Catalytic asymmetric Baeyer-Villiger oxidation in water by using Pt IIcatalysts and hydrogen peroxide: Supramolecular control of enantioselectivity

Article abstract of DOI:10.1002/chem.200900294

The enantioselective BaeyerVilliger oxidation of cyclic ketones is a challenging reaction, especially when using environmentally friendly oxidants. The reaction was carried out in water by using soft Lewis acid Pt^II complexes that have chiral diphosphines as well as monophosphines. Addition of a surfactant is crucial, which leads to the formation of micelles that act as nanoreactors in which the substrate and catalyst encounter each other in an ordered medium that in several cases positively influences both the conversion and the selectivity of the reactions. This is due to the combination of the hydrophobic effect (which confines the components of the reaction in the micelles), together with supramolecular interactions between the partners within the ordered palisade provided by the alkyl chains of the surfactant. For the oxidation of wieso-cyclobutanones, addition of surfactant allowed the reaction to proceed in high yields and the enantiometic excess (ee; 56%) was higher than in organic solvents. Subsequent extension to meso-cyclohexanones resulted in a general decrease in yields but an enhancement of enantioselectivity (ee up to 92%) moving from organic to water-surfactant media, regardless of the substrate or the catalyst employed. Different behaviour was observed with chiral cyclobutanones 7 and 10: with 7 the best catalyst was 1g, whereas with the larger substrate, 10, complexes 1a-b performed better in terms of enantioselectivity. Each combination of substrate, catalyst and surfactant is a new system and supramolecular reciprocal interactions together with the hydrophobic character of the counterparts play crucial roles. The asymmetric Baeyer-Villiger oxidation in water catalyzed by 1a-h in the presence of micelles is a viable reaction that often benefits from the hydrophobic effect, leading to substantial increases in enantioselectivity.

Full text of DOI:10.1002/chem.200900294

DOI: 10.1002/chem.200900294
Catalytic Asymmetric Baeyer–Villiger Oxidation in Water by Using
PtII Catalysts and Hydrogen Peroxide:
Supramolecular Control of Enantioselectivity
Alessandra Cavarzan,[a] Giulio Bianchini,[a] Paolo Sgarbossa,[b] Laurent Lefort,[c]
Serafino Gladiali,[d] Alessandro Scarso,*[a] and Giorgio Strukul*[a]
Dedicated to the Centenary of the Italian Chemical Society
Abstract: The enantioselective Baeyer–
Villiger oxidation of cyclic ketones is a
challenging reaction, especially when
using environmentally friendly oxi-
dants. The reaction was carried out in
water by using soft Lewis acid PtII com-
plexes that have chiral diphosphines as
well as monophosphines. Addition of a
surfactant is crucial, which leads to the
formation of micelles that act as nano-
reactors in which the substrate and cat-
alyst encounter each other in an or-
dered medium that in several cases
positively influences both the conver-
sion and the selectivity of the reactions.
This is due to the combination of the
hydrophobic effect (which confines the
components of the reaction in the mi-
celles), together with supramolecular
interactions between the partners
within the ordered palisade provided
by the alkyl chains of the surfactant.
For the oxidation of meso-cyclobuta-
nones, addition of surfactant allowed
the reaction to proceed in high yields
and the enantiometic excess (ee; 56%)
was higher than in organic solvents.
Subsequent extension to meso-cyclo-
hexanones resulted in a general de-
crease in yields but an enhancement of
enantioselectivity (ee up to 92%)
moving from organic to water–surfac-
tant media, regardless of the substrate
or the catalyst employed. Different be-
haviour was observed with chiral cyclo-
butanones 7 and 10: with 7 the best
catalyst was 1g, whereas with the
larger substrate, 10, complexes 1a–b
performed better in terms of enantiose-
lectivity. Each combination of sub-
strate, catalyst and surfactant is a new
system and supramolecular reciprocal
interactions together with the hydro-
phobic character of the counterparts
play crucial roles. The asymmetric
Baeyer–Villiger oxidation in water cat-
alyzed by 1a–h in the presence of mi-
celles is a viable reaction that often
benefits from the hydrophobic effect,
leading to substantial increases in
enantioselectivity.
