Synthesis of unsymmetrical diolate, oxametallacyclopentene, amido-alkoxide and thiolato-alkoxide complexes using dialkyl and diaryl titanium aminotroponiminate complexes: A route to unsymmetrical vicinal diols

Article abstract of DOI:10.1021/ja992662y

The reactivity of [TiR₂(Me₂ATI)₂] complexes, where Me₂ATI = N,N′-dimethylaminotroponiminate, or L, with CO or RNC in the presence of various organic electrophiles has been investigated. The compounds TiMe₂L₂ and TiPh₂L₂ react with CO and aldehydes or ketones to afford unsymmetrical diolate complexes that convert to the corresponding vicinal diols after hydrolysis. Phenyl acetylene also reacts to form the oxametallacyclopentene complex [Ti(OCMe₂CH=CPh)(Me₂ATI)₂]. Treatment of TiMe₂L₂ with RNC yields the free imine and a source of low-valent titanium. Trapping this intermediate with 2 equiv of benzaldehyde or benzil affords the titanium diolate or enediolate complex, respectively. When 1 equiv each of benzophenone and either N-tosylbenzaldimine or acetone were added to the intermediate, [Ti(Ph₂COCN(SO₂tol)HPh)(Me₂-ATI)₂] and [Ti(Ph₂COCOMe₂)(Me₂ATI)₂], respectively, were obtained. The titanium thiolato-alkoxide complex [Ti(Ph₂CSCOMe₂)(Me₂ATI)₂] was prepared by use of thiobenzophenone and acetone. This chemistry allows for the preparation of unsymmetrical diols and oxametallacyclopentene complexes from Ti(IV) dialkyls, CO, and either carbonyl compounds or alkynes. Amido-alkoxide and thiolato-alkoxide complexes can be prepared by the reaction of Ti(IV) dialkyl complex, 2 equiv of benzophenone, and either an imine or thioketone.

Full text of DOI:10.1021/ja992662y

11762
J. Am. Chem. Soc. 1999, 121, 11762-11772
Synthesis of Unsymmetrical Diolate, Oxametallacyclopentene,
Amido-Alkoxide and Thiolato-Alkoxide Complexes Using Dialkyl
and Diaryl Titanium Aminotroponiminate Complexes: A Route to
Unsymmetrical Vicinal Diols
Dietrich P. Steinhuebel and Stephen J. Lippard*
Contribution from the Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
ReceiVed July 27, 1999
Abstract: The reactivity of [TiR2(Me2ATI)2] complexes, where Me2ATI ) N,N′-dimethylaminotroponiminate,
or L, with CO or RNC in the presence of various organic electrophiles has been investigated. The compounds
TiMe2L2 and TiPh2L2 react with CO and aldehydes or ketones to afford unsymmetrical diolate complexes that
convert to the corresponding vicinal diols after hydrolysis. Phenyl acetylene also reacts to form the
oxametallacyclopentene complex [Ti(OCMe2CHdCPh)(Me2ATI)2]. Treatment of TiMe2L2 with RNC yields
the free imine and a source of low-valent titanium. Trapping this intermediate with 2 equiv of benzaldehyde
or benzil affords the titanium diolate or enediolate complex, respectively. When 1 equiv each of benzophenone
and either N-tosylbenzaldimine or acetone were added to the intermediate, [Ti(Ph2COCN(SO2tol)HPh)(Me2-
ATI)2] and [Ti(Ph2COCOMe2)(Me2ATI)2], respectively, were obtained. The titanium thiolato-alkoxide complex
[Ti(Ph2CSCOMe2)(Me2ATI)2] was prepared by use of thiobenzophenone and acetone. This chemistry allows
for the preparation of unsymmetrical diols and oxametallacyclopentene complexes from Ti(IV) dialkyls, CO,
and either carbonyl compounds or alkynes. Amido-alkoxide and thiolato-alkoxide complexes can be prepared
by the reaction of Ti(IV) dialkyl complex, 2 equiv of benzophenone, and either an imine or thioketone.
Introduction
The facile preparation of unsymmetrical 1,2-diols and 2-ami-
no alcohols is an important goal in synthetic chemistry.1 The
dihydroxylation and aminohydroxylation of olefins represents
a powerful method for preparing these compounds.2,3 An
alternative approach to the preparation of 1,2-functionalized
hydrocarbons is the metal-mediated coupling of two dissimilar
carbonyl compounds or the coupling of an imine with a carbonyl
compound. These coupling methods rely on the formation of
an η2-carbonyl complex, the metal-carbon bond of which
possesses sufficient nucleophilicity to attack mild electrophiles.
The requisite η2-carbonyl complex can be generated by treatment
of a low-valent metal fragment with a carbonyl compound or
by a multicomponent approach involving double alkyl migration
to CO (eq 1). In this paper, we describe our use of both methods
to prepare 1,2-diolate and amido-alkoxide complexes.
Figure 1. Representative metal-mediated syntheses of vicinal diols.
metals. In one of the first titanium-mediated syntheses of
unsymmetrical diols, acetone was coupled with cyclic ketones
to afford unsymmetrical diols.4 Little is known about the details
of the titanium chemistry involved in this reaction. Subsequently,
it was reported that treatment of equimolar amounts of Yb metal
and benzophenone in THF and HMPA with carbonyl com-
pounds or alkynes afforded unsymmetrical diols and allylic
alcohols.5 The structurally characterized Yb(II) η2-benzophenone
(1)
Several metal-mediated cross-coupling reactions of dissimilar
carbonyl compounds have been reported (Figure 1). These
methods employ low-valent group IV, group V, or lanthanide
(1) Wirth, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 61-63.
(2) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483-2547.
(3) Li, G.; Chang, H.-T.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1996, 35, 451-454.
(4) Corey, E. J.; Danheiser, R. L.; Chandrasekaran, S. J. Org. Chem.
1976, 41, 260-265.
(5) Hou, Z.; Takamine, K.; Aoki, O.; Shiraishi, H.; Fujiwara, Y.;
Taniguchi, H. J. Org. Chem. 1988, 53, 6077-6084.
10.1021/ja992662y CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/04/1999

Route to Unsymmetrical Vicinal Diols
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11763
would afford unsymmetrical diols. This approach offers versatil-
ity, since each of the reaction components can be varied.
Moreover, it is not limited to the use of aromatic ketones, and
the plentiful C1 source, carbon monoxide, would be used.
Electrophiles such as alkynes or imines would afford allylic
alcohols and 2-amino alcohols, also useful materials. An
alternative and complementary methodology that we wished to
explore was the coupling of two distinct carbonyl compounds
with a suitable low-valent metal complex.
Previous work in our laboratory demonstrated that zirconium
and hafnium tropocoronand dialkyls react with CO to form
isolable η2-ketone complexes. Chalcone, cyclohexenone, and
cyclohexyl phenyl ketone react with these complexes to yield
unsymmetrical zirconium diolates (eq 2).13,14 With this precedent
(2)
having been established, we wished to explore the scope of this
chemistry and to extend it to a range of carbonyl compounds
and other electrophiles as well as additional dialkylmetal starting
materials. Titanium was substituted for zirconium to facilitate
cleavage of the resultant metal diolate linkage under the reaction
conditions. Aminotroponiminate (R2ATI) ligands were used in
place of tropocoronands to facilitate the synthetic procedures
and derivatization steps.
Here we describe two complementary methods for the in situ
generation of titanium aminotroponiminate η2-carbonyl com-
plexes in order to prepare unsymmetrical diols and amido
alkoxide complexes. The first procedure employs a multicom-
ponent preparation of vicinal diols from titanium dialkyl
complexes, CO, and carbonyl compounds. The second involves
generation of transient low-valent titanium complexes to mediate
the coupling of ketones with electrophiles such as an imine and
other ketones. A portion of the former approach has been
reported in preliminary form.15
Figure 2. Syntheses of vicinal diols mediated by some well-defined
carbonyl compounds and metal-mediated syntheses of amino-alcohols
and amido-alkoxide complexes.
complex isolated from this reaction was a competent mediator
of the coupling reactions.6 Finally, a vanadium(II) reagent and
chelating, R-substituted aldehydes were employed to effect a
hetero-cross-coupling reaction.7 Many mechanistic pathways can
be envisioned for these transformations. Given the structure of
the Yb η2-benzophenone complex, it is intriguing to consider
that they all proceed by insertion of the electrophile into the
metal-carbon bond of the early transition metal or lanthanide
η2-carbonyl complex.
