Monocyclopentadienyltitanium aryloxide complexes: Preparation, characterization, and application in cyclization reactions

Article abstract of DOI:10.1021/om010755u

A variety of monocyclopentadienyltitanium aryloxide complexes were prepared, characterized by X-ray crystallography, and used to catalyze or mediate cyclization reactions. Structural characterization allowed for the comparison of steric parameters of various 2,6-disubstituted aryloxide ligands. Transformations of dienes and enynes - including the catalysis of a 1,6-diene cycloisomerization and the intramolecular Pauson - Khand reaction - were investigated. A titanium metallacycle was prepared from a sterically hindered enyne containing a trisubstituted olefin. The Pauson - Khand reaction of trimethylsilyl-substituted enynes was promoted to generate α-silylcyclopentenones.

Full text of DOI:10.1021/om010755u

Organometallics 2002, 21, 739-748
739
Mon ocyclop en ta d ien yltita n iu m Ar yloxid e Com p lexes:
P r ep a r a tion , Ch a r a cter iza tion , a n d Ap p lica tion in
Cycliza tion Rea ction s
Shana J . Sturla and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
Received August 16, 2001
A variety of monocyclopentadienyltitanium aryloxide complexes were prepared, character-
ized by X-ray crystallography, and used to catalyze or mediate cyclization reactions.
Structural characterization allowed for the comparison of steric parameters of various 2,6-
disubstituted aryloxide ligands. Transformations of dienes and enynessincluding the
catalysis of a 1,6-diene cycloisomerization and the intramolecular Pauson-Khand reactions
were investigated. A titanium metallacycle was prepared from a sterically hindered enyne
containing a trisubstituted olefin. The Pauson-Khand reaction of trimethylsilyl-substituted
enynes was promoted to generate R-silylcyclopentenones.
In tr od u ction
lyze the polymerization of olefins and a variety of
organic transformations.12 The catalysts are particularly
noted for the open nature of their active sites, which
allows for incorporation of R-olefins such as styrene into
polymers.9
Reactions that form new carbon-carbon bonds from
unsaturated compounds such as alkynes and olefins
have advanced dramatically by the application of low-
valent group 4 metal complexes. Examples include reac-
tions promoted by titanium or zirconium metallocenes
(Cp2MLn)1 or titanium-alkoxide complexes ((RO)2TiLn,
typically R ) i-Pr).2-5 Titanium-aryloxide complexes
mediate the formation of carbon-carbon bonds from
unsaturated functionality, and investigations have typi-
cally focused on ligation with 2,6-disubstituted aryl-
oxides.6 Recent examples of titanium-aryloxide cata-
lysts for organic transformations have also emerged.7,8
Furthermore, monocyclopentadienyl complexes9-11 cata-
We have been interested in the application of titanium
metallocene complexes to carbocyclization reactions,
particularly the intramolecular Pauson-Khand reaction
(eq 1).13-16 Titanocene dicarbonyl (Cp2Ti(CO)2) can serve
as a cyclocarbonylation catalyst for a variety of 1,6- and
(6) For recent and lead references, see: (a) Hill, J . E., Balaich, G.,
Fanwick, P. E., Rothwell, I. P. Organometallics 1993, 12, 2911-2924.
(b) Thorn, M. G.; Hill, J . E.; Waratuke, S. A.; J ohnson, W. S.; Fanwick,
P. E.; Rothwell, I. P. J . Am. Chem. Soc. 1997, 119, 8630-8641. (c)
Thorn, M. G.; Fanwick, P. E.; Rothwell, I. P. Organometallics 1999,
18, 4442-4447.
(1) For reviews of cyclization reactions mediated or catalyzed by
titanocene and zirconocene complexes, see: (a) Yasuda, H.; Nakamura,
A. Angew. Chem., Int. Ed. Engl. 1987, 26, 723-742. (b) Buchwald, S.
L.; Nielsen, R. B. Chem. Rev. 1988, 88, 1047-1058. (c) Broene, R. D.;
Buchwald, S. L. Science 1993, 261, 1696-1701. (d) Negishi, E.-i.;
Takahashi, T. Acc. Chem. Res. 1994, 27, 124-130. (e) Ohff, A.; Pulst,
S.; Lefeber, C.; Peulecke, N.; Arndt, P.; Burkalov, V. V.; Rosenthal, U.
Synlett 1996, 111-118. (f) Negishi, E.-i.; Takahashi, T. Bull. Chem.
Soc. J pn. 1998, 71, 755-769.
(7) (a) Balaich, G. J .; Rothwell, I. P. J . Am. Chem. Soc. 1993, 115,
1581-1583. (b) J ohnson, E. S.; Balaich, G. J .; Fanwick, P. E.; Rothwell,
I. P. J . Am. Chem. Soc. 1997, 119, 11086-11087. (c) Waratuke, S. A.;
Thorn, M. G.; Fanwick, P. W.; Rothwell, A. P.; Rothwell, I. P. J . Am.
Chem. Soc. 1999, 121, 9111-9119.
(8) Okamoto, S.; Livinghouse, T. J . Am. Chem. Soc. 2000, 122,
1223-1224.
(9) McKnight, A. L.; Waymouth, R. M. Chem. Rev. 1998, 98, 2587-
2598.
(2) Kulinkovich, O. G.; Sviridov, S. V.; Vaselevski, D. A. Synthesis
1991, 234-234.
(10) (a) Okuda, J . Chem. Ber. 1990, 123, 1649-1651. (b) Amor, F.;
Okuda, J . J . Organomet. Chem. 1996, 520, 245-248. (c) Okuda, J .;
Eberle, T.; Spaniol, T. P. Chem. Ber. 1997, 130, 209-215.
(11) (a) Shapiro, P. J .; Bunel, E.; Schaefer, W. P.; Bercaw, J . E.
Organometallics 1990, 9, 867-869. (b) Shapiro, P. J .; Cotter, W. D.;
Schaefer, W. P.; Labinger, J . A.; Bercaw, J . E. J . Am. Chem. Soc. 1994,
116, 4623-4640.
(12) Hydroboration of alkenes: (a) Bijpost, E. A.; Duchateau, R.;
Teuben, J . H. J . Mol. Catal. A: Chem. 1995, 95, 121-128. Hydrogena-
tion of imines: (b) Okuda, J .; Verch, S.; Spaniol, T. P.; Stu¨rmer, R.
Chem. Ber. 1996, 129, 1429-1431. (c) Okuda, J .; Verch, S.; Sturmer,
R.; Spaniol, T. P. J . Organomet. Chem. 2000, 605, 55-67. Aminoalkene
hydroamination/cyclization: (d) Tian, S.; Arredondo, V. M.; Stern,
C. L.; Marks, T. J . Organometallics 1999, 18, 2568-2570. Carbo-
alumination of olefins and preparation of a titanacyclopentene: (e)
Millward, D. B.; Cole, A. P.; Waymouth, R. M. Organometallics 2000,
19, 1870-1878.
(3) For intramolecular cyclization reactions mediated by (i-PrO)2TiLn,
see: (a) Urabe, H.; Hata, T.; Sato, F. Tetrahedron Lett. 1995, 36, 4261-
4264. (b) Urabe, H.; Takeda, T.; Sato, F. Tetrahedron Lett. 1996, 37,
1253-1256. (c) Urabe, H.; Sato, F. J . Org. Chem. 1996, 61, 6156-
6157. (d) Suzuki, K.; Urabe, H.; Sato, F. J . Am. Chem. Soc. 1996, 118,
8729-8730. (e) Urabe, H.; Suzuki, K.; Sato, F. J . Am. Chem. Soc. 1997,
119, 10014-10027. (f) Urabe, H.; Takeda, T.; Hideura, D.; Sato, F. J .
Am. Chem. Soc. 1997, 119, 11295-11305. (g) Urabe, H.; Sato, F. J .
Am. Chem. Soc. 1999, 121, 1245-1255.
(4) For recent and lead references of carbon-carbon bond forming
reactions mediated by (i-PrO)2TiLn, see: (a) Corey, E. J .; Rao, S. A.;
Noe, M. C. J . Am. Chem. Soc. 1994, 116, 9345-9346. (b) Lee, J .; Kim,
H.; Cha, J . K. J . Am. Chem. Soc. 1996, 118, 4198-4199. (c) Hideura,
D.; Urabe, H.; Sato, F. Chem. Commun. 1998, 271-272. (d) Williams,
C. M.; Chaplinski, V.; Schreiner, P. R.; de Meijere, A. Tetrahedron Lett.
1998, 39, 7695-7698. (e) Hamada, T.; Suzuki, D.; Urabe, H.; Sato, F.
J . Am. Chem. Soc. 1999, 121, 7342-7344.
(13) (a) Berk, S. C.; Grossman, R. B.; Buchwald, S. L. J . Am. Chem.