Keywords: Baeyer–Villiger oxida-
tion · hydrogen peroxide · micelles ·
platinum · water chemistry
Introduction
The Baeyer–Villiger (BV) oxidation reaction is a very old
chemical transformation that converts ketones into the cor-
responding esters or lactones by insertion of an oxygen
atom between the carbonyl carbon atom and the carbon
atom next to it. This highly valuable chemical transforma-
tion was first discovered in 1899[1] and subsequently convert-
ed into a catalytic process in 1993.[2] It has been reviewed
several times in the last ten years, with particular emphasis
on the choice of oxidant.[3] Despite its long history, the enan-
tioselective version of the BV oxidation is relatively recent.
Pioneering work by the groups of Bolm,[4] and Strukul,[5] re-
ported independently in 1994, demonstrated that with two
different catalyst and oxidant combinations, a certain degree
of stereocontrol in the rearrangement of the Criegee inter-
[a] A. Cavarzan, G. Bianchini, Dr. A. Scarso, Prof. Dr. G. Strukul
Dipartimento di Chimica, Universitꢀ Caꢁ Foscari di Venezia
Dorsoduro 2137, 30123 Venezia (Italy)
Fax : (+39)041-2348517
E-mail: alesca@unive.it
strukul@unive.it
[b] Dr. P. Sgarbossa
Dipartimento di Processi Chimici dell’Ingegneria
Universitꢀ degli Studi di Padova
Via F. Marzolo 9, 35131 Padova (Italy)
[c] Dr. L. Lefort
DSM Research, Innovative Synthesis and Catalysis
PO Box 18, 6160 MD Geleen (The Netherlands)
[d] Prof. Dr. S. Gladiali
Dipartimento di Chimica, Universitꢀ di Sassari
Via Vienna 2, 07100 Sassari (Italy)
7930
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FULL PAPER
mediate was possible, with enantiomeric excess (ee) values
up to 92 and 58%, respectively. At present, high conversions
together with high enantioselectivities can be achieved
either with chiral enantiopure organocatalysts[6] or with
chiral metal complexes. The latter are based on either tran-
sition metals such as Co,[7] Cu,[4,8] Pd,[9] Pt,[5,10] Zr,[11] Hf,[12]
or non-transition metals such as Mg[13] and Al.[14] These
complexes are all active towards meso or chiral cyclobuta-
none substrates, which are intrinsically much more reactive
than larger cyclic ketones. Oxidation of the latter was suc-
cessful only with PtII[2,5,10,15] or CuII[16] catalysts, with moder-
ate to good ee values. Among the synthetic catalysts used
for cyclohexanones, the organocatalyst developed by Peris
and Miller is noteworthy.[17] However, only biocatalytic BV
oxidations[18] performed with isolated enzymes or whole
cells containing cyclohexanone monooxygenases (CHMOs)
or BV monooxygenases (BVMOs) showed good conver-
sions, as well as enantioselectivity above 95%.[19] In addi-
tion, enzymatic BV oxidations are environmentally friendly;
water is used as the solvent and molecular oxygen used as
an atom-efficient oxidant. The substitution of organic and
especially chlorinated solvents with water and the use of O2
or H2O2 instead of peracids in oxidation processes are both
challenging topics for the development of environmentally
friendly chemical processes.
tion of H2O2 towards weakly reactive cyclopentanones and
cyclohexanones, leading to the corresponding lactones in
relatively good yields.[2] Such reactions have been extensive-
ly investigated, with emphasis on several aspects imparted
by the ligand employed, such as steric effects due to the di-
phosphine bite angle,[15a,b] P substitution,[15g] the electronic
effects associated with substitution by fluorine[15d] and oxy-
gen[15f], as well as catalyst speciation.[15h] PtII complexes that
have chiral enantiopure ligands gave good enantioselectivi-
ties both for five- and six-membered ring ketones in the de-
symmetrization[10,24] and the kinetic resolution[5,25] of cyclic
ketones in organic solvents.
