Stereoselective control by face-to-face versus edge-to-face aromatic interactions: The case of C3-TiIV amino trialkolate sulfoxidation catalysts

Article abstract of DOI:10.1002/chem.200902072

The stereoselective oxidation of differently functionalised benzyl phenyl sulfides has been examined by using enantiopure Ti^IV trialkanolamine complexes. These complexes efficiently catalyse the sulfoxidation with good stereoselectivities. The

Full text of DOI:10.1002/chem.200902072

FULL PAPER
DOI: 10.1002/chem.200902072
Stereoselective Control by Face-to-Face Versus Edge-to-Face Aromatic
Interactions: The Case of C3-TiIV Amino Trialkolate Sulfoxidation
ACTHUNTGRENNGCU atalysts
Gabriella Santoni,[a] Miriam Mba,[a] Marcella Bonchio,[b] William A. Nugent,[c]
Cristiano Zonta,*[a] and Giulia Licini*[a]
Dedicated to the Centenary of the Italian Chemical Society
Abstract: The stereoselective oxidation
of differently functionalised benzyl
phenyl sulfides has been examined by
using enantiopure TiIV trialkanolamine
complexes. These complexes efficiently
catalyse the sulfoxidation with good
stereoselectivities. The data highlight
the contribution to the stereoselectivity
of steric effects and non-covalent p–p
interactions between the aromatic rings
of the TiIV complex and those pertain-
ing to the substrates. Enantiomeric ex-
cesses have been correlated with the
electrostatic potential surfaces (EPS)
of the reacting sulfides. The overall
study leads to a mechanistic interpreta-
tion that explains the stereoselectivity
of the system and dissects the role of
aromatic and steric interactions in the
stereoselective process.
Keywords: C3 symmetry · catalytic
oxidation · Pi interactions · stereo-
selectivity · sulfoxidation
Introduction
portant role in the stabilization of molecules in solid and
liquid-crystal phases.[3] In biological systems these have been
identified as key factors in determining the structural and
thus functional properties of nucleic acids and proteins.[4]
Aromatic interactions have been investigated in a range of
model systems.[5,6]
The experimental quantification of the role of intermolecu-
lar interactions has been a subject of intense research in
recent years.[1] Molecular-recognition processes are intimate-
ly linked to many processes in chemistry and biology. Non-
covalent interactions contribute significantly to the binding
events of synthetic and natural systems, and they can be key
elements in energies involved in the transitions states, there-
fore determining the reactivity of natural and artificial sys-
tems.[2] Among these, interactions between aromatic rings
are judged to be responsible for many phenomena in chemi-
cal and biological sciences. As an example, they play an im-
The possibility of using these interactions has also attract-
ed scientists working in the field of stereoselective cataly-
sis.[7] Indeed, interactions among aromatic groups have been
shown to play a crucial role in some stereoselective reac-
tions involving artificial catalysts. As an early example,
Sharpless et al. reported on the influence of ligand–substrate
p-stacking interactions in the asymmetric dihydroxylation of
olefins.[8] Other important contributions have delineated the
powerful role of aromatic ring interactions in controlling
stereoselective reactions.[9] All of these results clearly indi-
cate that the ligand–substrate aromatic interaction can gen-
erally reduce the conformational degrees of freedom and
enhance the stereoselectivity in the selectivity-determining
transition state. In some of these studies, a quantitative
structure–reactivity relationship, involving the effect of the
substitution in the aromatic rings, has been carried out.
These studies have shown that the variation of the electronic
density in the interacting aromatic rings can cause a change
in stereoselectivity. This usually translates into a correlation
between the observed stereoselectivities and the Hammett
values of the aromatic substituents.
[a] Dr. G. Santoni, Dr. M. Mba, Dr. C. Zonta, Prof. G. Licini
Dipartimento Scienze Chimiche,
Universitꢀ di Padova, via Marzolo 1, Padova (Italy)
Fax : (+39)0498275239
E-mail: cristiano.zonta@unipd.it
giulia.licini@unipd.it
[b] Dr. M. Bonchio
ITM-CNR, via Marzolo 1
35131 Padova (Italy)
[c] W. A. Nugent
Vertex Pharmaceuticals, Inc.
130 Waverly Street, Cambridge, MA 02138 (USA)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902072.
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645

However, these approaches can lead to spurious results
for two reasons: 1) the substituents are directly conjugated
with the reactive site varying both the extent of the intermo-
lecular interactions and the reactivity of the system[10] and
2) the variation of the electrostatic distribution of an aro-
matic ring can be responsible not only for the variation of
the extent of the aromatic interaction, but it can also vary
the orientation of the interacting aromatic rings. In fact, it is
known that the electron density of the aromatic partners
can force the interaction to be face-to-face (called also p-
stacking) or edge-to-face (also referred as T-shaped or CH–
p interactions).[5h]
ide and the kinetic resolution by oxidation to the sulfone.
Both processes work in the same direction increasing the ee
of the product as the reaction proceeds. In this early experi-
ment, the pivotal role of the aromatic rings in the process
was unambiguously proved.[11b] The replacement of an aro-
matic ring with an aliphatic chain, either in the complex, in
the substrate or in the oxidant, resulted in a marked de-
crease in stereoselectivity. This prompted us to investigate
in more detail the catalytic system, and in particular the role
of aromatic interactions in the stereoselective process.
Herein we report a methodological study of the system in
which it emerges that aromatic interactions, and in particu-
lar the subtle interplay between edge-to-face and face-to-
face interactions, are responsible for the observed stereose-
lectivities. The analysis begins with a study of the effect of
the aromatic moieties in the three partners of the reaction:
catalyst, substrate and oxidant. This initial investigation is
followed by a structure–reactivity relationship study on the
effect of substitution of the aromatic ring of the substrate.
The substitution in the aromatic ring has been designed to
avoid conjugation between the substituent and the reactive
sulfur centre, so that the resulting variation of ee values
could be ascribed only to intermolecular interactions.
This study leads to: 1) the synthesis of a new series of sul-
fides and of the corresponding sulfoxides, 2) a quantitative
structure–reactivity analysis able to explain the stereoselec-
tivity of the reaction and 3) a dissection of the role of aro-
matic and steric interactions. The study is carried out by
using a combined experimental and computational ap-
proach.