Two additional results support the notion that η2-carbonyl
complexes are viable intermediates for coupling dissimilar
carbonyl compounds. Acetophenone reacts with an Me2AlCl-
stabilized η2-ketone zirconocene complex to yield a zirconium
diolate complex (Figure 2).8 In an extension of this work,
lithium-stabilized zirconocene aldehyde complexes were allowed
to react with aromatic aldehydes or ketones to afford vicinal
diols in good isolated yield.9 An interesting feature of these
two zirconocene systems is the presence of a Lewis acid (Li+
or Al3+) that could attenuate the reactivity of the carbonyl group
prior to insertion. Substitution of an imine for the carbonyl group
in this chemistry would afford 2-amino alcohols. The few
methods reported to date for the metal-mediated synthesis of
amino alcohols involve reaction of carbonyl compounds with
early metal η2-imine complexes (Figure 2).10-12
Experimental Section
General Information. Hexane and benzene were distilled from
sodium benzophenone ketyl under nitrogen. Toluene was distilled from
sodium, and halogenated solvents were distilled from calcium hydride
under nitrogen. Diethyl ether was passed through a column of activated
alumina, and pentane was passed through a column of Ridox catalyst
and alumina and then collected under vacuum. Benzaldehyde and trans-
cinnamaldehyde were distilled from potassium carbonate, whereas
acetophenone was distilled from calcium chloride; all three substrates
were degassed three times and stored in a drybox over molecular sieves.
Acetone was purified by preparation of the sodium iodide adduct,
distillation, and degassing. Phenyl acetylene was distilled under reduced
pressure and stored in a drybox. tert-Butyl isocyanide, xylyl isocyanide,
benzophenone, and benzil were used as received. CO gas (Airco) was
used directly from the tank. TiR2L2,16 where L ) Me2ATI, thiobenzo-
phenone,17 and the imines N-tosylbenzaldimine,18 t-BuNdCMe2,19,20
We were interested to establish that the three-component
coupling of a metal complex, CO, and carbonyl compound
(6) Hou, Z.; Yamazaki, H.; Kobayashi, K.; Fujiwara, Y.; Taniguchi, H.
J, Chem. Soc., Chem. Commun. 1992, 722-724.
(7) Freudenberger, J. H.; Konradi, A. W.; Pedersen, S. F. J. Am. Chem.
Soc. 1989, 111, 8014-8016.
(8) Waymouth, R. M.; Clauser, K. R.; Grubbs, R. H. J. Am. Chem. Soc.
1986, 108, 6385-6387.
(9) Askham, F. R.; Carroll, K. M. J. Org. Chem. 1993, 58, 7328-7329.
(10) Buchwald, S. L.; Watson, B. T.; Wannamaker, M. W.; Dewan, J.
C. J. Am. Chem. Soc. 1989, 111, 4486-4494.
(11) Roskamp, E. J.; Pedersen, S. F. J. Am. Chem. Soc. 1987, 109, 6551-
6553.
(12) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33, 4469-
4472.
(13) Scott, M. J.; Lippard, S. J. Organometallics 1998, 17, 466-474.
(14) Scott, M. J.; Lippard, S. J. J. Am. Chem. Soc. 1997, 119, 3411-
3412.
(15) Steinhuebel, D. P.; Lippard, S. J. Organometallics 1999, 18, 109-
111.
(16) Steinhuebel, D. P.; Lippard, S. J. Inorg. Chem., in press.
(17) Pedersen, B. S.; Scheibye, S.; Nilsson, N. H.; Lawesson, S.-O. Bull.
Soc. Chim. Belg. 1978, 87, 223-228.

11764 J. Am. Chem. Soc., Vol. 121, No. 50, 1999
Steinhuebel and Lippard
21
and 2,6-Me2C6H3NdCMe2 were prepared by following literature
CD3OD, 25 °C) NMR: δ 143.1, 129.1, 128.6, 128.4, 81.9, 74.1, 26.3,
26.2. HRMS (EI): calcd for C10H14O2 166.0994, found 166.0994.
[PhMeC(OH)C(OH)Me2] (4). A portion of TiMe2L2 (115 mg, 0.309
mmol) was dissolved in 15 mL of toluene in a 25-mL round-bottom
flask equipped with a stir bar and septum. This flask was removed
from the drybox and cooled to -78 °C, and acetophenone (32.5 µL,
0.309 mmol) was added. CO was purged through the solution for 20
min (10-20 psi), and at the 10 min point the cooling bath was removed.
The light red solution was stirred for an additional 2 h under CO
pressure. The reaction was worked up in a manner identical to that
described for 3 to yield 44 mg (79%) of the crystalline diol. TLC: Rf
procedures. Experiments were either performed in a nitrogen-filled
glovebox or by conventional Schlenk line techniques under argon.
Chromatographic purification of products was accomplished using silica
gel-60 (230-400 mesh) by a published method.22 Thin-layer chroma-
tography (TLC) analyses were performed on silica plates and visualized
by both aqueous ceric ammonium molybdate (CAM) stain and/or UV
irradiation. Routine NMR spectra were recorded on a Bruker AC 250,
Varian Unity, or Mercury 300 spectrometer at ambient probe temper-
ature and referenced to the internal 1H and 13C solvent peaks. NOESY
experiments were performed on a Varian 501 at 283 K. Infrared spectra
were recorded as pressed KBr disks with a BioRad FTS-135 FTIR
spectrometer. Mass spectra were determined on a Finnegan 4000 mass
spectrometer with 70-eV ionization.
)
0.29 (2:1:3 hexanes/EtOAc/CH2Cl2). 1H NMR (250 MHz,
CD3OD): δ 7.51 (2H, dd, J ) 8.7, 7.9 Hz), 7.21 (3H, m), 1.58 (3H,
s), 1.11 (3H, s), 1.09 (3H, s). 13C {1H} NMR (62.9 MHz, CD3OD): δ
147.2, 128.3, 127.5, 79.3, 76.1, 25.6, 25.6, 24.7. Anal. Calcd for
C11H16O2: C, 73.30; H, 8.95. Found: C, 73.07; H, 8.58.
Synthetic Procedures. [Ti(PhHCOCOMe2)(Me2ATI)2] (1). A
portion of TiMe2L2 (72 mg, 0.193 mmol) was dissolved in 15 mL of
a 1:1 toluene-benzene mixture in a 25-mL Schlenk flask equipped
with a stir bar and septum. This solution was cooled to -30 °C, and
benzaldehyde (19.6 µL, 0.193 mmol) was added. The flask was quickly
removed from the drybox, and CO was purged though the solution for
20 min (10-20 psi). The light red solution was stirred for an additional
1 h under a CO pressure. The solvent was evaporated and the flask
brought into the drybox. Extraction with ether, filtration, and evapora-
tion yielded a red solid. Diffusion of pentane into a saturated toluene
solution at -30 °C yielded small red needles suitable for X-ray
[PhCHdCH(H)C(OH)C(OH)Me2] (5). A portion of TiMe2L2 (140
mg, 0.376 mmol) was dissolved in 15 mL of toluene in a 25-mL round-
bottom flask equipped with a stir bar and septum. Cinnamaldehyde
(47.4 µL, 0.376 mmol) was dissolved in 5 mL of toluene, and both
vessels were removed from the drybox. The titanium complex was
cooled to -78 °C, and the aldehyde was added under argon. CO was
purged though the solution for 20 min (10-20 psi), and at the 10 min
point the cooling bath was removed. The light red solution was stirred
for an additional 2 h under a CO pressure, and TLC showed
consumption of cinnamaldehyde. Identical workup to that described
for 3 and flash chromatography (gradiant elution, 3:2 to 1:1 hexanes/
EtOAc) yielded 40 mg of the major product as a microcrystalline solid
(55%) and 8 mg (15%) of a minor product. TLC (major): Rf ) 0.37
(1:1 hexanes/EtOAc). 1H NMR (250 MHz, CD3OD): δ 7.38 (2H, d, J
) 7.8 Hz), 7.21 (3H, m), 6.61 (1H, d, J ) 16.0 Hz), 6.32 (1H, dd, J
) 6.8, 16.0 Hz), 3.96 (1H, d, J ) 7.3 Hz), 1.18 (3H, s), 1.17 (3H, s).
13C {1H} NMR (62.9 MHz, CD3OD): δ 138.7, 133.3, 130.2, 129.7,
128.7, 127.6, 80.7, 73.9, 26.5, 25.6. HRMS (EI): Calcd for C12H16O2
192.1150, Found 192.1149.