Soc. 1993, 115, 4912-4913. (b) Berk, S. C.; Grossman, R. B.; Buchwald,
S. L. J . Am. Chem. Soc. 1994, 116, 8593-8601.
(14) Sturla, S. J .; Buchwald, S. L. J . Org. Chem. 1999, 64, 5547-
5550.
(5) For reviews of reactions mediated by (i-PrO)2TiLn, see: (a) Sato,
F.; Urabe, H.; Okamoto, S. Synlett 2000, 753-775. (b) Sato, F.; Urabe,
H.; Okamoto, S. Chem. Rev. 2000, 100, 2835-2886.
10.1021/om010755u CCC: $22.00 © 2002 American Chemical Society
Publication on Web 01/24/2002

740 Organometallics, Vol. 21, No. 4, 2002
Sturla and Buchwald
1,7-enynes and demonstrates excellent functional group
tolerance, particularly for an early-metal complex.15
A
limitation of this method, however, is the reluctance of
the relatively bulky titanocene fragment to react with
sterically hindered alkynes or olefins. For example, we
have found that enynes such as 1 and 2 are not
cyclocarbonylated by Cp2Ti(CO)2.
F igu r e 1. Monocyclopentadienyltitanium aryloxide com-
plexes.
structural characterization of 2,6-diisopropylphenoxide
derivatives and demonstrated that complexes of this
type exhibit catalytic activity for alkene polymerization
(with appropriate activators such as MAO).
Resu lts a n d Discu ssion
Presented with the steric limitations of a titanocene-
based system and the volume of current literature
describing early-metal catalysts that have evolved
beyond a traditional metallocene framework,9,17 we felt
that more reactive catalysts for the Pauson-Khand
reaction might be prepared by exploring new ligand
frameworks. We sought a ligand set that would exhibit
reactivity analogous to titanocene complexes while
providing a less crowded coordination environment.
Considering the use of titanium-alkoxide and -aryl-
oxide6 complexes for cyclization reactions3,7,8 and
the open nature of monocyclopentadienyl catalysts,9
we chose to replace a cyclopentadienyl ligand of
the titanocene fragment with an aryloxide. Monocyclo-
pentadienyltitanium aryloxide complexes can be readily
prepared from the corresponding cyclopentadienyl-
titanium trichloride and an appropriate phenol.18
Phenols bearing substituents that provide a wide range
of steric and electronic properties are commercially
available or can be easily prepared, allowing for fine-
tuning of the aryloxide complexes' reactivity.
The first examples of mixed monocyclopentadienyl-
titanium aryloxide complexes were reported by Whitby,
who investigated their electrochemistry.18 Pure products
with 2,6-substituted-aryloxide ligands could be cleanly
isolated. These were prepared by two methods: reaction
of CpTiCl3 with the appropriate phenol and Et3N in
Et2O at room temperature or reaction of the corre-
sponding sodium phenolate with CpTiCl3 in toluene at
100 °C. More recently, researchers at Sumitomo Chemi-
cal Company have reported the preparation of mono-
cyclopentadienyltitanium aryloxide complexes by reac-
tion of CpTiCl3 or Cp*TiCl3 (pentamethylcyclopenta-
dienyltitanium trichloride) with various lithium phen-
oxides in Et2O, toluene, or CH2Cl2.19 This study provided
Syn th esis a n d Ch a r a cter iza tion of Mon ocyclo-
p en ta d ien yltita n iu m Ar yloxid e Com p lexes. We
have investigated the chemistry of the group of mono-
cyclopentadienyltitanium aryloxide complexes shown in
Figure 1. Dichlorides 3b and 3d were prepared as
described by Whitby.18 As anticipated, complex 3a ,
bearing sterically demanding 2,6-diphenyl substitution,
was easily prepared by the same method, using 2,6-
diphenylphenol and triethylamine.
We were interested in including the 2,6-dimethoxy-
phenolate ligand (complex 3c) in this study because of
the potential for chelation of the ortho methoxy sub-
stituents. This compound, however, could not be pre-
pared by the reported procedures. We found that use
of the corresponding potassium phenoxide in toluene
at room temperature provided for clean conversion to
the desired complex. The pentamethylcyclopentadienyl
analogue of 3a (4a ) was prepared from Cp*TiCl3
and the corresponding sodium phenolate. The penta-
methylcyclopentadienyl complex 4b19 was not prepared
or investigated in this study, but its X-ray crystal data
are included for structural comparison (Table 1).
The titanium dichlorides were isolated as highly
colored crystalline materials that were yellow, orange,
and red. Variation of substituents on the aryloxide
ligands allowed great flexibility for both steric and
electronic perturbations relative to a cyclopentadienyl
ligand. To provide an indication of how these param-
eters are affected in the mixed complexes, they were
structurally characterized by X-ray crystallography.
Representations of the crystal structures we have
obtained are shown in Figures 2-4.
The calculation of cone angles provides a means to
compare steric paramaters for a variety of ligands.20 For
reference, Tolman has estimated the symmetric cone
angle of a cyclopentadienyl ligand to be 136°.20 In the
case of aryloxide ligands, however, Wolczanski has put
forth a more appropriate spatial perception of this type
of ligand as a “wedge” since it does not fill a true conical
region.21 This spatial representation is analogous to a
model used to describe nucleophilic carbene ligands,
(15) (a) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J . Am. Chem.
Soc. 1996, 118, 9450-9451. (b) Hicks, F. A.; Kablaoui, N. M.; Buchwald,
S. L. J . Am. Chem. Soc. 1999, 121, 5881-5898.
(16) (a) Hicks, F. A.; Buchwald, S. L. J . Am. Chem. Soc. 1996, 118,
11688-11689. (b) Hicks, F. A.; Buchwald, S. L. J . Am. Chem. Soc. 1999,
121, 7026-7033.
(17) Britovsek, G. J . P.; Gibson, V. C.; Wass, D. F. Angew. Chem.,
Int. Ed. 1999, 38, 428-447.
(18) Fussing, I. M. M.; Pletcher, D.; Whitby, R. J . J . Organomet.
Chem. 1994, 470, 109-117.
(19) Nomura, K.; Naga, N.; Miki, M.; Yanagi, K.; Imai, A. Organo-
metallics 1998, 17, 2152-2154.
(20) Tolman, C. A. Chem. Rev. 1977, 77, 313-348.
(21) Wolczanski, P. T. Polyhedron 1995, 14, 3335-3362.

Monocyclopentadienyltitanium Aryloxides
Organometallics, Vol. 21, No. 4, 2002 741
Ta ble 1. Selected Bon d An gles (d eg) a n d Bon d Len gth s (Å)
3a a
3b
3c
4a
4b
R
Ph
i-Pr
OMe
Ph
i-Pr
Bond Lengths
Ti-O
1.7900(18)
2.2522(10)
2.2542(11)
2.0117(4)
1.760(4)
2.262(1)
2.262(1)
1.99
1.7781(18)
2.2710(10)
2.2680(1)
2.0420(3)
1.811(3)
1.772(3)
2.305(2)
2.305(2)
2.03
Ti-Cl(1)
Ti-Cl(2)
Ti-Cp
2.2693(13)
2.2865(14)
2.0310(4)
Angles
C-O-Ti
151.17(7)
101.23(5)
157
163.0(4)
104.23(7)
123
161.37(17)
102.24(3)
122
160.6(3)
98.70(5)
148
173.0(3)
103.45(5)
121
Cl(1)-Ti-Cl(2)
AL
Ah
59
94
37
53
92
a
Values are the average of those for the four nearly identical structures in the asymmetric unit.
F igu r e 4. ORTEP plot of the solid-state molecular struc-
ture of 4a . Thermal ellipsoids are shown at the 30%
probablility level.
F igu r e 2. ORTEP plot of the solid-state molecular struc-
ture of 3a . Thermal ellipsoids are shown at the 30%
probablility level.
F igu r e 5. Spatial perceptions of the conical displacement
of a cyclopentadienyl ligand and the wedge describing an
aryloxide ligand.
crystals were not obtained for the dimethyl complex
3d , values (AL ) 101°; AH ) 59°) were obtained by
computationally superimposing the methyl substitu-
ents onto the ligand framework of the DIPP complex
3b. Comparisons of the steric parameters derived from
each ligand (Table 1) reveal the distinct packing geom-
etry attained by each aryloxide. The most isotropic of
the aryloxides is the diisopropylphenoxide (DIPP) ligand
(3b , 4b ), and the most anisotropic is the diphenyl-
phenoxide (DPP) ligand (3a , 4a ), which is almost three
times as “long” (AL) as it is “high” (AH). The presence of
a Cp vs Cp* does not appear to significantly affect the
steric constraints of the aryloxide ligand.
