Synthesis of titanium alkoxide complexes with alkyl lactate ligands. Asymmetric epoxidation of cinnamyl alcohol

Article abstract of DOI:10.1016/j.jorganchem.2012.06.037

A family of titanium (IV) alkoxide compounds [{Ti(OPrⁱ) ₃(OLact)}₂], and [Ti(OPrⁱ)₂(OLact) ₂] (1-6) have been prepared by alcohol exchange of Ti(OPr ⁱ)₄ and the corresponding alkyl-2-hydroxy-alkylpropionate or alkyl lactate (LactOH = Benzyl-(S)-lactate, methyl-(S)-3-phenyllactate and menthyl-(S)-lactate. These alkoxide titanium (IV) compounds have been characterized by spectroscopic and electrochemical techniques. In addition, these chiral Lewis acid titanium compounds have been studied in the asymmetric epoxidation of cynnamyl alcohol, the obtained results show that these complexes with dynamic behaviour in solution exert low control of the enantioselectivity. Electronic and sterical effects of the ligands in the catalytic results have been studied.

Full text of DOI:10.1016/j.jorganchem.2012.06.037

Journal of Organometallic Chemistry 717 (2012) 172e179
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of titanium alkoxide complexes with alkyl lactate ligands. Asymmetric
epoxidation of cinnamyl alcohol
*
Yolanda Pérez, Isabel del Hierro , Mariano Fajardo
Departamento de Química Inorgánica y Analítica, E.S.C.E.T, Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
A family of titanium (IV) alkoxide compounds [{Ti(OPri)3(OLact)}2], and [Ti(OPri)2(OLact)2] (1e6) have
been prepared by alcohol exchange of Ti(OPri)4 and the corresponding alkyl-2-hydroxy-alkylpropionate
or alkyl lactate (LactOH ¼ Benzyl-(S)-lactate, methyl-(S)-3-phenyllactate and menthyl-(S)-lactate. These
alkoxide titanium (IV) compounds have been characterized by spectroscopic and electrochemical tech-
niques. In addition, these chiral Lewis acid titanium compounds have been studied in the asymmetric
epoxidation of cynnamyl alcohol, the obtained results show that these complexes with dynamic
behaviour in solution exert low control of the enantioselectivity. Electronic and sterical effects of the
ligands in the catalytic results have been studied.
Article history:
Received 8 March 2012
Received in revised form
20 June 2012
Accepted 26 June 2012
Keywords:
Titanium
Alkoxide
Alkyl lactate
Asymmetric epoxidation
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
Therefore, a series of unexplored chiral alkyl lactate ligands bearing
different substituents on the backbone and with hydroxyl and ester
Titanium compounds have been extensively investigated in the
modern chemistry due to their presence in the environment,
occurrence and effects on organisms, use in medicinal chemistry
[1], important role as metallic precursors in the synthesis of new
materials [2] and mainly due to their role as catalysts. Organo-
titanium derivatives offer a wide reactivity such as coordination of
a carbonecarbon multiple bonds, oxidative addition, reductive
functional groups have been evaluated for their potential utility
controlling clustering effect and asymmetric induction in the
catalytic process mentioned above.
2. Experimental
elimination, b-hydride elimination, addition reaction or their use as
2.1. General
carbanions source [3e5]; reactivity that justifies its versatility as
catalysts. One of the current trends in the chemistry is the use of
polydentate ligands for synthesis of titanium complexes which may
be applied as catalysts for fine organic reactions [6,7] or processes
of polymerization [8]. Within this field, ligands featuring anionic
oxygen donors (alkoxides, aryloxides) and especially alkoxides with
an additional intramolecular donor group attract the attention of
scientists [9].The presence of such a bond in molecules allows
control of the structural and electronic parameters of the titanium
derivatives such as the coordination number of titanium atom, as
well as, its coordination polyhedron and Lewis acidity and hence
variation in the catalytic properties [10].
All reactions have been performed using standard Schlenk tube
and dry box techniques under an atmosphere of dry nitrogen or
argon. Solvents were distilled from appropriate drying agents and
degassed before used. Benzyl (S)-(ꢀ)-lactate, methyl (S)-(ꢀ)-3-
phenyllactate and menthyl (S)-(ꢀ)-lactate have been purchased
from Aldrich and used as received. Ti(OPri)4 has been purchased
from Aldrich distilled and stored under an argon atmosphere prior
to use. FTIR spectra were recorded on a PerkineElmer PE 883 IR
spectrophotometer (4000e400 cmꢀ1) as nujol mulls between
polyethylene pellets and KBr disks. 1H, VT 1H DOSY NMR and 13C
{1H} NMR spectra were recorded on Varian FT-300 and Varian FT-
400 spectrometers and chemical shifts were measured relative to
residual 1H and 13C resonances in the deuterated solvents. Mass
spectrometry analyses were performed on a ULTRAFLEX III Bruker
instrument using ditranol as matrix. The electronic absorption
UVevis spectra were recorded in CH2Cl2 solution on a UVeVis
Analytik Jena Specord 200PC spectrophotometer.
