Facile syntheses of TiCl2(TADDOLate)(L2), efficient asymmetric ethylation of PhCHO, and an unexpected rearrangement of the tetramethyl analogue of the TADDOL ligand

Article abstract of DOI:10.1021/om980570w

Facile syntheses of TiCl₂(TADDOLate)L₂ (TADDOL = α,α,α′,α′-tetraphenyl-l,3-dioxolane-4,5- dimethanol; L = THF (1), AcOEt (2)) were developed from reactions of TiCl₄ with the TADDOL ligand in coordinating solvent L. The labile solvent ligands L can be replaced by a neutral bidentate ligand such as 1,2-bis(diphenylphosphino)ethane (dppe) or 3,3-dimethyl-2,4-pentanedione (diketone) to give TiCl₂(TADDOLate)(L₂) (L₂ = dppe (3), diketone (4)). The molecular structure of complex 3 shows a structure with two chlorides in trans positions, and the dppe ligand is trans to the strong alkoxide ligands. The most significant features of the structure are the long Ti-P(phosphine) bond distances observed, indicating considerable steric hindrance arising from the TADDOLate ligand in the complex. In a reaction of the TADDOL analogue α,α,α′,α′-tetramethyl-1,3-dioxolane-4,5- dimethanol with TiCl₄ in Et₂O, the unexpected complex 6 derived from rearrangement of the chiral diol ligand was obtained. This rearrangement is apparently mediated by TiCl₄ with the conversion of the 2,3-ketal-1,4-diol into the isomeric 3,4-ketal-1,2-diol. The asymmetric ethylations of benzaldehyde catalyzed by the complex 1, 2, or 3/Ti(O-J-Pr)₄ system are efficient, and the enantioselectivities are good, with values of enantiomeric excess up to 89%.

Full text of DOI:10.1021/om980570w

4822
Organometallics 1998, 17, 4822-4827
F a cile Syn th eses of TiCl2(TADDOLa te)(L2), Efficien t
Asym m etr ic Eth yla tion of P h CHO, a n d a n Un exp ected
Rea r r a n gem en t of th e Tetr a m eth yl An a logu e of th e
TADDOL Liga n d
Ming-Yuan Shao and Han-Mou Gau*
Department of Chemistry, National Chung-Hsing University, Taichung, Taiwan, ROC 402
Received J uly 7, 1998
Facile syntheses of TiCl2(TADDOLate)L2 (TADDOL ) R,R,R′,R′-tetraphenyl-1,3-dioxolane-
4,5-dimethanol; L ) THF (1), AcOEt (2)) were developed from reactions of TiCl4 with the
TADDOL ligand in coordinating solvent L. The labile solvent ligands L can be replaced by
a neutral bidentate ligand such as 1,2-bis(diphenylphosphino)ethane (dppe) or 3,3-dimethyl-
2,4-pentanedione (diketone) to give TiCl2(TADDOLate)(L2) (L2 ) dppe (3), diketone (4)). The
molecular structure of complex 3 shows a structure with two chlorides in trans positions,
and the dppe ligand is trans to the strong alkoxide ligands. The most significant features
of the structure are the long Ti-P(phosphine) bond distances observed, indicating consider-
able steric hindrance arising from the TADDOLate ligand in the complex. In a reaction of
the TADDOL analogue R,R,R′,R′-tetramethyl-1,3-dioxolane-4,5-dimethanol with TiCl4 in Et2O,
the unexpected complex 6 derived from rearrangement of the chiral diol ligand was obtained.
This rearrangement is apparently mediated by TiCl4 with the conversion of the 2,3-ketal-
1,4-diol into the isomeric 3,4-ketal-1,2-diol. The asymmetric ethylations of benzaldehyde
catalyzed by the complex 1, 2, or 3/Ti(O-i-Pr)4 system are efficient, and the enantioselectivities
are good, with values of enantiomeric excess up to 89%.