While it is difficult to quantify the number of electrons
donated from an aryloxide ligand, structural informa-
tion is often used as an estimate. Rothwell’s work with
aryloxide complexes, however, demonstrates little cor-
relation based on this approach.26 For example, the
angle of the M-O-C linkage along with the M-O bond
length could be considered indicative of the aryloxide-
F igu r e 3. ORTEP plot of the solid-state molecular struc-
ture of 3c. Thermal ellipsoids are shown at the 30%
probablility level.
imidazol-2-ylidenes.22,23 The steric environment of the
wedge can therefore be described by two parameters,
Spatial perceptions the angles AL and AH (Figure 5).24
Steric parameters for a wedge that describes each of
the aryloxide ligands of interest in this study were
calculated from the bond lengths and angles obtained
from structural data. To do so, a van der Waals radius
of 1.08 Å was assumed for each of the hydrogen atoms
from which distances were measured.25 Because single
(22) Arduengo, A. J ., III. Acc. Chem. Res. 1999, 32, 913-921.
(23) Herrmann, W. A.; Kocher, C. Angew. Chem., Int. Ed. Engl.
1997, 36, 2162-2187.
(24) J afarpour, L.; Nolan, S. P. J . Organomet. Chem. 2001, 617, 17-
27.
(25) Srinivasan, R.; Hariharan, M.; Vijayalakshmi, J . Curr. Sci.
1987, 56, 942-945.

742 Organometallics, Vol. 21, No. 4, 2002
Sturla and Buchwald
Ta ble 2. “Cp (DP P )Ti”-Med ia ted
Cycloca r bon yla tion of Tr im eth ylsilyl-Su bstitu ted
En yn es
metal bond order.21 Thus, as the M-O-C linkage
approaches linearity, a significant involvement of both
p orbitals may be inferred. Likewise, a shortening of the
M-O bond would reflect higher bond strength. Given
that the Cp* is more electron donating than Cp, by
electronic arguments alone, one would predict that the
pentamethylcyclopentadienyl-ligated complexes would
attain less π-donation from the aryloxide, thus contract-
ing the Ti-O-C bond angle. However, in moving from
the Cp to Cp* complexes, the Ti-O-C angle in fact
increases by 10° on average. The C-O bond distance is
either lengthened slightly or remains unchanged. Our
data therefore reinforce Rothwell’s warning against the
estimation of π-donation in niobium- and tantalum-
aryloxide complexes from bond angles.26 The expanded
Ti-O-C bond angle in the Cp* complexes is consistent
with the sterically demanding size of the Cp* ligand that
can “push” the aryloxide ligand away toward linearity
(in the Cp analogues, the aryloxide ligand is tilted
upward toward the Cp).
Cycliza t ion St u d ies. The monocyclopentadienyl-
titanium aryloxide complexes were activated by reduc-
tion of the Ti(IV) dichlorides with Grignard reagents or
n-BuLi at low temperature (-78 °C) to yield the formally
Ti(II)-olefin complexes. A resulting color change of the
solution from bright orange to deep brown was observed.
Metallacycles were generated when the monocyclo-
pentadienyl complex 3b (eq 3), but not the penta-
methylmonocyclopentadienyl complex 4a (eq 2), was
a
Unless otherwise indicated, yield is for isolated product of
b
>95% purity for an average for two or more runs. Yield deter-
mined by GC using an internal standard. c Yield represents the
combined average isolated yields of 66% and 15% for the trans-
(isomer shown) and cis-cyclopentenone isomers, respectively. The
crude reaction mixture is a 3:1 ratio of isomers.
1
the H NMR resonance for the olefinic proton, Ha, from
δ 5.65 to δ 2.97. Preliminary experiments also demon-
strated that such complexes were susceptible to carbo-
nylation. The monocyclopentadienyl complexes (3a -d )
were therefore investigated as catalysts for the Pauson-
Khand reaction.
The monocyclopentadienyltitanium aryloxide complex
3c served as an efficient catalyst for the cyclocarbonyl-
ation of enyne 5b (eq 4). In the example shown in eq 4,
the optimal catalyst was generated by reduction of Cp-
(DME)TiCl2 3c by n-BuLi in toluene.27,28 The highest
yields of cyclopentenone product 6b were realized when
the reaction was carried out under 1 atm of CO at 95
°C. The cyclization of more sterically hindered sub-
strates, however, benefited from the use of 2.1 atm of
CO (Table 2).
The monocyclopentadienyltitanium aryloxide com-
plexes exhibit reactivity comparable to titanocene com-
plexes but are somewhat less tolerant of certain func-
tional groups. For example, simple enynes containing
a malonic acid diester group as part of the alkyne-olefin
linker are excellent substrates for titanocene-catalyzed
reactions.15 These compounds were not suitable sub-
reduced in the presence of an enyne. Formation of
metallacycle 7 was evidenced by the distinct change in
(27) Negishi, E.-i.; Holmes, S. J .; Tour, J . M.; Miller, J . A.; Ceder-
baum, F. E.; Swanson, S. R.; Takahashi, T. J . Am. Chem. Soc. 1989,
111, 3336-3346.
(28) Hicks, F. A.; Berk, S. C.; Buchwald, S. L. J . Org. Chem. 1996,
61, 2713-2718.
(26) Steffey, B. D.; Fanwick, P. E.; Rothwell, I. P. Polyhedron 1990,
9, 963-968.

Monocyclopentadienyltitanium Aryloxides
Organometallics, Vol. 21, No. 4, 2002 743
strates for reactions with monocyclopentadienyltitanium
aryloxide complexes and produced complex product
mixtures.29
The monocyclopentadienyltitanium aryloxide com-
plexes (3) were further investigated for their perfor-
mance in cyclization reactions of sterically hindered
substrates for which titanocene complexes failed. When
3b was reduced in the presence of an enyne bearing a
trisubstituted olefin such as 8, the corresponding met-
allacycle 9 was indeed formed (eq 5). This substrate did
not form a metallacycle under similar conditions with
titanocene complexes.
Identification of complex 9 was challenging due to an
1
unusually low-field H NMR shift of δ 4.53 for Ha and
our inability to isolate single crystals despite the pres-
ence of the fluorenyl moiety. The metallacycle structure
was assigned in part based on characteristic 13C NMR
shifts in the metallacyclopentene ring (Figure 6), par-
ticularly the olefinic carbon bound to the Ti at δ 201.2.
In an analogous biscyclopentadienyl-ligated metalla-
cycle, for which a crystal structure was obtained, the
corresponding carbon resonance appears at δ 187.8.30
In titanocene-alkyne complexes, the corresponding
resonances are typically in the range of δ 106-135.31
The other three carbon resonances of the metallacyclic
portion of 9 (δ 144.5, 38.9, 72.4) also correlate closely
with the corresponding resonances of a known bis-
cyclopentadienylmetallacycle (δ 151.54, 39.80, 70.6).30
Furthermore, an HMBC32 NMR experiment indicates
a cyclized structure; the most compelling HMBC data
were cross-peaks from Ha to Cb and Cc (Figure 6). A
combination of these experiments with HMQC32 and
F igu r e 6. 1H and 13C assignments for metallacycle 9.
Sch em e 1. Qu en ch in g of Meta lla cycle 9
1
COSY32 data allowed for the assignment of 13C and H
(29) Side reactions are probably
a result of the experimental
procedure used: The dichloride complexes are reduced with n-BuLi
in the presence of the substrate. Addition of n-BuLi to the ester group
may compete with reduction of the dichloride. Catalyst activation in
the absence of a substrate also leads to diminished yields, however,
because binding of the substrate may inhibit decomposition pathways
for the putative Ti(II) species.
(30) Eriksson, M.; and Buchwald, S. L. Unpublished results. The
structure of the biscyclopentadienyl-ligated metallacycle is shown
below; 13C NMR data were obtained in C6D6.
(31) Rosenthal, U.; Oehme, G.; Burlakov, V. V.; Petrovskii, P. V.;
Shur, V. B.; Vol’pin, M. E. J . Organomet. Chem. 1990, 391, 119-122.
(32) The HMQC (heteronuclear multiple quantum coherence) ex-
periment correlates proton and carbon nuclei via 1J (C,H). A cross-peak
is observed between a carbon and attached protons. In the HMBC
(heteronuclear multible bond correlation) experiment, longer range
correlations via 2J (C,H) and 3J (C,H) are observed while 1J (C,H) are
suppressed. The commonly used homonuclear experiment, COSY
(correlation spectroscopy), indicates 1H-1H spin-coupling cross-peaks.
For guidelines and lead references see: Braun, S.; Kalinowski, H.-O.;
Berger, S. 150 and More Basic NMR Experiments, A Practical Course;
Wiley-VCH: Weinheim, 1998; Chapter 10.
resonances for compound 9 as shown in Figure 6. A
possible explanation for the unusual H NMR shift of
1
Ha is in close proximity to one of the arene rings of the
flourenyl group, as evidenced by NOE correlations.