Previously, we have study the control over the assembly of
titanium alkoxides using select ligands and their use as enantio-
selective catalysts in the epoxidation of cinnamyl alcohol [11].
* Corresponding author.
E-mail address: isabel.hierro@urjc.es (I. del Hierro).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2012.06.037

Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
173
2.2. Cyclic voltammetry
2.7. Synthesis of [{Ti(OPri)2(OMePhLact)2}2] (4)
The cyclic voltammograms were taken with a potentiostat/gal-
vanostat Autolab PGSTAT302 Metrohm. All experiments were
carried out using a conventional three electrode cell. Platinum was
used as working and reference electrode. A Pt wire was also used as
the auxiliary electrode. Electrochemical data were obtained using
0.2 mol Lꢀ1 solutions of hexafluorophospate tetrabutylammonium
in THF as supporting electrolyte. All solutions were deaerated by
bubbling high purity nitrogen. Ferrocene was employed as an
internal standard in THF solution.
Used methyl-(S)-(L)-3-phenyl-lactate (1.00 g, 5.60 mmol) and
Ti(OPri)4 (0.84 mL, 2.8 mmol).
d
¼ 1.18 (bs, 12 H, eOCH(CH3)2), 3.02
(bs, 4H, CH2Ph), 4.02 (s, 6H, CH3), 4.51, 4.72 and 5.11 (bs, 2H,
eOCH(CH3)2), 5.03 (s, 2H, CH(O)), 7.28 (m, 10H, C6H5). 13C{lH} NMR
(300 MHz, CDCl3, 25 ꢁC):
d
¼ 21.9 (eOCH(CH3)2), 40.7 (CH2Ph), 69.9
OCH3, 71.4 (CH(O)), 77.5 (eOCH(CH3)2), 127.2,128.4,128.8 and 136.6
(C6H5eCH2), 173.9 CO(]O). FTeIR (Nujolepolyethylene, cmꢀ1):
596(br), 699(s), 749(s), 814(m) 845(m), 907(w), 1012(s), 1104(s),
1195(s), 1282(s), 1330(m), 1375(s), 1454(m), 1496(w), 1669(s),
1740(s), 2927(s), 2976(s), 3028(m).
2.3. General synthesis
2.8. Synthesis of [{Ti(OPri)3(OMentLact)}2] (5)
Due to the similarity of synthesis 1e6 a general description is
supplied with specific details listed for each compound below. The
desired alkyl lactate ligand was slowly added to a stirring solution
of Ti(OPri)4 in CH2Cl2 (y25 mL), After 12 h, a clear reaction mixture
was obtained and the solvent and free isopropyl alcohol were
removed under vacuo to yield oils spectroscopically pure.
Used (1R,2S,5R)-menthyl (S)-(ꢀ)-lactate solution (1 gmL,
4.38 mmol) and Ti(OPri)4 (1.31 mL, 4.38 mmol). Colourless oil
spectroscopically pure. Yield: 99%. 1H NMR (300 MHz, CDCl3,
25 ꢁC):
d
¼ 0.75 (d, 3H, CH3), 1.20 (d, 18H, eOCH(CH3)2), 1.40 (d, 6H,
CH3), 1.00e2.00 (m, 9H, C6H9), 4.02 (m, 1H, C6H9) 4.45 (s, 3H,
eOCH(CH3)2), 4.78 (m, 1H, CHeO). 13C{1H} NMR (300 MHz, CDCl3,
25 ꢁC):
d
¼
16.1 (CHOeCH3), 21.9, (C6H8e(CH3)), 22.9
2.4. Synthesis of [{Ti(OPri)3(OBzLact)}2] (1)
(C6H8eCH(CH3))2, 26.7 (eOCH(CH3)2), 23.0, 31.9, 34.9, 46.6, 51.3
and 76.3 (C6H9), 83.5 (CHeO), 84.4 (eOCH(CH3)2), 185.1 CO(]O).
FTeIR (Nujolepolyethylene, cmꢀ1): 607(br), 697(m), 768(m),
816(m), 852(m), 925(w), 952(s), 997(s), 1050(s) 1129(s), 1262(s),
1328(m), 1376(s), 1455(m), 1671(s), 1742(w), 2868(s), 2927(s),
2961(s).