Herein we present the results of the catalytic asymmetric
BV oxidation of both meso and chiral cyclic ketones using
hydrogen peroxide, chiral enantiopure PtII catalysts, and a
surfactant. The surfactant plays a dual role: it enables solu-
bilization of the otherwise insoluble chiral catalyst, thus
avoiding chemical tagging of the chiral ligand with hydro-
philic substituents, and it enhances the enantioselectivity of
the reaction due to tighter catalyst–substrate interactions fa-
vored by the micellar supramolecular aggregate. The micelle
represents an anisotropic apolar medium in which alkyl
chains are much more ordered and reciprocally oriented
than a liquid alkane, therefore, it can be seen as a medium
in between liquid solvents and liquid crystals.[26] The driving
force for surfactant aggregation and substrate and catalyst
solubilization is the hydrophobic effect, which, under en-
tropic control, favors interaction between apolar surfaces
when these cannot be efficiently solvated by water.[27] PtII
catalysts were prepared using a wide range of chiral phos-
phorus ligands ranging from bidentate phosphines based on
atropisomeric biaryls (2a–e) or P-chiral groups (2 f), to
As an alternative reaction medium, water is witnessing a
sort of renaissance[20] due to its many advantages compared
with other media; in particular low cost, non-flammability
and environmental compatibility, demonstrated by its zero
E factor value.[21] In some cases it also enhanced selectivity
(chemo, regio, stereo and enantio) compared with the same
processes carried out in organic media. However, perform-
ing catalysis in water entails some challenging drawbacks,
such as the generally low solu-
bility of organic substrates and
most metal-complex catalysts in
water, together with the possi-
ble sensitivity of the latter to
the acidity and nucleophilicity
of water. To circumvent such
problems, possible solutions are
the use of soft Lewis acid com-
plexes, the synthesis of intrinsi-
cally water-soluble catalysts or
the employment of micellar or
other supramolecular systems.
PtII complexes that are active
in oxidations with H2O2 are in-
trinsically
compatible
with
water and have been successful-
ly tested in micellar media in
asymmetric sulfoxidation[22] and
the epoxidation of poorly reac-
tive terminal alkenes.[23] PtII
complexes that have bidentate
phosphine ligands were particu-
Scheme 1. Chiral catalysts PtII–1a–h employed in the asymmetric BV oxidation of cyclic ketones with 35%
larly successful for the activa- H2O2.
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7931

A. Scarso, G. Strukul et al.
monodentate ligands such as
monophosphine 2g[28] and phos-
phoramidite 2h.[29] (Scheme 1).
Results and Discussion
Catalyst characterization in mi-
cellar medium: The 1H and
31P NMR spectra of catalyst 1a
in D2O in the presence of
sodium dodecylsulfate (SDS) as
surfactant are reported in Fig-
ure 1a and b. Both spectra
demonstrate catalyst solubiliza-
tion by means of interaction
with the micellar system be-
cause no signals were detected
in the absence of SDS. The
1H NMR
spectrum
clearly
shows the presence of the aro-
matic resonances of the 2,2’-
bis(diphenylphosphino)-1-1’-bi-
naphthyl (BINAP) chiral ligand
and the 31P NMR spectrum
shows the presence of two
equivalent phosphorus atoms
with P–Pt coupling constants
typical of 1a. In Figure 1c the
2D DOSY spectrum shows the
resonances of the catalyst char-
acterized by the same diffusion
coefficient of the micelles, prov-
ing the reciprocal interaction
between the two. Moreover, to
better investigate the catalyst
position in the micelles, the
NOESY spectrum is also re-
ported
(Figure 1d),
which
shows positive cross peaks be-
tween the aromatic resonances
of 1a and the signal of the
methylene groups of SDS,
whereas negative cross peaks
are observed between different
aromatic resonances belonging
to the BINAP ligand. This
clearly indicates that the cata-
lyst resides in the apolar core of
the micelle, neither deeply
buried (because no cross peaks
were observed between 1a and
the terminal methyl group of
SDS) nor on the external sur-
Figure 1. NMR spectra of catalyst 1a in D2O in the absence and presence of SDS as surfactant. a) 1H;
b) 31P{1H}; c) DOSY spectrum with evidence of same diffusion coefficient for micelles and catalyst resonances
and d) NOESY spectrum with in evidence the cross peaks between catalyst and the methylene residues of the
surfactant.
face of the micelles (because no cross peaks were observed
with the methylene close to the sulfate moiety). This behav-
ior is different from that observed in asymmetric sulfoxida-
tion using the dimeric PtII complex [Pt((R)-binap)
(BF4)2 with SDS, in which the catalyst, because of its larger
size, did not dissolve into the hydrophobic core of the mi-
ACHTUNGTNER(NUNG m-OH)]2-
AHCTUNGTRENNUNG
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Enantioselective Baeyer–Villiger Oxidation in Water
FULL PAPER
celle but simply interacted as a countercation with the nega-
tive outer shell of the supramolecular aggregate.[22]
The same desymmetrization approach was applied to
meso-cyclohexanones. These substrates are more challenging
because of their intrinsically lower reactivity, which results
from lack of ring strain. The catalytic activity of catalyst 1a
was tested in the oxidation of 4-tert-butylcyclohexanone as a
model substrate in water, with a variety of surfactants as dis-
persing agents (Table 2).
