The first chiral zirconium(IV) catalyst for highly stereoselective sulfoxidation

Full text of DOI:10.1021/jo980677t

1326
J . Org. Chem. 1999, 64, 1326-1330
Sch em e 1a
Th e F ir st Ch ir a l Zir con iu m (IV) Ca ta lyst for
High ly Ster eoselective Su lfoxid a tion
Marcella Bonchio,*,‡ Giulia Licini,*,‡ Fulvio Di Furia,‡,†
Silvia Mantovani,‡ Giorgio Modena,‡ and
William A. Nugent§
Universita` di Padova, Dipartimento di Chimica Organica,
Centro Meccanismi Reazioni Organiche del CNR, via
Marzolo 1, I-35131 Padova, Italy, and The DuPont Central
Research & Development, P.O. Box 80328,
Wilmington, Delaware, 19880-0328
Received April 13, 1998
Catalytic enantioselective oxidations are among the
most challenging transformations in asymmetric synthe-
sis.1 In particular, together with stereoselective osmium-
catalyzed dihydroxylations2 and salen-manganese-me-
diated epoxidation,3 asymmetric oxidations catalyzed by
chiral titanium(IV) alkoxides play a major role in this
area.4-8 Chiral titanium(IV) alkoxides have been found
to mediate effectively some fundamental oxidative pro-
cesses such as allylic alcohol epoxidation,4 â-hydroxyamine
N-oxidation,5 sulfoxidation,6,7 and Baeyer Villiger oxida-
tion.8 In contrast, analogous zirconium(IV) catalysts have
been less extensively investigated. In the few example
reported so far, they typically exhibit lower catalytic
activity and poorer stereoselectivity compared with their
titanium counterparts.9 For example, in the epoxidation
of (E)-R-phenylcinnamyl alcohol by tert-butyl hydroper-
oxide (TBHP), Zr(i-PrO)4/(+)-diethyltartrate (DET) af-
fords the corresponding (R,R)-epoxide in low yield and
ee ) 10%, while the Ti(IV) analogue produces the (S,S)-
epoxide with ee > 95% in 75% yield.9a,10 Higher stereo-
selections were obtained in the Zr(IV)/(+)-dicyclohexyl-
a
Reagents and conditions: (a) Ti(i-PrO)4 (1 equiv), CH2ClCH2Cl
(DCE), 20 °C; (b) Ti(i-PrO)4 (0.75 equiv), CH2Cl2, 20 °C, followed
by solvent removal and hexane stripping; (c) PhCMe2OOH (CHP).
tartramide-mediated epoxidation of homoallylic alcohols,9b
which provides ee’s up to 77% with yields e 38%.
We recently reported that titanium complexes bearing
C3 symmetric trialkanolamine ligands 1a -c11,12 are ef-
fective catalysts for asymmetric sulfoxidation using alkyl
hydroperoxides as the stoichiometric oxidant (Scheme
1).7,13-15
When the oxidation is performed with cumyl hydro-
peroxide (CHP) in the presence of catalysts 2b or 3b, high
turnover numbers (TO) (1-2% catalyst loading) and
enantiomeric excesses (ee’s) in the range of 40-84% are
obtained.7
* To whom correspondence should be addressed.
‡ Universita` di Padova.
† Deceased on October 15, 1997.
§ The DuPont Central Research & Development.
(1) Ojima, I. Catalytic Asymmetric Synthesis; VCH Publisher: New
York, 1993. Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley-Interscience: New York, 1994.
(2) J ohnson, R. A.; Sharpless, K. B. In ref 1, Chapter 4.4, pp 103-
158. Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483. Balavoine, G. G. A.; Manoury, E. Appl. Organomet.
Chem. 1995, 9, 199.
(3) J acobsen, E. N. In ref 1, Chapter 4.2, pp 159-202. Katsuki, T.
Coord. Chem. Rev. 1995, 140, 189.
(4) J ohnson, R. A.; Sharpless, K. B. In ref 1, Chapter 4.4, pp 227-
272.
(5) Miyano, S.; Lu, L. D.-L.; Viti, S. M.; Sharpless, K. B. J . Org.
