desired product 3aa. And then the reaction applying 1-phenyl-2-
propyn-1-ols as the only substrates was performed under
optimized conditions and 1-phenyl-2-propyn-1-ones (1aʹ) were
given in the yield of 21%, but no product was detected in the
absence of Ag2CO3. Subsequently, the reaction of 1-phenyl-2-
propyn-1-ones (1aʹ) and morpholines was carried out under
optimized conditions or catalyst-free conditions giving the
desired product 3aa in the yield of 88% (scheme 4).
References and notes
1
2
R. F. Abdulla, L. A. Morgan, Synth Commun. 1982, 12, 351.
a) J. V. Greenhill, Chem. Soc. Rev. 1977, 6, 277. b) J. P. Michael, C. B.
Koning, D. Gravestock, G. D. Hosken, A. S. Howard, C. M. Jungmann,
R. W. M. Krause, A. S. Parson, S. C. Pelly, T. V. Stanbury, Pure Appl.
Chem. 1999, 71, 979. c) A. C. Spivey, R. Srikaran, C. M. Diaper, D. J.
Turner, Org. Biomol. Chem. 2003, 1, 1638.
3
4
a) G. Negri, C. Kascheres, A. J. Kascheres, J. Heterocycl. Chem. 2004,
41, 461. b) F. Al-Omran, A. A. El-Khair, J. Heterocycl. Chem. 2005,
42, 307. c) A. Muller, A. Maier, R. Neumann, G. Maas, Eur. J. Org.
Chem. 1998, 63, 1177. d) E. Bejan, Eur. J. Org. Chem. 1998, 63, 2907.
e) J. E. Foster, J. M. Nicholson, R. Butcher, J. P. Stables, I. O.
Edafiogho, A. M. Goodwin, M. C. Henson, C. A. Smith, K. R. Scott,
Bioorg. Med. Chem. 1999, 7, 2415.
a) M. Calle, L. A. Calvo, A. G. Ortega, A. M. Gonzalez-Nogal,
Tetrahedron 2006, 62, 611. b) N. D. Eddington, D. S. Cox, M.
Khurana, N. N. Salama, J. P. Stables, S. J. Harrison, A. Negussie, R. S.
Taylor, U. Q. Tran, J. A. Moore, J. C. Barrow, K. R. Scott, Eur. J. Med.
Chem. 2003, 38, 49. c) M. M. Abdelkhalik, A. M. Eltoukhy, S. M.
Agamy, M. H. Elnagdi, J. Heterocycl. Chem. 2004, 41, 431. d) G. Li,
K. Watson, R. W. Buckheit, Y. Zhang, Org. Lett. 2007, 9, 2043. e) J. D.
White, D. C. Lhle, Org. Lett. 2006, 8, 1081.
5
a) Y. C. Shi, H. J. Cheng, S. H. Zhang, Polyhedron 2008, 27, 3331. b)
M. Pešková, P. Sÿimunek, V. Bertolasi, V. Machác, Organometallics
2006, 25, 2025. c) J. Kim, J. W. H. wang, Y. Kim, M. H. Lee, Y. Han,
Y. Do, J. Organomet. Chem. 2001, 1, 620.
6
7
J. Y. Liu, G. E. Cao, W. Xu, J. Cao, W. L. Wang , Organometal. Chem.
2010, 24, 685.
a) P. G. Baraldi, D. Simoni, S. Manfredini, Synthesis 1983, 902. b) T.
Potesil, J. Chromatogr. 1984, 312, 387. c) E. J. Cone, R. H. Garner, A.
W. Hayes, J. Org. Chem. 1972, 37, 4436. d) D. F. Martin, G. A.
Janusonis, B. B. Martin, J. Am. Chem. Soc. 1961, 87, 73.
M. S. F. Lie Ken Jie, M. M. L. Lau, Lipids 2000, 35, 1135.
X. Q. Yu, L. X. Wang, X. J. Feng, M. Bao, Y. Yamamoto, Chem.
Commun. 2013, 49, 2885.
Scheme 4. The controlled experiments.
Based on the observations of the above experiments and
previous reports,15 a tentative pathway of this reaction was
proposed (scheme 5). In the presence of Ag2CO3, 1-phenyl-2-
propyn-1-ol (1a) transformed into 1-phenyl-2-propyn-1-one (1aʹ)
which reacted with morpholine giving the desired product (E)-1-
phenyl-3-morpholinoprop-2-en-1-one (3aa).16
8
9
10
11
12
S. Ueno, R. Shimizu, R. Kuwano, Angew. Chem. Int. Ed. 2009, 48,
4543.
D. Y. Yu, Y. N. Sum, A. C. C. Ean, M. P. Chin, Y. G. Zhang Angew.
Chem. Int. Ed. 2013, 52, 5125.
K. Xu, Z. L. Zhang, P. Qian, Z. G. Zha, Z. Y. Wang, Chem. Commun.
2015, 51, 11108.
E. Haak, Synlett. 2006, 12, 1847.
13
14
a) E. Haak, Eur. J. Org. Chem. 2007, 2007, 2815. b) David R.
Chisholm, Roy Valentine, Ehmke Pohl, Andrew Whiting, J. Org.
Chem. 2016, 81, 7557. c) Y. M. Kang, Y. J. Cho, S. J. Han, H. Y. Jang,
Org. Lett. 2016, 18, 272.
15
16
T. Ishikawa, T. Mizuta, K. Hagiwara, T. Aikawa, T. Kudo, S. Saito, J.
Org. Chem. 2003, 68, 3702.
a) R. Li, X. M. Wang, Z. B. Wei, C. R. Wu, F. Shi, Org. Lett. 2013, 15,
Scheme 5. The possible pathway of the reaction of 1a and 2a.
In conclusion, a simple and efficient method for the
synthesis of enaminones using propargyl alcohols and amines
was developed. And the reaction proceeded smoothly under mild
conditions in the presence of Ag2CO3 and can be applied to
prepare various enaminones with functional groups. Due to its
simplicity, this protocol may have potential application in
organic synthesis. Further studies of the detailed reaction
mechanism and the potential synthetic applications of this
reaction are currently underway in our laboratory.
17. b) M. Reisser, G. Maas, J. Org. Chem. 2004, 69, 4913. c) Z. W.
Chen, Y. L. Wen, H. Ding, G. T. Luo, M. Ye, L. X. Liu, J. Xue,
Tetrahedron Lett. 2017, 58, 13.
Acknowledgements
We gratefully acknowledge financial support from the
Chinese National Natural Science Foundation (No. 31170320)
and the Startup Foundation for Doctors of Binzhou Medical
University (BY2016KYQD05).
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.****