Catalytic activity in the BV oxidation of meso cyclic ke-
tones: Initially, the catalytic activity of catalyst 1a in water
was tested on 3-phenylcyclobutanone as a model substrate,
with commercial 35% H2O2 as the terminal oxidant. A wide
series of surfactants was employed to enhance both catalyst
and substrate solubility and steer selectivity (Table 1).
Table 2. Enantioselective BV oxidation of 4-tert-butyl-cyclohexanone
using 35% H2O2 in water and catalyst 1a mediated by different surfac-
tants.[a]
Table 1. Asymmetric BV oxidation of meso-3-substituted-cyclobutanones
in water with H2O2 catalyzed by chiral PtII complex 1a in the presence of
different surfactants.[a]
Entry
Medium
DCE
t [h]
Yield [%][b]
ee [%][c]
4
24
3
24
3
24
3
24
3
24
3
24
3
21
37
6
62
66
83
89
73
79
56
76
57
63
64
77
54
52
Entry
R
Medium
t [h]
Yield [%][b]
ee [%][c]
1
2
1
2
3
4
5
6
8
9
10
11
12
13
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Cy
Cy
Cy
Cy
CH2Cl2
5
5
5
86
80
76
71
95
81
94
99
98
80
96
98
37
10
15
31
28
27
22
56
31
26
19
32
H2O/SDS
H2O/SDS[d]
8
H2O/SDBS[e]
H2O/Triton-X100[f]
H2O/Triton-X114[g]
H2O/Triton-X405[h]
H2O/POA[i]
10
15
2
6
5
10
3
10
5
3
4
5
6
7
H2O/SDBS
5
22
22
24
24
5
5
24
24
H2O/SDSU[d]
H2O/SPAN 60[e]
H2O/Triton X-100
H2O/PTS
H2O/PTS[j]
CH2Cl2
H2O/SDS[d]
H2O/SDBS[e]
H2O/PTS[j]
24
7
[a] Experimental conditions: [Sub]0 =0.5m; [H2O2]=0.5m; [1a]=
1 mol%, solvent: water or CH2Cl2 0.5 mL, T=58C. [b] Yield determined
by GC analysis on HP-5 column. [c] ee determined on chiral GC column
Lipodex B, absolute configuration not assigned. [d] Sodium dodecylsul-
fate (75 mm). [e] Sodium dodecylbenzene sulfonate, (75 mm). [f] Polyoxy-
ethylene(10)isooctylphenyl ether (150 mm). [g] Polyoxyethylene(8)-
isooctyl cyclohexyl ether (150 mm). [h] Polyoxyethylene (40)isooctylphen-
yl ether (150 mm). [i] Polyoxyethylene alcohol (C12H25-C18H37)-
[a] Experimental conditions: [Sub]0 =0.05m, [H2O2]0 =0.07m, [1a]=
5 mol%, water 0.5 mL, T=RT. [ionic surfactants]=75 mm, [neutral sur-
factants]=150 mm, [PTS]=45 mm. [b] Yield determined by GC analysis
on HP-5 column. [c] ee determined on chiral GC column Lipodex B, (S)-
lactone as major enantiomer. [d] Sodium dodecansulfonic acid (75 mm).
[e] Sorbitan monostearate (150 mm).
(OCH2CH2)5
(45 mm).
(150 mm).