Protonolysis or deuteriolysis of metallacycle 9 with
aqueous acid (HCl or DCl) resulted in acyclic products
10H and 10D, indicating that under these conditions
retrocyclization occurs faster than protonation of the
Ti-C bond (Scheme 1). Quenching of the metallacycle
with anhydrous HCl (at either -78 or 25 °C) afforded
the cyclic product 11, but it was contaminated with the
acyclic product 10H along with compounds resulting
from the addition of HCl to the trisubstituted double
bonds. Reaction of 9 with triflic acid cleanly furnished
a 1:1 mixture of the cyclic and acyclic products 10H and

744 Organometallics, Vol. 21, No. 4, 2002
Sturla and Buchwald
11. To the best of our knowledge, metallacycle 9 is the
first example of an R,R-disubstituted titanacylopentene
that has been prepared from a trisubstituted olefin.33
Furthermore, such a hindered complex was not formed
from biscyclopentadienyltitanium complexes under simi-
lar conditions.
be isolated in excellent yield (90%, eq 6). This protocol
was superior to those attempted using n-BuLi/toluene
The cyclocarbonylation of trimethylsilyl-substituted
enynes generates R-silylcyclopentenones, which can be
useful synthetic intermediates. The cyclized products
can be protodesilylated to provide unsubstituted cyclo-
pentenones34 or converted to R-bromo- or R-iodocyclo-
pentenones.27,35 These are potential substrates for a
wide range of reactions.36 Although trimethylsilyl-
substituted enynes can be cyclized with stoichiometric
amounts of zirconocene or (η2-olefin)Ti(O-i-Pr)2 com-
plexes, such substrates are unreactive toward cycliza-
tion in the presence of titanocene complexes.13 We have
found, however, that replacement of a cyclopentadienyl
with an appropriate aryloxide ligand allows for the
cyclocarbonylation of trimethylsilyl-substituted enynes.
Table 2 illustrates several examples of the cyclocarbo-
nylation of trimethylsilyl-substituted enynes using the
DPP complex 3a . A variety of conditions were screened
and, although substoichiometric amounts of the metal
complex can be used for this reaction, efficient catalysis
was not realized. The disubstituted olefin 5e was
cyclocarbonylated in good yield with minor amounts of
the trans-cyclopentenone product being formed. Both
trans- and cis-cyclopentenone isomers were easily sepa-
rated by chromatography, and each was isolated in 66%
and 15% yield, respectively.
and warming to room temperature (24% conversion) or
95 °C (91% conversion to a mixture of isomers). Complex
3d was a more effective precatalyst than the sterically
demanding DIPP (3a ) or DPP (3b ) complexes, which
gave rise to only small amounts (5% was detected by
GC analysis) of the cyclized product. Introduction of CO
(16 psig) into the reaction mixture inhibited cyclization
such that diminished amounts of 12 were formed (23%
was detected by GC analysis), but no products of
carbonylative processes were observed. Attempts to use
CpTiCl3 as a catalyst precursor under the optimized
reaction conditions resulted in no cyclized product.
Su m m a r y a n d Con clu sion s
We have prepared several monocyclopentadienyltita-
nium aryloxide complexes and investigated their ap-
plication in carbon-carbon bond forming reactions
including cyclizations of enynes and dienes. The tita-
nium dichloride species were characterized by X-ray
crystallography, which allowed for the comparison of
steric parameters for each of the differently substituted
aryloxide ligands.
Catalysts for the cycloisomerization of dienes are of
interest due to the versatility of the cyclized products
as well as the ready availability of substrates.8,37 When
3d was reduced in the presence of a 1,6-diene, the
corresponding exo-olefinic cyclopentane product 12 could
(33) For the preparation of bicyclic cyclopentenones with angular
substituents from the corresponding trisubstituted olefins, see: Urabe,
H.; Hideura, D.; Sato, F. Org. Lett. 2000, 2, 381-383.
Of particular interest to our research was the ap-
plication of these complexes to the cyclocarbonylation
of enynes, specifically to sterically challenging enynes
that were unreactive with titanocene systems. Reduc-
tion of the dichloride complexes in the presence of
enynes provided corresponding metallacycles, which
were susceptible to protonolysis and CO insertion.
Furthermore, monocyclopentadienyltitanium aryloxide
complexes served as precatalysts for the cyclocarbon-
ylation of enynes. Substitution of an aryloxide ligand
for a cyclopentadienyl ligand allowed for the preparation
of titanacyclopentenes derived from trisubstituted ole-
fins and of R-trimethylsilylcyclopentenones, compounds
that could not be accessed using titanocene complexes.
The efficiency of the carbonylation and cyclization
reactions were dependent upon the substitution of the
aryloxide ligand. Metallacycles derived from trisubsti-
tuted olefins were obtained most efficiently from the
diisopropyl complex 3b. Phenyl-substituted enynes were
catalytically cyclocarbonylated using the dimethoxy
complex 3c. The cyclocarbonylation of trimethylsilyl-
substituted enynes was mediated most efficiently by the
diphenyl complex 3a . The optimal diene cycloisomer-
ization catalyst was the dimethyl complex 3d . The
benefit of employing ligands that allow for tuning of
steric or electronic parameters while maintaining over-
all reactivity is clearly demonstrated, and substituted
(34) (a) Loebach, J . L.; Bennett, D. M.; Danheiser, R. L. J . Am.
Chem. Soc. 1998, 120, 9690-9691. (b) Magnus, P.; Exon, C.; Albaugh-
Robertson, P. Tetrahedron 1985, 41, 5861-5869.
(35) Alimardanov, A.; Negishi, E.-i. Tetrahedron Lett. 1999, 40,
3839-3842.
(36) The following are representative examples demonstrating the
utility of R-halocyclopentenones. As componants of Pd-catalyzed cou-
pling reactions: (a) Negishi, E-i.; Owczarczyk, Z. R.; Swanson, D. R.
Tetrahedron Lett. 1991, 32, 4453-4456. (b) J ohnson, C. R.; Adams, J .
P.; Braun, M. P.; Senanayake, C. B. W. Tetrahedron Lett. 1992, 33,
919-922. (c) J ohnson, C. R.; Braun, M. P. J . Am. Chem. Soc. 1993,
115, 11014-11015. (d) Magriotis, P. A.; Vourloumis, D.; Scott, M. E.;
Tarli, A. Tetrahedron Lett. 1993, 34, 2071-2074. (e) Molander, G. A.;
Hiersemann, M. Tetrahedron Lett. 1997, 38, 4347-4350. (f) Rossi, R.;
Bellina, F.; Ciucci, D.; Carpita, A.; Fanelli, C. Tetrahedron 1998, 54,
7595-7614. Isoxazoline precursors: (g) Galli, C.; Marotta, E.; Righi,
P.; Rosini, G. J . Org. Chem. 1995, 60, 6624-6626. Asymmetric
dihydrofuran synthesis: (h) Arai, S.; Nakayama, K.; Suzuki, Y.; Hatano,
K-i.; Shioiri, T. Tetrahedron Lett. 1998, 39, 9739-9742. Cyclopropa-
nation substrates: (i) Arai, S.; Nakayama, K.; Hatano, K.-i.; Shioiri,
T. J . Org. Chem. 1998, 63, 9572-9575. (j) Arai, S.; Nakayama, K.;
Ishida, T.; Shiori, T. Tetrahedron Lett. 1999, 40, 4215-4218. Radical
cyclization substrates: (k) Sha, C.-K.; Santhosh, K. C.; Tseng, C.-T.;
Lin, C.-T. J . Chem. Soc., Chem. Commun. 1998, 397-398.
(37) (a) Bright, A.; Malone, J . F.; Nicholson, J . K.; Powell, J .; Shaw,
B. L. J . Chem. Soc., Chem. Commun. 1971, 712-713. (b) Grigg, R.;
Malone, J . F.; Mitchell, T. R. B.; Ramasubbu, A.; Scott, R. M. J . Chem.
Soc., Perkin Trans. 1 1984, 1745-1754. (c) Piers, W. E.; Shapiro, P.
J .; Bunel, E. E.; Bercaw, J . E. Synlett, 1990, 74-84. (d) Radetich, B.;
RajanBabu, T. V. J . Am. Chem. Soc. 1998, 120, 8007-8008. (e)
Heumann, A.; Moukhliss, M. Synlett 1998, 1211-1212. (f) Yamamoto,
Y.; Ohkishi, N.; Kameda, M.; Itoh, K. J . Org. Chem. 1999, 64, 2178-
2179. (g) Widenhoefer, R. A.; Perch, N. S. Org. Lett. 1999, 1, 1103-
1105. (h) Okamoto, S.; Livinghouse, T. Organometallics 2000, 19,
1449-1451.

