J. Am. Chem. Soc. 1999, 121, 7941-7942
7941
Highly Regioselective Alkyne Cyclotrimerization
Catalyzed by Titanium Complexes Supported by
Proximally Bridged p-tert-Butylcalix[4]arene Ligands
Oleg V. Ozerov, Folami T. Ladipo,* and Brian O. Patrick
Department of Chemistry, UniVersity of Kentucky
Lexington, Kentucky 40506-0055
ReceiVed March 8, 1999
Transition metal-catalyzed cycloaddition is involved in many
of the most useful synthetic methods for assembling complex
organic molecules.1 Many transition metals catalyze the cyclo-
trimerization of alkynes to yield substituted benzenes.1,2 However,
the reaction rarely proceeds with high regioselectivity.1d Highly
regiocontrolled synthesis of arenes is very attractive since arenes
are important building blocks in organic synthesis. Our interest
in the influence of ancillary ligands on organic transformations
mediated by the group 4 metals led us to synthesize titanium
complexes supported by a 1,2-alternate, dimethylsilyl-bridged
p-tert-butylcalix[4]arene (DMSC) ligand. Whereas alkoxides have
been effectively used as ancillary ligands in early transition metal
organometallic chemistry,3 the application of calixarenes as ancil-
lary ligands in organotransition metal chemistry is relatively
unexplored.4 Herein, we describe highly regioselective, catalytic
cyclotrimerization of terminal alkynes by DMSC-based titanium
complexes.
Figure 1. Molecular structure of 1, showing the atom labeling scheme.
titanium center (Figure 1).7,8 The calix[4]arene ligand clearly
imposes different stereochemical environments at the two titanium-
bound chlorides. That is, the steric environment around the endo
chloride [Cl(1a), located inside the calix[4]arene cavity, above
the centers of two aromatic rings] is more crowded than that
around the exo chloride [Cl(2a)]. The solid-state structure of 1 is
maintained in solution, as evidenced by the presence of two
1
inequivalent SiMe2 group methyls in both the H and 13C NMR
spectra.6 The endo Me is strongly shielded compared to the exo
Me, most likely due to ring current effect.5,9
At 80 °C, in C6D6, and in the presence of excess sodium, 1
catalyzed the cyclotrimerization of terminal acetylenes (HCtCR;
R ) Ph, p-C6H4Me, or SiMe3) to 1,2,4-trisubstituted benzenes
with excellent regioselectivity (g97%) and in excellent yield
(Table 1, entries 1-3). 1H and 13C NMR and GC-MS analysis of
the reaction mixtures showed that no acyclic oligomers were
5
The reaction of (DMSC)H2 with TiCl4 furnished [(DMSC)-
TiCl2] (1) in excellent yield, as an air- and moisture-sensitive
orange solid6 (eq 1). An X-ray crystallographic study of 1
1
present. H and 13C NMR revealed induction periods of 20-40
min before any cyclotrimerization product could be detected.
Presumably, the induction period is required to produce NaCt
CR (R ) Ph, p-C6H4Me, or SiMe3) and to allow it to react with
1 to generate the corresponding bis(alkynyl)Ti(IV) species
[(DMSC)Ti(CtCR)2].10 Reductive elimination11 of RCtC-Ct
CR would give a putative Ti(II) intermediate which oxidatively
couples two alkyne molecules to yield titanacyclopentadiene
species (Scheme 1); metallacyclopentadiene intermediates have
been implicated in alkyne cyclotrimerization reactions.2c,f,12-15 The
rate of formation of NaCtCR evidently depends on the amount
established that the calix[4]arene ligand exists in 1,2-alternate
conformation and that a tetrahedral environment exists about the
(1) See, for example: (a) Ojima, I.; Tzamarioudaki, M.; Zhaoyang, L.;
Donovan, R. J. Chem. ReV. 1996, 96, 635. (b) Negishi, E. In ComprehensiVe
Organic Synthesis; Trost, B. M., Ed.; Permagon: Oxford, 1991; Vol. 5, pp
1163-1184. (c) Tamao, K.; Kobayashi, K.; Ito, Y. Synlett 1992, 539. (d)
Schore, N. E. Chem. ReV. 1988, 88, 1081. (e) Trost, B. M. Angew. Chem.,
Int. Ed. Engl. 1986, 25, 1.
(2) See, for example: (a) McAllister, D. R.; Bercaw, J. E.; Bergman, R.
G. J. Am. Chem. Soc. 1977, 99, 1666. (b) Volhardt, K. P. C. Angew. Chem.,
Int. Ed. Engl. 1984, 23, 539. (c) Strickler, J. R.; Bruck, M. A.; Wigley, D. E.