Used benzyl (S)-(ꢀ)-lactate (1.00 mL, 6.21 mmol) and Ti(OPri)4
(1.86 mL, 6.21 mmol). Colourless oil spectroscopically pure. Yield:
99%. 1H NMR (300 MHz, CDCl3, 25 ꢁC):
18H, ꢀOCH(CH3)2), 1.25 (bs, 3H, CH3), 4.56 (bs, 1H, CHOeCH3), 5.43
(bs, 2H, PheCH2), 4.77, 4.93 and 5.10 (bs, 3H, eOCH(CH3)2), 7.27 (m,
5H, C6H5).
d
¼
1.19 (bs,
2.9. Synthesis of [{Ti(OPri)2(OMentLact)2}2] (6)
13C{lH} NMR (300 MHz, CDCl3, 25 ꢁC):
d
¼ 21.6 (CH3), 26.2
(eCH(CH3)2), 72.0 (eCH2Ph), 77.4 (eOCH(CH3)2), 126.0, 126.2 and
127.9 (C6H5), 186.1 CO(]O). FTeIR (Nujolepolyethylene, cmꢀ1):
612(br), 697(m), 730(m), 914(w), 950(w) 1025(m),1054(m) 1105(s),
1134(s), 1262(m), 1329(w), 1376(s), 1455(s), 1494(w), 1670(s),
1741(w), 2854(m), 2924(s), 2965(s).
Used (1R,2S,5R)-Menthyl (S)-(ꢀ)-lactate solution (1 g,
4.38 mmol) and Ti(OPri)4 (0.66 mL, 2.20 mmol). Colourless oil
spectroscopically pure. Yield: 99%. 1H NMR (300 MHz, CDCl3,
25 ꢁC):
d
¼ 0.78 (d, 6H, CH3), 1.20 (d, 12H, eOCH(CH3)2), 1.43 (d,12H,
CH3), 1.00e2.00 (m, 18H, C6H9), 4.02 (m, 2H, C6H9) 4.45 (s, 2H,
eOCH(CH3)2), 4.78 (m, 2H, CHeO). 13C{1H} NMR (300 MHz, CDCl3,
2.5. Synthesis of [{Ti(OPri)2(OBzLact)2}2] (2)
25 ꢁC):
d
¼
16.5 (CHOeCH3), 21.5, (C6H8e(CH3)), 21.7
(C6H8eCH(CH3))2, 26.2 (eOCH(CH3)2), 22.7, 31.86, 34.8, 46.6, 51.2
and 76.6 (C6H9), 83.4 (CHeO), 84.3 (eOCH(CH3)2), 185.9 CO(]O).
FTeIR (Nujolepolyethylene, cmꢀ1): 617(br), 697(m), 717(m),
851(m), 925(w), 953(m), 1000(s), 1050(m) 1127(s), 1260(m),
1329(m), 1362(s), 1375(s), 1456(m), 1675(s), 1742(w), 2855(s),
2924(s), 2961(s).
Used benzyl (S)-(ꢀ)-lactate (1.00 mL, 6.21 mmol) and Ti(OPri)4
(mL, 3.10 mmol). Colourless oil spectroscopically pure. Yield: 99%.
1H NMR (300 MHz, CDCl3),
d
¼ 1.19 (bs, 12H, eOCH(CH3)2), 1.25 (bs,
6H, CH3), 4.56 (bs, 2H, CHOeCH3), 5.43 (bs, 4H, PheCH2), 4.77, 4.93
and 5.10 (bs, 2H, eOCH(CH3)2), 7.27 (m, 10H, C6H5). 13C{lH} NMR
(300 MHz, CDCl3, 25 ꢁC):
d
¼ 21.9 (CH3), 25.9 (eOCH(CH3)2), 72.4
(eCH2Ph), 78.0 (eOCH(CH3)2), 126.2, 128.0 and 143.4 (C6H5), 186.6
CO(]O). FTeIR (Nujolepolyethylene, cmꢀ1): 606(br), 698(s),
733(s), 816(s), 910(w), 949(w) 1025(s), 1098(s) 1104(s), 1138(s),
1205(m), 1265(m), 1330(w), 1375(s), 1452(s), 1495(w), 1665(s),
1731(m), 2871(m), 2934(s), 2981(s), 3029(w).
2.10. General procedure for the catalytic asymmetric epoxidation
(epoxycinnamyl alcohol)
A flame dried 250 ml two-necked flask was fitted dropping
funnel and flushed with nitrogen, and charged with 2 g of activated,
powdered 4A molecular sieves, 0.54 g (0.79 mmol) of titanium
complex and 100 ml of dry CH2Cl2. After the mixture was cooled
to ꢀ20 ꢁC and 5.7 ml of a 5.5 M solution of TBHP in nonane
(31.4 mmol) was added. The mixture was allowed to stir at ꢀ20 ꢁC
for 1 h and then treated with 3.2 ml of a 4.8 M solution of freshly
distilled (E)-3-phenyl-2-propenol (cinnamyl alcohol) in CH2Cl2
(15.7 mmol), added dropwise over 1 h. The resulting homogeneous
solution was stored 5 h to ꢀ20 ꢁC. After the reaction mixture is
quenched with 0.4 ml of a 10% aqueous solution of sodium
hydroxide saturated with sodium chloride. After the cold bath is
removed and stirred mixture is maintained 10 min. Then the
mixture was treated with MgSO4 and Celite, and after the solution
is filtered, washing with Et2O. The volatiles were removed in vacuo
2.6. Synthesis of [{Ti(OPri)3(OMePhLact)}2] (3)
Used methyl (S)-(ꢀ)-3-phenyl-lactate (1.00 g, 5.60 mmol) and
Ti(OPri)4 (1.66 mL, 5.60 mmol). Yellowish oil spectroscopically pure.
l
Yield: 99%. H NMR (300 MHz, CDCl3, 25 ꢁC):
d
¼ 1.18 (bs, 18 H,
eOCH(CH3)2), 3.02 (bs, 2H, CH2Ph), 4.02 (s, 3H, CH3), 4.51, 4.72 and
5.11 (bs, 3H, eOCH(CH3)2), 5.03 (s, 1H, CH(O)), 7.28 (m, 5H, C6H5).