Our investigation into aromatic interactions in catalysis
grew from studies on the stereoselective sulfoxidation cata-
lysed by C3-symmetric enantiopure titanium(IV) amino tri-
alkolates complexes 1 (Scheme 1).[11] In previous studies it
Scheme 1. Synthesis of the trialkanolamines and of the corresponding ti-
tanatranes (R,R,R)-1a and (S,S,S)-1b.[11f]
has been shown that trialkanolamines bind tightly to a tita-
nium centre in a tetradentate fashion affording single, mon-
onuclear C3 complexes. These complexes furnish, upon addi-
tion of tert-butyl (TBHP) or cumyl hydroperoxide (CHP),
the corresponding alkyl peroxo complexes, which are able to
oxidize both secondary amines[12] and alkyl aryl sulfides, the
latter in high enantiomeric excess (ee).[11b] These systems
have also proven to be efficient when embedded in fluori-
nated polymeric membranes.[13]
Results and Discussion
As noted above, the effect of the aromatic ring in the reac-
tion partners was first investigated. In particular, the per-
formances of catalysts, (R,R,R)-1a and the corresponding
alkyl (S,S,S)-1b have been compared. The reactions involve
the use of three different substrates bearing zero (methyl n-
octyl sulfide 2), one (methyl tolyl sulfide 3) or two (benzyl
tolyl sulfide 4b) aromatic moieties, respectively, and two dif-
ferent oxidants: the “aliphatic” TBHP and the “aromatic”
CHP (Scheme 2).
In the quest for catalyst optimisation, it has been found
that the nature of the ligand, substrate and alkyl peroxide
are all relevant parameters, as far as reactivity and stereose-
lectivity are concerned. (R,R,R)-tri(1-phenylethanol)amine
(1a) in conjunction with CHP provides the most reactive
system also featuring the highest stereoselectivity. In partic-
ular, ee values up to 84% have been found in the sulfoxida-
tion of benzyl phenyl sulfides favouring the S enantiomer
with a sulfoxide/sulfone 77:23 ratio.[11b] Efficient stereoselec-
tive sulfoxidation of aryl benzyl sulfides has been reported
with another TiVI catalyst, bearing (S,S)- or (R,R)-1,2-di-
phenyl-1,2-ethanediol as the ligand, with TBHP[14] and the
The experiments have been carried in the presence of a
large excess of substrate to avoid the subsequent kinetic-res-
olution process of the sulfoxide leading to the formation of
Bolm catalyst (VOACHTUNGTRENNUNG
(acac)2/Schiff base ligands/H2O2)[15] Fur-
thermore, it was found that the enantiomeric excess of the
products originated from two different and consecutive ste-
reoselective processes: the asymmetric oxidation to sulfox-
Scheme 2. Oxidation of sulfides (2, 3 and 4b) catalysed by in situ formed
(R,R,R)-1a or (S,S,S)-1b with CHP or TBHP (reaction conditions: [2–
4]0 =0.24m; sulfide/oxidant/catalyst 100:10:1; 1,2-dichloroethane (DCE);
À208C.).
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C3-TiIV Amino Trialkolate Sulfoxidation Catalysts
FULL PAPER
the sulfone. By using this protocol the pseudo-first order
rate constants and stereoselectivities of the oxidation of sul-
fides 2, 3 and 4b to the corresponding sulfoxides 5, 6 and 7b
have been determined (Figures 1 and 2).
obtained when both the catalyst and the oxidant possess an
aromatic group 1a/CHP (Table 1S, entries 12 and 8 and
Figure 2, data on the left). In this case the reactivity trend
2@4b>3 does not parallel the substrate nucleophilicity. In
fact, benzyl tolyl sulfide 4b reacts twice as fast as methyl p-
tolyl sulfide 3.
The important role of the aromatic system is also evident
when examining the stereoselectivity of the process. By
using the fully aromatic oxidizing system 1a/CHP, very low
ee values have been obtained with the fully aliphatic methyl
n-octyl sulfide 2. Moreover, the enantiomeric excess for the
oxidation of benzyl p-tolyl sulfide 4b is consistently higher,
approximately double, that for methyl p-tolyl sulfoxide 3
(Figure 3). These data illustrate that stereoselectivity, and to
some extent reactivity, strongly depend on the presence of
aromatic groups in both reaction partners. This suggests a
primary role for specific interactions among the p groups in
the stereoselective step.
Figure 1. Pseudo-first-order rate constants for oxidation of sulfides (2, 3
and 4b) catalysed by in situ formed (S,S,S)-1b with CHP or TBHP.
Figure 3. Enantiomeric excess for the oxidation of sulfides (2, 3 and 4b)
catalysed by in situ formed (R,R;R)-1a and (S,S,S)-1b with CHP or
TBHP.
To discern the role of the aromatic units present in the
catalytic system, differently substituted benzyl p-tolyl sul-
fides have been prepared. This family of sulfides has been
chosen for two reasons. The first is the good stereoselectivity
observed for the unsubstituted compound 4b. The second is
the opportunity to study substrates in which the substitution
at the benzylic rings will have minimal impact on the reac-
tivity of the sulfur atom.
Substituents in the benzyl systems have been chosen to
vary the electronic and steric properties of the substrate. In
particular, we synthesized compounds in which the aromatic
rings have similar electrostatic characteristics with varying
amounts of steric hindrance (4a–e), with halogens (4h–j),
with strongly electron-withdrawing (4k–n) and electron-do-
nating (4 f–g) groups, a meta,meta disubstituted analogue
(4l) and a sulfide containing a pentafluorophenyl ring (4o).
The last system has been chosen because it is known to pref-
erentially form face-to-face interactions with unsubstituted
phenyl rings.[17]
Figure 2. Pseudo-first-order kinetic constants for the oxidation of sulfides
(2, 3 and 4b) catalysed by in situ formed (R,R,R)-1a with CHP or TBHP.
The data confirm the better performance, in terms of ste-
reoselectivity and reactivity, of catalyst (R,R,R)-1a relative
to the fully aliphatic (S,S,S)-1b. The ligand effect on the sul-
foxidation rate is likely explained by the more acidic charac-
ter of the benzylic alcohol functions of (R,R,R)-1a, which
results in a stronger Lewis acidity of the TiIV metal centre.
Due to the electrophilic character of the oxygen-transfer
process by the d0 titanium–peroxo species, the expected rel-
ative reactivity of the sulfides should be 2@3>4b, as a
function of their nucleophilicity.[16] This is indeed what we
found either with the aryl-free system 1b/TBHP (see
Table 1S, entries 1, 5 and 9 in the Supporting Information
and Figure 1, data on the right) or when the aryl functionali-
ty is present just in the oxidant 1b/CHP (Table 1S, entries 2,
6 and 10 and Figure 1, data on the left) or just in the catalyst
1a/TBHP (Table 1S, entries 3, 7 and 11 and Figure 2, data
on the right). Interestingly, a rather different behaviour is
Oxidations have been carried out by using the (R,R,R)-
1a/CHP oxidizing system and slightly more concentrated
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647

G. Licini, C. Zonta et al.
Table 1. Stereoselective oxidation of sulfides 5a–o (0.54m) catalysed by
in situ formed (R,R,R)-2b (0.0054m) with CHP (0.054m) in DCE at
À208C.[a]
conditions than with the first experiments, ([4a–o]0 =0.54m)
and, as before, a tenfold excess of substrate has been used
to avoid possible variation of ee values of the product due
to kinetic resolution.[18] The ee values were determined
before purification of the reaction mixture by using
1H NMR spectroscopy in the presence of (R)-(À)-1-(9-an-
thryl)-2,2,2-trifluoroethanol as
a chiral solvating agent
Ar
Yield
[%][b]
ee
log([S]/[R])
EPS
[kJmolÀ1
]
(CSA) or via chiral HPLC. The absolute configuration
[d]
[%][c]
U
(always S) has been assigned on the basis of the upfield shift
1
1
2
98
89
52
54
0.50
0.52
À84
À90
in the H NMR spectra of the diagnostic methyl protons of
the p-tolyl group observed in the presence of the (R)-(À)-
CSA or downfield shift when (S)-(+)-CSA has been used.