Monocyclopentadienyltitanium Aryloxides
Organometallics, Vol. 21, No. 4, 2002 745
mmol) were combined in toluene (5 mL). After stirring the
mixture for 1 h, a solution of CpTiCl3 (130 mg, 0.59 mmol) in
toluene (2 mL) was added. The mixture was stirred for 12 h,
filtered through Celite with additional toluene, and concen-
trated in vacuo on a vacuum line in the glovebox. Crystalliza-
tion from a saturated solution of toluene layered with hexanes
aryloxide ligands are valuable in this respect. Monocy-
clopentadienyltitanium aryloxide complexes exhibit re-
activity related to titanocene complexes and allow for
the cyclization of more sterically demanding substrates.
Exp er im en ta l Section
1
afforded 126 mg (72% yield) of a red solid, mp 92-95 °C. H
Gen er a l Con sid er a tion s. All manipulations involving air-
sensitive materials were conducted in a Vacuum Atmospheres
glovebox under an atmosphere of argon or nitrogen, or using
standard Schlenk techniques under argon, in flame-dried
glassware. Melting points were determined with a Mel-Temp
II from Laboratory Devices. Celite was dried at 200 °C under
vacuum for 24 h and stored in an argon-filled glovebox.
Resealable Schlenk tubes were purchased from Kontes. Unless
it is described as dry, Et2O was used directly from a bottle
stored on the benchtop. Toluene, THF, and dry Et2O were
purified by a solvent dispensing system,38 involving passage
through alumina columns under argon, or by distillation from
sodium/benzophenone ketyl under argon. C6D6 was distilled
from sodium. Anhydrous DMF was purchased from Aldrich
and used without further purification. Cyclopentadienyltita-
nium trichloride (CpTiCl3) and pentamethylcyclopentadien-
yltitanium trichloride (Cp*TiCl3) were purchased from Strem
Chemicals, Inc., stored at -20 °C in an argon-filled glovebox,
and used without further purification. 2,6-Diphenylphenol was
purchased from Aldrich and used without further purification.
Technical grade 2,6-diisopropylphenol was purchased from
Aldrich, purified by vacuum distillation (72 °C, 0.4 mm), and
stored in a Schlenk tube under argon. CO (scientific grade,
minimum purity 99.997%) was purchased from MG Industries.
Cp(DIPP)TiCl2 3b,18 Cp(DM)TiCl2 3d ,18 and 5e27 were
prepared as previously described. Titanium complexes were
stored and handled in an argon-filled glovebox. Flash chro-
matography was performed on E. M. Science Kieselgel 60
(230-400 mesh). Substrates were stored in the glovebox to
prevent decomposition over long periods of time. Substrates
that were transferred into the glovebox during periods of the
year when the humidity in the laboratory was high were
filtered through a plug of alumina (in the glovebox) to remove
adventitious moisture. Unless otherwise indicated, yields refer
to isolated yields of compounds of greater than 95% purity as
NMR (500 MHz, C6D6): δ 6.68 (t, J ) 8.2 Hz, 1 H); 6.24 (s, 5
H); 6.23 (d, J ) 8.5 Hz, 2 H); 3.30 (s, 6 H). 13C{1H} NMR (75
MHz, C6D6): δ 151.6, 123.5, 123.1, 120.9, 106.0, 56.4. IR
(KBr): 2935, 1590. Anal. Calcd for C13H14TiCl2O3: C, 46.43;
H, 4.20; Cl, 20.82. Found: C, 46.23; H, 4.05, Cl, 21.08.
P en ta m eth ylcyclop en ta d ien yltita n iu m Dich lor id e 2,6-
Dip h en ylp h en oxid e (4a ). A resealable Schlenk tube was
charged with NaH (105 mg, 4.38 mmol) and 2,6-diphenyl-
phenol (366 mg, 1.49 mmol) in an argon-filled glovebox. The
Schlenk tube was removed from the glovebox and attached to
a Schlenk line. Under a flow of argon, toluene (10 mL) was
added. The flask was sealed and heated at 100 °C for 30 min.
The reaction mixture was cooled to 25 °C, and a solution of
Cp*TiCl3 in toluene (10 mL) was added. The flask was sealed
and heated at 100 °C for 20 h, then cooled and transferred to
an argon-filled glovebox. The solution was filtered through a
plug of Celite. The Celite was rinsed with additional toluene,
and the combined solutions were concentrated in vacuo on a
vacuum line in the glovebox to give an orange solid. The crude
solid was dissolved in warm toluene (25 mL), layered with
hexanes (75 mL), and cooled at -20 °C for 2 days. The solvent
was decanted, and the crystals were rinsed with hexanes and
dried in vacuo on a vacuum line in the glovebox to yield 360
mg (49%) of the title compound as orange needles, mp 222-
226 °C. 1H NMR (300 MHz, C6D6): δ 7.64 (d, J ) 7.7 Hz, 4 H);
7.33 (t, J ) 7.6 Hz, 4H); 7.20-7.14 (m, 4H); 6.92 (t, J ) 7.3
Hz, 1H); 1.46 (s, 15H). 13C{1H} NMR (125 MHz, C6D6): δ 138.2,
134.6, 132.1, 131.4, 131.0, 128.7, 127.2, 123.4, 12.2. IR (KBr,
cm-1): 3055, 2911, 2371, 1403. Anal. Calcd for C28H28TiCl2O:
C, 67.46; H, 5.67. Found: C, 67.32; H, 5.61.
4,4-Bis(ter t-bu tyldim eth ylsilyloxym eth yl)-1-ph en ylh ept-
6-en -1-yn e (5b). An Et2O solution of DIBAL (14 mL, 1.0 M,
14 mmol) was added to a solution of 2-allyl-2-(3-phenylprop-
2-ynyl)malonic acid diethyl ester13 (2.04 g, 6.50 mmol) in dry
Et2O at 0 °C. The reaction mixture was allowed to warm to
25 °C. After 24 h, additional DIBAL (7 mL of a 1.0 M Et2O
solution, 7 mmol) was added. After an additional 48 h, the
reaction mixture was quenched by the careful addition of 1.5
mL of MeOH. The resulting mixture was added to a separatory
funnel with 1 M HCl and Et2O. The layers were separated,
and the Et2O solution was rinsed with brine, dried with
MgSO4, filtered, and concentrated. A white solid was obtained
by flash chromatography (2:1 Et2O/hexanes). TBSCl (2.65 g,
17.4 mmol) was added to a solution of this material and
imidazole (1.77 g, 26.0 mmol) in DMF (15 mL) at 0 °C. The
reaction mixture was allowed to warm to room temperature
and stirred for 24 h. The reaction mixture was added to a
separatory funnel with Et2O. The Et2O solution was rinsed
twice with 1 M aqueous HCl, once with saturated aqueous
NaHCO3, and once with brine. The Et2O solution was dried
with MgSO4, filtered, and concentrated. Purification by flash
chromatography (hexanes-3% Et2O/hexanes) afforded 1.31 g
1
estimated by H NMR. Elemental analyses of organometallic
compounds were performed by H. Kolbe, Mu¨lheim an der
Ruhr, Germany. Elemental analyses for all other compounds
were performed by Atlantic Microlabs, Inc., Norcross, GA.
Mon ocyclop en t a d ien ylt it a n iu m Dich lor id e 2,6-Di-
p h en ylp h en oxid e (3a ). Triethylamine (0.95 mL, 6.8 mmol)
was added to a solution of CpTiCl3 (1.32 g, 6.0 mmol) and 2,6-
diphenylphenol (1.50 g, 6.1 mmol) in dry Et2O (200 mL) under
argon at 25 °C, and the reaction mixture was stirred for 12 h.
A white precipitate formed, and the Et2O solution was cannula-
filtered39 into a dry Schlenk flask. The solids were rinsed with
additional dry Et2O (50 mL), and the resulting solution was
cannula-filtered. The combined Et2O solutions were concen-
trated in vacuo on a Schlenk line. Recrystallization in an
argon-filled glovebox from a saturated solution of toluene
layered with hexanes afforded 2.20 g (85% yield) of a yellow
solid, mp 169-171 °C. 1H NMR (300 MHz, C6D6): δ 7.52 (d, J
) 7.0 Hz, 2 H); 7.30 (t, J ) 7.8 Hz, 2 H); 7.15 (m, 8 H); 5.55 (s,
5 H). 13C{1H} NMR (125 MHz, C6D6): δ 164.1, 138.0, 133.3,
130.8, 130.5, 129.0, 127.6, 124.4, 120.7. IR (KBr): 3105, 3058,
3025, 2361, 2339. Anal. Calcd for C23H18TiCl2O: C, 64.48; H,
4.24. Found: C, 64.48; H, 4.25.
1
(44% yield) of the title compound as a colorless oil. H NMR
(300 MHz, C6D6): δ 7.49 (dd, J ) 7.0, 1.3 Hz, 2 H); 7.15 (m, 3
H); 5.97 (m, 1 H); 5.29 (dd, J ) 17.0, 1.2 Hz, 1 H); 5.14 (dd, J
) 9.9, 1.6 Hz, 1 H); 3.60 (dd, J ) 18.4, 9.4, 4 H); 2.47 (s, 2 H);
2.38 (d, J ) 7.3, 2 H); 0.98 (d, J ) 1.0 Hz, 18 H); 0.09 (d, J )
3.9 Hz, 12 H). 13C NMR (75 MHz, C6D6): δ 134.4, 131.9, 128.5,
124.72, 124.67, 118.2, 87.8, 64.1, 44.5, 35.9, 26.3, 22.5, 18.7,
-5.16, -5.20. IR (neat): 3076, 2954, 2929, 2857, 1639, 1598.