[PhHC(OH)C(OH)Ph2] (6). A portion of TiPh2L2 (52 mg, 0.105
mmol) was dissolved in 15 mL of CH2Cl2 in a 25-mL round-bottom
flask equipped with a stir bar and septum. This solution was cooled to
-30 °C and benzaldehyde (11 µL, 0.105 mmol) added. The flask was
quickly removed from the drybox, CO was purged through the solution
for 15 min (10-20 psi), and the light red solution was stirred for an
additional 4 h under a CO pressure. The reaction was worked up in a
manner identical to that described for 3, except that 5:1:0.5 hexanes/
CH2Cl2/EtOAc was used, to yield 21.6 mg (70%) of the crystalline
diol. Vapor diffusion of hexanes into a saturated chloroform solution
at room temperature afforded colorless blocks that were used for
elemental analysis. TLC: Rf ) 0.28 (5:1:0.5 hexanes/CH2Cl2/EtOAc).
1H NMR (250 MHz, CD3OD): δ 7.60 (2H, d, J ) 7.5 Hz), 7.15 (13H,
m), 5.55 (1H, s). 13C {1H} NMR (62.9 MHz, CD3OD): δ 147.6, 146.5,
142.3, 129.9, 128.9, 128.8, 128.4, 128.0, 127.9, 127.8, 127.4, 82.0,
76.9. Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.82;
H, 6.22.
[Me2C(OH)C(OH)Ph2] (7). TiPh2L2 (110 mg, 0.221 mmol) was
dissolved in 15 mL of CH2Cl2 in a 25-mL round-bottom flask equipped
with a stir bar and septum. Acetone (16.3 µL, 0.122 mmol) was
dissolved in 5 mL of CH2Cl2 in a vial, and both flasks were withdrawn
from the drybox. The acetone solution was added to the titanium
complex at -78 °C, and CO was purged though the solution for 20
min; at the 10 min point the cooling bath was removed. The light red
solution was stirred for an additional 3 h under a CO pressure (10-15
psi). The reaction was worked up in a manner identical to that described
for 3 by using 5:1:0.5 hexanes/CH2Cl2/EtOAc to yield 27.4 mg (52%)
of a crystalline diol. TLC: Rf ) 0.21 (5:1:0.5 hexanes/CH2Cl2/EtOAc).
1H NMR (250 MHz, CD3OD): δ 7.67 (4H, d, J ) 8.3 Hz), 7.18 (6H,
m), 1.24 (6H, s). 13C {1H} NMR (62.9 MHz, CD3OD): δ 147.0, 129.8,
128.3, 127.6, 83.5, 77.4, 27.3. Anal. Calcd for C16H18O2: C, 79.31; H,
7.49. Found: C, 79.03; H, 7.58.
1
crystallography. H NMR (C6D6): δ 7.52 (4H, d, J ) 7.9 Hz), 7.13
(3H, m), 6.82 (4H, q, J ) 9.3 Hz), 6.51 (1H, s), 6.27 (4H, m), 3.38
(3H, s), 3.20 (9H, s), 1.49 (3H, s), 1.38 (3H, s). 1H NMR (CD2Cl2): δ
7.21 (9H, m), 6.49 (6H, m), 6.15 (1H, s), 3.44 (9H, s), 3.42 (3H, s),
1.28 (3H, s), 1.07 (3H, s). Anal. Calcd for TiC28H34N4O2: C, 66.40;
H, 6.77; N, 11.06. Found: C, 66.21; H, 6.78; N, 11.38.
[Ti(Ph2COCOMe2)(Me2ATI)2] (2). A portion of TiPh2L2 (100 mg,
0.201 mmol) was dissolved in 15 mL of toluene in a 25-mL Schlenk
flask equipped with a stir bar and septum. Acetone (14.8 µL, 0.201
mmol) was dissolved in 5 mL of toluene in a vial capped by a septum,
and both flasks were withdrawn from the drybox. The acetone solution
was added to the titanium complex at -78 °C, and the solution was
purged with CO for 20 min (10-20 psi); after 10 min, the cooling
bath was removed. The light red solution was stirred for an additional
1.5 h under a positive pressure of CO, and the solvent was then
removed. The dark red residue was extracted with benzene and then
evaporated to dryness. Vapor diffusion of pentane into a saturated
benzene solution yielded large red blocks (47 mg, 40%) suitable for
X-ray crystallography. 1H NMR (250 MHz, C6D6, 25 °C): δ 7.91 (4H,
d, J ) 7.1 Hz), 7.14 (8H, m), 6.85 (4H, t, J ) 9.9), 6.28 (4H, m), 3.23
(12H, s), 1.78 (6H, s). Anal. Calcd for TiC34H38N4O2: C, 70.10; H,
6.57; N, 9.62. Found: C, 70.57; H, 6.90; N, 9.60.
[PhHC(OH)C(OH)Me2] (3). A portion of TiMe2L2 (104 mg, 0.279
mmol) was dissolved in 15 mL of toluene in a 25-mL round-bottom
flask equipped with a stir bar and rubber septum. This solution was
cooled to -30 °C, and benzaldehyde (29 µL, 0.279 mmol) was added.
The flask was quickly removed from the drybox, and CO was bubbled
through the solution for 20 min at 0 °C (10-20 psi). The light red
solution was stirred for an additional 2 h under positive CO pressure.
The reaction was quenched with 3 M aqueous HCl and the biphasic
mixture stirred for 1 h. The solution was extracted three times with
CH2Cl2, dried with MgSO4, filtered, and evaporated to dryness. Flash
chromatography on silica gel (1:1:2 hexanes/EtOAc/CH2Cl2) yielded
the product as a colorless, crystalline solid (28 mg, 60%). TLC: Rf )
0.26 (1:1:1 hexanes/EtOAc/CH2Cl2). 1H NMR (250 MHz, CD3OD, 25
°C): δ 7.33 (5H, m), 4.53 (1H, s), 1.20 (6H, s). 13C{1H} (62.9 MHz,
(18) Jennings, W. B.; Lovely, C. J. Tetrahedron Lett. 1988, 29, 3725-
3728.
(19) Quast, H.; Meichsner, G.; Seiferling, B. Chem. Ber. 1987, 120, 225-
230.
(20) Weingarten, H.; Chupp, J. P.; White, W. A. J. Org. Chem. 1967,
32, 3246-3249.
[PhCHdCH(H)C(OH)C(OH)Ph2] (8). A portion of TiPh2L2 (112
mg, 0.222 mmol) was dissolved in 10 mL of CH2Cl2 in a 25-mL round-
bottom flask equipped with a stir bar and septum. Cinnamaldehyde
(28.5 µL, 0.222 mmol) was dissolved in 5 mL of toluene, and both
(21) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J. Am. Chem. Soc.
1992, 114, 1708-1719.
(22) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923-
2925.

Route to Unsymmetrical Vicinal Diols
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11765
vessels were removed from the drybox. An analogous procedure to 5
was used, and flash chromatography (5:1:0.5 hexanes/CH2Cl2/EtOAc)
yielded 50.0 mg of the product as a microcrystalline solid (70%).
TLC: Rf ) 0.26 (5:1:0.5 hexanes/CH2Cl2/EtOAc). 1H NMR (250 MHz,
CD3OD): δ 7.59 (2H, d, J ) 8.6 Hz), 7.43 (2H, d, J ) 8.8 Hz), 7.23
(11H, m), 6.49 (1H, d, J ) 15.8 Hz), 6.22 (1H, dd, J ) 15.8, 6.7 Hz),
5.14 (1H, d, J ) 6.7). 13C {1H} NMR (125.77 MHz, CD3OD): δ 144.8,
143.8, 136.7, 133.7, 128.7, 128.7, 128.4, 127.9, 127.6, 127.3, 126.9,
126.8, 126.7, 126.2, 80.3, 76.8.
[Ti(Ph2COCOPh2)(Me2ATI)2] (13). A benzene solution of t-BuNC
(33 µL, 0.293 mmol) and benzophenone (106 mg, 0.586 mmol) was
added to a solution of TiMe2L2 (109 mg, 0.293 mmol) in a 3:1 mixture
of benzene-ether at -30 °C. The brown solution was warmed to room
temperature and stirred for 1 h, and then the solvent was removed.
Vapor diffusion of pentane into a saturated toluene solution at -30 °C
1
yielded a red crystalline mass. H NMR (250 MHz, C6D6, 25 °C): δ
7.75 (8H, d, J ) 6.7 Hz), 6.98 (12H, m), 6.78 (4H, q, J ) 11.2 Hz),
6.23 (4H, t, J ) 7.7 Hz), 6.15 (2H, d, J ) 10.0 Hz), 3.14 (12H, s).
13C{1H} (75 MHz, C6D6, 25 °C): δ 164.7, 149.9, 136.1, 129.3, 127.5,
126.5, 120.7, 105.5, 41.6. Anal. Calcd for TiC44H42N4O2: C, 74.78;
H, 5.99; N 7.93. Found: C, 74.68; H, 6.25; N, 7.87.