Chem. 1983, 48, 3608.
(6) (a) Kagan, H. B. In ref 1, Chapter 4.3, pp 203-226, and
references therein. (b) Mata, E. G. Phosphorus, Sulfur Silicon 1996,
117, 231, and references therein. (c) Brunel, J .-M.; Kagan, H. B. Synlett
1996, 404. (d) Superchi, S.; Rosini, C. Tetrahedron: Asymmetry 1997,
8, 349. (e) Yamanoi, Y.; Imamoto, T. J . Org. Chem. 1997, 62, 8560. (f)
Reetz, M. T.; Merk, C.; Naberfeld, G.; Rudolph, J .; Griebenow, N.;
Goddard, R. Tetrahedron Lett. 1997, 38, 5273.
We now report that a partially hydrolyzed zirconium
catalyst bearing the same polydentate ligand 1b can
provide even higher levels of enantioselection with a
larger number of alkyl aryl sulfides. Stereoselective
sulfoxidations mediated by this new catalyst are char-
acterized by (i) good catalytic performance (2% catalyst
loading), (ii) ee’s in the range 80-90%, resulting from
the cooperativity of two oxidative stereoselective pro-
cesses (vide infra), and (iii) the opposite enantioselection
as compared with the corresponding titanium-catalyzed
oxidations. Moreover, sulfinyl componds with poor steric
differentiation between the two substituents at the sulfur
atom (sterically balanced), such as benzyl, tert-butyl,
(7) Di Furia, F.; Licini, G.; Modena, G.; Motterle R.; Nugent, W. A.
J . Org. Chem. 1996, 61, 5175.
(8) Loop, M.; Payn, A.; Kanger, T.; Pehk, T. Tetrahedron Lett. 1996,
37, 7583.
(11) (a) Nugent, W. A.; RajanBabu, T. V.; Burk, M. J . Science 1993,
259, 479. (b) Nugent, W. A.; Harlow, R. L. J . Am. Chem. Soc. 1994,
116, 6142.
(9) (a) Finn, M. G.; Sharpless, K. B. In Asymmetric Synthesis, Vol.
5; Morrison, J . D., Ed.; Academic Press: Orlando, 1995; pp 247-308.
(b) Ikegami, S.; Katsuki, T.; Yamaguchi, M. Chem. Lett. 1987, 83. (c)
Rossiter, B. E.; Sharpless, K. B. J . Org. Chem. 1984, 49, 3707
(10) The only other available direct comparison between Ti(IV) and
Zr(IV)/tartrate catalysts concerns the asymmetric epoxidation of (Z)-
hex-3-enol. The two systems afford the 3R,4S epoxide, respectively with
ee’s ) 50% [ref 9c] and 31% [ref 9b] (30% and 7% chemical yields).
(12) For a recent review on C3 symmetric chiral ligands see: Moberg,
C. Angew. Chem., Int. Ed. 1998, 37, 248.
(13) Bonchio, M.; Licini, G.; Modena, G.; Moro, S.; Bortolini, O.;
Traldi, P.; Nugent, W. A. Chem. Commun. 1997, 869.
(14) Bonchio, M.; Di Furia, F.; Licini, G.; Modena, G.; Moro, S.;
Nugent, W. A. J . Am. Chem. Soc. 1997, 119, 6935.
(15) Nugent, W.; Licini, G.; Bonchio, M.; Bortolini, O.; Finn, M. G.;
McCleland, B. W. Pure Appl. Chem. 1998, 70, 1041.
10.1021/jo980677t CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/30/1999

Notes
J . Org. Chem., Vol. 64, No. 4, 1999 1327
Sch em e 2a
Ta ble 1. 6b-Ca ta lyzed Oxid a tion of Meth yl-p-tolylsu lfid e
7 by CHP a
entry
no.