Anal. Calcd for C27H46O2Si2: C, 70.70; H, 10.12. Found: C,
70.68; H, 9.99.
Mon ocyclop en t a d ien ylt it a n iu m Dich lor id e 2,6-Di-
m eth oxyp h en oxid e (3c). In an argon-filled glovebox, KH
(100 mg, 2.5 mmol) and 2,6-dimethoxyphenol (80 mg, 0.52
(38) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H. Organometal-
lics 1996, 15, 1518-1520.
(39) In this procedure, cannula filtration refers to transferring the
liquid from a liquid/solid mixture, under argon, by a stainless steel
cannula fitted on one end with a dry glass-fiber filter.
9-Allyl-9-(3-(tr im eth ylsilyl)-2-p r op yn yl)flu or en e (5c). A
hexane solution of n-BuLi (5 mL, 1.61 M, 8 mmol) was added

746 Organometallics, Vol. 21, No. 4, 2002
Sturla and Buchwald
to a solution of 9-allylfluorene (1.6 g, 7.8 mmol) in THF (20
mL) at 0 °C. The resulting slurry was warmed to 25 °C and
stirred for 2 h, producing a clear red solution. The solution
was cooled to -78 °C and 3-bromo-1-(trimethylsilyl)-1-propyne
(1.4 mL, 9.9 mmol) was added. The mixture was warmed to
25 °C and stirred for 12 h. The reaction mixture was quenched
with H2O, and the aqueous mixture was extracted with Et2O.
The organic layer was rinsed with brine, dried with MgSO4,
filtered, and concentrated. Purification by flash chromatogra-
phy (hexanes-1:24 Et2O/hexanes) afforded 2.07 g (84% yield)
of a pale yellow oil. 1H NMR (300 MHz, C6D6): δ 7.55 (m, 2
H); 7.48 (m, 2 H); 7.19 (m, 4 H); 5.32 (ddt, J ) 17.1, 9.9, 7.2
Hz, 1 H); 4.86 (m, 1 H); 4.67 (m, 1 H); 2.84 (d, J ) 7.2 Hz, 2
H); 2.52 (s, 2 H); 0.14 (s, 9 H). 13C NMR (75 MHz, C6D6): δ
149.4, 140.9, 133.8, 127.7, 127.3, 124.1, 120.1, 118.0, 104.9,
87.5, 52.5, 41.6, 30.8, 0.01. IR (neat): 3069, 2958, 2175, 1945,
1908. Anal. Calcd for C22H24Si: C, 83.50; H, 7.65. Found: C,
83.68; H, 7.59.
N-Allyl-N-(3-(tr im eth ylsilyl)-2-p r op yn yl)a n ilin e (5f). A
hexane solution of n-BuLi (6.5 mL, 1.74 M, 11 mmol) was
added to a solution of N-allylaniline (1.50 g, 11.3 mmol) in THF
(20 mL) at -78 °C. After 5 min, 3-bromo-1-(trimethylsilyl)-1-
propyne (1.6 mL, 11 mmol) was added, producing, over the
course of 10 min, a red solution. The reaction mixture was
warmed to 25 °C over 4 h and stirred for 8 h. The resulting
solution was added to a separatory funnel with 1 N aqueous
HCl (60 mL) and Et2O (100 mL). The layers were separated
and the Et2O solution was rinsed twice with 1 N aqueous HCl,
once with saturated aqueous NaHCO3, and once with brine.
The solution was dried with MgSO4, filtered, and concentrated.
Purification by flash chromatography (two successive columns,
first hexanes-1:19 Et2O/hexanes, then hexanes-1:39 Et2O/
hexanes) afforded 1.9 g (70% yield) of a pale yellow oil. 1H NMR
(300 MHz, C6D6): δ 7.19 (m, 2 H); 6.78 (m, 3 H); 5.64 (ddt, J
) 17.2, 10.2, 5.2 Hz, 1 H); 5.09 (dd, J ) 17.2, 1.7 Hz, 1 H);
4.98 (dd, J ) 10.2, 1.7 Hz, 1 H); 3.78 (s, 2 H); 3.72 (d, J ) 5.2
Hz, 2 H); 0.12 (s, 9 H). 13C NMR (75 MHz, C6D6): δ 148.8,
134.4, 129.3, 118.3, 116.3, 114.5, 103.0, 88.5, 53.7, 40.9, 0.0.
IR (neat): 2958, 2169. Anal. Calcd for C15H21NSi: C, 74.03;
H, 8.70. Found: C, 74.07; H, 8.71.
Gen er a l P r oced u r e for th e Con ver sion of En yn es to
Cyclop en ten on es. In an argon-filled glovebox, a dry reseal-
able Schlenk tube was charged with the Cp(OAr)TiCl2, toluene,
and the substrate. The Schlenk tube was sealed, removed from
the glovebox, and attached to a Schlenk line. Under a flow of
argon, the solution was cooled to -78 °C and a solution of
n-BuLi in hexanes was added dropwise. The reaction mixture
was allowed to warm to 25 °C over the course of 2 h and stirred
at 25 °C for 1 h. To prevent the formation of products resulting
from the addition of butene to the substrate, it was important
that the reaction was allowed to warm under a flow of argon,
rather than in a sealed flask. The flask was subsequently
sealed and attached to the CO source. The flask was evacuated
and backfilled with CO at least three times, then filled to the
desired pressure of CO. The Schlenk tube was sealed and
heated at the temperature indicated for 24 h. It is important
to take appropriate safety precautions when using carbon
monoxide, particularly at elevated pressure. All operations
should be carried out in an efficient fume hood behind a blast
shield. After allowing the reaction mixture to cool to room
temperature, the CO pressure was carefully released in the
hood and the reaction mixture was quenched by the addition
of 2-5 mL of Et2O. Over the course of 15 min, a precipitate
formed. The mixture was then filtered through a plug of silica
gel with the aid of additional Et2O, concentrated, and purified
by flash chromatography.
at 95 °C. Purification by flash chromatography (1:9 Et2O/
hexanes) afforded 64 mg (79% yield) of a white solid, mp 84
°C. H NMR (300 MHz, C6D6): δ 7.86 (m, 2 H); 7.24 (m, 2 H);
1
7.10 (m, 1 H); 3.47 (dd, J ) 12.1, 9.5 Hz, 2 H); 3.23 (dd, J )
17.4, 9.5 Hz, 2 H); 2.48 (m, 3 H); 1.95 (m, 1 H); 1.83 (m, 1 H);
0.98 (s, 9 H); 0.85 (s, 9 H); 0.72 (m, 2 H); 0.09 (d, J ) 1.1 Hz,
6 H); -0.09 (d, J ) 1.5 Hz, 6 H). 13C NMR (75 MHz, C6D6): δ
206.3, 181.6, 134.7, 132.5, 129.0, 128.8, 66.9, 66.0, 52.4, 43.3,
42.1, 36.4, 34.3, 26.1, 25.9, 18.5, 18.3, -5.3 (2C). IR (neat):
2954, 2928, 2896, 2856, 1704, 1650. Anal. Calcd for C28H46O2-
Si2: C, 69.09; H, 9.53. Found: C, 69.24; H, 9.79.
7,7-(9-F lu or en yl)-2-(tr im eth ylsilyl)bicyclo[3.3.3]oct-1-
en -3-on e (6c). The general procedure employing Cp(DPP)-
TiCl2 3a (172 mg, 0.40 mmol), n-BuLi (520 µL, 1.63 M, 0.85
mmol), toluene (8 mL), and CO (1.3 atm) was used to convert
5c (120 mg, 0.38 mmol) to the title compound at 25 °C.
Purification by flash chromatography (1:99-1:9 Et2O/hexanes),
followed by rinsing with hexanes, afforded 73 mg (56% yield)
of a white solid, mp 190-192 °C (decomp). 1H NMR (500 MHz,
C6D6): δ 7.53 (d, J ) 7.6 Hz, 2 H); 7.44 (d, J ) 7.0 Hz, 1 H);
7.23-7.14 (m, 3 H); 7.06 (t, J ) 7.3, 1 H); 3.46 (quintet, J )
8.9 Hz, 1 H); 2.93 (d, J ) 16.8 Hz, 1 H); 2.69 (d, J ) 17.7, 1
H); 2.49 (dd, J ) 13.4, 7.3 Hz, 1 H); 2.24 (dd, J ) 12.8, 8.5 Hz,
1 H); 1.82 (dd, J ) 12.8, 10.7 Hz, 1 H); 1.51 (dd, J ) 13.7, 8.5
Hz, 1 H); 0.32 (s, 9 H). 13C NMR (125 MHz, C6D6): δ 192.0,
166.2, 154.5, 154.4, 140.0, 139.7, 136.7, 127.7, 127.5, 127.4,
123.4, 123.2, 120.1, 120.0, 102.9, 59.5, 53.7, 46.1, 45.8, 39.6,
1.5. IR (neat): 3556, 2962, 2280, 1618 cm-1. Anal. Calcd for
C23H24OSi: C, 80.20; H, 7.03. Found: C, 80.48; H, 7.01.