The results are reported in Table 1.
3
4
5
99
82
99
59
51
71
0.59
0.49
0.77
À66
À66
À54
The data highlight a marked variation in the stereoselec-
tivities as a consequence of the variation of the benzyl aro-
matic ring. Yields up to> 99% have been obtained for all
the reactions (and a distinct variation of the ee values has
been observed from the highest excess of the 9-anthryl-sub-
stituted sulphide 7e (ee=71%) to the lowest represented by
the pentafluorophenyl ring 7o (ee=45%). The impact of
the electron-withdrawing/-donating capability of the sub-
stituents on the stereoselectivity of the reaction is immedi-
ately evident. For example, the comparison among the p-
nitro (4n) and p-methoxy (4g)-substituted rings (Table 1,
entries 7, and11) shows a significant difference in the ee
values. On the other hand, aromatic groups with similar
electronic features, such as benzene, naphthalene and an-
thracene (entries 1 and 3–5) also exhibit a large variation in
ee. Thus both steric and electronic contributions must be
considered in any model that seeks to rationalize these re-
sults.
6
7
8
9
87
99
92
90
57
58
50
54
0.52
0.57
0.48
0.52
À116
À92
À56
À46
10
11
12
13
99
95
92
73
60
53
49
47
0.60
0.51
0.47
0.44
À47
À36
À15
1
To shed light on the nature and role of the intermolecular
interactions between the catalyst and substrate in the transi-
tion state we investigated, by means of DFT calculations,
the structure of the active peroxo complex. It is generally
accepted that in the alkyl hydroperoxide activation by d0
early transition metals, like TiIV, the active species is an h2-
coordinated alkyl peroxo complex (Scheme 3). Moreover,
14
15
99
72
52
45
0.50
0.42
À87
73
[a] Reaction conditions: [4a–o]0 =0.54m; sulfide/CHP/catalyst (R,R,R)-1a
100:10:1; DCE; À208C; reactions were carried out on a 5 mmol scale.
[b] Isolated yield, based on oxidant. [c] Determined by 1H NMR spec-
troscopy by using (À)-(R)-Pirkleꢂs alcohol. [d] Calculated electrostatic
surface potential by using the program package Spartan (EPS).
Scheme 3. Formation of the TiIV h2-alkyl peroxo complex 8a.
Table 2. Experimental and calculated distances of TiIV–h2alkyl peroxo
complexes.
the nucleophilic attack of the sulfide to the electrophilic
[19]
À
peroxo oxygen (O2) is along the antibonding s* (O1 O2).
Atoms[a]
X-ray[b]
RHF/3-21G(*)[c]
B3LYP/LANL2DZ[d]
This particular conformation of the alkyl peroxo–TiIV
complex (R,R,R)-8a has been studied by the DFT method
(B3LYP) by using the LANL2DZ basis set. In the mini-
mised structure, the h2 peroxo group occupies the upper
axial position of the titanatrane structure, wherein the dis-
tances and angles are in line with previous studies (Table 2,
Figure 4).[11d,20]
À
Ti O(1)
1.913
1.469
2.269
2.299
1.903
1.496
2.117
2.397
1.911
1.520
2.300
2.416
À
O(1) O(2)
À
Ti O(2)
À
Ti N
[a] For oxygen labelling see Scheme 3. [b] See reference [20a]. [c] See ref-
erence [11d]. [d] The energy of the structure has been minimised by
using Gaussian 03 software.[21]
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C3-TiIV Amino Trialkolate Sulfoxidation Catalysts
FULL PAPER
Scheme 4. Suggested mechanism for the nucleophilic attack of the sub-
strate (along the s* bond of the peroxo bond perpendicular to the plane
of the paper). The two possible diasteromeric attacks for the sulphide are
shown.
Figure 4. B3LYP/LANL2DZ-optimised structure of 8a and calculated
electrostatic potential surface.
Among the possible conformations that the cumyl moiety
can adopt, the more stable shows an edge-to-face interaction
between the aromatic ring of the trialkanolamine ligand and
the phenyl group of the cumyl hydroperoxide. In Figure 4, it
is possible to observe the Van der Waals surface of the mini-
mized structure of the reactive complex (R,R,R)-8a. The
structure has been oriented to show the reactive trajectory
of the nucleophilic attack of the substrate, above and per-
pendicular to the plane of the paper: in this stabilized con-
formation the peroxo–TiIV complex displays a structural
pocket in which the aromatic interactions can play a primary
role. Two possible approaches of the substrates, yielding the
two enantiomeric sulfoxides, are dictated by the shape of
the pocket and the directionality of the s* bond of the re-
acting sulfide. As a consequence, two diastereomeric attacks
can be envisaged (Scheme 4).
ACHTUNGTRENtNUNG ies. Since the present study utilizes mono- and polysubsti-
tuted aromatic rings in addition to the naphthyl, anthryl and
pentafluorophenyl groups, the diverse cross-sections of aro-
matic rings could not be readily described by using the
Hammett substituent constants, as shown in previous works
on aromatic interactions.[5 h] Instead, calculated electrostatic
potential surfaces (EPSs) seem more appropriate to gener-
ate a scale that describes the properties of the aromatic
groups employed in this study.[1c] The calculated values of
the EPSs at the centre of each of the aromatic groups are in-
cluded in Table 1.
A plot of the experimental log([S]/[R]) against the ring
centre EPSs of the aromatic moieties of the benzyl groups
rules out any straightforward interpretation of the data (Fig-
ure 5a). However, a division of the aromatic systems into
If the sulfide is reacting with
the pro-S lone pair its benzyl
ring is interacting edge-to-face
with the catalytic system 8a.
On the other hand, in the case
of the pro-R lone-pair attack,
the benzyl group is interacting
face-to-face. From this obser-
vation, the preference for the
pro-S attack indicates the ten-
dency of the benzyl ring to par-
ticipate in a stabilizing edge-
to-face interaction or/and to
avoid the face-to-face one. A
confirmation of this assump-
tion comes from the fact that
the pentafluorophenyl 4o (and
to some extent also nitroben-
zene 4m), known to largely
favour stacking interactions
with
unsubstituted
phenyl
rings, displays the lower ee
values of all the series.