[6b]b
(M)
catalyst
(%)
time
(h)
conv
ee
(%)c,d
8:9d
(%)e
1
2
3
4
5
6
7
0.095
0.046
0.022
0.022
0.010
0.005
0.0005
10
4
2
2
1
3
5
18
3
21
21
27
100
100
100
23
46
26
35:65
25:75
30:70
80:20
80:20
100:0
100:0
86 (R)
86 (R)
85 (R)
66 (R)
40 (R)
9 (R)
a
Reagents and conditions: (a) Zr(n-BuO)4 (1 equiv), DCE, 20
°C; (b) i. H2O (2.5 equiv), N2, CH2Cl2, 20 °C; ii. solvent removal;
iii. Zr(n-BuO)4 (1 equiv), CH2Cl2, 20 °C, iv. solvent removal; v.
hexane stripping.
0.5
0.05
18
1 (S)
a
b
[7]0 ) [CHP] ) 1.08 M, in DCE at 0 °C. Calculated per Zr
atom. c Conversions based on the oxidant and calculated as conv.
n-butyl, or isopropyl aryl sulfoxides, can be obtained with
) ([8] + 2[9])/[CHP]0. Determined by GC analysis. e Determined
d
high ee’s by direct asymmetric oxidation.16
by HPLC analysis.
aggregation of the chiral zirconium species in the pres-
ence of water.17 In many cases hydrolyzed alkoxides of
early transition metals have shown an improved catalytic
activity and selectivity.6a,f,11,15 Indeed, both the reactivity
and enantioselectivity of the Zr(IV)-based system were
significantly enhanced by the addition of traces of water
to the reaction mixture (eq 1).19 With this modification,
conversion to products was complete in 4 h and (R)-8 was
obtained in 49% ee (8:9 ) 76:24). We ascribed this result
to the formation of a partially hydrolyzed Zr(IV) poly-
nuclear complex which then becomes the active catalyst.
To verify this hypothesis, the partially hydrolyzed cata-
lyst 6b was prepared by reacting a stoichiometric amount
of ligand 1b with Zr(n-BuO)4 in the presence of 2.5 equiv
of water (Scheme 2, path b). While a detailed study on
the hydrolysis conditions (equivalents of water, rate of
addition, concentration of the reagents, etc.) is currently
under investigation, preliminary results indicate that a
stoichiometric amount of water affords a poorly reactive
catalyst, behaving similarly to the anhydrous system 5b,
whereas an excess of water (13 equiv) provides a complex
that is only slightly soluble in the reaction medium.
The procedure described in Scheme 2, path b, affords
a white powder which reproducibly analyzes according
to the minimal formula 6b (see Experimental Section).
Indeed, complex 6b effectively catalyzes the oxidation of
7 (100% conversion in 4 h, 44% ee, (R), 8:9 ) 76:24)
without the requirement for extra water addition.
Optimization of the reaction conditions, namely, cata-
lyst and substrate concentrations, temperature, order of
addition of reagents, etc., allowed us to improve the
enantioselectivity of this process up to 86% (Table 1).
We discovered that such high enantioselectivity could
be achieved using only 2% of catalyst 6b, provided that
[6b] > 0.02 M. The data of Table 1, in particular the
constancy of the ee’s and of the product distribution for
entries 1-3, suggest that this concentration limit is
critical to the stability of the chiral Zr(IV) active species.
In fact, both a reduced catalytic activity and a lower
enantioselectivity were obtained at [6b] ) 0.01 M (com-
pare entries 4 and 5 at equal product distribution). For
[6b] e 0.005 M also the chemoselectivity of the oxidation
changes dramatically (compare, for analogous conversion
of the oxidant, the product distributions in entries 4 and
6), consistent with a major structural modification of the
active catalyst. Moreover when a sub-millimolar concen-
tration of 6b is used (entry 7), a reversal in the sense of
asymmetric induction in the oxidation of 7 is observed.