[PhHC(OH)C(OH)MePh)] (9). A portion of TiMePhL2 (96 mg,
0.221 mmol) was dissolved in 15 mL of toluene in a 25-mL round-
bottom flask equipped with a stir bar and septum. Benzaldehyde (22.5
µL, 0.221 mmol) was added at -78 °C, and CO was purged though
the solution for 15 min (10-20 psi). The light red solution was stirred
for an additional 2 h under a CO pressure (10-15 psi). The reaction
was worked up in a manner identical to that described for 3 using 3:1:
0.5 hexanes/CH2Cl2/EtOAc to yield 33.5 mg (66%) of an equal mixture
of diastereomeric diols that matched spectra reported in the literature.9
TLC: Rf ) 0.18 (3:1:0.5 hexanes/CH2Cl2/EtOAc). 1H NMR (250 MHz,
CDCl3): δ 7.23 (20H, m), 4.84 (1H, s), 4.76 (1H, s), 1.63 (3H, s),
1.38 (3H, s).
[Ti(Ph2COCN(SO2tol)HPh)(Me2ATI)2] (14). To a benzene solution
of benzophenone (50.96 mg, 0.269 mmol), N-tosylbenzaldimine (72.4
mg, 0.269 mmol), and t-BuNC (31.5 µL, 0.269 mmol) was added a
cold solution of TiMe2L2 (100 mg, 0.269 mmol) in benzene. The red-
brown solution was stirred overnight and filtered, and then the solvent
was removed. The dark solid was dissolved in hot benzene (8 mL)
and filtered, and after cooling, pentane was carefully layered on the
solution. Storage for 1 day at room temperature yielded large red blocks
contaminated with a small amount of long red needles that could be
separated by hand. The sample for elemental analysis and X-ray
crystallography was crystallized a second time from benzene/pentane
[Ti(Me2C(O)HCdCPh)(Me2ATI)2] (10). A solution of TiMe2L2
(147 mg, 0.395 mmol) in benzene was treated with phenyl acetylene
(47.7 µL, 0.434 mmol) in a 25-mL Schlenk flask. The flask was
removed from the drybox, and CO (10-20 psi) was carefully purged
through the solution for 7 min and then stirred under a CO atmosphere
for 1 h. The solvent was removed and the flask brought into the drybox.
The red residue was extracted with Et2O and filtered, and the ether
was removed to yield a red foam. This material was dissolved in a
minimum amount of CH2Cl2, and diffusion of pentane at -30 °C over
2 days yielded red microcrystalline material (110 mg, 2 crops, 54%).
1H NMR (250 MHz, C6D6, 25 °C): δ 7.10 (2H, s), 6.97 (1H, m), 6.88
(6H, m), 6.57 (1H, s), 6.21 (6H, m), 3.12 (12H, s), 1.67 (6H, s). 13C{1H}
(75 MHz, CD2Cl2, 25 °C): δ 207.0, 164.9, 152.9, 152.7, 135.9, 127.4,
125.9, 123.4, 120.8, 112.4, 88.0, 44.2, 30.5. IR (KBr, cm-1) 3075, 3009,
2954, 2906, 2865, 2792, 1590, 1569, 1509, 1450, 1422, 1401, 1378,
1365, 1346, 1267, 1229, 1148, 1101, 1039, 981, 965, 909, 886, 807,
738, 759, 704, 645, 604, 570, 546, 594. The peak due to the dichloro-
methane solvate molecule is not included in the foregoing list. Anal.
Calcd for TiC29H34N4O‚0.15CH2Cl2: C, 67.95; H, 6.71; N, 10.87.
Found: C, 67.70; H, 6.36; N, 10.54.
1
(75 mg, 36%). H NMR (300 MHz, CDCl3, 25 °C): δ 7.56 (2H, d, J
) 6.3 Hz), 7.20 (4H, m), 7.0 (4H, m), 6.86 (2H, m), 6.75 (14H, m),
6.17 (2H, d, J ) 7.5 Hz), 5.91 (2H, d, J ) 11.1 Hz), 3.85 (3H, s), 3.29
(3H, s), 3.19 (3H, s), 2.72 (3H, s), 1.93 (3H, s). 13C {1H} NMR (75
MHz, C6D6): δ 165.4, 165.2, 164.5, 163.9, 163.8, 163.3, 149.1, 146.8,
141.2, 139.4, 139.3, 136.8, 136.4, 136.3, 135.2, 134.9, 129.9, 127.8,
127.6, 127.2, 127.1, 126.9, 126.8, 126.5, 126.1, 125.3, 124.9, 123.0,
121.8, 118.7, 115.1, 114.1, 112.7, 112.1, 111.5, 109.9, 97.2, 80.1, 44.9,
43.9, 42.6, 42.1, 41.1, 38.6, 21.3. IR (KBr, cm-1) 3064, 3031, 2867,
2813, 1567, 1512, 1452, 1420, 1402, 1355, 1304, 1264, 1230, 1172,
1141, 1087, 1038, 981, 947, 920, 887, 803, 793, 747, 699, 680, 669,
617, 591, 566, 530, 501, 421. Anal. Calcd for TiC45H45N5SO3: C, 68.95;
H, 5.79; N 8.93. Found: C, 69.14; H, 6.51; N, 9.13.
[Ti(Ph2CSCOMe2)(Me2ATI)2] (15). A portion of TiMe2L2 (59 mg,
0.158 mmol) was dissolved in 15 mL of benzene and frozen. In a
separate vial, xylyl isocyanide (21 mg, 0.158) and thiobenzophenone
(31 mg, 0.158) were dissolved in 5 mL of benzene. This solution was
added to the thawed solution of metal complex, and stirring was
continued for 1.5 h. Neat acetone (11.6 µL, 0.158 mmol) was then
added to the brown solution, which resulted in an immediate color
change to red. The solution was stirred for an additional hour, filtered,
and then evaporated to dryness. The red solid was dissolved in a
minimum amount of warm benzene, and after cooling, pentane was
diffused into the solution to yield red-brown crystals (45 mg, 42%)
that were suitable for X-ray crystallography. 1H NMR (300 MHz, C6D6,
25 °C): δ 7.84 (4H, m), 7.05 (6H, m), 6.84 (4H, t, J ) 10.8 Hz), 6.29
(6H, m), 3.27 (6H, s), 3.09 (6H, s), 1.74 (6H, s). 13C{1H} (75 MHz,
CDCl3, 25 °C): δ 165.3, 164.1, 148.9, 135.6, 135.4, 128.5, 126.8, 125.2,
120.9, 113.6, 110.9, 98.3, 86.1, 44.0, 29.5. A benzene solvate molecule
[Ti(PhHCOCOPhH)(Me2ATI)2] (11). A benzene solution of t-
BuNC (43.4 µL, 0.384 mmol) was added dropwise to a -30 °C solution
of TiMe2L2 (143 mg, 0.384 mmol) and benzaldehyde (78.0 µL, 0.768
mmol) in benzene. The light red solution became slightly darker and
was stirred for 4 h. The solution was then filtered and the solvent
evaporated. The residue was dissolved in hot benzene, and after cooling
to room temperature, pentane was layered on the solution. Red blocks
(149 mg, 69%) formed that were suitable for X-ray crystallography.
1H NMR (C6D6): δ 7.38 (4H, d, J ) 7.0 Hz), 7.06 (6H, m), 6.85 (4H,
t, J ) 10.2 Hz), 6.55 (2H, s), 6.31 (6H, m), 3.35 (12H, s). 13C{1H} (75
MHz, C6D6, 25 °C): δ 165.5, 144.2, 136.2, 128.5, 127.7, 127.5, 120.6,
112.5, 102.8, 40.5. Anal. Calcd for TiC32H34N4O2: C, 69.31; H, 6.18;
N, 10.10. Found: C, 68.89; H, 6.45; N, 10.15.
1
was identified by X-ray crystallography and H NMR spectroscopy
and the peaks are not listed above. Anal. Calcd for TiC34H38N4OS‚
C6H6: C, 70.99; H, 6.55; N, 8.28. Found: C, 71.10; H, 6.57; N, 8.40.
Collection and Reduction of X-ray Data. All crystals were covered
with Paratone-N (Exxon) and then removed from the drybox for
examination. Suitable single crystals were attached to the tips of quartz
fibers and transferred to a Bruker CCD X-ray diffraction system with
graphite-monochromatized Mo KR radiation (λ ) 0.710 73 Å) con-
trolled by a pentium-based PC running the SMART software package.