In tr od u ction
ligands used in the asymmetric syntheses, the R,R,R′,R′-
tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs) are
interesting and had been studied extensively8 due to
excellent enantioselectivities obtained and due to the
adjustible electronic state or steric environments through
the replacements of R-phenyl substituents. In general,
the active catalytic species are generated in situ from
mixing Ti(OR)xCl4-x with a TADDOL ligand. In terms
of synthetic approaches, besides the synthesis of Ti-
(TADDOLate)29 and Cp′TiCl(TADDOLate)10 complexes,
much attention had focused on the synthesis of the
TiCl2(TADDOLate) catalysts11 used in the asymmetric
Diels-Alder reactions developed by Narasaka and co-
workers.3b
To explore the Ti-TADDOLate complex systems, we
here report facile syntheses of TiCl2(TADDOLate)L2
from reactions of the TADDOL ligand with TiCl4 in
coordinating solvent L. In these complexes, the weakly
coordinated L ligands can be replaced easily by neutral
bidentate ligands such as 1,2-bis(diphenylphosphino)-
ethane (dppe) and 3,3-dimethyl-2,4-pentanedione (di-
Though titanium(IV) species had been extensively
used in mediating many types of organic reactions, the
incorporations of the Lewis acidities of titanium(IV)
species and of the enantioselectivities with the addition
of chiral ligands had not gained much attention before
the discovery of asymmetric epoxidation of allylic alco-
hols by Sharpless and co-workers in 1980.1 Since then,
asymmetric catalysis using chiral titanium complexes
has become an intensely studied subject, mainly due to
diversified asymmetric reaction types provided by chiral
titanium complexes. The systems studied include asym-
metric epoxidations,2 asymmetric Diels-Alder reac-
tions,3 asymmetric aldol condensation reactions,4 asym-
metric synthesis of cyanohydrins,5 and asymmetric
allylations6 or alkylations.7 Among numerous chiral
(1) Katsuki, T.; Sharpless, K. B. J . Am. Chem. Soc. 1980, 102, 5976.
(2) (a) Finn, M. G.; Sharpless, K. B. Asymmetric Synthesis; Academic
Press: Orlando, FL, 1985; Vol. V, p 247. (b) Corey, E. J . J . Org. Chem.
1990, 55, 1693. (c) Woodard, S. S.; Finn, M. G.; Sharpless, K. B. J .
Am. Chem. Soc. 1991, 113, 106. (d) Finn, M. G.; Sharpless, K. B. J .
Am. Chem. Soc. 1991, 113, 113.
(3) (a) Chapuis, C.; J urczak, J . Helv. Chim. Acta 1987, 70, 436. (b)
Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.; Nakashima, M.;
Sugimori, J . J . Am. Chem. Soc. 1989, 111, 5340.
(4) (a) Duthaler, R. O.; Hafner, A. Chem. Rev. 1992, 92, 807. (b)
Keck, G. E.; Krishnamurthy, D. J . Am. Chem. Soc. 1995, 117, 2363.
(c) Carreira, E. M.; Lee, W.; Singer, R. A. J . Am. Chem. Soc. 1995,
117, 3649.
(5) Bolm, C.; Mu¨ller, P. Tetrahedron Lett. 1995, 36, 1625.
(6) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-
Ronchi, A. J . Am. Chem. Soc. 1993, 115, 7001.
(8) (a) Schmidt, B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1991,
30, 99. (b) Corey, E. J .; Matsumura, Y. Tetrahedron Lett. 1991, 32,
6289. (c) Gothelf, K. V.; Hazell, R. G.; J ørgensen, K. A. J . Am. Chem.
Soc. 1995, 117, 4435. (d) Haase, C.; Sarko, C. R.; DiMare, M. J . Org.
Chem. 1995, 60, 1777. (e). Gothelf, K. V.; Thomsen, I.; J ørgensen, K.
A. J . Am. Chem. Soc. 1996, 118, 59. (f) Seebach. D.; Marti, R. E.;
Hintermann, T. Helv. Chim. Acta 1996, 79, 1710.
(9) Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.; Hunziker,
D.; Petter, W. Helv. Chim. Acta 1992, 75, 2171.
(10) Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-Streit,
P.; Schwarzenbach, F. J . Am. Chem. Soc. 1992, 114, 2321.
(11) Seebach, D.; Dahinden, R.; Marti, R. E.; Beck, A. K.; Plattner,
D. A.; Ku¨hnle, N. M. J . Org. Chem. 1995, 60, 1788.
(7) Chan, A. S. C.; Zhang, F.-Y.; Yip, C.-W. J . Am. Chem. Soc. 1997,
119, 4080.
10.1021/om980570w CCC: $15.00 © 1998 American Chemical Society
Publication on Web 10/08/1998

TiCl2(TADDOLate)(L2)
Organometallics, Vol. 17, No. 22, 1998 4823
5.52 (s, 2H), 2.72 (br, 2H), 2.46 (br, 2H), 0.66 (s, 6H) ppm. 13C-
{1H} NMR (CDCl3): δ 144.7, 143.0, 133.5, 132.8, 130.5, 129.3,
128.2, 127.8, 127.3, 127.1, 126.8, 111.1, 100.9, 80.5, 27.3, 20.9
ppm. Anal. Found: C, 70.35; H, 5.31. Calcd for C57H52O4P2-
Cl2Ti: C, 69.73; H, 5.34.
ketone) with the formation of TiCl2(TADDOLate)(L2).
In a reaction of the tetramethyl analogue of the TAD-
DOL ligand with TiCl4, an unexpected rearrangement
of the chiral diol ligand mediated by TiCl4 was observed.
In this study, asymmetric ethylations of benzaldehyde
with the catalytic system 1, 2, or 3/Ti(O-i-Pr)4 were
conducted to give good enantioselectivities of (S)-1-
phenylpropanol.