To extend the scope of this
analysis to all the other sub-
strates, we decided to consider
the electrostatic properties of
all the series of benzyl moie-
Figure 5. Plot of observed stereoselectivities expressed as log([S]/[R]) versus electrostatic potential surfaces
EPS [kJmolÀ1] for: a) all the compounds, b) for compounds with substituents not hindered in para or meta po-
2
2
*
*
sitions ( ,c: R =0.93) and with a hindered substituent in the para position ( ,d: R =0.85), c) for the
halogen series and d) for the unsubstituted aromatic series.
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649

G. Licini, C. Zonta et al.
three different classes gives prominence to the role of elec-
trostatic and steric interactions. The contribution of the elec-
trostatic factor is unambiguous if we focus our attention to
eight sulfides 4a–c,h,l–o with aromatic groups substituted by
functions containing a steric hindrance, out of the ring
2
*
plane, comparable to a phenyl ring ( ,c: R =0.93) and
with the four sulfides 4 f,g,i,k with a slightly more hindered
2
*
substituent in the para position ( ,d: R =0.85) (Fig-
ure 5b). These plots extend across a wide electrostatic distri-
bution with a good correlation. It covers rings from the pen-
tafluorophenyl (4o) (lower stereoselectivity, ee=45%),
which is known to favour stacking interactions, to the dime-
thylamino-substituted ring (4 f) known to favour the edge-
to-face conformation (ee=57%). This sequence suggests a
defined and important role of electrostatics to the final ste-
Figure 6. Plot of observed stereoselectivities expressed as log([S]/[R])
versus van der Waals radii or width of the polycondensed aromatic ring,
À
&
orthogonal to the C C bond [ꢃ] for derivatives 4h–j (F, Cl, Br) ( c:
2
2
^
R =0.84), 4a 2-naphtyl, 4c 1-naphtyl and 9-anthryl 4e ( ,c: R =
ACHTUNGTRENNUNGreoselection, revealing at the same time, an additive contri-
0.99).
bution of steric effects when a more hindered substituent is
present in the para position (second correlation). This effect
may be explained assuming a steric clash between the para
substituent and the aromatic ring of the complex in the case
of the pro-(R) attack. The presence of a disubstituted me-
thoxy ring (4l) suggests that meta substituents do not inter-
fere sterically with the outcome of the reaction.
The impact of the para steric factor is even more evident
in the series of rings substituted in the para position with
halogens (4h–j in Figure 5c). The three different halogens
are known to have a similar influence on the electrostatic
properties of the aromatic rings.[22] This is underlined by
their similar EPSs. Among this series it is clear that the in-
creasing steric size in the para position has an additive
effect of the selectivity, favouring the formation of the S
sulfoxides. The additive influence of the steric size on the
stereoselectivity is also observed in the series constituted by
polycondensed aromatic systems naphthyl and antryl (4c–e
Figure 5d).
stituents In fact, edge-to-face interactions are favoured by
electron-rich aromatic rings displaying negative EPS poten-
tials. On the other hand it is not affected by the presence of
substituents with higher steric hindrance. In the other ap-
proach, yielding the R enantiomer, the benzyl ring of the
sulfide approaches the peroxo function forming a face-to-
face interaction with one phenyl ring of the ligand
(Scheme 4b). This interaction is eventually favoured by elec-
tron-withdrawing groups and, due to the presence of the
cumyl ring, highly disfavoured by hindered aromatic rings.
As the EPS of the benzyl ring becomes less negative, the
stacking interaction becomes more favourable. For example,
the pentafluorophenyl group 4o, which has the most positive
EPS and is known to give a face-to-face interaction, displays
the lowest ee.
The contribution of the steric influences on the course of
sulfoxidation is also evident. The highest ee values are ob-
tained for molecules displaying hindered groups in para po-
sitions, as shown by the halogen series 4h–j (F, Cl, Br), or
when more hindered groups are present, as shown by the in-
creasing ee values in the phenyl 4a, 1-naphtyl 4c and 9-an-
thryl 4e series. These more hindered molecules are less
prone to undergo the pro-(R) attack as a result of disfav-
oured stacking interactions as a consequence of steric repul-
sions with the cumyl aromatic ring.
Interestingly, what emerges from this analysis is that the
selectivity of the process, that is, the discrimination between
the diastereomeric transition states, obtained by only vary-
ing the electrostatic interactions of the aromatic partners is
linear even if moderate. Indeed, comparing similar steric
hindrances, the ee values observed for the most electron-
poor substituent (pentafluoro 4o) and the most electron-
rich substituent (methoxy 4g) only differ by 13%. This cor-
responds at À208C to an energy difference of approximately
1 kJmolÀ1, in line with the experimental energies observed
for p–p interactions. Much higher differences are observed
for variation of the steric features of reacting partners with
comparable EPSs and they linearly depend on the VDW
radii of the halogen atoms in the para position or the dimen-
In this series, the increased dimensions of the aromatic
systems (2-naphthyl 4d, 1-naphthyl, 4c and 9-anthryl 4e) af-
fords even larger differences in stereoselectivities, reaching
the maximum value for the 9-anthryl derivative 4e. (ee=
71%). Worthy of notice is the linear correlation that is ob-
tained by plotting the experimental log([S]/[R]) values
against the VDW radii of the halogens (F: 1.30, Cl: 1.75, Br:
2
&
1.95 ꢃ) ( ,c: R =0.84) and the width orthogonal to the
À
C C bond of the polycondensed aromatic ring, (2-naphthyl:
5.41, 1-naphthyl: 6.57, 9-anthryl: 8.99 ꢃ) ( ,c R =0.99;
2
^
Figure 6), which indicates that the additive steric contribu-
tion of the benzyl moieties in the periphery can be also
quantified, at least to a certain extent.
On the basis of the above analysis we suggest that the two
diastereomeric approaches, yielding opposite enantiomers,
are modulated by the occurrence of different intermolecular
interactions between the aryl groups of the catalyst and the
substrate. In particular, the favoured one, which affords the
S sulfoxide, is characterised by a stabilizing edge-to-face in-
teraction of the benzyl group with an aromatic ring of the
catalyst (Scheme 4a). This approach is, therefore, more fav-
oured by benzyl groups possessing electron-donating sub-
650
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Chem. Eur. J. 2010, 16, 645 – 654

C3-TiIV Amino Trialkolate Sulfoxidation Catalysts
FULL PAPER
Method B: DBU (16.6 mmol) and a solution of p-thiocresol (16.6 mmol)
in acetonitrile (10 mL) were added in this order to a solution of the
benzyl chloride (16.6 mmol) in acetonitrile (20 mL). The mixture was
stirred at RT until consumption of the starting materials was observed as
judged by TLC or GCMS. Water (30 mL) was added, the layers were sep-
arated and the aqueous one was extracted with CH2Cl2 (3ꢄ25 mL). The
combined organic layers were washed with brine (1ꢄ50 mL), dried on
Na2SO4 and concentrated under reduced pressure. The product was puri-
fied by flash chromatography on silica gel.
sions of the polycondensed aromatic systems. The reason
why aromatic rings are important elements in the final ste-
reoselectivity should be attributed to both effects, in which
the steric features have a larger role than the electrostatic
distribution.