13C{lH} NMR (300 MHz, CDCl3, 25 ꢁC):
d
¼ 25.9 (eCH(CH3)2), 41.4
(CH2Ph), 70.9 (OCH3), 72.2 (CH(O)), 82.4 (eOCH(CH3)2), 126.2, 128.1,
130.0 and 138.5 (C6H5eCH2), 184.7 CO(]O). FT-I.R. (Nujol, cmꢀ1):
523(s), 615(br), 687(s), 756(s), 796(s), 812(m), 854(s), 999(s),
1115(s), 1329(s), 1349(s), 1361(s), 1376(s), 1451(m), 1464(m),
1670(s), 1741(s), 2623(w), 2655(w). Ti2C38O8H72: Calc: C 60.63, H
9.64. Found: C 60.27, H 9.46%.
getting a yellow oil. Ee determined by HPLC with a chiralpack AD-H
l
250 ꢂ 4.6
m
m column from VWR International Eurolab. H NMR

174
Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
(300 MHz, CDCl3, 25 ꢁC):
1 H, eCH), 3.81 (dd, 1 H, eCH2), 3.94 (d, 1 H, eCH), 4.06 (dd, 1 H,
eCH2), 7.2e7.4 (m, 5 H, C6H5).
d
¼ 2.15 (br s, 1 H, eOH), 3.22e3.25 (m,
3. Results and discussion
The titanium alkoxides Ti(OPri)4ꢀn(OBzLact)n (n
¼
1(1),
n ¼ 2(2)); Ti(OPri)4ꢀn(OMePhLact)n (n ¼ 1(3), n ¼ 2(4)) and Ti(O-
Pri)4ꢀn(OMentLact)n (n ¼ 1(5), n ¼ 2(6)) have been prepared by
reaction of Ti(OPri)4 with the corresponding stoichiometric amount
of alkyl-2-hydroxy-alkylpropionate or alkyl lactate to release one or
two equivalents of PriOH as shown in Scheme 1. The products are
isolated as yellowish or colourless oils with a reduced moisture
sensitive compared with Ti(OPri)4 what indicates the formation of
titanium compounds with higher coordination number.
Compounds 1e6 have been characterized by FTeIR, 1H, 13C, VT
1H NMR and 1H DOSY NMR spectroscopy. 1H and 13C NMR spectra of
the isolated compounds indicate that the desired alcoholysis
exchange reaction has taken place cleanly. In the 1H NMR spectra an
increase in the integral of the signals associated with alkyl lactate
ligands and a decrease of the integrals of the isopropoxide signals
are observed upon substitution. The solution 1H NMR spectra of
Ti(OPri)3(ORLact) (1 and 5) are straightforward with only signal for
the isopropoxide group and a single set of resonances for the cor-
responding alkyl lactate ligands. Neververtheless, the resonance of
the methyne OCH(CH3)2 and methyl OCH(CH3)2 groups of the iso-
propoxide ligands, as well as, those corresponding to polydentade
ligands appears as broad signals indicating the existence of flux-
ionality in the solution state structure. Alkyl-2-hydroxy-alkylpro-
pionate compounds contain one alkoxide unit and one ester group,
both functions separated by two carbon atoms, that allows these
compounds to act as chelating ligands by occupying two coordi-
nation sites on the metal centre.
Fig. 1. VT 1H NMR of complex 3 in the methine OCH and methyl OCH(CH3)3 regions.
for methyne septet due to isopropoxide ligands, the broad signal
centred at 4.00 ppm is assigned to the methyl substituent of the
alkyl lactate ligand. As the temperature is lowered significant
broadening of the proton resonances are observed, chemical shifts
are also temperature dependent. At ꢀ10 ꢁC the chelating alkyl
lactate methyl resonance splits into at least three, indicating the
presence of chemically different ester groups. In addition, the
Fig. 1 illustrates the VT 1H NMR of complex 3 in deuterated
toluene. At room temperature three broad resonances are observed
Scheme 1. Numbering scheme of alkyl-2-hydroxy-alkylpropionate or alkyl lactate compounds.

Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
175
complex 4
O
O
complex 3
O
RO
R
O
O
OR
O
RO
O
O
OR
OR
RO
RO
Ti
Ti
Ti
Ti
O
R
O
OR
Methyl-(S)-3-phenyl-lactate
O
O
RO
OR
O
O
2000
1800
1600
wavenumber (cm-1)
1400
1200
1000
Fig. 2. Possible structures of Ti(OPri)3(OMePhLact) 3 at low temperature.
Fig. 4. FT infrared spectrum of complexes Ti(OPri)3(OMePhLact) 3 and Ti(OPri)2(O-
MePhLact)2 4 in comparison with free methyl-(L)-phenyllactate.
is the existence of a monomeredimer equilibrium or an “on/off”
mechanism that involves dissociation and re-coordination of the
neutral donor (C]O) group, as previously observed for these types
of ligands [15] (Fig. 3).
isopropoxide signals splits into several overlapping resonances and
the broad signal due to the methyl groups of the isopropoxide
ligands becomes two doublets at ꢀ50 ꢁC supporting the existence
of non equivalent isopropoxide groups. Chemical shifts observed
for complexes (1, 3 and 5) indicate the formation of the TieO bond
by alcoholysis and involvement of ester groups in chelation to
titanium. In particular, there is a big shift of the methylenic 13C
signal to high frequency upon complexation. As examples in the 13C
The FT-infrared spectra of free lactate,
3 and 4 in the
2000e1000 cmꢀ1 range are compared in Fig. 4. The nasym(C]O)
band associated to the free lactate was observed at 1747 cmꢀ1. Two
strong absorption bands appear at 1741 and 1670 cmꢀ1 in the
NMR spectrum of complex 5, the dC values for the free L-menthyl
lactate compound and DdC values upon complexation are 83.5, 17.6
[CH(OH)] and 186.1, 10.4 [CO2R] ppm, respectively. The most likely
explanation is a dimeremonomer exchange process; but the
question about their structure in solution cannot be answered
unequivocally. As proposed for similar aminoethanolate [12],b-
diketonate [13] or tartrate ligands [14], several geometric isomers
are possible being the most likely structures to be adopted the
dimer bridged via isopropoxide groups or the dimer bridged via
lactate ligands. There is no NMR evidence for the formation of
disproportionation products such as the bis-alkyl lactate 4 and free
Ti(OPri)4 (Fig. 2).
(1R,2S,5R)-Menthyl (S)-lactate
Ti(OPri)3(OMentLac)
Ti(OPri)2(OMentLac)2
The solution 1H NMR spectra of Ti(OPri)2(ORLact)2 (2,4 and 6) at
room temperature shows also broad signals indicating a dynamic
behaviour in solution. In addition, in complex 4 spectrum three
resonances are observed for the methine groups of the isoprop-
oxide ligands. This situation can be explained by firstly, the disso-
ciation in solution of the weak (C]O) / M dative bond giving rise
to an interconversion equilibrium between geometrical isomers
octahedrically coordinated through five coordinated species.
Secondly, by the existence of some degree of oligomerization, that
200
250
300
(nm)
350
400
λ
Fig. 5. Electronic spectra at UVevis region of the free ligand and mono and disub-
stituted titanium complexes Ti(OPri)3(OMentLact) 5 and Ti(OPri)2(OMentLact)2 6.
Fig. 3. Mechanism on/off by dissociation and re-coordination of the neutral donor (C]O) group.

176
Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
Fig. 6. DOSY 1H NMR spectra of complexes Ti(OPri)3(OMentLact) 5 and Ti(OPri)2(OMentLact)2 6 in CDCl3, 400 MHz.
carbonyl region for complexes 3 and 4. The first is due to an
uncoordinated ester unit, the second to ester groups bound to
titanium through the carbonyl oxygen. The presence of different
lactate ester groups is therefore indicated by both the IR and NMR
spectra.
The electronic spectrum of the L-menthyl lactate ligand shows
a band at 233 nm, assigned to the cromophore group (C]O). After
complexation, monosubstituted 5 and disubtituted 6 titanium
compounds shows very similar spectra; in both cases a very broad
band appears in the region 210e260 nm. Absorption maxima in the

Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
177
ligands in solution. For this purpose we have studied also a family of
titanium alkoxide complexes, the parent Ti(OPri)4 and the related
[{Ti(OPri)2(OMent)2}2] [7] and [Ti(OMent)4] [8] (MentO ¼ 1R,2S,5R-
(ꢀ)-menthoxo) previously synthesized and characterized by our
group [11]. In the DOSY spectra of all complexes under study proton
resonances describe a unique 2D peak horizontal line in the diffu-
sion dimension, meaning that all of them belong to a single
compound, the signals are well resolved and can be classified
according to their self diffusion coefficients. As previously estab-
lished aggregation state of Ti(OPri)4 in solution is 1.4, due to the
existence of a monomer dimer equilibrium [18], its diffusion peak is
centred at D ¼ 1.99.10ꢀ9 m2/s. Diffusion peak of 7 is centred at
a lower value D7 ¼ 8.91.10ꢀ10 m2/s, as expected, since this
compound has been proposed to be a dimer in solution. Homoleptic
complex 8 posseses bulky alkoxide ligands which imposed a high
sterical demand, on basis of other spectroscopic techniques we
have previously proposed this compound to be a monomer with
a tetrahedral environment around titanium. Nevertheless, the
diffusion coefficient value measured is D8 ¼ 6.30.10ꢀ10, lesser than
that of 7, which suggests also some degree of oligomerization in
solution (See supporting information). Complexes 5 and 6 show D
values of 1.58. 10ꢀ9 and 1.35.10ꢀ9, respectively. Both values are
comparable taking into account the molecular size difference, an
unequivocally suggest that both complexes are dimeric in solution.