Syn th esis of TiCl2(TADDOLa te)(3,3-d im eth yl-2,4-p en -
ta n ed ion e) (4). To a solution of complex 2 (0.76 g, 1.00 mmol)
in 20 mL of CH2Cl2 was added 3,3-dimethy-2,4-pentanedione
(0.14 mL, 1.00 mmol) at room temperature. The resulting
solution changed color from colorless to orange and was stirred
for 1 h. The solution was dried in vacuo to remove any volatile
materials to give a pale yellow product containing traces of
impurities. Attempts to further purify the product by recrys-
tallization gave little improvement. 1H NMR (CDCl3): δ 7.20-
7.58 (m, 20H), 5.21 (s, 2H), 2.21 (s, 6H), 1.43 (s, 6H), 0.71 (s,
6H) ppm. 13C{1H} NMR (CDCl3): δ 212.29, 144.53, 141.30,
129.10, 127.73, 127.59, 127.24, 127.12, 127.05, 111.06, 102.28,
80.99, 60.56, 27.21, 27.11, 21.83 ppm. Anal. Found: C, 63.87;
H, 6.03. Calcd for C38H40O6Cl2Ti: C, 64.15; H, 5.67.
Syn th esis of 6‚OEt2. To a solution of R,R,R′,R′-tetramethyl-
1,3-dioxolane-4,5-dimethanol (0.980 g, 4.50 mmol) in 30 mL
of Et2O was added TiCl4 (0.865 g, 4.50 mmol) at room
temperature. The yellowish brown solution was stirred for 1
h, filtered, and cooled to -25.0 °C to afford colorless crystals
(1.25 g, 62.5%), mp 103.8-104.1 °C dec. 6‚OEt2: 1H NMR
(CDCl3) δ 8.89 (br, 1H), 4.37 (br, 1H), 4.03 (br, 1H), 3.54 (q,
4H), 1.71 (s, 3H), 1.61 (s, 3H), 1.57 (s, 3H), 1.49 (s, 3H), 1.28
(s, 3H), 1.27 (s, 3H), 1.19 (t, 6H) ppm; 13C{1H} NMR (CDCl3)
δ 112.9, 89.9, 87.3, 83.4, 80.6, 66.0, 28.8, 27.7, 26.4, 25.7, 23.7,
22.4, 14.8 ppm. Anal. Found: C, 40.47; H, 7.23. Calcd for
Exp er im en ta l Section
Rea gen ts a n d Gen er a l Tech n iqu es. R,R,R′,R′-Tetraphen-
yl-1,3-dioxolane-4,5-dimethanol12 (TADDOL), R,R,R′,R′-tetra-
methyl-1,3-dioxolane-4,5-dimethanol,12 and 3,3-dimethyl-2,4-
pentanedione13 were prepared according to literature proce-
dures. TiCl4 (Merck) was freshly distilled prior to use, and
bis(diphenylphosphino)ethane (Aldrich) was used without
further purification. Benzaldehyde and ethyl acetate were
distilled and stored over molecular sieves. Solvents were dried
by refluxing for at least 24 h over P2O5 (dichloromethane) or
sodium/benzophenone (diethyl ether, tetrahydrofuran) and
were freshly distilled prior to use. Deuterated solvents (Ald-
rich) were dried over molecular sieves. All syntheses and
manipulations were carried out under a dry dinitrogen atmo-
sphere.
Syn th esis of TiCl2(TADDOLa te)(THF )2 (1). To a solu-
tion of TADDOL (0.466 g, 1.00 mmol) in 20 mL of Et2O at room
temperature was added TiCl4 (0.247 g, 1.30 mmol) with
stirring. After the solution was stirred for 30 min, 5.0 mL of
THF was added. The resulting yellowish brown solution was
stirred further for 1 h and then the solution was concentrated
to ∼10 mL. The concentrated solution was cooled to -25 °C
to give colorless crystals (0.503 g, 62.7%), mp 81.3-83.0 °C.
The second crop (0.225 g, 28.0%) was obtained with further
concentration of the filtrate and cooling. 1‚OEt2: 1H NMR
(CDCl3) δ 7.59 (m, 4H), 7.46 (m, 4H), 7.21-7.34 (m, 12H), 5.35
(s, 2H), 4.10 (m, 8H), 3.48 (q, 4H), 1.87 (br, 8H), 1.21 (t, 6H),
0.64 (s, 6H) ppm; 13C{1H} NMR (CDCl3) δ 144.3, 142.7, 129.7,
127.7, 127.5, 127.2, 127.0, 111.2, 101.3, 80.1, 71.8, 65.8, 27.2,
25.4, 15.2 ppm. Anal. Found: C, 64.86; H, 6.62. Calcd for
C43H54O7Cl2Ti: C, 64.42; H, 6.79.