Conclusion
Method C: KOH (11.27 mmol) was added to a solution p-thiocresol
(18.8 mmol) in absolute ethanol (60 mL). The mixture was heated at
808C and at this temperature a solution of the corresponding benzyl
chloride (9.39 mmol) in ethanol (15 mL) was added. The mixture was re-
fluxed for 2 h, then cooled to RT, quenched with water (50 mL) and con-
centrated. The residue was partitioned in water (50 mL) and CHCl3
(40 mL). The layers were separated and the aqueous one was extracted
with CHCl3 (3ꢄ40 mL). The combined organic layers were washed with
brine (1ꢄ90 mL), dried on Na2SO4 and concentrated under reduced pres-
sure. The product was purified by flash chromatography on silica gel.
The results observed in the oxidation of a series of benzyl
tolyl sulfides with catalyst (R,R,R)-1a indicate that the
origin of the substituent-dependent enantioselectivity in the
oxygen-transfer reactions of sulfides is given by the competi-
tion of face-to-face and edge-to-face interactions between
the ligand backbone and substrates, interactions occurring in
the pheriphery of the systems involved in the reaction and
not directly influencing the oxygen-transfer process. Even
though these intermolecular interactions are weak, the
direct contact reached between the aromatic rings of the re-
agent and of the ligand in the transition state is able to mod-
ulate the observed selectivity. The results also reveal that
the stereoselective catalytic reaction provides a sensitive
probe to investigate weak intermolecular interactions, such
as p–p interactions and the additive steric contributions in
transition states. The results provide useful information for
understanding the influence of electronic and steric effects
in catalysts possessing aromatic backbones or substituents
on aromatic substrates and for the design of novel ligands.
1-Naphthylmethyl p-tolyl sulfide (4c): Method C; orange oil; yield: 70%;
1H NMR (250 MHz, CDCl3): d=8.17 (d, J=8.0 Hz, 1H), 7.99 (d, J=
7.3 Hz, 1H), 7.78 (d, J=7.7 Hz, 1H), 7.61–7.49 (m, 2H), 7.38–7.24 (m,
4H), 7.10 (d, J=8.0 Hz, 2H), 4.54 (s, 2H), 2.35 ppm (s, 3H); 13C NMR
(62.9 MHz, CDCl3): d=136.72, 133.89, 133.02, 132.74, 131.39, 131.03,
129.60, 128.73, 128.12, 127.25, 126.14, 125.76, 125.20, 123.92, 37.88,
21.05 ppm; MS (70 eV): m/z: 115 (26), 141 (100), 264 (18) [M+]; elemen-
tal analysis calcd (%) for C18H16S: C 81.77, H 6.10; found: C 81.42, H
6.07.
2-Naphthylmethyl p-tolyl sulfide (4d): Method A; white solid; yield:
89%; m.p. 94–968C; 1H NMR (250 MHz, CDCl3): d=7.83–7.75 (m, 3H),
7.73 (s, 1H), 7.65–7.44 (m, 3H), 7.25 (d, J=8.0 Hz, 2H), 7.06 (d, J=
8.0 Hz, 2H), 4.24 (s, 2H), 2.31 ppm (s, 3H); 13C NMR (62.9 MHz,
CDCl3): d=136.60, 135.17, 133.23, 132.49, 132.29, 130.79, 129.60, 128.18,
127.65, 127.60, 127.33, 127.01, 126.02, 125.70, 40.08, 21.01 ppm; MS
(70 eV): m/z: 115 (23), 141 (100), 264 (20) [M+]; elemental analysis calcd
(%) for C18H16S: C 81.77, H 6.10; found: C 81.53, H 6.04.
9-Anthracenylmethyl p-tolyl sulfide (4e): Method A; yellow solid; yield:
60%; m.p. 124–1288C; H NMR (250 MHz, CDCl3): d=8.30 (s, 1H), 8.20
Experimental Section
1
(d, J=8.4 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H), 7.48–7.30 (m, 6H), 7.08 (d,
J=7.8 Hz, 2H), 4.95 (s, 2H), 2.30 ppm (s, 3H); 13C NMR (62.9 MHz,
CDCl3): d=136.49, 133.55, 131.35, 130.29, 129.92, 129.65, 129.02, 127.78,
127.50, 126.05, 124.90, 124.03, 32.51, 21.01 ppm; MS (70 eV): m/z: 191
(100), 314 (10) [M+]; elemental analysis calcd (%) for C22H18S: C 86.84,
H 5.92; found: C 84.03, H 5.77.
General methods: Chemicals and solvents were purchased from commer-
cial suppliers and used as supplied. Sulfides 4a, 4b, 4g, 4h and 4i were
prepared as previously reported.[15] Complexes (R,R,R)-1a and (S,S,S)-1b
were synthesized as previously reported.[11f] 1H (250 MHz) and 13C NMR
(62.9 MHz) spectra were recorded with a Bruker AVANCE 250 spec-
trometer at 208C by using CDCl3 as the solvent. Chemical shifts are
given in ppm relative to TMS as the internal standard. Coupling con-
stants (J) are reported in Hz. Chiral HPLC was performed by using a Li-
chrosorb S100, (S,S)-Dach DNB chiral column eluting with n-hexane/i-
propanol 80:20. Specific rotations were recorded on a Perkin–Elmer 241
(4-Dimethylaminobenzyl) p-tolyl sulfide (4 f): Method B; white solid;
yield: 73%; m.p. 85–878C; 1H NMR (250 MHz, CDCl3): d=7.33 (d, J=
8.0 Hz, 2H), 7.27 (d, J=8.8 Hz, 2H), 7.16 (d, J=8.0 Hz, 2H), 6.76 (d, J=
8.8 Hz, 2H), 4.14 (s, 2H), 3.00 (s, 6H), 2.41 ppm (s, 3H); 13C NMR
(62.9 MHz, CDCl3): d=149.53, 135.80, 133.17, 129.96, 129.63, 129.45,
124.93, 112.40, 40.43, 38.97, 20.88 ppm; MS (70 eV): m/z: 118 (12), 134
(100), 257 (100) [M+]; elemental analysis calcd (%) for C16H19NS: C
74.66, H 7.44, N 5.44; found: C 74.30, H 7.47, N 5.41.
polarimeter at 258C in the solvents indicated. The sodium
D line
(589 nm) was used unless otherwise indicated. The units of a are 10À1
degcm2 gÀ1. Enantiomeric excesses and absolute configurations were de-
1
termined by H NMR spectroscopy (CDCl3, 250 MHz) in the presence of
(R)-1-(9-anthryl)-2,2,2-trifluoroethanol or by chiral HPLC as indicated.