The temperature of the crystal was maintained with a Bruker LT-2A
nitrogen cryostat. Procedures for data collection and reduction have
been previously reported.23 Space groups were determined by examining
systematic absences and confirmed by the successful solution and
refinement of the structures. The structures were solved by using either
the direct methods program SIR-92,24 XS, or Patterson methods and
[Ti(PhCOCOPh)(Me2ATI)2] (12). A benzene solution of t-BuNC
(28 µL, 0.247 mmol) and benzil (52 mg, 0.247) was added to a cold
solution of TiMe2L2 (92 mg, 0.247 mmol) in benzene. The brown
solution was warmed to room temperature, stirred for 3 h, and then
evaporated to dryness. Vapor diffusion of pentane into a saturated THF
solution at -30 °C yielded a brown crystalline mass that was washed
1
with pentane and dried (80 mg, 59%). H NMR (250 MHz, C6D6, 25
°C): δ 7.85 (4H, d, J ) 7.5 Hz), 7.11 (4H, t, J ) 7.4 Hz), 6.96 (2H,
m), 6.73 (4H, t, J ) 10.1 Hz), 6.21 (6H, m), 3.35 (12H, s). 13C {1H}
NMR (75 MHz, C6D6): δ 164.2, 145.9, 137.4, 136.2, 127.9, 127.2,
126.1, 121.2, 112.7, 40.7. IR (KBr, cm-1) 3061, 3004, 2869, 2801,
1958, 1871, 1758, 1686, 1600, 1588, 1512, 1425, 1427, 1400, 1357,
1267, 1229, 1149, 1135, 1101, 1067, 1037, 982, 925, 912, 888, 828,
730, 749, 722, 695, 657, 623, 531, 505, 488, 531, 419. Anal. Calcd for
TiC32H32N4O2: C, 69.56; H, 5.84; N 10.14. Found: C, 69.68; H, 6.31;
N, 9.62.
(23) Feig, A. L.; Bautista, M. T.; Lippard, S. J. Inorg. Chem. 1996, 35,
6892-6898.
(24) Burla, M. C.; Camalli, M.; Cascarano, G.; Giacovazzo, C.; Polidori,
G.; Spagna, R.; Viterbo, D. J. Appl. Crystallogr. 1989, 22, 389-393.

11766 J. Am. Chem. Soc., Vol. 121, No. 50, 1999
Steinhuebel and Lippard
Figure 3. ORTEP diagrams (starting from left) of 1, 2, 11, 14, and 15 showing 50% thermal ellipsoids and selected atom labels.
then refined by full-matrix least-squares and Fourier techniques with
SHELXTL-PLUS.25 In general, all non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were either located from difference
Fourier maps (1 and 2) and refined isotropically or assigned idealized
positions and given a thermal parameter 1.2 times the thermal parameter
of the carbon atom to which each was attached (11, 14, and 15).
Absorption corrections were performed with the SADABS program.26
Both 14 and 15 crystallize as benzene solvates. In 14‚C6H6 and 15‚
(25) SHELXTL: Structure Analysis Program. 5.1; Bruker Analytical
X-ray Systems; Madison, WI, 1997.

Route to Unsymmetrical Vicinal Diols
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11767
Table 1. Summary of X-ray Crystallographic Data
complex
formula
fw
1
2
11
14‚C6H6
15‚C6H6
C28H34N4O2Ti
506.49
C34H38N4O2Ti
582.58
C32H34N4O2Ti
554.53
C51H41N5O3STi
861.93
C40H44N4OSTi
676.75
space grp
a, Å
b, Å
P21/n
P21/c
P1h
P1h
P1h
13.336(11)
14.275(9)
14.095(8)
16.222(2)
15.452(2)
11.892(2)
10.384(3)
13.028(4)
13.305(5)
118.10(2)
92.91(4)
110.73(2)
1432.2(8)
2
13.233(4)
13.823(4)
13.863(3)
60.514(15)
88.66(2)
87.33(2)
2205.0(10)
2
10.9698(7)
13.1873(9)
14.6300(9)
115.080(1)
94.619(1)
109.801(2)
1740.0(2)
2
c, Å
R, deg
â, deg
γ, deg
V, Å3
Z
106.81(5)
91.81(1)
2568(3)
4
1.310
-85
0.365
3.70-46.54
10205
3642
2979.4(7)
4
1.299
-85
0.325
3.64-56.56
18065
6876
F
calc, g/cm3
T, °C
1.286
-85
0.334
3.60-56.56
8199
5843
3282
1.298
-85
0.291
3.08-56.46
13993
9759
5559
1.292
-85
0.344
3.18-56.46
11039
7714
4813
µ(Mo KR), mm-1
2θ limits, deg
total no. of data
no. of unique data
obsd dataa
2167
5728
no. of param
452
522
352
0.0868
0.1680
0.506, -0.454
520
0.0595
0.1577
0.761, -0.537
424
0.0526
0.1331
0.624, -0.539
Rb
0.0745
0.1096
0.255, -0.292
0.0349
0.0928
0.295, -0.509
wR2 c
max, min peaks, e/Å3
2
2
a Observation criterion: I > 2σ(I). b R ) ∑||Fo| - |Fc||/∑|Fo|. c wR2 ) {∑[w(Fo - Fc2)2]/∑[w(Fo )2]}1/2
.
Table 2. Selected Bond Distances and Anglesa
C6H6 the carbon atoms of the benzene molecule were refined aniso-
tropically and hydrogen atoms were added. Partially labeled ORTEP
plots of all structures displaying 50% thermal ellipsoids are presented
in Figure 3. Crystallographic data including selected bond distances
and angles can be found in Tables 1 and 2; full crystallographic details
are included in the Supporting Information, Tables S1-S15.
complex
distances (Å)
angles (deg)
1
Ti-O(1)
1.888(4)
1.862(4)
2.109(4)
2.104(4)
2.121(5)
2.106(4)
1.407(6)
1.417(6)
N(1)-Ti-N(4)
155.0(2)
160.2(2)
155.7(2)
81.2(2)
Ti-O(2)
N(3)-Ti-O(1)
O(2)-Ti-N(2)
O(1)-Ti-O(2)
N(3)-Ti-O(2)
Ti-N(1)
Ti-N(2)
Ti-N(3)
94.8(2)
Ti-N(4)
Results and Discussion
O(1)-C(19)
O(2)-C(26)
Preparation of Unsymmetrical Diols. A three-component
coupling of dialkyl titanium complexes, CO, and carbonyl
compounds was achieved. Solutions of TiMe2L2 react rapidly
with CO. By analogy with previous work on zirconium,13 we
assume that double alkyl migration to CO occurs to produce
[Ti(η2-Me2CO)(Me2ATI)2], which could not be isolated. Upon
addition of electrophiles, however, coupled products were
obtained. A benzene solution of TiMe2L2 and 1 equiv of
benzaldehyde reacted rapidly and cleanly with CO to afford a
C(19)-C(26) 1.576(7)
C(26)-C(27) 1.509(8)
C(19)-C(20 1.521(7)
2
Ti-N(1)
Ti-N(2)
Ti-N(3)
Ti-N(4)
Ti-O(1)
Ti-O(2)
2.078(1)
2.134(1)
2.139(1)
2.079(1)
1.875(1)
1.862(1)
N(4)-Ti-N(1)
O(2)-Ti-N(2)
O(1)-Ti-N(3)
O(1)-Ti-O(2)
157.24(5)
161.08(5)
162.05(5)
80.37(4)
Ti-O(1)-C(19) 121.27(8)
O(1)-Ti-N(4)
92.03(4)
C(19)-C(32) 1.610(2)
1
single product (eq 3). The H NMR spectrum of this material
11
14
Ti-N(1)
Ti-N(2)
Ti-N(3)
Ti-N(4)
Ti-O(1)
Ti-O(2)
Ti-N(1)
Ti-N(2)
Ti-N(3)
Ti-N(4)
Ti-N(5)
Ti-O(1)
2.085(4)
2.109(4)
2.086(4)
2.105(4)
1.878(3)
1.872(3)
2.092(3)
2.087(3)
2.099(3)
2.077(3)
2.110(3)
1.864(2)
N(4)-Ti-O(2)
N(1)-Ti-N(3)
N(2)-Ti-O(1)
O(1)-Ti-O(2)
162.7(2)
156.0(2)
163.2(2)
81.5(1)
Ti-O(1)-C(19) 118.8(3)
(3)
N(4)-Ti-N(1)
N(3)-Ti-O(1)
N(2)-Ti-N(5)
Ti-N(5)-C(32) 114.7(2)
Ti-O(1)-C(19) 123.0(2)
160.9(1)
162.3(1)
165.5(1)
C(19)-C(32) 1.568(5)
in C6D6 consisted of two 3H singlets at 1.49 and 1.38 ppm,
assigned to the protons on inequivalent methyl groups of the
diolate ligand. In addition to aromatic peaks, two broad
resonances at 3.38 and 3.20 ppm were observed for the methyl
groups of the ATI ligand. The formulation of this complex as
the unsymmetrical diolate [Ti(PhHCOCOMe2)(Me2ATI)2] (1)
was confirmed by X-ray crystallography (Figure 3). The
coordination geometry of 1 is nearly octahedral and the short
Ti-O distances of 1.862(4) and 1.888(4) Å suggest that
titanium-oxygen bond formation helps to drive this reaction.