The first value is larger by a factor of approximately D5/D6 ¼ 1.17. On
the basis of the correlation, diffusion coefficients/molecular radii,
given by the StokeseEinstein equation, [D ¼ kT/(6phr)], and the
radii/volume of a sphere (Vyr3), the ratio of the radii values r6/
r5y1.17, unambiguously demonstrates that 6 it is almost 1.6 times
the size of 5, which confirms its dimeric structure .
0
i / A
-0.05x10-4
-0.10x10-4
-0.15x10-4
-0.20x10-4
-0.25x10-4
A
B
-3.00 -2.50 -2.00 -1.50 -1.00 -0.50
0
0.50 1.00
E / V
Fig. 7. Cyclic voltammogram of compound Ti(OPri)3(OBzLact) 1 in THF 0.2 M [Bu4N]
[PF6], at Pt working electrode, vs Fc/Fcþ, scan rate 200 mV/s.
range of 210e240 nm are attributed to ligand to metal charge
transfer transition for true four-coordinate Ti (IV). Furthermore,
strong well defined absorption peaks observed at higher wave-
number are indicative of the presence of titanium species with
higher coordination environments (Fig. 5) [16].
The analysis by MALDI-TOF mass spectrometry in ditranol as
matrix was performed in order to get extra information, the spectra
for monosubstituted lactate titanium derivatives shows fragments
with the isotopic distribution of two titanium atoms what supports
the presence of the dimer. As example, for complex 3 the molecular
ion peak is not present, but the peak m/z 767 corresponding to the
loss of an isopropyl fragment [Mꢀ(CH3)2CHþ] is observed. In the
mass spectra of disubstituted alkyl lactate derivatives the molecular
ion peak is not present, and the fragmentation pattern observed is
similar to those of their monosubstituted counterparts.
3.1. Electrochemical studies and redox chemistry
In the present study we have carried out diffusion ordered NMR
spectroscopy (DOSY) measurements for complexes 5 and 6 to
resolve the presence of mono and/or dinuclear titanium complexes
directly in solution (Fig. 6). The idea is to differentiate the content of
solution according to translational diffusion coefficients. Diffusion
coefficients are related to the speed of molecules motion in liquids
and depend on the size of dissolved compounds. According to the
StokeseEinstein equation the diffusion coefficient for a molecule is
inversely proportional to the hydrodynamic radius [17]. We ex-
pected that dinuclear titanium complexes should exhibit smaller
self diffusion coefficients as compared to mononuclear complexes,
which minor size and weight. Firstly, we have defined a model
system to examine reliability of this technique to distinguish
between mono and dinuclear titanium complexes with alkoxide
As an alternative means of assessing the electronics of ligand
binding, voltammetric techniques have been employed to deter-
mine redox behaviour for the compounds discussed herein. These
studies have been carried out with a platinum disk electrode in THF
solutions with Bu4NPF6 as supporting electrolyte, potentials are
reference to the Fc/Fcþ couple used as internal standard. Fig. 7
shows the CV response of complex 1, the cathodic sweep reveals
two reduction processes A and B associated to titanium species,
Ti(IV)/Ti(III) and Ti(III)/Ti(II) reductions, at ꢀ1.04 and ꢀ1.93 V,
respectively; because electrochemical reduction does not occur on
the ligand in this region. The lack of an associated reoxidation peak
in the reverse scan, as well as, the appearance of extra peaks at less
negative potentials shows the instability of the species electro-
generated; the cathodic peak at ꢀ1.93 V can be considered a result
of the spontaneous conversion of initial complexes into other
species through ligand release, as previously observed in titanium
species with oxygen donor ligands [19]. Complex 2 shows a similar
electrochemical behaviour, but a slight shift of the cathodic peaks
towards more negative potentials are observed indicating a higher
stability of the disubstituted complexes.
i / A
0.2x10-4
Fc
F
0.1x10-4
0x10-4
In compounds 5 and 6 the reduction process is also irreversible.
The more electron donating substituents, methyl and menthyl
moieties, in the lactate ligands make these derivatives more diffi-
cult to be reduced; the reduction peak associated to the couple
Ti(IV)/Ti(III) shifts to ꢀ1.91 mV (peak E) in the monosubstituted
compound 5. The peak current is proportional to the square root of
the potential scan rate and its magnitude indicates that it is a 1
electron reaction (See Fig. 8). For disubstituted complex 6 the
reduction peak goes beyond the range imposed by the solvent.