[j] Polyoxyethanyl-a-tocopheryl
sebacate
As expected, the observed catalytic activity is lower than
that observed for cyclobutanones even though a higher cata-
lyst loading was employed (in some cases the system is not
catalytic because the yield is lower than the catalyst load-
ing). As observed in Table 2, the use of different micellar
media slows down the reactivity compared with a common
organic solvent such as dichloroethane (DCE). On the other
hand, enantioselectivity was improved in the micellar
medium, increasing from 66% in DCE to 89% in water–
SDS. Such enhancement in stereocontrol is better under-
stood if expressed in terms of enantiomeric ratio[31] (chlori-
nated solvent 83:17, water–SDS 94.5:5.5) which is directly
correlated to the DDG° between the two diastereomeric
transition states leading to enantiomeric lactones. Moving
from chlorinated solvent to water–SDS medium almost dou-
bles the DG°: an increase of about 3.1 kJmolÀ1 is observed,
which is a rather impressive result if one considers that only
the reaction medium has changed. Such a high degree of
control in the catalytic reaction arises from supramolecular
attractive and repulsive interactions caused by the more or-
dered nano-environment provided by the micelle. In fact,
As expected, the ring strain of the cyclobutanone allows
the catalyst to afford good yields of lactone in an ordinary
organic medium, albeit with moderate ee values. When
switching to a water–surfactant medium, catalytic activity
decreases and longer reaction times are required to ensure
almost quantitative conversions. When using anionic surfac-
tants, the enantioselectivity of the reaction in water is mark-
edly lowered compared with the same reaction in dichloro-
methane, whereas with neutral surfactants a higher ee value
(56%) was achieved by employing the recently developed
tenside
polyoxyethanyl-a-tocopheryl
sebacate
(PTS)
(Table 1, entry 9).[30] Changing the R substituent in the sub-
strate to cyclohexyl did not change the overall behavior,
again the use of anionic surfactants resulted in lower ee
values and the use of PTS ensured comparable enantioselec-
tivity and yield compared to chlorinated solvents, but after
longer reaction times.
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A. Scarso, G. Strukul et al.
the catalyst is surrounded by the highly oriented alkyl
chains of the surfactant compared with the same catalyst in
a bulk apolar solvent. To reach the catalyst, the substrate
has to pass through the alkyl chains of the surfactant and
this results in a more controlled interaction between the cat-
alyst and the substrate. Analogously, in the rate-determining
step of the reaction, the solvation of the transition states
leading to the two enantiomeric products are also more con-
trolled. A comparison with asymmetric reactions in chiral
liquid crystals is therefore viable, in which the reaction
occurs in a highly enantioselective fashion due to the high
degree of order imparted by the alignment of the molecules
of the medium.[32] Both in the latter system and in micelles,
the orientation of the molecules is a consequence of supra-
molecular interactions, but whereas for liquid crystals these
interactions arise by enthalpic contributions of intermolecu-
lar interaction, for micelles they are caused by entropic con-
tribution arising from the hydrophobic effect imparted by
water.
Different anionic surfactants, such as sodium dodecylben-
zene sulfonate (SDBS) and dodecansulfonic acid sodium
salt (characterized by either a larger hydrophobic portion or
a less polar head, respectively), performed better in terms of
activity but were less selective in enantiodiscrimination com-
pared with SDS. Even neutral surfactants like Triton-X100
or SPAN 60 provided the enantioenriched lactone with up
to 77% ee. The cationic surfactant cetyltrimethyl ammonium
bromide (CTABr) was unsuccessful; catalytic conversion
was supressed most likely because of the bromide counter-
anion binding to the catalyst, leading to [Pt((R)-binap)Br2]
as an inactive complex.
different steric requirements of the catalysts, this difference
might also be attributed to their different positioning in the
micelles because the monomeric catalyst prefers to reside in
the apolar core of the micelle, whereas the dimeric catalyst
remains on the external surface of the anionic SDS mi-
celles.[22] Other chiral ligands based on the binaphthyl back-
bone showed good enantioselectivities, higher than in the or-
ganic solvent, but lower yields than catalyst 1a. P-chiral cat-
alyst 1 f showed lower enantioselectivity, whereas catalysts
with hindered monophosphines, such as 1g, were poorly
enantioselective with meso-cyclohexanones. Catalyst 1h was
completely inactive, probably due to high steric hindrance
around the PtII metal center.
Using the combination of catalyst 1a and SDS as the best
catalytic system, the catalytic performance was improved by
varying catalyst loading, temperature and other experimen-
tal parameters (Table 4). Lactone yields were improved
Table 4. BV reaction of 4-tert-butylcyclohexanone with H2O2 and SDS
catalyzed by 1a in water under different experimental conditions.[a]
Entry
T
[8C]
Cat. load.