Sulfoxides 7a, 7b, 7g, 7h and 7i have been previously reported in an
enantioenriched form.[21] Sulfoxide 7k has been reported in racemic form
only.[23]
4-Bromobenzyl p-tolyl sulfide (4j): Method A; white solid; yield: 86%;
m.p. 73–768C; 1H NMR (250 MHz, CDCl3): d=7.37 (d, J=8.4 Hz, 2H),
7.18 (d, J=8.0 Hz, 2H), 7.11–7.04 (m, 4H), 3.98 (s, 2H), 2.30 ppm (s,
3H); 13C NMR (62.9 MHz, CDCl3): d=136.96, 136.94, 131.69, 131.46,
131.11, 130.46, 129.67, 120.88, 39.27, 21.28 ppm; MS (70 eV): m/z: 63
(13), 90 (30), 169 (100), 292 (2) [M+], 294 (2) [M++2]; elemental analysis
calcd (%) for C14H13BrS: C 57.35, H 4.47; found: C 57.12, H 4.14.
Synthesis of thioethers: General procedure
Method A: Sodium (38.4 mmol) was dissolved in absolute ethanol
(30 mL) under nitrogen at 08C. p-Thiocresol (32 mmol) was added to this
solution followed by a solution of the corresponding benzyl chloride
(32 mmol) in ethanol (100 mL). The mixture was stirred at RT until con-
sumption of the starting materials was observed as judged by TLC or
GCMS. Water (100 mL) was added, the layers were separated and the
aqueous one was extracted with CH2Cl2 (3ꢄ75 mL). The combined or-
ganic layers were washed with NaOH 5% (1ꢄ150 mL) and brine (1ꢄ
150 mL), dried on Na2SO4 and concentrated under reduced pressure. The
product was purified by flash chromatography on silica gel.
p-Tolyl 4-trifluoromethyllbenzyl sulfide (4k): Method A; white solid;
yield: 68%; m.p. 89–918C; 1H NMR (250 MHz, CDCl3): d=7.51 (d, J=
8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.19 (d, J=8.0 Hz, 2H), 7.07 (d, J=
8.0 Hz, 2H), 4.06 (s, 2H), 2.31 ppm (s, 3H); 13C NMR (62.9 MHz,
CDCl3) d=142.12 (q, J=1.4 Hz), 137.16, 131.38, 131.24, 129.73, 129.05,
125.31 (q, J=3.8 Hz), 124.12 (q, J=271.9 Hz), 39.49, 21.04 ppm; MS
(70 eV): m/z: 109 (17), 159 (100), 282 (53) [M+]; elemental analysis calcd
(%) for C15H13F3S: C 63.82, H 4.64; found: C 63.54, H 4.66.
Chem. Eur. J. 2010, 16, 645 – 654
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651

G. Licini, C. Zonta et al.
4-Cianobenzyl p-tolyl sulfide (4l): Method A; white solid; yield: 96%;
m.p. 102–1058C; 1H NMR (250 MHz, CDCl3): d=7.54 (d, J=8.0 Hz,
2H), 7.29 (d, J=8.0 Hz, 2H), 7.17 (d, J=8.0 Hz, 2H), 7.06 (d, J=8.0 Hz,
2H), 4.04 (s, 2H), 2.31 ppm (s, 3H); 13C NMR (62.9 MHz, CDCl3) d=
143.69, 137.48, 132.13, 131.65, 130.73, 129.76, 129.45, 118.77, 110.74, 39.80,
21.04 ppm; MS (70 eV): m/z: 89 (17), 116 (100), 123 (19), 239 (56) [M+],
240 (10) [M++1]; elemental analysis calcd (%) for C15H13NS: C 75.27, H
5.47, N 5.86; found: C 74.98, H 4.49, N 5.83.
7.49–7.46 (m, 3H), 7.31–7.19 (m, 4H), 7.10 (d, J=8.8 Hz, 1H), 4.26 (AB,
d, J=12.4 Hz, 1H), 4.13 (AB, d, J=12.4 Hz, 1H), 2.39 ppm (s, 3H);
13C NMR (62.9 MHz, CDCl3): d=141.65, 139.62, 133.07, 132.86, 130.89,
129.76, 129.57, 128.11, 127.83, 127.73, 127.63, 126.82, 126.26, 124.44, 64.07,
21.43 ppm; MS (70 eV): m/z: 115 (23), 141 (100), 280 (1) [M+]; elemental
analysis calcd (%) for C18H16OS: C 77.11, H 5.75; found: C 77.47, H 5.70.
9-Anthracenylmethyl p-tolyl sulfoxide (7e): White solid; yield: 99%;
1
m.p. 142–1458C; 71% ee (S), determined by H NMR spectroscopy in the
4-Nitrobenzyl p-tolyl sulfide (4m): Method A; yellow solid; yield: 96%;
m.p. 102–1058C; H NMR (250 MHz, CDCl3): d=7.07–7.37 (m, 8H), 4.09
presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À147.0 (c=
1.0 in dichloromethane); 1H NMR (250 MHz, CDCl3): d=8.44 (s, 1H),
8.00–7.97 (m, 4H), 7.45–7.39 (m, 4H), 7.12 (d, J=8.3 Hz, 2H), 7.01 (d,
J=8.3 Hz, 2H), 5.31 (AB, d, J=13.2 Hz, 1H), 4.96 (AB, d, J=13.2 Hz,
1H), 2.28 ppm (s, 3H); 13C NMR (62.9 MHz, CDCl3): d=141.67, 139.81,
131.20, 131.07, 129.36, 129.06, 128.56, 126. 37, 124.99, 124.09, 123.79,
121.19, 57.63, 21.30 ppm; MS (70 eV): m/z: 191 (100), 330 (1) [M+]; ele-
mental analysis calcd (%) for C22H18OS: C 79.96, H 5.49; found: C 77.57,
H 5.51.
1
(s, 2H), 2.32 ppm (s, 3H); 13C NMR (62.9 MHz, CDCl3): d=145.86,
137.68, 131.87, 130.52, 129.84, 129.55, 128.21, 123.62, 39.62, 21.09 ppm;
MS (70 eV): m/z: 78 (25), 90 (23), 123 (22), 136 (20), 213 (22), 259 (100)
[M+]; elemental analysis calcd (%) for C14H13NO2S: C 64.84, H 5.05, N
5.40; found: C 64.80, H 5.02, N 5.38.
