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J . Org. Chem. 2001, 66, 2990-2994
Gen er a tion of Rea ctive Low -Va len t Tita n iu m Sp ecies Usin g
Μeta l-Αr en es a s Efficien t Or ga n ic Red u cta n ts for TiCl3:
Ap p lica tion s to Or ga n ic Syn th esis
Shyam Rele, Sanjay Talukdar, Asoke Banerji, and Subrata Chattopadhyay*
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
schatt@apsara.barc.ernet.in
Received November 8, 2000
A comprehensive study on the use of metal-arene systems as organic reductants for TiCl3 has
resulted in an efficient method for the generation of highly reactive low-valent titanium (LVT)
reagents. The activated titanium species could be prepared by refluxing a mixture of substoichio-
metric amounts of arenes, TiCl3, and Li/Mg in THF or DME. Among the LVT reagents screened,
TiCl3-Li-naphthalene-THF (reagent I) was the best for coupling of carbonyls to olefins. The
reagent could carry out the McMurry olefination of both aromatic and aliphatic substrates at a
lower temperature and in a much reduced time as compared to the conventional procedures. Subtle
changes in the method of preparation of the LVT reagents influenced the stereoisomeric ratio of
the olefins. The reagent was also useful for the synthesis of O- and N- heterocycles and vicinal
diamines via intramolecular carbonyl coupling and reductive duplication of imines, respectively.
In tr od u ction
nations as potential organic reductants in organometallic
electron transfer processes prompted us to explore their
utility as efficient organic reductants for the generation
of the activated LVT reagents.
Due to the unique features of high oxophilicity and
reducing power, low valent titanium (LVT) reagents have
gained widespread acceptance in organic synthesis.1 In
particular, the remarkable scope of LVT reagents to effect
reductive coupling of carbonyls (McMurry reaction) has
resulted in a variety of applications such as synthesis of
strained olefins,1 heterocyclic compounds,1c,2 and macro-
cyclic ring systems1,3 to complex natural products includ-
ing paclitaxel.4
For this purpose, a lexicon of reactive LVT reagents
have been developed by reducing titanium salts with a
variety of inorganic reducing agents5 such as Zn, Mg, Li,
C8K, Zn-Cu, LAH, etc. In contrast, the soluble organic
reductants have received scarce attention6 for this pur-
pose. Recent reports7 on the use of metal-arene combi-
Earlier, it has been shown by us8-10 and others11 that
the reducing ability of LVT-based reagents can be
rationally tuned by the simple addition of cosolvents,8
external ligands,9 and chemical redox agents.10 We envis-
aged that the use of metal-arenes for reducing Ti salts
might produce the LVT species which would be coordi-
nated with the arenes. The coordination, in turn, might
activate the LVT reagents by augmenting the electron
density on the LVT species and also possibly by increas-
ing their solubility in an organic medium. In this context,
it is worth noting that another SET agent, the low-valent
Sm species, scores over the LVT species in terms of their
reactivity. This may be partly attributed12 to the solubil-
ity of the Sm species in a variety of polar solvents. The
LVT-based reagents, on the other hand, are insoluble in
organic solvents, which affects their reactivity neces-
sitating prolonged heating in most of the LVT-mediated
reactions including McMurry olefination. In addition,
* To whom correspondence should be addressed. Fax: 91-22-550-
5151.
(1) (a) McMurry, J . E. Chem. Rev. 1989, 89, 1513. (b) Lenoir, D.
Synthesis 1989, 883. (c) Furstner, A.; Bogdanovic, B. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2442. (d) Dushin, R. G. In Comprehensive
Organometallic Chemistry II; Hegedus, L. S., Ed.; Pergamon: Oxford,
1995; Vol. 12, p 1071.