J. Am. Chem. Soc. 1990, 112, 2814. (d) Heeres, H. J.; Heeres, A.; Teuben, J.
H. Organometallics 1990, 9, 1508. (e) Hill, J. E.; Fanwick, P. E.; Rothwell,
I. P. Organometallics, 1990, 9, 2211. (f) Smith, D. P.; Strickler, J. R.; Gray,
S. D.; Bruck, M. A.; Holmes, R. S.; Wigley, D. E. Organometallics 1992,
11, 1275. (g) Hill, J. E.; Balaich, G.; Fanwick, P. E.; Rothwell, I. P. Organo-
metallics 1993, 12, 2911. (h) van der Linden, A.; Schaverien, C. J.; Meijboom,
N.; Ganter, C.; Orpen, A. G. J. Am. Chem. Soc. 1995, 117, 3008. (i) Sigman,
M. S.; Fatland, A. W.; Eaton, B. E. J. Am. Chem. Soc. 1998, 120, 5130.
(3) See, for example: (a) Johnson, E. S.; Balaich, G. J.; Fanwick, P. E.;
Rothwell, I. P. J. Am. Chem. Soc. 1997, 119, 11086. (b) Bonanno, J. B.;
Lobkovsky, E. B.; Wolczanski, P. T. J. Am. Chem. Soc. 1994, 116, 11159.
(c) Miller, R. L.; Toreki, R.; Lapointe, R. E.; Wolczanski, P. T.; Van Duyne,
G.; Roe, D. C. J. Am. Chem. Soc. 1993, 115, 5570. (d) Balaich, G. J.; Hill, J.
E.; Waratuke, S. A.; Fanwick, P. E.; Rothwell, I. P. Organometallics 1995,
14, 4, 656. (e) Arney, D. J.; Wexler, P. A.; Wigley, D. E. Organometallics
1990, 9, 1282. (f) Chisholm, M. H.; Rothwell, I. P. In ComprehensiVe
Organometallic Chemistry; Wilkinson, G., Gillard, R. D., McCleverty, J. A.,
Eds.; Permagon: Oxford, 1988; Vol. 2, Chapter 15.3.
(6) Anal. Calcd for C46H58Cl2O4SiTi (1): C, 67.23; H, 7.11; Cl, 8.63.
Found: C, 67.39; H, 7.37; Cl, 8.73. 1H NMR (C6D6) δ 7.17 (br, 4H, arom
CH), 7.07 (d, J ) 2 Hz, 2H, arom CH), 6.93 (d, 2H, arom CH), 4.50 (d, J )
14.3 Hz, 1H, calix-CH2), 4.46 (d, J ) 14.3 Hz, 1H, calix-CH2), 3.89 (s, 4H,
calix-CH2), 3.39 (d, J ) 14.3 Hz, 1H, calix-CH2), 3.26 (d, J ) 14.3 Hz, 1H,
calix-CH2), 1.39 (s, 18H, t-Bu), 1.23 (s, 18H, t-Bu), 0.32 (s, 3H, exo-SiCH3),
-1.46 (s, 3H, endo-SiCH3). Full characterization data are available as
Supporting Information.
(7) Crystal data: space group, monoclinic C2/c; Z ) 4, a ) 20.750(1) Å,
b ) 17.0434(9) Å, c ) 17.1877(9) Å, â ) 124.79(1)°, V ) 4991.9(4) Å3,
R(F g 4σ(F)) ) 0.123, GOF ) 1.19. Data for 1 were collected at 173 K on
a Nonius Kappa CCD diffractometer. The calixarene moiety resides on an
inversion center, although the moiety itself does not possess an inversion center.
Thus, the structure was modeled with Si1 and Ti1 occupying the same position
with 50% occupancies and equivalent thermal parameters. Two large peaks
roughly 2.2 Å from Ti1 were labeled as Cl1 and Cl2 and given 50%
occupancies, which subsequently led to the discovery of two smaller peaks
roughly 1.8 Å from Si1, which were labeled C23 and C24, respectively. Full
structural details are available as Supporting Information.
(8) Selected interatomic distances (Å): Ti1-Cl1 ) 2.243(9), Ti1-Cl2 )
2.198(6), Ti1-O1 ) 1.712(4), Ti1-O2 ) 1.708(5). Selected bond angles
(deg): Cl1-Ti1-Cl2 ) 106.0(3), Cl1-Ti1-O1 ) 110.4(3), Cl1-Ti1-O2
) 111.8(3), Cl2-Ti1-O1 ) 110.7(2), Cl2-Ti1-O2 ) 111.6(3), O1-Ti1
-O2 ) 106.4(2).
(9) Gunther, H. NMR Spectroscopy: An Introduction; Wiley: New York,
1980; pp 77-86.
(10) Under our reaction conditions, [(DMSC)TiCl2] (1) does not react with
sodium metal even after 48 h.
(4) See, for example: (a) Zanotti-Gerosa, A.; Solari, E.; Giannini, L.;
Floriani, C.; Re, N.; Chiesi-Villa, A.; Rizzoli, C. Inorg. Chim. Acta. 1998,
270, 298. (b) Castellano, B.; Zanotti-Gerosa, A.; Solari, E.; Floriani, C.
Organometallics 1996, 15, 4894. (c) Giannini, L.; Caselli, A.; Solari, E.;
Floriani, C.; Chiesi-Villa, A.; Rizzoli, C.; Re, N.; Sgamellotti, A. J. Am. Chem.
Soc. 1997, 119, 9709. (d) Olmstead, M. M.; Sigel, G.; Hope, H.; Xu, X.;
Power, P. P. J. Am. Chem. Soc. 1985, 107, 8087.
(5) Fan, M.; Zhang, H.; Lattman, M. Organometallics 1996, 15, 5216.
10.1021/ja990740b CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/17/1999