3,5-Dimethoxybenzyl p-tolyl sulfide (4n): Method A; white solid; yield:
89%; m.p. 92–948C; 1H NMR (250 MHz, CDCl3): d=7.23 (d, J=8.0 Hz,
2H), 7.07 (d, J=8.0 Hz, 2H), 6.42 (d, J=2.2 Hz, 2H), 6.33 (d, J=2.2 Hz,
2H), 4.00 (s, 2H), 3.74 (s, 6H), 2.31 ppm (s, 3H); 13C NMR (62.9 MHz,
CDCl3): d=160.66, 140.05, 136.56, 132.44, 130.68, 129.59, 106.64, 99.35,
55.26, 40.01, 21.01 ppm; MS (70 eV): m/z: 151 (100), 274 (36) [M+]; ele-
mental analysis calcd (%) for C16H18O2S: C 70.04, H 6.61; found: C
70.51, H 6.59.
4-Dimethylaminobenzyl p-tolyl sulfoxide (7 f): White solid; yield: 87%;
m.p. 123–1258C; 57% ee (S); [a]2D5 =À120.1 (c=1.0 in dichloromethane);
1H NMR (250 MHz, CDCl3): d=7.30 (d, J=8.3 Hz, 2H), 7.23 (d, J=
8.3 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 6.59 (d, J=8.8 Hz, 2H), 4.05 (AB,
d, J=12.6 Hz, 1H), 3.88 (AB, d, J=12.6 Hz, 1H), 2.93 (s, 6H), 2.40 ppm
(s, 3H); 13C NMR (62.9 MHz, CDCl3): d=150.33, 141.29, 131.55, 131.17,
129.44, 124.58, 116.36, 112.19, 63.55, 40.40, 21.44 ppm; MS (70 eV): m/z:
118 (15), 134 (100), 257 (10) [M+ÀO]; elemental analysis calcd (%) for
C16H19NOS: C 70.29, H 7.00, N 5.12, S 11.73; found: C 69.47, H 7.89, N
5.34,S 10.53.
2,3,4,5,6-Pentafluorobenzyl p-tolyl sulfide (4o): Method A; white solid;
yield: 83%; m.p. 64–668C; 1H NMR (250 MHz, CDCl3): d=7.28 (d, J=
7.7 Hz, 2H), 7.11 (d, J=7.7 Hz, 2H), 4.05 (s, 2H), 2.35 ppm (s, 3H);
13C NMR (62.9 MHz, CDCl3) d=144.83 (dm, J=249.0), 140.23 (dm, J=
253.3), 138.53, 137.29 (dm, J=253.6 Hz), 133.19, 129.82, 112.63 (dt, J=
17.6, 4.0 Hz), 27.47, 21.05 ppm; MS (70 eV): m/z: 45 (20), 123 (58), 181
(100), 304 (66) [M+]; elemental analysis calcd (%) for C14H9F5S: C 55.26,
H 2.98; found: C 54.98, H 2.93.
4-Methoxybenzyl p-tolyl sulfoxide (7g): White solid; yield: 99%; 58% ee
1
(S), determined by H NMR spectroscopy in the presence of (R)-1-(9-an-
thryl)-2,2,2-trifluoroethanol; [a]2D5 =À106.4 (c=1.0 in dichloromethane)
(lit.[21] [a]2D0 =À87 (c=0.2 in chloroform) for>99% ee); all analytical
data are in agreement with those previously reported.[15]
Asymmetric oxidation of sulfides: General procedure: A two-necked
25 mL flask was charged with the corresponding sulfide (5 mmol), cata-
lyst (R,R,R)-1a (24 mg, 0.05 mmol) and dry 1,2-dichloroethane (6 mL)
under nitrogen. The resulting solution was cooled to À208C and a solu-
tion of CumOOH (95 mg, 0.5 mmol) in dry 1,2-dichloroethane (3.2 mL)
was added. The mixture was stirred at À208C until complete consump-
tion of the oxidant (iodometric test). 5% Sodium metabisulfite (10 mL)
was added and the mixture was stirred for 30 min at RT. The layers were
separated and the aqueous one extracted with CH2Cl2 (3ꢄ10 mL). The
combined organic layers were washed with 10% NaOH (1ꢄ30 mL) and
brine (1ꢄ30 mL), dried on Na2SO4 and concentrated under reduce pres-
sure. The product was purified by flash chromatography on silica gel.
4-Fluorobenzyl p-tolyl sulfoxide (7h): White solid; yield: 99%; 50% ee
(S), determined by 1H NMRspectroscopy (CDCl3, 250 MHz) in the pres-
ence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À118.4 (c=1.0 in
dichloroethane) (lit.[21] [a]D20 =À109 (c=0.4 in chloroform) for 71% ee);
all analytical data are in agreement with those previously reported.[15]
4-Chlorobenzyl p-tolyl sulfoxide (7i): White solid; yield: 90%; 54% ee
1
(S), determined by H NMR spectroscopy (CDCl3, 250 MHz) in the pres-
ence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À108.6 (c=1.0 in
dichloroethane) (lit.[21] [a]D20 =À140 (c=0.5 in chloroform) for 98% ee);
all analytical data are in agreement with those previously reported.[15]
4-Bromobenzyl p-tolyl sulfoxide (7j): White solid; yield: 99%; m.p. 155–
1598C; 60% ee (S), determined by 1H NMR spectroscopy (CDCl3,
250 MHz) in the presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol;
[a]2D5 =À123.0 (c=1.0 in dichloromethane); 1H NMR (250 MHz, CDCl3):
d=7.37 (d, J=8.4 Hz, 2H), 7.27–7.23 (m, 4H), 6.84 (d, J=8.4 Hz, 2H),
3.96 (s, 2H), 2.40 ppm (s, 3H); 13C NMR (62.9 MHz, CDCl3): d=141.80,
139.25, 131.93, 131.48, 129.64, 128.08, 125.87, 124.36, 62.49, 21.43 ppm;
MS (70 eV): m/z: 56 (30), 89 (21), 90 (26), 169 (100), 171 (99), 308 (1)
[M+], 310 (1) [M++2]; elemental analysis calcd (%) for C14H13BrOS: C
54.38, H 4.24; found: C 54.50, H 4.25.
Benzyl p-tolyl sulfoxide (7a): White solid; yield: 98%; 56% ee (S), deter-
mined by chiral HPLC; HPLC: tR =11.1 (S), 16.8 min (R); [a]2D5 =À143.2
(c=1.0 in acetone) (lit.[21] [a]D20 =À235.2 (c=0.7 in acetone) for 94% ee);
all analytical data are in agreement with those previously reported.[21]
4-Methylbenzyl p-tolyl sulfoxide (7b): White solid; yield: 89%; 54% ee
1
(S), determined by H NMR spectroscopy (CDCl3, 250 MHz) in the pres-
ence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À110.1 (c=1.0 in
dichloroethane) (lit.[21] [a]D20 =À43 (c=0.5 in chloroform) for>99% ee);
all analytical data are in agreement with those previously reported.[15]
1-Naphthylmethyl p-tolyl sulfoxide (7c): White solid; yield: 99%; m.p.
