A. J. Clark et al. / Tetrahedron Letters 42 (2001) 1999–2001
2001
Table 1.
(compared to their alkene analogues) is not surprising
and often characteristic of cyclisation onto alkynes.2,3
References
1. Bowman, W. R.; Bridge, C. F.; Brookes, P. J. Chem.
Soc., Perkin Trans. 1 2000, 1.
Substrate
Ligand
Solvent
15:16a
15 (E:Z)
2. (a) Giese, B.; Kopping, B.; Go¨bel, T.; Dickhaut, J.;
Thoma, G.; Kulicke, K. J.; Trach, F. Org. React. 1996,
48, 301; (b) Curran, D. P.; Sisko, J.; Yeske, P. E.; Liu, H.
Pure Appl. Chem. 1993, 65, 1153; (c) Jasperse, C. P.;
Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237.
3. Choi, J.-K.; Hart, D. J. Tetrahedron 1985, 41, 3959.
4. (a) Curran, D. P.; Chen, C.-T. J. Org. Chem. 1989, 54,
3140; (b) Curran, D. P.; Chen, M.-H.; Spletzer, E.; Churl,
M. S.; Chang, C.-T. J. Am. Chem. Soc. 1989, 111, 1,
8872.
14a
14a
14a
14b
2
2
17
2
CH2Cl2
C6H6
THF
25:1 (96)
74:1 (94)
1:20 (95)
10:1 (96)
2:5
1:4
1:4
1:2
CH2Cl2
a Percentage yield of combined products in brackets.
5. Curran, D. P.; Chen, M.-H.; Kim, D. J. Am. Chem. Soc.
1989, 111, 6265.
6. (a) Nagashima, H.; Ozaki, N.; Ishii, M.; Seki, K.;
Washiyama, M.; Itoh, K. J. Org. Chem. 1993, 58, 464; (b)
Iwamatsu, S.-I.; Matsubara, K.; Nagashima, H. J. Org.
Chem. 1999, 64, 9625; (c) Iwamatsu, S.-I.; Kondo, H.;
Matsubara, K.; Nagashima, N. Tetrahedron 1999, 55,
1687.
Scheme 6.
7. (a) Clark, A. J.; Filik, R. P.; Thomas, G. H. Tetrahedron
Lett. 1999, 40, 4885; (b) Clark, A. J.; Dell, C. P.; Ellard,
J. M.; Hunt, N. A.; McDonagh, J. P. Tetrahedron Lett.
1999, 40, 8619; (c) Clark, A. J.; Duncalf, D. J.; Filik, R.
P.; Haddleton, D. M.; Thomas, G. H.; Wongtap, H.
Tetrahedron Lett. 1999, 40, 3807; (d) Clark, A. J.; Filik,
R. P.; Haddleton, D. M.; Radique, A.; Sanders, C. J.;
Thomas, G. H.; Smith, M. E. J. Org. Chem. 1999, 64,
8954.
Scheme 7.
8. (a) Forti, L.; Ghelfi, F.; Pagnoni, U. M. Tetrahedron
Lett. 1996, 37, 2077; (b) Forti, L.; Ghelfi, F.; Libertini,
E.; Pagnoni, U. M.; Soragni, E. Tetrahedron 1997, 53,
17761; (c) Ghelfi, F.; Bellesia, F.; Forti, L.; Ghirardini,
G.; Grandi, R.; Libertini, E.; Montemaggi, M. C.;
Pagnoni, U. M.; Pinetti, A.; DeBuyck, D.; Parsons, A. F.
Tetrahedron 1999, 55, 1687.
9. Udding, J. H.; Tuijp, K. C. J. M.; Vanzanden, M. N. A.;
Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59,
1993.
the intermediate vinyl radical is less reactive towards
hydrogen abstraction than those derived from the cor-
responding reactions of terminal alkynes 14a–b
(Scheme 6). Finally, we investigated the reaction of the
deactivated 2-bromo-precursor 21. Reaction with 30
mol% CuBr(2) at room temperature did not lead to any
observed reaction. Instead stirring with the more acti-
vated ligand system CuBr(17) was required. Even with
this more activated catalyst system the reaction only
proceeded to 50% conversion after 48 h giving a 1:1
mixture of the two products 22 and 23 in 35% isolated
yield (70% based on recovered starting material)
(Scheme 7).
10. Hay, A. S. J. Org. Chem. 1962, 27, 3320. This reaction
(Eglington reaction) has been reviewed, see: Patai, S. In
The Chemistry of Functional Groups, Supplement C, Part.
1; Wiley: New York, 1983, p. 529.
11. Typical procedure is as follows: To a mixture of 14a (0.1
g, 0.28 mmol) and CuBr (0.012 g, 0.08 mmol) under N2
was added a solution of 2 (0.015 g, 0.08 mmol) in dry
CH2Cl2 (2.3 ml). The resulting solution was stirred at
ambient temperature for 24 h. The crude mixture was
passed through a short silica plug eluting with CH2Cl2.
After evaporation of the solvent and chromatography
15a and 16a were isolated in a combined 96% yield.
In conclusion, we have demonstrated that a range of
haloacetamides may undergo 5-exo atom transfer radi-
cal cyclisations onto alkynes mediated by CuX(2) or
CuX(17) complexes at room temperature. No cyclisa-
tion products arising from 6-endo cyclisation were
observed in this study for either the terminal or disub-
stituted alkynes. The relatively slow rate of conversion
.