Resu lts a n d Discu ssion
The Zr(IV) catalyst 5b was first prepared in situ under
anhydrous conditions (Scheme 2, path a), by reacting Zr-
(n-BuO)4 with 1b using the same protocol developed for
the analogous Ti(IV) system 2b (Scheme 1, path a).7
System 5b showed little catalytic activity. Oxidation
of the model substrate methyl p-tolylsulfide 7 (1.08 M)
by CHP (0.054 M) in the presence of 5b (0.0054 M) (eq
1) proceeded slowly (10% conversion of the oxidant in 4
h), affording (R)-methyl-p-tolyl sulfoxide 8 in low enan-
tiomeric excesses (23%). Furthermore, despite the large
excess of the starting sulfide (20 equiv) with respect to
the oxidant, a significant amount of the corresponding
sulfone 9 was also obtained (8:9 ) 80:20). Worthy of
notice is the reversed sense of asymmetric induction
exhibited by 5b as compared to the analogous Ti(IV)
system 2b. Thus, in reactions employing the same ligand
(R,R,R)-1b, Zr (IV) and Ti(IV) catalysts lead to the
preferential formation respectively of (R)-8 and (S)-8
sulfoxide.
Therefore, the stereoselection of the oxidation can be
controlled by the choice of group 4 metal. This behavior,
which has been also observed for the asymmetric epoxi-
dation of allylic alcohols by Ti(IV) and Zr(IV)/tartrate
ester complexes,9a must be understood in terms of the
structure of the active metal species in solution.
Previous studies on the interaction of ligands 1 with
Ti(IV) and Zr(IV) alkoxides have shown that while the
former affords monomeric complexes, in the case of
zirconium, polynuclear aggregates are produced in solu-
tion.11,15,17 In this light, the inversion of the stereochem-
ical outcome of the Zr(IV)-mediated oxidation can likely
be ascribed to a change of the geometry of the chiral
metal catalyst induced by the aggregation phenomenon.18
Since the polynuclear nature of the catalyst seemed
to have a strong influence on the stereochemical outcome
of the oxidation, the Zr(IV)/1b catalytic system was tested
under nonanhydrous conditions so as to promote the self-
(16) Compare for example the ee’s obtained for the analogous
substrates with the Kagan protocol which are 7, 34, 20, and 63%,
respectively. Pitchen, P.; Duna˜ch, E.; Deshmukh, M. N.; Kagan, H. B.
J . Am. Chem. Soc. 1984, 106, 8188.
(17) Nugent, W. A. J . Am. Chem. Soc. 1992, 114, 2768.
(18) A similar argument has been used to address the behavior of
Mg(II)/chiral bis(oxazoline) catalysts: Desimoni, G.; Faita, G.; Gamba
Invernizzi, A.; Righetti, P. Tetrahedron 1997, 53, 7671.
(19) The model reaction was performed by adding to the reaction
mixture (1 mL) a saturated solution of water in 1,2-dichloroethane (20
µL).

1328 J . Org. Chem., Vol. 64, No. 4, 1999
Notes
Ta ble 2. 6a -c-Ca ta lyzed Oxid a tion of
Meth yl-p-tolylsu lfid e 7 by CHP a
entry no.
ligand
time (h) conv (%)b,c
8:9c
ee (%)d
1
2
3
(S,S,S)-1a
(R,R,R)-1b
(R,R,R)-1c
48
5
26
72
100
100
54:46 10 (S)
25:75 86 (R)
30:70 9 (R)
a
[7]0 ) [CHP] ) 1.08 M, [6a ] ) 0.1 M per Zr atom, [6b] ) [6c]
b
) 0.022 M per Zr atom, in DCE at 0 °C. Conversions based on
the oxidant and calculated as conv. ) ([8] + 2[9])/[CHP]0. c De-
d
termined by GC analysis. Determined by HPLC analysis.
F igu r e 2. Plot of reagent (%) and ee (%) vs time (h) in the
oxidation of (±)-8 (1.08 M) with CHP [1.08 M] catalyzed by 6b
(4.4 × 10-2 M) in DCE at 0 °C.