[mol%]
H2O2
[equiv]
SDS
[mm]
t
Yield
[%][b]
ee
G
G
[h]
[%][c]
3
24
3
24
3
24
3
24
3
24
3
24
3
6
8
5
11
5
13
13
23
2
5
4
6
4
83
89
81
89
81
89
87
89
64
74
81
84
75
92
1
2
3
4
5
6
7
25
25
25
60
25
25
25
5
5
1.3
3
75
75
A catalyst screening was performed using both monomer-
ic and dimeric PtII complexes with chiral C2-symmetric di-
phosphines, as well as monomeric catalysts endowed with
chiral monophosphines (Table 3). It is worth noting that the
same chiral ligand BINAP behaved differently when present
in the monomeric, more selective catalyst compared with a
dimeric catalyst (Table 3, entries 1 and 2). In addition to the
10
5
1.3
1.3
1.3
1.3
1.3
75
75
5
37.5
150
300
5
5
24
8
[a] Experimental conditions: [Sub]0 =0.05m, water 0.5 mL. [b] Yield de-
termined by GC analysis on HP-5 column. [c] ee determined on chiral
GC column Lipodex B, (S)-lactone as major enantiomer.
Table 3. BV reaction of 4-tert-butylcyclohexanone with H2O2 catalyzed
by different catalysts 1 in water–SDS medium.[a]
either by using a larger amount of oxidant or catalyst, or by
performing the reaction at higher temperature. No detri-
mental effect on the enantioselectivity was observed at
higher temperatures. At 608C the lactone can be obtained
in 23% yield and 89% ee.
Surfactant concentration was another crucial parameter
that strongly affected both yields and enantioselectivities.
Increasing surfactant concentration above the critical micel-
lar concentration (8 mm for SDS) caused an increase in ac-
tivity as well as selectivity, due principally to a better solubi-
lization of the catalyst. Larger concentrations of surfactant
mean larger micelles and possible variation from the usual
spherical version of the micelle to more elongated shapes,
Entry
Catalyst
Yield
[%][b]
ee
Abs. Configuration
[%][c]
1
2
3
4
5
6
1a
8
3
5
5
7
7
89
78
82
82
66
16
S
S
S
S
S
R
[Pt((R)-binap)ACHTUNGTRENNUNG(m-OH)]2
1b
1e
1 f
1g
[a] Experimental conditions: [Sub]0 =0.05m, [H2O2]0 =0.07m, [cat.]
5 mol%, [SDS]=75 mm, water 0.5 mL, T=RT, 24 h reaction time.
[b] Yield determined by GC analysis on HP-5 column. [c] ee determined
on chiral GC column Lipodex B.
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Enantioselective Baeyer–Villiger Oxidation in Water
FULL PAPER
causing a different reciprocal positioning of catalyst and
substrate, which may affect both catalytic activity and enan-
tioselectivity. Overall, an intermediate SDS concentration of
75 mm was the best compromise between activity and selec-
tivity.
After optimizing these parameters, the scope of the reac-
tion was investigated, operating at 608C with 5 mol% cata-
lyst, 1.3 equiv H2O2, and [SDS]=75 mm. For meso-cyclohex-
anones, a decrease in yield was observed compared with the
reaction in organic chlorinated solvent, but much higher
enantioselectivities were observed for all substrates, as re-
ported in Table 5.
tant type on the enantioselectivity of the BV reaction.
Higher ee values were obtained by using neutral surfactants
compared with anionic surfactants for meso-cyclobutanones,
whereas exactly the opposite was true for meso-cyclohexa-
nones. No clear explanation is possible because several pa-
rameters affect the stereochemical outcome of the reaction,
but at first glance a relationship between the reciprocal solu-
bility and the positioning of the substrates in the micelles
seems plausible. Smaller meso-cyclobutanones are less hy-
drophobic and hence more deeply solubilized in the apolar
core of the micelle by using neutral surfactants, whereas
better enantioselectivity was obtained with the more hydro-
phobic meso-cyclohexanones, which reside in the smaller hy-
drophobic core of anionic surfactants.
Table 5. BV oxidation of meso-cyclohexanones with H2O2 catalyzed by
1a with SDS in water.[a]
Catalytic activity in the BV oxidation of chiral racemic
cyclic ketones: The optimized catalytic system was tested on
chiral racemic cyclobutanones with the aim of comparing ac-
tivity and enantioselectivity levels with meso cyclic ketones.