(2) (a) Nayak, S. K.; Banerji, A. J . Chem. Soc., Chem. Comm. 1990,
150. (b) Furstner, A.; J umbam, D. N. Tetrahedron 1992, 48, 5991. (c)
Furstner, A.; Ernst, A.; Krause, H.; Ptock, A. Tetrahedron, 1996, 52,
7328. (d) Furstner, A.; Hupperts, A. J . Am. Chem. Soc. 1995, 117, 4468.
(e) Furstner, A.; Hupperts, A.; Ptock, A.; J anssen, E. J . Org. Chem.
1994, 59, 5215.
(3) (a) Furstner, A.; Seidel, G. Synthesis 1995, 63. (b) Furstner, A.;
Seidel, G.; Kopiske, C.; Kruger, C.; Mynott, R. Liebigs Ann. 1996, 655.
(4) (a) Nicolaou, K. C.; Yang, Z.; Liu, J . J .; Ueno, H.; Nantermet, P.
G.; Guy, R. K.; Claiborne, C. F.; Renaud, J .; Couladouros, E. A.;
Paulvannnan, K.; Sorensen, E. J . Nature 1994, 367, 630. (b) Nicolaou,
K. C.; Liu, J . J .; Yang, Z.; Ueno, H.; Sorensen, E. J .; Claiborne, C. F.;
Guy, R. K.; Hwang, C. K.; Nakada, M.; Nantermet, P. G. J . Am. Chem.
Soc. 1995, 117, 634. (c) Nicolaou, K. C.; Yang, Z.; Liu, J . J .; Nantermet,
P. G.; Claiborne, C. F.; Renaud, J .; Guy, R. K.; Shibayama, K. J . Am.
Chem. Soc. 1995, 117, 645.
(6) There is only one report on the use of Na-naphthalenide in the
preparation of LVT reagent for annulation reactions. However, no
systematic study has been done, see: Clive, D. L. J .; Zhang, C.;
Keshava Murthy, K. S.; Hayward, W. D.; Diagneault, S. J . Org. Chem.
1991, 56, 6447.
(7) (a) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877 and
references therein. (b) Lai, Y.-H. Synthesis 1981, 585 and references
therein. (c) Rieke, R.; Kim, S.-H. J . Org. Chem. 1998, 63, 5235. (d)
Kahn, B. E.; Rieke, R. D. Organometallics 1988, 7, 463.
(8) (a) Nayak, S. K.; Banerji, A. J . Org. Chem. 1991, 56, 1940. (b)
Banerji, A.; Nayak, S. K. J . Chem. Soc., Chem Commun. 1991, 1432.
(9) (a) Balu, N.; Nayak, S. K.; Banerji, A. J . Am. Chem. Soc. 1996,
118, 5932. (b) Talukdar, S.; Nayak, S. K.; Banerji, A. Full. Sci. Technol.
1995, 3, 327. (c) Nayak, S. K.; Kadam, S.; Talukdar, S.; Banerji, A. J .
Indian Inst. Sci. 1994, 74, 401.
(10) Talukdar, S.; Nayak, S. K.; Banerji, A. J . Org. Chem. 1998, 63,
4925.
(11) (a) Lipski, T. A.; Hilfiker, M. A.; Nelson, S. G. J . Org. Chem.
1997, 62, 4566. (b) Mukaiyama, T.; Kagayama, A.; Shiina, I. Chem.
Lett. 1998, 1107. (c) Ganauser, A.; Pierobon, M.; Bluhm, H. Angew.
Chem., Int. Ed. Engl. 1998, 37, 101.
(5) For different recipes for the generation of activated LVT re-
agents, see: (a) Cintas, P. Activated Metals in Organic Synthesis; CRC
Press: Boca Raton, 1996. (b) Fu¨rstner, A. Active Metals - Preparation,
Characterization, Applications. VCH: Weinheim, 1996. (c) Rieke, R.;
Bales, S. F. J . Am. Chem. Soc. 1974, 96, 1775.
10.1021/jo001586a CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/12/2001