Ta ble 3. 6b-Ca ta lyzed Ster eoselective Oxid a tion of Alk yl
Ar yl a n d Dia lk ylsu lfid es by CHP a
entry
no.
time conv
(h)
ee
(%)b SO:SO2
(%)e,f
c,e
R
R′
1
2
3
4
5
6
7
8
9
Ph
p-Me-C6H4
Me
Me
5
5
4
6
6
100c
100c
100d
100d
100d
94c
29:71c
89f (R)
86f (R)
89e (R)
86e (R)
88e (R)
91f (R)
91f (R)
77f (R)
79f (R)
14e (S)
8e (S)
25:75c
32:68e
32:68e
52:48e
37:63c
28:72c
44:56c
22:78c
60:40e
60:40e
p-MeO-C6H4 Me
p-Cl-C6H4
2-Naph
p-Me-C6H4
p-Me-C6H4
Ph
Ph
Bn
n-Oct
Me
Me
n-Bu
i-Pr
t-Bu
Bn
F igu r e 1. Plot of reagent, products (%), and ee (%) vs time
(h) in the oxidation of 7 (1.08 M) with CHP [1.08 M] catalyzed
by 6b (4.4 × 10-2 M) in DCE at 0 °C.
6
21
19
6
2
2
100c
33c
95c
Thus, in the system under examination, at high dilution
and under high turnover conditions (TO > 200), both the
reactivity (reduced overoxidation to sulfone) and the
sense of sterereoselection parallel those observed with
the monomeric Ti(IV) complex 4. 7,14,15 Taken as a whole,
these experimental observations indicate that the excess
of the hydroperoxide affects the solution integrity and
in particular the degree of oligomerization of the active
Zr(IV) species.
The influence of the chiral ligand 1 on the reactivity
and enantioselectivity of the hydrolyzed catalysts 6 is
illustrated in Table 2.
As already observed in the Ti(IV)-mediated oxidations,
also in the case of the Zr(IV) system ligand 1b affords a
catalyst with superior performance.
The kinetic profile for the oxidation of 7 by CHP in
the presence of 6b (Figure 1) provides insight into the
course of the reaction. Two consecutive reactions take
place, namely, the oxidation of the sulfide to the sulfoxide
and a subsequent second oxygen transfer to yield the
corresponding sulfone. The time variation of the sulfoxide
concentration, which goes through a maximum for t ) 2
h, indicates that the oxygen transfer to sulfoxide is the
faster of the two oxidative processes.20
10
11
Me
Me
100d
100d
a
Reaction conditions: [substrate]0 ) [CHP]0 ) 1.08 M, [6b] )
4.6 × 10-2 M per Zr atom in DCE at 0 °C. Conversions based on
b
the oxidant and calculated as conv. ) ([SO] + 2[SO2])/[CHP]0.
c Determined by GC analysis. Determined on the isolated prod-
d
ucts. e Determined by 1H NMR analysis. f Determined by HPLC
analysis.
resolution22 via further oxidation to sulfone. It should be
noted that the ee of the sulfoxide steadily increases
during the reaction. This indicates that both processes
cooperate in building up the same enantiomer. This
proposal is directly supported by the analysis of the
kinetic resolution of the (()-8 catalyzed by 6b, where
(R)-8 can be recovered with ee up to 93% (Figure 2).
It is noteworthy that, compared with the Ti(IV)/1b/
CHP system,7 the Zr(IV) catalyst affords higher enanti-
oselectivity in both oxidation steps.23 The cooperative
effect of asymmetric oxidation and kinetic resolution
provides a useful strategy for obtaining sulfoxides with
high ee’s from processes that are moderately stereose-
lective,21,24 although causing an ineluctable depletion of
the chemical yields of the product of interest.
The scope of the Zr(IV)-based enantioselective sulfoxi-
dation is revealed in Table 3.
The method appears to be fairly general for the alkyl
aryl sulfides since ee’s in the range 80-90% are obtained
Indeed, two independent stereoselective processes oc-
cur in solution:21 the asymmetric oxidation producing
methyl p-tolyl sulfoxide 8 and its subsequent kinetic
(20) This observation, which may reflect a metal-promoted nucleo-
philic oxidation of the sulfinyl moiety (see ref 14), is currently under
investigation.
(21) For other stereoselective sulfoxidations involving cooperative
asymmetric oxidation and kinetic resolution see: Komatsu, N.; Hashi-
zume, M.; Sugita, T.; Uemura, S. J . Org. Chem. 1993, 58, 4529. Nagata,
T.; Imagawa, K.; Yamada, T.; Mukaiama, T. Bull. Chem. Soc. J pn.