In fact, chiral substrates 7 and 10, which have sterically de-
manding residues in close proximity to the carbonyl moiety,
showed higher ee values compared with meso-cyclobuta-
nones. As a general observation, it is also interesting to note
that this catalytic system allows the formation of BV oxida-
tion products only, with no epoxide formation. This high
chemoselectivity is in contrast with the general behavior of
peracids, such as, for example, m-chloroperbenzoic acid,
which provides preferential epoxidation rather than BV oxi-
dation, and is related to the peculiar nucleophilic oxidation
mechanism provided by PtII catalysts.[25]
As can be seen in Table 6, the oxidation of racemic 7 can
lead to a “normal lactone” 8 (NL) when the more substitut-
ed carbon atom migrates, and to an “abnormal lactone” 9
(AL) when the migrating species is the less substituted
carbon atom. Overall, the reaction is a double parallel kinet-
ic resolution BV reaction and the concomitant competition
for NL and AL allows products to be obtained with high ee
values and high conversions. Both in organic and in micellar
media, NL formation is largely favored, although the AL re-
gioisomer is obtained with the best enantioselectivity. The
screening of the different catalysts indicates that the yields
of 8+9 are generally similar in the two media with the ex-
ceptions of catalysts 1b, 1g, and 1h, in which significant
yield improvement is observed in the micellar medium. Sim-
ilarly, the regioselectivities are also comparable in both
media, although slightly better results are systematically ob-
served in water. The opposite holds for the enantioselectivi-
ties; these in fact are generally slightly better in CH2Cl2 with
the exceptions of catalysts 1 f and especially 1h, in which,
remarkably, conversion to the lactone is greatly increased in
the micellar medium. Interestingly, with the monophosphine
derivative 1g, ee values above 80% were observed in both
chlorinated and aqueous media. Higher yields in the latter
system were obtained when anionic surfactants were em-
ployed.
Entry
R
Medium
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
DCE
H2O/SDS
DCE
H2O/SDS
DCE
H2O/SDS
DCE
3
7
12
5
31
9
28
8
53
79
40
66
34
69
35
74
Ph
Me
Et[d]
Pr[d]
H2O/SDS
[a] Experimental conditions: [Sub]0 =0.05m; [H2O2]=0.07m; [1a]
5 mol%, [surfactant]=75 mm, water 0.5 mL, T=608C, 24 h reaction
time. [b] Yield determined by GC analysis on HP-5 column. [c] ee deter-
mined on chiral GC column Lipodex B, (S)-lactone as major enantiomer.
[d] ee determined on chiral GC column CHIRALDEX g-TA.
Although the difference in behavior between meso-cyclo-
butanones and meso-cyclohexanones is clear as far as reac-
tivity is concerned, the differences in enantioselectivity be-
tween the two substrate classes deserve further discussion.
In fact, in both chlorinated and aqueous media all catalysts
tested showed moderate asymmetric induction with the cy-
clobutanone substrates and much better results with the cy-
clohexanones. The preference for one enantiomer over the
other of the lactone is a direct consequence of which migra-
tion of the methylene residue adjacent to the carbonyl
occurs in the rate-determining step. In both types of sub-
strates, the R substituent is remote from the carbonyl coor-
dinated to the metal site.[25] It is therefore likely that with
cyclobutanones, such migration is less sensitive to the steric
constraint imparted by the chiral ligand because of the
smaller -CH2-CO-CH2- angle typical for an sp2 carbon (close
to 908 in cyclobutananones but close to 1208 in cyclohexa-
nones). This implies that methylene migration is much
better controlled by the catalystꢁs steric properties in a more
rigidly held six-membered ring compared with a “loose”
four-membered ring. Also noteworthy is the effect of surfac-
The same study was extended to a larger, but still structur-
ally similar chiral cyclobutanone (Table 7).
Chem. Eur. J. 2009, 15, 7930 – 7939
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7935

A. Scarso, G. Strukul et al.
Table 6. Asymmetric BV oxidation of 7 with H2O2 catalyzed by chiral PtII complexes 1.[a]
Oxidation of 10 using cata-
lysts 1a and 1b required longer
reaction times than 7, but dis-
played an increase in enantiose-
lectivity on changing from
CH2Cl2 to water with anionic
surfactants, similarly to that ob-
served in Table 6. Similarly to
the oxidation of the smaller
chiral cyclobutanone 7, oxida-
tion of 10 by using catalyst 1g
was highly enantioselective, but
a drastic decrease in yield was
observed. These observations
led to the conclusion that even
for structurally similar sub-
strates it is rather difficult to
predict catalytic behavior, and
each combination of substrate,
Cat.