However, in both cases important anodic peaks associated to the
reoxidation processes are observed at ꢀ1,10 (peak F) and ꢀ1.50 V,
-0.1x10-4
Fc+
-0.2x10-4
E
-0.3x10-4
-3.00 -2.50 -2.00 -1.50 -1.00 -0.50
0
0.50 1.00 1.50
E / V
Fig. 8. Cyclic voltammogram of compound Ti(OPri)3(OMentLact) 5 in THF 0.2 M [Bu4N]
[PF6], at Pt working electrode, vs Fc/Fcþ, scan rate 100 mV/s.

178
Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
Table 1
Carried out at ꢀ20 ꢁC in CH2Cl2 as solvent and 12 h as reaction time.
Compound
Catalyst/substrate ratio
1/10 (mol/mol)
ee (%)
1/2 (mol/mol)
Ee (%)
Yield (%)
Yield (%)
1
2
3
4
5
6
6
13
5
11
6
50
47
51
50
9
26
25
18
36
32
19
10
21
for 5 and 6, respectively, indicating that the reactions of the
reduced and more stable intermediates are much slower.
substituents, there is not a clear correlation. Complex 2 with the
highest size group bonded to the ester function shows the best ee.
On the contrary, complex 6 with also a bulky ester substituent
shows the lowest yield and ee. The third ligand under study
methyl-(S)-3-phenyllactate, with the bulky substituent directly
bonded to the asymmetric carbon shows results similar to those
obtained with Benzyl-(S)-(ꢀ)-lactate. The low ee obtained disclose
that the stereocontrol by alkyl lactate ligands is not efficient enough
possibly due to the dynamic behaviour of these systems in solution.
Like have been verified by other authors, organotitanium chiral
rigid systems exert better control in asymmetric processes [20].
Complex 3 with a phenyl and methyl substituents shows also an
irreversible cyclic voltammogram. The formal potential for the
Ti(IV)/Ti(III) couple has a substantially lesser negative value than
those obtained for complexes discussed above, ꢀ0.63 V. Moreover
the reduced species have considerable stability, an associated
anodic wave is observed at ꢀ0.12 V (See Supporting information).
This result is reasonable since the more electron withdrawing
phenyl group decreases the electronic density on the Ti(IV) atom
and consequently the reduction process is shifted to a less negative
potential.
Finally, a study has been undertaken to determine the feasibility
of performing the epoxidation reaction of cinnamyl alcohol in an
enantioselective way using these titanium alkoxo derivatives
bearing alkyl lactate ligands. The nature of the ligands, half of
tartrate, and the dimeric structure of compounds 1e6 should help
to simulate a Sharpless transition state to enhance the enantiose-
lectivity control in the transfer oxygen. When cinnamyl alcohol is
epoxidized at ꢀ20 ꢁC with a catalyst/substrate/t-butyl hydroper-
oxide (t-BuOOH) ratio of 1/10/20 using CH2Cl2 as solvent and
compounds 1e6, with reaction times of 12 h and in presence of
molecular sieves, the (2S,3S)-epoxide is obtained with 9e51% yield
(see Table 1), the enantiomeric excess (ee) is 5e13%.
The use of a ratio 1:2 titanium/substrate led to a slight increase
of the ee value to 13e25% with comparable yield. The obtained
results in terms of activity and enantioselectivity are low, far away
from other catalyst; but some tendencies can be establish
depending on the catalyst structure. The best results are obtained
when using the disubstituted titanium complexes, Ti(Oi-
Pr)2(ORLact)2, in accordance with the Sharpless structure catalyst
with two diol functions to coordinate to titanium centre, and two
carbonyl functions available to donate electron density to the
metallic centre in order to be six coordinated. Complexes 2, 4 and 6
with two alkyl lactate ligands are also pseudo octahedrically
coordinated with the carbonyl groups involved in an on/off
mechanism completing the titanium sphere. Attending the struc-
ture of the ligand used as chiral auxiliary, the S configuration of the
asymmetric carbon that supports the hydroxyl group, gets prefer-
entially to the (2S,3S)-epoxide. Complexes 2 and 4 with electron
withdrawing phenyl substituyents on the ligand are better lewis
acid as supported by their less negative reduction potentials, so the
catalytic reaction proceeds with better yields in comparison with
complex 6. Taking into account the sterical demand imposed by the
4. Conclusions
In conclusion, a family of new optically active alkyl lactate mono
and disubstituted isopropoxo titanium derivatives have been
prepared and characterized by spectroscopic and electrochemical
techniques. On basis on VT and DOSY 1H NMR a dimeric structure is
proposed for these compounds. VT 1H NMR and FTIR show the
presence of coordinated and uncoordinated ester groups, indicating
the existence of an on/off equilibrium between dimeric species. In
addition, these chiral Lewis acid titanium compounds have been
studied in the asymmetric epoxidation of cynnamyl alcohol.