3-P h en yl-6-(tr im eth ylsilyl)-3-a za bicyclo[3.3.0]oct-5-en -
7-on e (6d ). The general procedure employing Cp(DPP)TiCl2
3a (35 mg, 0.10 mmol), n-BuLi (130 µL, 1.6 M, 0.20 mmol),
toluene (4 mL), and CO (2.1 atm) at 95 °C was used to convert
5d (70 mg, 0.29 mmol) to the title compound. Purification by
flash chromatography (1:4 Et2O/hexanes) afforded 73 mg (68%
yield) of a white solid, mp 126-127 °C. 1H NMR (500 MHz,
C6D6): δ 7.27 (dd, J ) 8.5, 7.3 Hz, 2 H); 6.84 (t, J ) 7.3 Hz, 1
H); 6.43 (d, J ) 8.5, 2 H); 3.91 (d, J ) 16.2 Hz, 1 H); 3.66 (d,
J ) 16.2 Hz, 1 H); 3.18 (t, J ) 8.5 Hz, 1 H); 2.59 (m, 1 H); 2.22
(dd, J ) 17.3, 6.9 Hz, 1H); 2.01 (dd, J ) 10.4, 8.5 Hz, 1 H);
1.72 (dd, J ) 17.3, 4.5 Hz, 1 H); 0.26 (s, 9 H). 13C NMR (125
MHz, C6D6): δ 188.0, 147.8, 136.2, 129.5, 128.2, 117.4, 112.5,
51.4, 49.3, 45.6, 41.1, -1.3. IR (neat): 3366, 2959, 1691, 1622,
1598. Anal. Calcd for C16H21NOSi: C, 70.81; H, 7.81. Found:
C, 70.80; H, 7.79.
3-Ben zyl-8-m eth yl-6-(tr im eth ylsilyl)-3-azabicyclo[3.3.0]-
oct -5-en -7-on e (6e). The general procedure employing Cp-
(DPP)TiCl2 3a (43 mg, 0.10 mmol), n-BuLi (130 µL, 1.63 M,
0.21 mmol), toluene (4 mL), and CO (2.1 atm) at 95 °C was
used to convert 5e (80 mg, 0.29 mmol) to the title compound.
Purification by flash chromatography (1:5 Et2O/hexanes to 1:3
1
Et2O/hexanes) afforded 51 mg (59% yield) of a yellow oil. H
NMR (500 MHz, C6D6): δ 7.34 (d, J ) 7.5 Hz, 2 H); 7.23 (t, J
) 7.5 Hz, 2 H); 7.13 (m, 1 H); 3.81 (dd, J ) 17.7, 1.2 Hz, 1 H);
3.43 (s, 2 H); 2.90 (t, J ) 7.5 Hz, 1 H); 2.85 (dd, J ) 17.7, 2.1
Hz, 2 H); 2.54 (m, 1 H); 1.84 (dq, J ) 7.3, 4.6 Hz, 1 H); 1.47
(dd, J ) 11.0, 8.2, 1 H); 1.09 (d, J ) 7.3 Hz, 3 H); 0.23 (s, 9 H).
13C NMR (125 MHz, C6D6): δ 212.9, 190.0, 139.2, 134.2,
128.8, 128.7, 127.5, 60.0, 57.3, 55.9, 54.9, 48.0, 13.6, -1.3. IR
(neat): 2961, 2791, 1702, 1621. Anal. Calcd for C18H25NOSi:
C, 72.20; H, 8.42. Found: C, 72.33; H, 8.44. The relative
stereochemistry was anticipated to be trans based on the
geometry of the starting material, and this was confirmed by
an NOE difference experiment indicating a 4.4% enhancement
of the methine resonance (δ 2.54) upon irradiation of the
methyl resonance (δ 1.09).
7,7-Bis(ter t-b u t yld im et h ylsilyloxym et h yl)-3-p h en yl-
[3.3.0]bicyclooct-1-en -3-on e (6b). The general procedure
employing Cp(DME)TiCl2 3c (10 mg, 0.03 mmol), n-BuLi (37
µL, 1.61 M, 0.06 mmol), toluene (2.4 mL), and CO (1 atm) was
used to convert 7b (77 mg, 0.17 mmol) to the title compound
9-Bu t-2-yn yl-9-(3-m eth ylbu t-2-en yl)flu or en e (8). A hex-
ane solution of n-BuLi (31 mL, 1.6 M, 50 mmol) was added to
a solution of fluorene (8.3 g, 50 mmol) in THF (100 mL) at
-78 °C. The resulting slurry was warmed to 25 °C and stirred
for 30 min, producing a clear solution. The solution was

Monocyclopentadienyltitanium Aryloxides
Organometallics, Vol. 21, No. 4, 2002 747
recooled to -78 °C, and 1-bromo-2-butyne (4.4 mL, 50 mmol)
was added. The reaction mixture was warmed to 25 °C and
stirred for 12 h. Saturated aqueous NH4Cl was added, and the
mixture was extracted with Et2O (approximately 400 mL). The
organic layer was dried with MgSO4, filtered, and concentrated
to afford a yellow oil. This material was purified by vacuum
distillation (120-130 °C, 0.01 mm) to provide 11 g (quantita-
tive yield) of 9-but-2-ynylfluorene as a white solid. To a solution
of this compound (3.3 g, 15 mmol) in THF at 0 °C was added
a hexane solution of n-BuLi (10.5 mL, 1.6 M, 15 mmol). The
reaction mixture was allowed to warm to 25 °C, stirred for 1
h, and then cooled to -78 °C. A solution of the 3-methyl-2-
butenyl methanesulfonate (generated in situ, immediately
prior to use, from 3-methyl-2-butene-1-ol (3 mL, 30 mmol),
Et3N (4.5 mL, 32 mmol), and MsCl (2.3 mL, 30 mmol) in THF
(60 mL)) was added to the 9-but-2-ynylfluorenyllithium solu-
tion. The reaction mixture was warmed to 25 °C and stirred
for 12 h. Saturated aqueous NH4Cl was added, and the mixture
was extracted with Et2O (200 mL). The Et2O solution was
rinsed with brine, dried with MgSO4, filtered, and concen-
trated. Purification by flash chromatography (hexanes-1:19
Et2O/hexanes) afforded 1.5 g (34% yield) of a viscous oil. 1H
NMR (500 MHz, C6D6): δ 7.57 (m, 4 H); 7.20 (m, 4 H); 4.89 (t,
J ) 7.3 Hz, 1 H); 2.92 (d, J ) 7.0 Hz, 2 H); 2.60 (q, J ) 2.4 Hz,
2 H); 1.46 (t, J ) 2.4 Hz, 3 H); 1.39 (s, 3H); 1.31 (d, J ) 0.9
Hz, 3 H). 13C NMR (125 MHz, C6D6): δ 150.4, 140.9, 133.5,
128.3, 127.6, 127.2, 124.1, 120.2, 120.1, 77.7, 76.9, 53.2, 36.2,
29.7, 25.7, 18.1, 3.3. IR (neat): 2915, 1448. Anal. Calcd for
the proton resonance at δ 7.72 was observed upon irradiation
at δ 4.45 and vice versa. However, irradiation at δ 4.45 had
no influence on the resonance at δ 7.24. Irradiation at δ 7.72
also resulted in enhancement of the resonance at δ 6.91.
9-cis-2-Bu ten yl-9-(3-m eth yl-2-bu ten yl)flu or en e (10H an d
10D). Metallacycle 9 was prepared as described from enyne 8
(30 mg, 0.10 mmol) and Cp(DIPP)TiCl2 3b (34 mg, 0.10 mmol).