15
Ti-N(1)
Ti-N(2)
Ti-N(3)
Ti-N(4)
Ti-O(1)
Ti-S(1)
2.083(2)
2.126(2)
2.103(2)
2.142(2)
1.831(2)
N(1)-Ti-N(4)
N(3)-Ti-S(1)
N(2)-Ti-O(1)
O(1)-Ti-S(1)
Ti-O(1)-C(20) 131.4(2)
97.99(9)
155.07(9)
163.77(7)
155.28(9)
79.85(6)
2.4245(9) Ti-S(1)-C(19)
a Numbers in parentheses are estimated standard deviations of the
last significant figure. Atoms are labeled as indicated in Figure 3.
When the crude reaction mixture was treated with 3 M
aqueous HCl, a single organic product was isolated in 60% yield
after chromatography (Scheme 1). The spectroscopic features
of this compound in C6D6 include two singlets for the inequiva-
lent methyl groups and a singlet for the methine proton,
(26) Program written by Professor George Sheldrick at University of
Go¨ttingen which corrects data collected on Bruker CCD and multiwire
detectors for absorption and decay.

11768 J. Am. Chem. Soc., Vol. 121, No. 50, 1999
Steinhuebel and Lippard
Scheme 1
These studies demonstrate that the multicomponent synthesis
of unsymmetrical diols from CO, titanium dialkyl complexes
and carbonyl compounds proceeds (Scheme 1) in good yield
with few side products. In most cases, either the titanium diolate
complex or free diol can be isolated. The results presented are
consistent with double alkyl migration to form an unobserved,
reactive titanium η2-ketone complex that subsequently couples
with aldehydes and ketones (eq 4). The proposed intermediate
η2-ketone complex must be a mild nucleophile, since no
evidence for deprotonation of added ketones has been obtained.
An important experimental feature of these reactions is that the
electrophile be present in solution upon the addition of CO,
which allows immediate trapping of the putative η2-ketone
complex and avoids decomposition.
consistent with the diol [PhHC(OH)C(OH)Me2] (3). Acetophe-
none also undergoes clean coupling with TiMe2L2 and CO under
similar conditions to afford diol 4 in 79% yield after hydrolysis.
In this case, however, the carbonyl was added at low temperature
since TiMe2L2 will slowly transfer a methyl group to ketones.
Alkenes insert into η2-benzophenone zirconocene com-
plexes.27 We were therefore interested in determining the
products of a reaction with an enone and a η2-carbonyl complex
generated in situ. trans-Cinnamaldehyde was employed as the
coupling partner to furnish the corresponding diol 5 in 55%
yield. No product resulting from acetone addition to the γ
position of cinnamaldehyde was observed, although a small
amount of another product was observed; this material is the
diol resulting from the homo-pinacol coupling of cinnamalde-
hyde.28,29
(4)
This coupling methodology is novel because both alkyl
migration to CO and carbonyl coupling can occur in a single
reaction sequence. Moreover, the Ti-ATI system appears to be
unique in that no significant scrambling of the η2-ketone
intermediate with the coupling partner is observed.31,32 It is
noteworthy that previous examples of carbonyl insertion into
preformed η2-carbonyl adducts relied on a Lewis acid additive
(Li+, AlR3) and utilized zirconium, the strong metal-oxygen
bonds of which provide a significant driving force for the
reaction. The present system does not require any additives and
yields diolates directly from alkyl complexes. The unique nature
of the ATI ligand system for this carbonyl coupling is further
highlighted by the fact that the {Cp2Ti}2+ fragment is not able
to mediate this reaction. Direct reaction of aromatic ketones
with [Cp2Ti(PMe3)2] yields fulvenes, whereas [Cp2Ti(CO)2]
converts enones to homopinacol coupling products.33,34 The
carbonylation of certain titanocene dialkyls affords Cp2Ti(CO)2
and the corresponding dialkyl ketone.35 The reaction described
in the present work is stoichiometric in titanium but utilizes
simple starting materials that should allow maximum flexibility
in the synthesis of unsymmetrical diols.
By analogy to the reactions performed with TiMe2L2,
carbonylation of TiPh2L2 followed by trapping with benzalde-
hyde and hydrolysis yielded diol 6 in 70% yield. The carbonyl
coupling reactions mediated by TiPh2L2 complexes are clean,
except for a small amount of biphenyl formed by decomposition
of TiPh2L2, as detected by analysis of the crude reaction
1
1
mixtures by TLC and H NMR. The H NMR spectrum of 6
consisted of a complicated aromatic region and a singlet for
the methine proton at 5.55 ppm in CD3OD. Acetone also served
as an electrophile to yield the diolate complex 2. The 1H NMR
spectrum of this compound consisted of a broad 6H singlet at
1.78 ppm and an even broader 12H singlet at 3.23 ppm. The
appearance of the inequivalent methyl groups of the ligand as
a broad singlet could be the result of fluxional behavior. The
structure has been verified by X-ray crystallography. The nearly
octahedral geometry and short Ti-O bond lengths, 1.862(1) and
1.875(1) Å, compare well with the structural features of 1
(Figure 3). Hydrolysis of 2 yielded the expected diol 7. Reaction
of TiPh2L2 with CO and trans-cinnamaldehyde yielded diol 8.
In this case, however, no additional product could be detected
by TLC or 1H NMR spectroscopy. The spectroscopic properties
of 8 are nearly identical to those of 5, consistent with trans
olefin geometry. Curiously, it has been reported that mixtures
of Mg, TiCl4 and bulky diaryl ketones result in products
consistent with 1,4-addition to enones.30 Such a reaction has
not been observed under our conditions.
Preparation of an Oxametallacyclopentene Complex. Use
of an alkyne as coupling partner was examined in order to gauge
the reactivity of the putative η2-carbonyl compound. The
resultant oxametallacyclopentene complex should afford an
allylic alcohol after hydrolysis. A benzene solution of TiMe2L2
and 1 equiv of phenyl acetylene reacted cleanly with CO to
afford a red complex that could be recrystallized by diffusion
of pentane into a dichloromethane solution at -35 °C (eq 5).
1
The H NMR spectrum of 10 in C6D6 consists of two singlets
(6 and 12 protons) at 1.67 and 3.12 ppm in addition to a 1H
singlet at 6.57 ppm. These spectral data are consistent with
The mixed alkyl-aryl complex TiMePhL2 also reacts with
benzaldehyde and CO to yield an equal mixture of diastereo-
meric diols 9 after hydrolysis. This assignment was based on
comparison with previously reported spectra.9 Analysis of the
TiMePhL2 crude reaction mixture after hydrolysis by 1H NMR
spectroscopy and TLC did not reveal any other products.
(31) Giannini, L.; Solari, E.; De Angelis, S.; Ward, T. R.; Floriani, C.;
Chiesi-Villa, A.; Rizzoli, C. J. Am. Chem. Soc. 1995, 117, 5801-5811.
(32) Giannini, L.; Caselli, A.; Solari, E.; Floriani, C.; Chiesi-Villa, A.;
Rizzoli, C.; Re, N.; Sgamellotti, A. J. Am. Chem. Soc. 1997, 119, 9709-
9719.
(33) Gleiter, R.; Wittwer, W. Chem. Ber. 1994, 127, 1797-1798.
(34) Schobert, R.; Maaref, F.; Du¨rr, S. Synlett 1995, 83-84.
(35) Fachinetti, G.; Floriani, C. J. Chem. Soc., Chem. Commun. 1972,
654-655.
(27) Erker, G.; Rosenfeldt, F. J. Organomet. Chem. 1982, 224, 29-42.
(28) Chuche, J.; Wiemann, J. Bull. Soc. Chim. Fr. 1968, 1497-1503.
(29) Barden, M. C.; Schwartz, J. J. Am. Chem. Soc. 1996, 118, 5484-
5485.
(30) Pons, J.-M.; Santelli, M. Tetrahedron 1990, 46, 513-522.

Route to Unsymmetrical Vicinal Diols
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11769
insertion of phenyl acetylene into the Ti-C bond of the η2-
of an aldehyde or ketone with a proposed η2-alkyne titanium
complex, generated in situ by reacting an alkyne and Ti(O-i-
Pr)4 with 2 equiv of i-PrMgCl, yields the corresponding allylic
alcohol after hydrolysis; analogous chemistry has also been
reported with tantalum and zirconium.37,39,40 Mixtures of Yb
and benzophenone in HMPA/THF react with diphenylacetylene
to yield allylic alcohols.5 Our multicomponent preparation of
oxametallacyclopentene complexes provides a rare case where
an alkyne inserts into an η2-ketone complex, that was derived
from CO, with good regiochemistry at room temperature.