Syn th esis of TiCl2(TADDOLa te)(AcOEt)2 (2). To a
solution of TADDOL (0.466 g, 1.00 mmol) in 30 mL of ethyl
acetate at room temperature was added TiCl4 (0.247 g, 1.30
mmol). The resulting solution was stirred for 1 h and then
was cooled to 4.0 °C to afford colorless crystals (0.347 g, 45.7%),
mp 119.0-121.4 °C dec. 1H NMR (CDCl3): δ 7.51 (m, 8H),
7.25-7.36 (m, 12H), 5.21 (s, 2H), 4.19 (q, 4H), 2.12 (s, 6H),
1.26 (t, 6H), 0.71 (s, 6H) ppm. 13C{1H} NMR (CDCl3): δ 174.1,
144.5, 141.1, 129.2, 127.9, 127.5, 127.3, 111.1, 102.4, 80.6, 77.2,
62.0, 27.1, 21.1, 14.1 ppm. Anal. Found: C, 61.65; H, 5.85.
Calcd for C39H44O8Cl2Ti: C, 61.67; H, 5.84.
Syn th esis of TiCl2(TADDOLa te)(d p p e) (3). To a solu-
tion of TADDOL (0.466 g, 1.00 mmol) in 20 mL of Et2O at room
temperature was added TiCl4 (0.247 g, 1.30 mmol), and the
solution was stirred for 30 min. Then 5.0 mL of THF was
added and the resulting solution was stirred for 1 h to give a
yellowish brown solution. The solvent was removed and was
subsequently replaced with 30 mL of CH2Cl2. Then dppe (0.40
g, 1.00 mmol) was added and the reaction mixture was stirred
for 1 h. The solution was filtered and dried completely to give
the product in quantitative yield. Colorless crystals could be
obtained from crystallization of the product in CH2Cl2 at -25.0
°C; mp 92.8-94.0 °C. 1H NMR (CDCl3): δ 7.09-7.71 (m, 40H),
C
15H31O5Cl3Ti: C, 40.53; H, 7.04.
Gen er a l P r oced u r es for Eth yla tion of Ben za ld eh yd e.
To a solution of 0.1 mmol of complex 1, 2, or 3 and 0-1.5 mmol
of Ti(O-i-Pr)4 in 2.5 mL of toluene at 0 °C was added with
vigorous stirring 0.1 mL (1.0 mmol) of PhCHO followed by
addition of 1.2 mmol of ZnEt2. The solution was warmed to
room temperature. After a total reaction time of 3 h, the
solution was quenched with saturated aqueous NH4Cl solution
(5 mL), ethyl acetate (5 mL) was added, and the mixture was
filtered with the aid of Celite. The filtrate was extracted with
ethyl acetate (3 × 5 mL), dried over MgSO4, filtered and
concentrated. The sample was chromatographed through a
short column containing silica gel to remove any nonvolatile
material, and the solvent was removed to give a crude sample
for HPLC analysis.
P h ysica l Mea su r em en ts. 1H NMR spectra were obtained
with a Varian Gemini-200 (200 MHz) or a Varian VXR-300
(300 MHz) spectrometer, and 13C NMR spectra were recorded
1
with the Varian VXR-300 (75.43 MHz) spectrometer. The H
and 13C chemical shifts were measured relative to tetrameth-
ylsilane as the internal reference. Melting points were
measured with a Bu¨chi 535 instrument, and the temperatures
were not calibrated. Elemental analyses of complexes were
performed using a Heraeus CHN-O-RAPID instrument.
Cr ysta l Str u ctu r e Deter m in a tion s. Crystals of 3 and 6
in sealed capillaries were used for X-ray diffraction studies.
The diffraction intensities were collected on a Siemens P4
diffractometer equipped with graphite-monochromated Mo KR
radiation (λ ) 0.710 73 Å). An absorption correction was
performed on the sample of complex 3. All refinements and
calculations were carried out with the Siemens SHELXTL
PLUS software package on an SGI Indigo computer. Absolute
structure determinations were performed on both samples. The
positions of heavy atoms for the structures were determined
by direct methods, and the remaining non-hydrogen atoms
were located from successive difference Fourier map calcula-
tions. The refinements were carried out using full-matrix
least-squares techniques. All non-hydrogen atoms were re-
fined as individual anisotropic atoms. The hydrogen atoms,
except the hydroxy hydrogen of complex 6, which was also
located from the successive difference Fourier map calcula-
(12) (a) Carmack, M.; Kelley, C. J . J . Org. Chem. 1968, 33, 2171.
(b) Matteson, D. S.; Beedle, E. C.; Kandil, A. A. J . Org. Chem. 1987,
52, 5034. (c) Toda, F.; Tanaka, K. Tetrahedron Lett. 1988, 29, 551.
(13) J ohnson, A. W.; Markham, E.; Price, R. Organic Syntheses;
Baumgarten, H. E., Ed.; Wiley: New York, 1973; Collect. Vol. V, p
785.