Although the obtained values in terms of activity and enantiose-
lectivity show low control of the enantioselectivity by these
complexes probably due to their dynamic behaviour, dialkyl lactate
diisopropoxo titanium derivatives with electron withdrawings
substituents led to the best results.
Acknowledgements
This work was financially support by DGICYT (project BQU-
2002-04638-CO2-01). We would like thanks for Carmen Force and
Sandra Carretero for their assistance with the 1H DOSY NMR
experiments.
Appendix A. Supplementary material
Supplementary material associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
jorganchem.2012.06.037.

Y. Pérez et al. / Journal of Organometallic Chemistry 717 (2012) 172e179
179
[11] Y. Pérez, S. Morante-Zarcero, I. hierro, I. Sierra, M. Fajardo, A. Otero, Chirality
18 (2006) 44e48 (8b). Y. Pérez, S. Morante-Zarcero, I. Sierra, P. Gómez-Sal, M.
Fajardo, A. Otero, I. Hierro. Inorg. Chim. Acta. 360 (2007) 607e618.
[12] A.C. Jones, T.J. Leedham, P.J. Wright, M.J. Crosbie, K.A. Fleeting, D.J. Otway,
P. O’Brien, M.E. Pembled, J. Mater. Chem. 8 (1998) 1773e1777.
[13] R.J. Errington, J. Ridland, W. Clegg, R.A. Coxall, J.M. Sherwood, Polyhedron 17
(1998) 659e674.
[14] M.G. Finn, K. Barry Sharpless, J. Am. Chem. Soc. 113 (1991) 113e126.
[15] J. Lewinski, P. Horeglad, K. Wójcik, I. Justyniak, Organometallics 24 (2005)
4588e4593.
[16] B.A. Borgias, S.R. Cooper, Y.B. Koh, K.N. Raymond, Inorg. Chem. 23 (1984)
1009.
[17] (a) V.P. Ananikov, S.S. Zalesskiy, V.V. Kachala, I.P. Beletskay, J. Organomet.
Chem. 696 (2011) 400e405;
(b) G.S. Kapur, E.J. Cabrita, S. Berger, Tetrahedron Lett. 41 (2000) 7181e7185;
(c) G. Kagan, W. Li, R. Hopson, P.G. Williard, Org. Lett. 12 (2010) 520e523.
[18] D.C. Bradley, R.C. Mehrotra, D.P. Gaur, Metal Alkoxides, Academic Press,
1978.
[19] N.R. de S. Basso, P.P. Greco, C.L.P. Carone, P.R. Livotto, L.M.T. Simplício, Z.N. da
Rocha, G.B. Galland, J.H.Z. dos Santos, J. Mol. Catal. A: Chem. 267 (2007)
129e136.
References
[1] K.M. Buettner, A.M. Valentine, Chem. Rev. (2011). http://dx.doi/org/10.1021/
cr1002886.
[2] X. Chen, S.S. Mao, Chem. Rev. 107 (2007) 2891e2959.
[3] F. Sato, H. Urabe, S. Okamoto, Chem. Rev. 100 (2000) 2835e2886.
[4] C. Delas, S. Okamoto, F. Sato, Tetrahedron Lett. 43 (2002) 4373e4375.
[5] Y. Qian, J. Huang, M.D. Bala, B. Lian, H. Zhang, Chem. Rev. 103 (2003) 2633e2690.
[6] K.E. Henegar, M. Cebula, Org. Process Res. Dev. 11 (2007) 354e358.
[7] D.J. Ramón, M. Yus, Chem. Rev. 106 (2006) 2126e2208.
[8] (a) G.J.P. Britovsek, V.C. Gibson, D.F. Wass, Angew. Chem., Int. Ed. 38 (1999)
428e447;
(b) B. Wang, Coord. Chem. Rev. 250 (2006) 242e258.
[9] (a) K.V. Zaitsev, M.V. Bermeshev, A.A. Samsonov, J.F. Oprunenko, A.V. Churakov,
J.A.L. Howard, S.S. Karlov, G.S. Zaitseva, New J. Chem. 32 (2008) 1415e1431;
(b) E.Y. Tshuva, I. Goldberg, M. Kol, Z. Goldschmidt, Inorg. Chem. 40 (2001)
4263e4270;
(c) J.K. Day, R.E. Baghurst, R.R. Strevens, M.E. Light, M.B. Hursthouse, B.F. Stengel,
I.A. Fallis, S. Aldridge, New J. Chem. 31 (2007) 135e143.
[10] (a) H. Hu, H. Gao, K. Song, F. Liu, J. Long, L. Zhang, F. Zhu, Q. Wu, Polymer 49
(2008) 4552e4558;
[20] A.G. Olivero, B. Weidmann, D. Seebach, Helv. Chim. Acta 7 (1981) 2485e2488.
(b) P. Sudhakar, J. Polym. Sci. Part A: Polym. Chem. 46 (2008) 444.