Reactivity of [TiMe2(Me2ATI)2] with Isocyanides: Trap-
ping with Benzaldehyde. Reaction of an imine with η2-ketone
complexes generated in situ should afford amido-alkoxide
complexes. Unlike reactions with other electrophiles that yielded
clean products however, the imines did not. We therefore
decided to reverse the order of the coupling reaction, by first
forming an η2-imine complex and then treating the material with
a carbonyl compound. A reaction of 1 equiv of 2,6-Me2C6H3-
NC with TiMe2L2 in C6D6 solution gave a surprisingly simple
1H NMR spectrum after about 1 h (eq 7). Similar results were
acetone complex.
(5)
Phenyl acetylene can insert into the Ti-C bond of an η2-
acetone complex in either of two ways, depicted as 10a or 10b.
If the insertion reaction is considered to proceed in a stepwise
manner, electronic considerations favor attack â to the phenyl
ring so that the developing negative charge can be stabilized at
a benzylic position (eq 6). The effect of steric factors on the
(7)
obtained with t-BuNC. The major product of this reaction has
been identified as the imine 2,6-Me2C6H3NdCMe2, whereas
with t-BuNC, t-BuNdCMe2 was formed. The assignment of
imine products was confirmed by independent synthesis.19,21
The formation of imines suggested that reduction to afford
low-valent titanium species had occurred. Reasoning that such
a transient titanium species should be a reductant, we repeated
the chemistry described in eq 7 in the presence of benzaldehyde
as a trapping agent. A noticeable change in color to a much
lighter red was apparent, and there was a new, diamagnetic
Me2ATI-containing product present in addition to t-BuNdCMe2.
The use of 2 equiv of benzaldehyde resulted in a clean NMR
spectrum consisting of a 2H singlet at 6.55 ppm and a broad
12-proton singlet at 3.35 along with aromatic resonances. The
resulting, crystalline complex (11) was identified by X-ray
diffraction as the anti-pinacol coupling product of benzaldehyde
(Figure 3). The Ti-O bond distances of 1.872(3) and 1.878(3)
Å and the coordination geometry compare well with those in
other Me2ATI-containing titanium diolate complexes reported
here. In this reaction, benzaldehyde most likely traps the low-
valent titanium species formed after imine elimination. Insertion
of another molecule of benzaldehyde accounts for the formation
of 11, although radical pathways are also possible.
(6)
regiochemistry is difficult to predict since it is not clear whether
the acetone geminal methyl groups or the {Ti(Me2ATI)2}2+
fragment is sterically more demanding. The regiochemistry of
alkyne insertion could not be determined solely by 1H and 13
C
NMR spectroscopy and it has not been possible to obtain X-ray
diffraction quality crystals of 10. A NOESY experiment in C6D6,
however, clearly revealed a cross-peak between the singlet at
1.67 ppm, which was assigned to the geminal methyl groups,
and the vinylic methine singlet at 6.57 ppm. These data are
consistent with alkyne insertion where the phenyl group is
directed away from the two methyl groups of the η2-acetone
unit (10a). Similar insertion regiochemistry has been observed
for the reaction of hexyne with [Cp2Zr(Ph2CO)]2 and of phenyl
acetylene with the zirconocene aluminum η2-carbonyl complex
(Figure 4).8,27,36
Attempts to hydrolyze 10 and isolate the corresponding allylic
alcohol yielded mixtures of products under a variety of
conditions, as determined by TLC and NMR spectroscopy. The
reaction of iodine with oxametallacyclopentene complexes has
been reported in the literature to afford the alkenyl iodide,37
but treatment of 10 with I2 in THF afforded multiple
products.
These results demonstrate that imine elimination reactions
provide a convenient source of low-valent titanium through
reaction of isocyanides with TiR2L2. In principle, this low-valent
titanium source should allow the synthesis of unsymmetrical
diols by reductive coupling of two dissimilar carbonyl com-
pounds. Such an approach would complement our previously
described three-component method. Compounds such as ace-
tone, phenyl acetylene, and styrene either do not react with the
species formed by reaction of TiMe2L2 with isocyanides or yield
There are numerous early metal-mediated syntheses of allylic
alcohols. The thermolysis of a titanacyclopentadiene complex
and benzophenone affords an oxametallacyclopentene insertion
product or allylic alcohol after hydrolysis (Figure 4).38 Treatment
1
(36) Peulecke, N.; Ohff, A.; Tillack, A.; Baumann, W.; Kempe, R.;
Burlakov, V. V.; Rosenthal, U. Organometallics 1996, 15, 1340-1344.
(37) Harada, K.; Urabe, H.; Sato, F. Tetrahedron Lett. 1995, 36, 3203-
3206.
(38) Hill, J. E.; Balaich, G.; Fanwick, P. E.; Rothwell, I. P. Organo-
metallics 1993, 12, 2911-2924.
mixtures, however, as determined by H NMR spectroscopy.
(39) Takai, K.; Ishiyama, T.; Yasue, H.; Nobunaka, T.; Itoh, M.; Oshiki,
T.; Mashima, K.; Tani, K. Organometallics 1998, 17, 5128-5132.
(40) Buchwald, S. L.; Watson, B. T.; Huffman, J. C. J. Am. Chem. Soc.
1987, 109, 2544-2546.

11770 J. Am. Chem. Soc., Vol. 121, No. 50, 1999
Steinhuebel and Lippard
1
addition to t-BuNdCMe2 were observed by H NMR (eq 8).
(8)
1
One complex was assigned as 13 from its H NMR spectrum.
The other, 13a, has a singlet at ∼2.8 ppm, an unusual chemical
shift region for the methyl groups of the Me2ATI ligand. It has
not been possible to purify this material since it can only be
generated with 13, from which it is difficult to separate. It was
therefore characterized by its reactivity. The addition of an
additional 1 equiv of benzophenone completely consumed 13a,
affording 13. The addition of 1 equiv of acetone to a mixture
of 13a and 13 gave 2 and 13. These two reactions strongly
suggest that mixtures of the η2-benzophenone complex [Ti(Ph2-
CO)(Me2ATI)2] and 13 are generated when benzophenone is
slowly added to TiMe2L2 and an isocyanide.
Reactivity of [TiMe2(Me2ATI)2] with Isocyanides, Ketones,
and Imines: Preparation of an Amido-Alkoxide Complex.
Since the reaction of 1 equiv of benzophenone with TiMe2L2
and isocyanides yielded mixtures of 13 and 13a, we predicted
that simultaneous addition of another trapping agent such as an
imine would result in the formation of an amido-alkoxide
complex. N-Tosylbenzaldimine was selected because it is not
sterically demanding, and the tosyl group increases both the
electrophilicity and crystallinity of the imine. Equimolar amounts
of N-tosylbenzaldimine, benzophenone, and t-BuNC in C6D6
react with TiMe2L2 to yield a red-brown color and a complex
NMR spectrum showing several products, although the major
species had a spectrum consistent with a product having low
symmetry (14). Free t-BuNdCMe2 could also be detected in
the reaction mixture.
When the reaction was scaled up, a red-brown crystalline
complex could be isolated. The 1H NMR spectrum of this
material in C6D6 consisted of five 3H singlets and a complicated
aromatic region. The 13C NMR spectrum also confirmed the
low symmetry of the complex and the IR spectrum contained
an intense band at 919 cm-1 consistent with the presence of a
sulfonamide group. This combination of spectral data supported
the assignment of this material as the amido-alkoxide [Ti(Ph2-
COCN(SO2tol)HPh)(Me2ATI)2] (14), which was confirmed by
an X-ray crystallographic study that revealed nearly octahedral
coordination geometry (Figure 3). As expected, the 2.110(3) Å
Ti-N(tosyl) bond is slightly longer than the average Ti-N(Me2-
ATI) distance of 2.09 Å and the Ti-O distance of 1.864(2) Å
is slightly shorter than the Ti-O distance in 2. Although X-ray
quality crystals of 14 can be readily obtained, preparing bulk
samples completely free of impurities for elemental analysis
has proved to be difficult. The insertion of an imine into η2-
carbonyl complexes is not common. Metal-mediated prepara-
tions of 2-amino alcohols more commonly involve insertion of
carbonyl compounds into Zr, Nb and Sm η2-imine complexes
(Figure 2).43,44
Figure 4. Selective metal-mediated synthesis of allylic alcohols and
oxametallacyclopentenes.