4824 Organometallics, Vol. 17, No. 22, 1998
Shao and Gau
Ta ble 1. Cr ysta llogr a p h ic Da ta for Com p lexes 3
a n d 6
(IV)-TADDOLate complexes, TiCl2(TADDOLate)L2 (L
) THF (1), EA (2)), after removing the solvent com-
pletely. In these reactions, a 30% excess of TiCl4 is
required to secure the complete consumption of the
TADDOL ligand. The coordinating solvent L ligands
in complexes 1 and 2 are rather facile and can be
replaced easily by various neutral bidentate ligands
which are more coordinative than the coordinating L
ligands such as a bidentate dppe (bis(diphenylphosphi-
no)ethane) and diketone (3,3-dimethyl-2,4-pentanedi-
one) ligand.14 When 1 molar equiv of dppe reacted with
complex 1, the complex TiCl2(TADDOLate)(dppe) (3)
was isolated in nearly quantitative yield. However, 3,3-
dimethyl-2,4-pentanedione, which is a more weakly
bonding ligand than THF, is not able to replace the
coordinated THF’s in complex 1 completely. Fortu-
nately, it easily replaces the coordinating ethyl acetates
in complex 2 to afford the complex TiCl2(TADDOLate)-
(diketone) (4) after removing the solvent and AcOEt in
vacuo. Unlike the TiCl2(TADDOLate) catalysts, which
are unstable and need to be stored at low temperatures,
complexes 1-4 are stable at room temperature under
a dinitrogen atmosphere for at least 1 week. Besides,
all of these complexes except complex 4 crystallize easily
from suitable solvents to afford suitable crystals for
structural studies.
3
6
formula
fw
C
981.7
57H52O4P2Cl2Ti
C11H21O4Cl3Ti‚OEt2
445.6
cryst syst
space group
a (Å)
b (Å)
c (Å)
monoclinic
P21
orthorhombic
P212121
8.498(2)
15.026(2)
18.120(2)
9.767(2)
23.389(3)
11.796(2)
107.07(2)
2465.8(7)
2
â (deg)
V (Å3)
2313.8(7)
4
Z
Dcalcd (g cm-3
)
1.322
0.394
1.279
0.734
4.0-45.0
2θ-θ
3457
abs coeff (mm-1
range (deg)
scan type
)
4.0-50.0
2θ-θ
no. of rflns collected
no. of indep rflns
no. of obsd rflns
9334
8608 (Rint ) 3.53%) 2995 (Rint ) 1.82%)
7681 (σ > 2.0σ(I))
1.02(5)
2577 (σ > 2.0σ(I))
1.00(10)
218
0.045
0.058
absolute structure
no. of refined params 595
Ra for significant rflns 0.040
b
Rw for significant
rflns
0.053
goodness of fitc
1.22
1.31
a
b
2 1/2
R ) [∑(Fo - Fc)/∑Fo]. Rw ) [∑w(Fo - Fc)2/∑wFo
] .
c The
goodness of fit equals [∑w(Fo - Fc)2/(Nrflns - Nparams)]1/2
.
Sch em e 1
Rea ction of r,r,r′,r′-Tetr a m eth yl-1,3-d ioxola n e-
4,5-d im eth a n ol w ith TiCl4. To further study the
steric effect of the chiral titanium complexes, the
structurally less steric R,R,R′,R′-tetramethyl-1,3-diox-
olane-4,5-dimethanol was reacted with TiCl4 in Et2O to
afford the unexpected product 6. Instead of the two
methyl signals expected for the chiral ligand in a
complex with a structure similar to that of complex 1
1
or 2, H NMR of complex 6 reveals six distinct methyl
signals, indicating a structure having all six methyl
groups magnetically inequivalent. The solid-state struc-
ture of 6 reveals a surprisingly rearranged product
mediated apparently by TiCl4. On the basis of this
structure, a likely mechanism (Scheme 2) for this rather
unique reaction is proposed. To give complex 6, the
chiral ligand needs to coordinate to TiCl4 in a bidentate
fashion through one hydroxy and one ketal group for
the formation of the six-coordinate intermediate 5. Due
to the activation by the Ti(IV) metal, the ketal O-CMe2
bond breaks heteroleptically to give a strong Ti-
O(alkoxide) bond and subsequently a ring-closure pro-
cess proceeds by the attack of the dangling +CMe2 on
the uncoordinated hydroxy group to form a new ketal
ring. Finally, the other ketal oxygen attaches to the
titanium metal with simultaneous evolution of 1 molar
equiv of HCl to give the monomeric titanium complex
6. Thus, the rearranged chiral ligand bonds to the Ti
metal center in a tridentate fashion through one hy-
droxy, one alkoxy, and one ketal oxygen. Though a
similar rearrangement had been reported by Cotton et
al.15 in a reaction of a Re(III) derivative with a chiral
diop ligand having a similar 1,3-dioxolane skeleton, to
our knowledge this is the first example of the rear-
rangement of the 1,3-dioxolane-4,5-dimethanol skeleton
mediated by an early Ti group metal. In this unique
reaction, the preferential bonding of a ketal oxygen to
tions, were considered as riding on the carbon atoms with a
C-H bond length of 0.96 Å; the hydrogen atom temperature
factors were fixed at 0.08 Å. The hydrogen atoms were
included for refinements in the final cycles. The crystal-
lographic data for complexes 3 and 6 are summarized in Table
1.