1995, 68, 3241. Adam, W.; Korb, M. N.; Roschmann, K. J .; Saha-Mo¨ller.
J . Org. Chem. 1998, 63, 3423, and references 6e, 7.
(22) Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J . Org.
Chem. 1993, 58, 7624. Scettri, A.; Bonadies, F.; Lattanzi, A.; Senatore,
A.; Soriente, A. Tetrahedron: Asymmetry 1996, 6, 657.
(23) As an example, in the oxidation of 7 at product distribution
8:9
) 84:16, 6b and 2b systems afford ee’s of 60% and 33%,
respectively. Likewise, kinetic resolution of (()-8 at 35% conversion
provides ee’s of 41% and 22%, respectively.
(24) Krontil, W.; Kleewein, A.; Faber, K. Tetrahedron: Asymmetry
1997, 8, 3251.

Notes
J . Org. Chem., Vol. 64, No. 4, 1999 1329
a
0.5m × 2 mm glass column packed with 3% FFAP on
for the oxidation of a variety of substrates with different
stereoelectronic features. Neither the presence of aro-
matic substituents with diverse electronic character
(entries 1-4) nor substitution with a 2-naphthyl group
(entry 5) has a meaningful effect on the enantioselecitiv-
ity of the process. Likewise, enantioselectivity is not
significantly diminished by elongation (entry 6) or in-
creased bulkiness (entries 7-9) of the alkyl substituent.
The latter observation stands in contrast to previously
reported metal-mediated sulfoxidation reactions where
a significant steric differentiation between the two
residues linked to the sulfur atom is typically required
for high enantioselectivity.6a,16 On the other hand, di-
alkylsulfides (entries 10 and 11) afford the corresponding
sulfoxides in very low ee’s and with the opposite absolute
configuration. Therefore, inspection of data reported in
Table 2 seems to indicate that the molecular recognition
mechanism of the chiral Zr(IV) oxidant operates through
noncovalent aromatic interactions (edge to face or face
to face) with the substrate.7,25 Although further investi-
gation will be required to substantiate this hypothesis,
it should be noted that poor enantioselectivities are
indeed observed only for sulfides lacking the aromatic
substituent. Studies aimed at elucidating both the cata-
lyst structure and the reaction mechanism as well as at
extending the scope of the Zr(IV)/1b-based system are
currently being pursued.
Chromosorb WAW DMCS (80-100 mesh) or a Hewlett-Packard
5890 Series II GC equipped with a SE-30 15 m × 0.25 mm (i.d.)
capillary column.
Ch em ica ls. Dichloromethane was distilled over CaH2 and
stored over molecular sieves. 1,2-Dichloroethane (DCE) was
washed three times with 10% concentrated H2SO4 and with
water several times until a pH of 7, dried over CaCl2 overnight,
distilled over P2O5, and stored over molecular sieves. Cumyl
hydroperoxide (80% in cumene, Fluka) was stored over molecular
sieves at 0 °C. Zirconium tetra-n-butoxide (80% in n-butanol,
Aldrich) was stored under nitrogen. Sulfides were prepared
accordingly to literature by alkylation of the corresponding
sodium arylthiolates.29 Enantiopure trialkanolamines 1 were
prepared following the literature procedure.11b
Syn th esis of Ca ta lyst 6b. Ligand 1b (46 mg, 0.12 mmol)
was dissolved in dry dichloromethane (3 mL) under nitrogen and
magnetic stirring. Water (5.7 µL, 0.32 mmol) was added and the
solvent removed under reduced pressure (12 mmHg). After
addition of dry dichloromethane (3 mL), zirconium(IV) tetra-n-
butoxide (80% in n-BuOH, 50 µL, 0.11 mmol) was added. The
solution was stirred for 15 min, then the solvent was removed
under reduced pressure. The recovered material was dissolved
in dichloromethane (3 mL), and the solvent was removed again
under vacuum. After washing with hexane (6 mL), the solvent
was removed under vacuum, yielding a white solid (61 mg) that
was dried under high vacuum (0.1 mmHg) for 1 h and stored
under nitrogen. 6b 1H NMR shows a complex and well-resolved
spectrum consistent with the presence of a major species being
a stable nonsymmetric aggregate in which 1b and n-BuO are
present in a 2:1 molar ratio (see Supporting Information).