The reaction mixture was divided into two equal portions, and
each was treated with 1 N aqueous HCl (200 µL) or DCl (20
wt % % in D2O, 200 µL) at 0 °C and warmed to room
temperature. The mixture was added to H2O and extracted
with Et2O. The Et2O solution was dried with MgSO4, filtered,
and concentrated. Purification by flash chromatography (hex-
anes-1:50 Et2O/hexanes) provided 5 mg (35% yield) of the title
compound as a colorless oil. 1H NMR (500 MHz, C6D6): δ 7.56
(dd, J ) 7.0, 1.5 Hz, 2 H); 7.32 (dd, J ) 7.0, 1.5 Hz, 2 H); 7.18
(m, 4 H); 5.15 (m, 1 H); 5.01 (m, 1 H); 4.85 (tt, J ) 7.5, 1.5 Hz,
1 H); 2.72 (d, J ) 7.0 Hz, 2 H); 2.69 (d, J ) 7.0 Hz, 2 H); 1.38
(s, 3 H); 1.36 (d, J ) 6.0 Hz, 3 H); 1.32 (s, 3 H). 13C NMR (125
MHz, C6D6): δ 13.1, 18.0, 25.7, 36.5, 38.0, 55.0, 120.0, 120.2,
123.7, 125.6, 126.0, 127.1, 127.3, 133.2, 141.4, 150.5. HRMS
1
(m/z): M+ calcd for C22H24, 288.1873; found, 288.1871. The H
NMR of 10D matched that for 10H, with the absence of peaks
at 5.15 and 5.01 ppm.
1-Eth yliden e-4,4-(9-flu or en yl)-2-isopr opylcyclopen tan e
(11). Metallacycle 9 was prepared as described from enyne 8
(55 mg, 0.19 mmol) and Cp(DIPP)TiCl2 3b (68 mg, 0.20 mmol)
in toluene (8 mL). TfOH from a freshly opened ampule (36
µL, 0.40 mmol) was added to the solution at -78 °C, and the
reaction mixture was stirred for 5 h. The reaction mixture was
warmed to room temperature and added to a separatory funnel
with H2O and Et2O (40 mL). The layers were separated, and
the organic solution was rinsed with saturated aqueous
NaHCO3, dried with MgSO4, filtered, and concentrated. Puri-
fication by column chromatography (hexanes; compound 11
is the least polar component of the product/ligand mixture)
provided 10 mg (18% yield) of the title compound as a colorless
oil. 1H NMR (500 MHz, C6D6): δ 7.62 (m, 2 H); 7.53 (d, J )
7.3 Hz, 1 H); 7.30-7.17 (m, 5 H); 5.40 (m, 1 H); 2.96 (m, 1 H);
2.66 (dd, J ) 16.5, 2.4 Hz, 1 H); 2.47 (d, J ) 2.5 Hz, 1 H); 2.06
(dd, J ) 12.9, 10.5 Hz, 1 H); 1.98 (m, 1 H); 1.70 (ddd, J )
12.9, 8.2, 1.8 Hz, 1 H); 1.51 (d, J ) 6.7 Hz, 3 H); 0.91 (d, J )
7.0 Hz, 3 H); 0.85 (d, J ) 7.0 Hz, 3 H). 13C NMR (125 MHz,
C6D6): δ 154.7, 154.2, 151.7, 145.6, 140.6, 139.7, 127.7, 127.5,
127.4, 127.3, 123.5, 122.9, 120.0, 117.0, 55.8, 49.6, 42.1, 39.7,
31.7, 21.2, 16.9, 15.0. IR (neat): 2910. HRMS (m/z): M+ calcd
for C22H24, 288.1873; found, 288.1864.
4,4-(9-F lu or en yl)-1-m et h yl-2-m et h ylen ecyclop en t a n e
(12). In an argon-filled glovebox, Cp(DM)TiCl2 3d (18 mg, 0.06
mmol), 9,9-diallylflourene40 (87 mg, 0.35 mmol), and THF (2.4
mL) were combined in a resealable Schlenk tube. The flask
was removed from the glovebox, attached to a Schlenk line,
and cooled to -78 °C. An Et2O solution of cyclohexyl-MgCl (60
µL, 2.0 M, 0.12 mmol) was added; the solution was allowed to
warm to 25 °C over the course of 2 h and was stirred at room
temperature for 1 h. Concentration of the crude reaction
mixture and purification by flash chromatography (hexanes)
yielded 78 mg (90% yield) of the cyclized product as a white
solid. The 1H NMR was consistent with reported data.8
C
22H22: C, 92.26; H, 7.74. Found: C, 92.15; H, 7.90.
Tita n a cyclop en ten e (9). In an argon-filled glovebox, a
resealable Schlenk tube was charged with Cp(DIPP)TiCl2 3b
(173 mg, 0.50 mmol), enyne 8, and toluene (20 mL). The flask
was removed from the box, attached to a Schlenk line, and
cooled to -78 °C. Under a flow of argon, a hexane solution of
n-BuLi (0.64 mL, 1.63 M, 1.05 mmol) was slowly added. The
solution was stirred at -78 °C for 1.5 h, slowly warmed to 25
°C, and stirred for 2 h, producing a dark brown solution. The
reaction mixture was concentrated in vacuo on a Schlenk line,
and the flask was sealed and transferred to the glovebox. The
resulting residue was dissolved in pentane, filtered through a
pad of Celite, and concentrated to afford 289 mg (95% yield)
of a brown solid, mp 132-133 °C, that was 90% pure by 1H
NMR. Efforts to purify this compound resulted in material of
diminished purity; the complex was always cleanest immedi-
atly upon isolation. Furthermore, attempts at purification by
chromatography in the glovebox using alumina (dried at 200
°C under high vacuum for 24 h) resulted in the isolation of
compund 10H. Although the presence of small amounts of
impurities was detected by NMR, they did not appear to
1
complicate the interpretation of spectra. H NMR (500 MHz,
C6D6): δ 7.72 (d, J ) 7.5 Hz, 1 H); 7.62 (d, J ) 6.5 Hz, 1 H);
7.59 (d, J ) 7.5 Hz, 1 H); 7.24 (m, 3 H); 7.14 (m, 2 H); 7.10 (t,
J ) 7.8 Hz, 1 H); 7.01 (t, J ) 7.5 Hz, 1 H); 6.91 (t, J ) 7.8 Hz,
1 H); 4.54 (m, 1 H); 3.35 (m, 1 H); 3.43 (m, 1 H); 3.02 (d, J )
17.3 Hz, 1 H); 2.89 (d, J ) 17.3 Hz, 1 H); 2.49 (t, J ) 12.0, 1
H); 2.22 (ddd, J ) 12.3, 7.8, 2.3 Hz, 1 H); 1.96 (s, 3 H), 1.38 (s,
3 H); 1.30 (d, J ) 7.0 Hz, 3 H); 1.19 (d, J ) 6.5 Hz, 3 H); 0.83
(s, 3 H). 13C NMR (125 MHz, C6D6): δ 201.3, 160.8, 153.0,
150.9, 144.5, 141.2, 139.7, 136.8, 128.3, 128.1, 127.6, 127.5,
127.4, 123.9, 123.4, 122.8, 121.3, 120.2, 120.0, 113.6, 72.4, 52.5,
46.5, 46.0, 38.9, 29.0, 26.5, 24.5, 23.7. IR (KBr): 2959, 1654,
1634. HRMS (m/z): M+ calcd for C39H44TiO, 576.2872; found,
Ack n ow led gm en t . We thank Dr. William Davis
of the MIT X-ray Facility for determination of the
crystal structures of 3a , 3c, and 4a . We thank Dr.
J effrey Simpson of the MIT Department of Chemistry
Instrumentation Facility (DCIF) for performing 2D
NMR experiments with metallacycle 9. We thank Dr.
Alan Heyduk for helpful assistance with calculations of
1
576.2862. The 1D H and 13C NMR peaks for the metallacycle
were assigned, as shown in Figure 6, based on a series of NMR
experiments including gCOSY, DEPT135, HMQC, HMBC, and
NOE difference experiments.32 Indicative HMBC cross-peaks
were observed as follows: the methyl proton resonances at δ
1.96 with the olefin carbon resonances at δ 201.2, 144.5; the
proton resonances at δ 2.89, 3.02 with the carbon resonance
at δ 144.5; the proton resonance at δ 4.45 with the carbon
resonances at δ 46.0, 72.4, 144.5. An NOE enhancement of
(40) Knight, K. S.; Wang, D.; Waymouth, R. M.; Ziller, J . J . Am.
Chem. Soc. 1994, 116, 1845-1854.

748 Organometallics, Vol. 21, No. 4, 2002
Sturla and Buchwald
the titanium aryloxide angles. We thank Dr. Magnus
Eriksson for the preparation and characterization of
the metallacycle described in ref 30. We thank Dr. Alex
Muci for assistance in the preparation of the manu-
script. S.J .S. acknowledges the Ford Foundation and
the American Chemical Society, Division of Organic
Chemistry, sponsored by Pfizer, Inc., for graduate
fellowships. We are grateful for support of this work by
the National Institutes of Health (GM46059) and the
National Science Foundation (instrumentation grants
DBI-9729592 and CHE-9808061).
Su p p or tin g In for m a tion Ava ila ble: Listings of X-ray
structural data for complexes 3a , 3c, and 4a . Heteronuclear
and 1H NMR spectra for 9. This material is available free of
charge via the Internet at http://pubs.acs.org.
OM010755U