Resu lts a n d Discu ssion
Syn th esis a n d Ch a r a cter iza tion s of Com p lexes
1-4. Reactions of TiCl4 with a TADDOL ligand in the
coordinating solvent THF or ethyl acetate (AcOEt) and
further reactions with neutral bidentate ligands such
as dppe and diketone are outlined in Scheme 1. Unlike
the usual preparation of Ti-TADDOLate complexes
from reactions of the TADDOL ligand with titanium
alkoxides, it was found in our laboratory recently that
the TADDOL ligand reacts easily with 1.3 molar equiv
of TiCl4 in a coordinating solvent such as THF or AcOEt
(EA) to give clean and quantitative yields of titanium-
(14) Gau, H.-M.; Lee, C.-S.; Lin, C.-C.; J iang, M.-K.; Ho, Y.-C.; Kuo,
C.-N. J . Am. Chem. Soc. 1996, 118, 2936.
(15) Chen, J .-D.; Cotton, F. A. J . Am. Chem. Soc. 1991, 113, 2509.

TiCl2(TADDOLate)(L2)
Organometallics, Vol. 17, No. 22, 1998 4825
Sch em e 2
F igu r e 1. Molecular structure of 3. The hydrogens, except
the hydrogens attached to chiral carbons, are omitted for
clarity. Bond lengths (Å): Ti-Cl(1), 2.325(1); Ti-Cl(2),
2.345(1); Ti-P(1), 2.813(1); Ti-P(2), 2.801(1); Ti-O(1),
1.782(2); Ti-O(2), 1.771(2). Bond angles (deg): O(1)-Ti-
O(2), 98.7(1); P(1)-Ti-P(2), 75.3(1); Cl(1)-Ti-Cl(2), 157.2-
(1); Ti-O(1)-C(1), 146.0(2); Ti-O(2)-C(4), 153.0(2).
a hydroxy group is demonstrated. In addition, this
reaction feature provides a way to convert 2,3-ketal-1,4-
diol into 3,4-ketal-1,2-diol.
a result, the weaker phosphorus donors are pushed
away from the metal center and the stronger alkoxide
donors of the TADDOLate ligand remain insensitive or
shorten slightly in order to compensate for the weak Ti-
(IV)-P bonds. The structural features in complex 3
strongly suggest that the TiCl2(TADDOLate) moiety
already provides steric environments suitable for achiev-
ing high enantioselectivities in asymmetric catalysis.
Molecu la r Str u ctu r e of Com p lex 3. The dppe
complex 3 was subjected to an X-ray structural analysis,
and the solid-state structure (Figure 1) shows that the
relative positions of bonding ligands in the six-coordi-
nate complex are governed exclusively by the relative
bonding abilities of the ligands, in which the weakest
dppe ligand is trans to the strongest alkoxide donors,
leaving two chlorides trans to each other with a molec-
ular symmetry of C2. The Ti-O distances at 1.771(2)
and 1.782(2) Å are about normal compared to those in
other titanium alkoxides containing two or more alkox-
ide ligands. Although the Ti-Cl distances (2.325(1) and
2.345(1) Å) are also normal, the chloride ligands bend
significantly away from the alkoxide ligands with a Cl-
Ti-Cl angle of 157.2(1)°. This structural distortion is
likely due to the bonding effect of the strong O-Ti
multiple bonds and/or due to the steric effect of the
bulky TADDOLate ligand. The most significant struc-
tural feature about complex 3 is the unusually long
Ti-P distances at 2.801(1) and 2.813(1) Å, which are
about 0.20-0.30 Å longer than the distances in Ti-
phosphine complexes.16 These bond distances are the
longest Ti-P(phosphine) distances so far observed, and
they are even longer than the distances in many
phosphine complexes of the much larger 4d zirconium
or 5d hafnium metal.17 The long Ti-P distances can
be attributed primarily to the mutual repulsion of the
steric bulk of the TADDOLate and the dppe ligands. As
Molecu la r Str u ctu r e of Com p lex 6. The molecular
structure of complex 6 with selected bond lengths and
bond angles is shown in Figure 2. The complex 6 is a
six-coordinate titanium(IV) complex containing three
chlorides, one alkoxide, one hydroxide, and one ether
donor. Relative to the dialkoxide complex 3, the Ti-
O(alkoxide) bond in complex 6 is somewhat weaker,
with a Ti-O(3) distance of 1.816(3) Å. This weak bond
is mainly due to the constraint of the five-membered
chelate ring formed from the rearranged chiral ligand
with titanium metal. In general, a strong Ti-O(alkox-
ide) bonding requires a large Ti-O-C angle in order to
achieve better oxygen to metal π donation. However,
the Ti-O(3)-C(2) angle at 116.0(3)° is only slightly
larger than the sp3 angle and is substantially smaller
than the usual angles of 140-160° for titanium alkox-
ides. In contrast, the Ti-Cl distances are shorter by
∼0.07 Å for complex 6 than the Ti-Cl distances for
complex 3. The hydroxy hydrogen is located from the
successive Fourier difference map in the X-ray struc-
tural analysis and is found to hydrogen-bond to a diethyl
ether oxygen with an H‚‚‚OEt2 distance of 1.516 Å and
a close to linear O(1)-H‚‚‚OEt2 angle of 158.2°. The Ti-
O(hydroxy) distance at 2.104(3) Å is substantially longer
(16) (a) Gardner, T. G.; Girolami, G. S. Angew. Chem., Int. Ed. Engl.