Despite the complexity of the spectrum, different signals corre-
sponding to the different set of protons can be recognized as
follows. 1H NMR (CDCl3), δ (ppm): 0.82 (3H, t, J ) 7.2 Hz);
1.16-1.47 (4H, m); 2.43-3.60 (18H, m); 4.73 (1H, t, J ) 4.7 Hz);
5.14-6.13 (6H, m); 6.43 (2H, m); 6.87-8.10 (28-35H, m). On
the basis of 1H NMR evidence and elemental analyses the
minimal formula [Zr2(N(CH2CHPhO)3)2(n-BuO)(OH)]‚nH2O, n
) 3 or 4, can be proposed for catalyst 6b. Different batches of
catalyst 6b, displaying analogous reactivity, afforded elemental
analysis consistent with the empirical composition reported
above. Two representative elemental analyses are as follows: for
n ) 3, MW ) 1075.5. Anal. Calcd for C52H64N2O11Zr2: C, 58.07;
H, 6.00; N, 2.60. Found: C, 58.30; H, 5.42; N, 2.56. For n ) 4,
MW ) 1093.5. Anal. Calcd for C52H66N2O12Zr2: C, 57.11; H, 6.08;
N, 2.56. Found: C, 57.11; H, 5.76; N, 2.44.
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR spectra were recorded on a
Bruker AC-200 SY (200 MHz) or a AC-250 (250 MHz) instru-
ment. Helium fast atom bombardment (FAB) mass spectra were
collected on a single quadrupole instrument (HP-ENGINE). The
helium atom gun was operated at an accelerating voltage of 8
kV and heating current of 10 µA. Test samples were prepared
by dissolving the complex under investigation (0.1 mg) in
3-nitrobenzyl alcohol (NBA) used as the liquid matrix. Enan-
tiomeric excesses were determined directly on reaction mixtures
by HPLC analysis performed on a Water-Associates HPLC/GPC
(FDP) 201 pump and a Water-Associates 440 UV detector (λ )
254 nm) with a Lichrosorb S100 CSP-DACH-DNB [(250 × 4.0
mm (i.d.)] chiral column26 with n-hexane/2-propanol (8:2) as
eluent, flow rate of 1.6 mL/min, P ) 800 psi, reactions with p-Tol-
S-Me, p-Tol-S-n-Bu Ph-S-t-Bu, p-Tol-S-i-Pr; flow rate of 0.9 mL/
min, P ) 700 psi, reaction with Me-S-n-Oct; flow rate of 2.0 mL/
min, P ) 1000 psi, reaction with Ph-S-Bn. For the other
substrates, sulfoxide ee’s were determined directly on the crude
product mixture by 1H NMR in the presence of (R)-(-)-1-(9-
anthryl)-2,2,2-trifluoroethanol27 (Fluka). Absolute configurations
were assigned via HPLC analysis according to the elution order
on a (S,S)-CSP-DACH-DNB chiral column26 in which the (S)
enantiomer of the selected sulfoxides is eluted before the (R) one,
FAB MS data (%) (NBA): 1096 (14); 1078 (23); 973 (13); 843
(15); 735 (17); 586 (35); 464 (67); 413 (55); 351 (96); 242 (100).
Partially hydrolyzed zirconium catalysts 6a and 6c, bearing
ligands 1a and 1c respectively, have been synthesized following
the procedure described above. In both cases highly hygroscopic,
vitreous white solids were obtained, whose catalytic activity have
been tested without further characterization.
Gen er a l P r oced u r e for th e Asym m etr ic Su lfoxid a tion .
