L. G. Quan, J. K. Cha / Tetrahedron Letters 42 (2001) 8567–8569
8569
O
H
Cl2Ti(OPh)2
OH
c-C6H11MgCl
OH
H
+
19
18
17
solvent
temperature
yields
85%
THF
0 °C
-
THF
rt
36%
30%
15%
26%
-
55%
50%
49%
69%
74%
THF
50 °C
toluene
ether
dioxane
rt
rt
rt
Scheme 3.
There are common limitations in the stoichiometric/cat-
alytic titanocene-mediated cyclization of d,o-enones and
the present procedure employing titanium(IV) phenox-
ide—a Grignard reagent: the formation of six-mem-
bered rings leading to the cyclohexanols failed in both
methods. In addition, both procedures were intolerant
of additional substitution on the mono-substituted
olefins.
Chem. Rev. 1996, 96, 635; (h) Montgomery, J. Acc. Chem.
Res. 2000, 33, 467.
2. Hewlett, D. F.; Whitby, R. J. J. Chem. Soc., Chem.
Commun. 1990, 1684.
3. (a) Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc.
1995, 117, 6785; (b) Crowe, W. E.; Rachita, M. J. J. Am.
Chem. Soc. 1995, 117, 6787; (c) Kablaoui, N. M.; Buch-
wald, S. L. J. Am. Chem. Soc. 1996, 118, 3182. See also:
(d) Mandal, S. K.; Amin, S. R.; Crowe, W. E. J. Am.
Chem. Soc. 2001, 123, 6457.
4. For recent reviews, see: (a) Kulinkovich, O. G.; de Mei-
jere, A. Chem. Rev. 2000, 100, 2789; (b) Sato, F.; Urabe,
H.; Okamoto, S. Chem. Rev. 2000, 100, 2835; (c) Sato, F.;
Urabe, H.; Okamoto, S. Synlett 2000, 753.
5. (a) Kasatkin, A.; Sato, F. Tetrahedron Lett. 1995, 36,
6079; (b) Lee, J.; Kang, C. H.; Kim, H.; Cha, J. K. J.
Am. Chem. Soc. 1996, 118, 291; (c) Lee, J.; Kim, H.; Cha,
J. K. J. Am. Chem. Soc. 1996, 118, 4198.
6. Prepared by palladium-mediated coupling of commer-
cially available 4-pentenylzinc bromide with benzoyl chlo-
ride: Negishi, E.-i.; Bagheri, V.; Chatterjee, S.; Luo,
F.-T.; Miller, J. A.; Stoll, A. T. Tetrahedron Lett. 1983,
24, 5181.
In summary, the dichlorotitanium diphenoxide–cyclo-
hexylmagnesium chloride-mediated cyclization of d,o-
enones was found to closely parallel the stoichiometric
and catalytic titanocene-mediated processes for the for-
mation of cis-substituted cyclopentanols, while a differ-
ent pathway was predominant for d,o-enals. Additional
comparison studies of the ‘titanocene’- and ‘dialkoxy-
titanium(II)’-mediated reactions would be of mechanis-
tic and synthetic interest.10
Acknowledgements
7. (a) For previous uses of titanium aryloxides, see: Thorn,
M. G.; Hill, J. E.; Waratuke, S. A.; Johnson, E. S.;
Fanwick, P. E.; Rothwell, I. P. J. Am. Chem. Soc. 1997,
119, 8630 and references cited therein; (b) cf. Seebach, D.
In Modern Synthetic Methods; Scheffold, R., Ed.; Verlag:
Aarau, Switzerland, 1983; Vol. 3, p. 223.
8. (a) Lee, J.; Kim, Y. G.; Bae, J. G.; Cha, J. K. J. Org.
Chem. 1996, 61, 4878; (b) Lee, J.; Cha, J. K. J. Org.
Chem. 1997, 62, 1584; (c) Lee, J.; Ha, J. D.; Cha, J. K. J.
Am. Chem. Soc. 1997, 119, 8127.
We thank the National Science Foundation (CHE98-
13975) for financial support.
References
1. For general reviews, see: (a) Negishi, E.-i. Acc. Chem.
Res. 1987, 20, 65; (b) Negishi, E.-i.; Takahashi, T. Syn-
thesis 1988, 1; (c) Buchwald, S. L.; Nielsen, R. B. Chem.
Rev. 1988, 88, 1047; (d) Broene, R. D.; Buchwald, S. L.
Science 1993, 261, 1696; (e) Takahashi, T. J. Synth. Org.
Jpn. 1993, 51, 1145; (f) Buchwald, S. L.; Broene, R. D. In
Comprehensive Organometallic Chemistry II; Hegedus, L.
S., Ed.; Pergamon: Oxford, 1995; Vol. 12, Chapter 7.4;
(g) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J.
9. Reetz, M. T. Organotitanium Reagents in Organic Synthe-
sis; Springer-Verlag: New York, 1986.
10. In contrast to the successful Kulinkovich cyclopropana-
tion reactions by employing titanium alkoxides, the use
of ‘titanocene’ or ‘zirconocene’ in the cyclopropanation
reaction of esters gave the cyclopropanols in very low
yields: Lee, J.; Cha, J. K. Unpublished results.