1988, 27, 1693. (b) Hitchcock, P. B.; Lappert, M. F.; MacKinnon, I. A.
J . Chem. Soc., Chem. Commun. 1993, 1015. (c) Binger, P.; Langhauser,
F.; Wedemann, P.; Gabor, B.; Mynott, R.; Kru¨ger, C. Chem. Ber. 1994,
127, 39. (d) Spaltenstein, E.; Palma, P.; Kreutzer, K. A.; Willoughby,
C. A.; Davis, W. M.; Buchwald, S. L. J . Am. Chem. Soc. 1994, 116,
10308. (e) van Doorn, J . A.; van der Heijden, H. Organometallics 1995,
14, 1278. (f) Ernst, R. D.; Freeman, J . W.; Stahl, L.; Wilson, D. R.;
Arif, A. M.; Nuber, B.; Ziegler, M. L. J . Am. Chem. Soc. 1995, 117,
5075.
(17) (a) Stein, B. K.; Greichs, S. R.; Ellis, J . E. Organometallics 1987,
6, 2017. (b) van den Hende, J . R.; Hessen, B.; Meetsma, A.; Teuben, J .
H. Organometallics 1990, 9, 537. (c) Wielstra, Y.; Gambarotta, S.; Spek,
A. L. Organometallics 1990, 9, 572. (d) Gozum, J . E.; Wilson, S. R.;
Girolami, G. S. J . Am. Chem. Soc. 1992, 114, 9483.

4826 Organometallics, Vol. 17, No. 22, 1998
Shao and Gau
Ta ble 2. Asym m etr ic Ad d ition of Dieth ylzin c to
Ben za ld eh yd ea
complex Ti(O-i-Pr)4
entry
no.
(amt,
(amt,
conversion selectivity ee
mmol)
mmol)
temp
(%)
(%)
(%)
1
2
3
4
5
6
7
2 (0.1)
2 (0.1)
2 (0.1)
2 (0.1)
1 (0.1)
1 (0.1)
3 (0.1)
0 °C-rt
0 °C-rt
0 °C-rt
0 °C-rt
0 °C-rt
rt
86
100
100
100
100
100
100
95
>99
100
100
100
100
100
19
74
84
87
89
78
85
0.5
1.0
1.5
1.5
1.5
1.5
0 °C-rt
a
The complex, Ti(O-i-Pr)4, benzaldehyde (1.0 mmol), and Et2Zn
(1.2 mmol) were mixed at 0 °C (except entry 6) and the reaction
mixture was warmed to room temperature (rt). The conversions
and the selectivities are based on the 1H NMR spectra. The ee
values were determined by HPLC with a Chiralcel-OD column
from Daicel. The configuration is S in all cases.
of enantioselectivities, the addition of Ti(O-i-Pr)4 to the
reaction systems speeded up the asymmetric reaction
to a point of 100% conversion in 3 h. It was found that
the addition of Ti(O-i-Pr)4 also suppressed the formation
of the reduction product 8 to a negligible amount. The
use of a higher ratio of Ti(O-i-Pr)4 relative to the chiral
ligand has been previously reported in other systems.7,18
The asymmetric ethylation reaction was also carried out
using complex 1 as catalyst under conditions otherwise
identical with those for entry 4, and the ee value
improved slightly from 87% to 89% (entry 5). When the
catalytic system and the reagent were mixed and
reacted at ambient temperature (entry 6), the ee value
decreased to 78%. It appeared that mixing the reac-
tants with the catalyst at 0 °C gave better enantiose-
lectivities. With the use of 10 mol % of complex 3 and
1.5 molar equiv of Ti(O-i-Pr)4, the asymmetric ethylation
(entry 7) gave the chiral product with an ee value of
85%.