156–1598C; 59% ee (S), determined by 1H NMR spectroscopy in the
presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À58.7 (c=1.0
p-Tolyl 4-trifluoromethylbenzyl sulfoxide (7k): White solid; yield 95%;
53% ee (S), determined by 1H NMR spectroscopy (CDCl3, 250 MHz) in
the presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À97.6 (c=
1.0 in dichloroethane); all analytical data are in agreement with those
previously reported.[15]
1
in dichloromethane); H NMR (250 MHz, CDCl3): d=8.01–7.98 (m, 1H),
7.87–7.78 (m, 2H), 7.52–7.49 (m, 2H), 7.33–7.14 (m, 5H), 7.02 (d, J=
7.0 Hz, 1H), 4.69 (AB, d, J=12.4 Hz, 1H), 4.33 (AB, d, J=12.4 Hz, 1H),
2.36 ppm (s, 3H); 13C NMR (62.9 MHz, CDCl3): d=141.61, 139.95,
133.52, 131.81, 130.90, 129.55, 129.50, 129.40, 129.04, 128.65, 126.44,
125.84, 125.80, 125.07, 124.22, 123.33, 62.19, 21.30 ppm; MS (70 eV): m/z:
115 (25), 141 (100), 280 (2) [M+]; elemental analysis calcd (%) for
C18H16OS: C 77.11, H 5.75; found: C 76.86, H 5.80.
4-Cianobenzyl p-tolyl sulfoxide (7l): White solid; yield: 92%; m.p. 180–
1848C; 49% ee (S), determined by 1H NMR spectroscopy (CDCl3,
250 MHz) in the presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol;
[a]2D5 =À129.0 (c=1.0 in dichloromethane); 1H NMR (250 MHz, CDCl3):
d=7.53 (d, J=8.3 Hz, 2H), 7.28–7.23 (m, 4H), 7.06 (d, J=8.3 Hz, 2H),
4.11 (AB, d, J=12.6 Hz, 1H), 3.96 (AB, d, J=12.6 Hz, 1H), 2.41 ppm (s,
3H); 13C NMR (62.9 MHz, CDCl3): d=149.11, 148.59, 148.45, 136.94,
131.45, 131.10, 130.45, 129.66, 120.88, 39.27, 21.05 ppm; MS (70 eV): m/z:
89 (25), 116 (100), 139 (60), 255 (8) [M+]; elemental analysis calcd (%)
for C15H13NOS: C 70.56, H 5.13, N 5.49; found: C 70.37, H 5.15, N 5.46.
2-Naphthylmethyl p-tolyl sulfoxide (7d): White solid; yield: 82%; m.p.
1
164–1678C; 51% ee (S) determined by H NMR spectroscopy in the pres-
ence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À40.3 (c=1.0 in
dichloromethane); 1H NMR (250 MHz, CDCl3): d=7.83–7.71 (m, 3H),
652
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Chem. Eur. J. 2010, 16, 645 – 654

C3-TiIV Amino Trialkolate Sulfoxidation Catalysts
FULL PAPER
4-Nitrobenzyl p-tolyl sulfoxide (7m): White solid; yield: 73%; m.p. 162–
1668C; 47% ee (S), determined by 1H NMR spectroscopy (CDCl3,
250 MHz) in the presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol;
[a]2D5 =À129.0 (c=1.0 in dichloromethane); 1H NMR (250 MHz, CDCl3):
d=8.10 (d, J=8.8 Hz, 2H), 7.26 (brs, 4H), 7.11 (d, J=8.8 Hz, 2H), 4.17
(AB, d, J=12.8 Hz, 1H), 4.00 (AB, d, J=12.8 Hz, 1H), 2.41 ppm (s, 3H);
13C NMR (62.9 MHz, CDCl3): d=147.59, 142.11, 138.36, 136.28, 131.19,
129.76, 124.12, 123.22, 61.80, 21.40 ppm; MS (70 eV): m/z: 89 (25), 116
(100), 139 (60), 275 (8) [M+]; elemental analysis calcd (%) for
C14H13NO3S: C 61.07, H 4.76, N 5.09; found: C 60.84, H 5.05, N 5.06.
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3,5-Dimethoxybenzyl p-tolyl sulfoxide (7n): White solid; yield: 99%;
m.p. 115–1208C; 52% ee (S), determined by 1H NMR spectroscopy
(CDCl3, 250 MHz) in the presence of (R)-1-(9-anthryl)-2,2,2-trifluoroe-
thanol; [a]2D5 =À115.0 (c=1.0 in dichloromethane); 1H NMR (250 MHz,
CDCl3): d=7.34 (d, J=8.2 Hz, 2H), 7.28 (d, J=8.2 Hz, 2H), 4.11 (m,
1H), 3.87 (m, 1H), 4.11 (AB, d, J=12.4 Hz, 1H), 3.87 (AB, d, J=
12.4 Hz, 1H), 3.70 (6H, s), 2.41 ppm (s, 3H); 13C NMR (62.9 MHz,
CDCl3): d=160.56, 142.02, 141.61, 139.72, 131.43, 129.51, 128.31, 125.89,
124.46, 107.98, 100.58, 64.22, 55.20, 21.36 ppm; MS (70 eV): m/z: 151
(100), 152 (19), 290 (1) [M+]; elemental analysis calcd (%) for
C16H18O3S: C 66.18, H 6.25; found: C 66.47, H 6.23, S 10.63.
2,3,4,5,6-Pentafluorobenzyl p-tolyl sulfoxide (7o): White solid; yield:
1
72%; m.p. 117–1228C; 45% ee (S), determined by H NMR spectroscopy
in the presence of (R)-1-(9-anthryl)-2,2,2-trifluoroethanol; [a]2D5 =À75.8
(c=1.0 in dichloromethane); 1H NMR (250 MHz, CDCl3): d=7.30 (d,
J=8.0 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 4.16 (AB, d, J=12.8 Hz, 1H),
4.08 (AB, d, J=12.8 Hz, 1H), 2.42 ppm (s, 3H); 13C NMR (62.9 MHz,
CDCl3) d=145.45 (dm, J=250.6 Hz), 142.60, 140.96 (dm, J=255.71 Hz),
139.03, 137.30 (dm, J=252.01 Hz), 50.18, 21.38 ppm; MS (70 eV): m/z: 45
(17), 78 (15), 181 (100), 304 (66), 320 (4) [M+]; elemental analysis calcd
(%) for C14H9F5OS: C 52.50, H 2.83; found: C 52.09, H 2.85.
´
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Acknowledgements
Financial support from MIUR, FIRB 2003 CAMERE-RBNE03JCR5
project, University of Padova, Assegni di Ricerca 2006 (M.M.) and
COST ACTION D40 Innovative Catalysis—New Processes and Selectivi-
ties.
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Received: July 24, 2009
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