The main problem is probably that it is difficult to reduce these
substrates, and for this reason we turned to more potent oxidants.
Reactivity of [TiMe2(Me2ATI)2] with Benzil: Preparation
of an Enediolate Complex. Addition of equimolar amounts of
benzil and t-BuNC to a solution of TiMe2L2 in benzene yielded
one new complex and t-BuNdCMe2, as determined by NMR
spectroscopy (12, Figure 5). This material can be crystallized
by diffusion of pentane into a THF solution of the complex
1
and the H NMR spectrum of the solid in C6D6 consists of a
12H singlet and a complicated aromatic region integrating for
20H. The IR spectrum of solid 12 contains a weak stretch at
1600 cm-1 and the 13C spectrum has a peak at 145.9 ppm
consistent with the presence of an enediolate complex.41
Spectroscopic data and elemental analysis also confirm the
formation of a titanium enediolate complex, 12. Group IV
enediolate complexes are common although titanium examples
appear to be rare.42
Reactivity of [TiMe2(Me2ATI)2] with Isocyanides and
Benzophenone. The addition of 2 equiv of benzophenone and
t-BuNC to a solution of TiMe2L2 afforded a red solution that
1
contained t-BuNdCMe2. The H NMR spectrum of the solid
isolated from this reaction consisted of a singlet at 3.14 ppm
and the aromatic region integrated for 30 protons. By analogy
with the benzaldehyde reaction product, this complex was
formulated as the diolate [Ti(Ph2COCOPh2)(Me2ATI)2] (13,
Figure 5). When 1 equiv of benzophenone and t-BuNC were
added slowly to a C6D6 solution of TiMe2L2, two complexes in
(41) Erker, G.; Czisch, P.; Schlund, R.; Angermund, K.; Kru¨ger, C.
Angew. Chem., Int. Ed. Engl. 1986, 25, 364-365.
(42) Hofmann, P.; Stauffert, P.; Frede, M.; Tatsumi, K. Chem. Ber. 1989,
122, 1559-1577.

Route to Unsymmetrical Vicinal Diols
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11771
Figure 5. Carbonyl, imine, and thiocarbonyl coupling reactions mediated by TiMe2(Me2ATI)2 complexes and isocyanides.
Synthesis and Characterization of a Thiolato-Alkoxide
Complex. The formation of two titanium-oxygen bonds
provides a strong driving force for the formation of 13 even
when only 1 equiv of benzophenone is added. Substitution of
thiobenzophenone was therefore attempted to effect the forma-
tion of [Ti(SCPh2)(Me2ATI)2]. Addition of a blue C6D6 solution
of thiobenzophenone and 2,6-Me2C6H3NC to TiMe2L2 yielded
a reddish solution that contained the free imine and a single,
Addition of acetone yielded a light red solution, the 1H NMR
spectrum of which consisted of a 6H singlet at 1.74 ppm and
two 6H singlets at 3.09 and 3.27 ppm (15, Figure 5). This
spectrum was similar to that of 2, the major difference being
the resolution of the broad singlet corresponding to the four
methyl groups of the ATI ligand in 2 into two, 6H singlets.
This result is consistent with formation of the unsymmetrical
thiolato-alkoxide complex [Ti(Ph2CSCOMe2)(Me2ATI)2] (15),
an assignment verified by X-ray crystallography. The overall
structural features of 15 are similar to those of 2 (Figure 3).
The Ti-O distance of 1.831(2) Å is slightly shorter than the
Ti-O distance in 2, the stronger bond most likely compensating
for weaker sulfur donation. The Ti-S distance of 2.4245(9) Å
is slightly longer than representative Ti-S distances of 2.339(2)
and 2.318(2) Å in CpTiOAr(SBn)2.45 The isolation of 15 is
consistent with the formation of [Ti(SCPh2)(Me2ATI)2], as
written in eq 9. Early transition metal thioaldehyde complexes
have been isolated for both Ti and Zr and structurally character-
ized for Ti.46,47 The same â-hydroxy thiol has been prepared
by the conceptually similar reaction of equimolar amounts of
thiobenzophenone, acetone and Yb metal.48 Reaction of
[TiMe2(Me2ATI)2] with thiobenzophenone and CO under our
1
new titanium complex (eq 9). This complex has a H NMR
(9)
signal at ∼2.77 ppm, close to the chemical shift of the methyl
groups in the putative [Ti(OCPh2){Me2ATI}2] compound 13a.
Although it was encouraging that only one major product formed
in this reaction, it has not been possible to purify it. As with
[Ti(OCPh2)(Me2ATI)2], its characterization was based on re-
activity.
1
standard conditions generated 15, as determined by H NMR
spectroscopy.
(45) Firth, A. V.; Stephan, D. W. Organometallics 1997, 16, 2183-2188.
(46) Park, J. W.; Henling, L. M.; Schaefer, W. P.; Grubbs, R. H.
Organometallics 1990, 9, 1650-1656.
(47) Buchwald, S. L.; Nielsen, R. B. J. Am. Chem. Soc. 1988, 110, 3171-
(43) Imamoto, T.; Nishimura, S. Chem. Lett. 1990, 1141-1142.
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Fujiwara, Y. J. Org. Chem. 1996, 61, 372-375.

11772 J. Am. Chem. Soc., Vol. 121, No. 50, 1999
Steinhuebel and Lippard
Mechanistic Considerations. The production of imine from
TiMe2L2 and isocyanides occurs rapidly to generate a species
that reacts like a source of low-valent titanium. Double alkyl
migration with the isocyanide to generate an η2-imine complex
is most likely the first step. There could be many factors that
cause elimination of the imine. The electronic contributions that
influence this reaction have been difficult to delineate. We focus
our discussion on steric factors, which can play an important
role in determining the stability of the imine complex. Molecular
modeling of the putative intermediate [Ti(η2-Me2CN(t-Bu))(Me2-
ATI)2] suggests that severe steric interactions take place between
the methyl and t-Bu groups of the imine and the methyl groups
of the ATI ligand. Thus, elimination of imine and formation of
reduced titanium products appear to be more favorable than a
sterically congested η2-imine complex.
Alkynes and azobenzenes do not yield diamagnetic products,
consistent with our earlier observations that only good oxidants,
or those that can form Ti-O bonds, react with the proposed
low-valent titanium complex.
Conclusions
We have described a novel, multicomponent system for the
preparation of unsymmetrical diols from carbonyl compounds,
CO, and aminotroponiminate ligated titanium dialkyl complexes.
A reactive, titanium η2-carbonyl complex is proposed to be a
key intermediate. Utilization of an alkyne as the electrophilic
partner allows an oxametallacyclopentene complex to be
prepared. All of these reactions proceed efficiently at ambient
temperature and do not require the use of Lewis acid additives.
In contrast, treatment of the dialkyl titanium complexes with
isocyanides leads to elimination of imine and formation of one
or more low-valent titanium complexes. This titanium species
can be trapped either by 2 equiv of a readily oxidized carbonyl
compound or by a dicarbonyl compound to yield stable Ti(IV)
diolate complexes. Use of 1 equiv of benzophenone and either
acetone or an imine results in the preparation of titanium diolate
or amido-alkoxide complexes. Thiobenzophenone can also be
coupled with acetone by this methodology.
Titanium η2-imine complexes have been prepared previously
by the reaction of isocyanides with titanium dialkyl complexes.
These compounds eliminate imine upon treatment with different
pyridine bases, forming reduced titanium complexes.49,50
Titanocene metallacycles also react with isocyanides to yield
isolable iminoacyl complexes that eliminate imine in solution.51
Such reductive elimination reactions have been used in the
catalytic synthesis of cyclopentenones from enynes.52
Attempts to trap these low-valent species with soft donors
that stabilize Ti(II) complexes, such as PMe3, pyridine, or
t-BuNC, have not been successful.53,54 The resulting paramag-
netism makes rapid screening of reaction mixtures difficult.
Acknowledgment. We thank the National Science Founda-
tion for support of this research and Dr. J. Mareque for assistance
with the NOESY experiment.
Supporting Information Available: Tables and figures
reporting bond distances, angles, and positional and thermal
parameters for compounds 1, 2, 11, 14, and 15, including CIF
files. This material is available free of charge via the Internet
at http://pubs.acs.org.
(49) Durfee, L. D.; Fanwick, P. E.; Rothwell, I. P.; Folting, K.; Huffman,
J. C. J. Am. Chem. Soc. 1987, 109, 4720-4722.
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I. P. Inorg. Chem. 1989, 28, 3095-3096.
(51) Ca´mpora, J.; Buchwald, S. L.; Gutie´rrez-Puebla, E.; Monge, A.
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