F igu r e 2. Molecular structure of 6‚OE t 2. The solvated
diethyl ether and the hydrogens, except those attached to
chiral carbons C(2) and C(3) and the hydroxy hydrogen,
are omitted for clarity. Bond lengths (Å): Ti-Cl(1), 2.284-
(2); Ti-Cl(2), 2.246(2); Ti-Cl(3), 2.261(2); Ti-O(1), 2.104-
(3); Ti-O(3), 1.816(3); Ti-O(4), 2.369(5); O(1)-H, 1.105;
H‚‚‚OEt2, 1.516. Bond angles (deg): Cl(1)-Ti-Cl(2), 101.1-
(1); Cl(1)-Ti-Cl(3), 98.2(1); Cl(2)-Ti-Cl(3), 96.2(1); Cl-
(1)-Ti-O(3), 153.3(1); O(1)-Ti-O(3), 77.1(2); O(3)-Ti-
O(4), 72.5(1); O(1)-Ti-O(4), 74.5(1); Ti- O(1)-C(1), 114.6(3);
Ti-O(3)-C(2), 116.0(3); O(1)-H‚‚‚OEt2, 158.2.
by 0.3 Å than the Ti-O(alkoxide) bond distance. Though
the Ti-O(ketal) bond is considered to be a type of Ti-
OR2 bonding, the Ti-O(ketal) distance at 2.369(5) Å is
extremely long compared to the usual Ti-OR2 distances
from 2.1 to 2.20 Å. The rearranged chiral ligand bonds
to the titanium metal in a facial tridentate bonding
mode, and the two five-membered chelate rings have a
O(1)-Ti-O(3) angle of 77.1(2)° and a O(3)-Ti-O(4)
angle of 72.5(1)°.
Con clu sion s
Asym m etr ic Eth yla tion of Ben za ld eh yd e. Ethyl-
ation reactions of benzaldehyde in the presence of
complexes 1, 2, or 3 with or without the addition of Ti-
(O-i-Pr)4 were carried out (eq 1), and the results are
In summary, facile and high-yield syntheses of TiCl2-
(TADDOLate)L2 (L ) THF, AcOEt) have been demon-
strated. The weakly coordinating solvent ligands can
be replaced easily by any neutral ligands, and this
synthetic approach provides ways to prepare diversified
TiCl2(TADDOLate)L2 complexes containing all sorts of
monodentate or bidentate ligands as long as the replac-
ing ligands are better bonding than the coordinated
solvents. In this study, the reactions of complex 1 or 2
with bidentate ligand dppe or diketone are demon-
strated. The surprising, first reported rearrangement
of the R,R,R′,R′-tetramethyl-1,3-dioxolane-4,5-dimetha-
nol ligand mediated by TiCl4 is also reported. A similar
rearrangement is not observed for the TADDOL moiety
containing bulky R-phenyl groups. In the asymmetric
ethylation of benzaldehyde, the reactions with catalytic
systems of 10 mol % of complex 1, 2, or 3 and 1.5 molar
equiv of Ti(O-i-Pr)4 very cleanly efficiently give (S)-1-
phenylpropanol with good enantioselectivities. It seems
likely that better enantioselectivities can be achieved
through the adjustment of the catalytic systems either
on the TADDOLate substituents or on the supplemen-
tary nonchiral ligands. Further investigations on the
shown in Table 2. When the reactant was mixed with
10 mol % of complex 2 at 0 °C for 3 h without the
addition of Ti(O-i-Pr)4 and the reaction solution was
warmed to room temperature (entry 1), 86% of the
benzaldehyde was found to be converted to the desired
1-phenylpropanol (7) along with the reduction product
PhCH2OH (8) in a ratio of 95:5. The enantiomeric
excess of (S)-1-phenylpropanol was only 19%. However,
with the addition of Ti(O-i-Pr)4 to the reaction system
(entries 2-4), the enantioselectivities improved dra-
matically. The best result was obtained with an ee
value of 87% in a system with the addition of 1.5 molar
equiv of Ti(O-i-Pr)4. Besides the dramatic improvement
(18) Weber, B.; Seebach, S. Tetrahedron 1994, 50, 7473.

TiCl2(TADDOLate)(L2)
Organometallics, Vol. 17, No. 22, 1998 4827
synthesis of monomeric or higher nuclear titanium-
TADDOLate complexes and on the studies of the
catalytic behaviors of these complexes are currently
underway.
Republic of China for financial support (Grant No. NSC
87-2113-M-005-008).
Su p p or tin g In for m a tion Ava ila ble: Tables giving X-ray
crystallographic data, including final coordinates, bond lengths,
bond angles, and anisotropic displacement coefficients for
complexes 3 and 6 (19 pages). Ordering information is given
on any current masthead page.
Ack n ow led gm en t. Valuable suggestions about this
paper from Dr. Albert S. C. Chan are appreciated, and
we also thank the National Science Council of the
OM980570W