In a Schlenck apparatus, under nitrogen and with magnetic
stirring, catalyst 6b (14.3 mg, 0.027 mmol) and eventually an
internal standard were dissolved in 0.5 mL of dry DCE. After
cooling at 0 °C, cumyl hydroperoxide (0.100 mL, 0.54 mmol) and,
after 1 h, the sulfide (0.54 mmol) were subsequently added. The
reaction was monitored via GC and HPLC, after quenching the
hydroperoxide with triphenylphosphine or di-n-butylsulfide. The
homogeneous and colorless solution was stirred at 0 °C until
complete consumption of the oxidant (iodometric test), warmed
at room temperature, and poured into a 5% sodium metabisulfite
aqueous solution. The mixture was extracted with chloroform,
the organic layers were washed with brine and dried over
MgSO4, and the solvent was removed under vacuum. Yields were
determined via quantitative GC analysis or on product isolation
and product distributions via quantitative GC analysis or 1H
NMR (see Tables 1-3). Products were purified via radial
chromatography over silica gel (petroleum ether/ethyl acetate).
The sulfoxides and sulfones spectral data match those already
1
and/or via H NMR in the presence of (R)-(-)-1-(9-anthryl)-2,2,2-
trifluoroethanol27 by comparison of authentic samples with
known configuration7,28 (see Tables 1-3). Gas-chromatographic
analyses were performed using a Varian 3700 GC equipped with
(25) For a recent discussion on chiral molecular recognition mech-
anisms based either on steric destabilization of the pathway leading
to the minor enantiomer or stabilization via secondary catalyst-
substrate interaction of the transition state producing the major
enantiomer see: Quan, R. W.; Li, Z.; J acobsen, E. N. J . Am. Chem.
Soc. 1996, 118, 8156.
(26) (a) Gargano, G.; Gasparrini, F.; Misiti, D.; Palmieri, G.; Pierini,
M.; Villani, C. Chromatographia 1987, 24, 505. (b) Altomare, C.;
Carotti, A.; Cellamare, S.; Fanelli, F.; Gasparrini, F.; Villani, C.;
Carrupt P.-A.; Testa, B. Chirality 1993, 5, 527.
(27) (a) Pirkle, W. H.; Beare, S. D. J . Am. Chem. Soc. 1968, 90, 6250.
(b) Pirkle, W. H.; Hoover, D. J . Top. Stereochem. 1982, 13, 263-331.
(28) (a) Brunel, J . M.; Diter, P.; Duetsch, M.; Kagan, H. B. J . Org.
Chem. 1995, 60, 8086. (b) Rebiere, F.; Samuel, O.; Ricard, L.; Kagan,
H. B. J . Org. Chem. 1991, 56, 5991, and references therein.
(29) Peach, M. E. In The Chemistry of Thiol Group, Part 2; Patai,
S., Ed.; J ohn Wiley & Sons, Ltd.: Bristol, England, 1974; Chapter 16,
pp 721-784.

1330 J . Org. Chem., Vol. 64, No. 4, 1999
Notes
reported.7,16,28 Ee’s were determined directly on the reaction
Ack n ow led gm en t . We thank Prof. F. Gasparrini
(University of Rome) for the generous gift of the Li-
chrosorb S100 CSP-DACH-DNB chiral column and Prof.
O. Bortolini (University of Ferrara) for performing the
FAB-MS experiments. Financial support by CNR,
MURST, and the DuPont Aid to Education (ATE)
program is gratefully acknowledged.
1
mixture before purification by chiral HPLC28 or by H NMR in
the presence of (R)-(-)-1-(9-anthryl)-2,2,2-trifluoroethanol.27
P r oced u r e for th e Kin etic Stu d y of th e Ster eoselective
Oxid a tion of Meth yl-p-Tolylsu lfid e (7) a n d th e Kin etic
Resolu tion of (±)-Meth yl-p-Tolyl Su lfoxid e (8). The reaction
solutions were prepared as described above using 1,3,5-trichlo-
robenzene as internal standard. At the reaction times stated in
Figures 1 and 2, two samples of the mixture (0.025 mL) were
taken out and immediately quenched with an excess of tri-
phenylphosphine, for the determination of conversion and
product distribution (GC analysis), and di-n-butylsulfide for the
ee determination of 8 (HPLC analysis).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR (CDCl3) of
6b (1 page). See any current masthead page for ordering
information.
J O980677T