1a
Medium
T [8C]
t [h]
Yield [%][b] (8+9)
dr (8/9) [%][b]
ee 8 [%][c]
ee 9 [%][c]
CH2Cl2
H2O/SDS
CH2Cl2
25
25
5
1
3
5
5
5
2
3
1
5
2
5
5
5
2
3
2
95
96
96
96
71
93
94
94
87
94
70
96
92
16
21
94
83:17
80:20
79:21
83:17
78:12
85:15
78:12
81:19
80:20
80:20
73:27
76:24
76:24
82:18
74:26
77:23
9
14
16
11
16
10
17
11
14
19
24
26
24
61
26
33
49
58
64
56
59
48
53
49
34
52
83
81
83
64
26
63
1a
H2O/SDS
CH2Cl2
H2O/SDS
CH2Cl2
H2O/SDS
CH2Cl2
H2O/SDS
CH2Cl2
5
5
5
5
5
5
5
5
1b
1c
1 f
catalyst, and surfactant is
a
completely new system, al-
though these systems often pro-
vide better results than those
obtained in organic media.
H2O/SDS
H2O/SDBS
H2O/TritonX100
CH2Cl2
5
5
5
5
1g
1h
Conclusions
H2O/SDS
5
[a] Experimental conditions: [Sub]0 =0.5m; [H2O2]=0.5m; [cat.] 1% mol, [ionic surfactants]=75 mm, [neutral
surfactants]=150 mm; solvent: water or CH2Cl2 0.5 mL. [b] Yield and diastereoisomer ratio determined by GC
analysis on HP-5 column. [c] ee determined on chiral HPLC using Chiracel OD-H column, absolute configura-
tion not assigned.
The catalytic systems reported
showed good activity within
hours in the catalytic asymmet-
ric BV oxidation of cyclic ke-
tones in water with the aid of
surfactants. In particular, the
results observed for meso-cyclo-
hexanones are, to the best of
our knowledge, among the best
reported in terms of enantiose-
lectivity and second only to en-
zymatic catalysis,[18] when the
unusual aqueous medium is
used. Mild experimental condi-
tions, such as low temperature
and low catalyst loading
(<5 mol%) enabled moderate
to good yields as well as good
enantioselectivities in several
examples. Whereas for meso-cy-
clobutanones enhancement of
enantioselectivity was observed
with the neutral PTS surfactant,
Table 7. Asymmetric BV oxidation of 10 with H2O2 catalyzed by chiral PtII complexes 1.[a]
Cat.
Medium
t [h]
Yield [%][b] (11+12)
dr (11/12) [%][b]
ee 11 [%][c]
ee 12 [%][d]
[d]
CH2Cl2
6
24
24
24
6
24
24
24
88
27
81
43
93
90
73
15
82:18
83:17
85:15
84:16
86:14
86:14
89:11
81:19
0
19
16
8
56
78
68
65
H2O/SDS
H2O/PTS
1a
H2O/TritonX100
[e]
CH2Cl2
2
43
1b
1g
H2O/SDS
CH2Cl2
H2O/SDS
29
35[f]
77[f]
63
99[g]
84[g]
with
meso-cyclohexanones
[a] Experimental conditions: [Sub]0 =0.5m; [H2O2]=0.5m; [cat.] 1 mol%, [ionic surfactants]=75 mm, [neutral
surfactants]=150 mm; [PTS]=45 mm; solvent: water or CH2Cl2 (0.5 mL), T=58C. All ee values were deter-
mined by chiral HPLC using Chiracel OD-H column. [b] Yield and diastereoisomer ratio determined by GC
analysis on HP-5 column. [c] (À)-(1S,5R)-lactone 11b as major enantiomer. [d] (À)-(1R,5R)-lactone 12a as
major enantiomer. [e] Data from ref. [25]. [f] (À)-(1R,5S)-lactone 11a as major enantiomer. [g] (À)-(1S,5S)-lac-
tone 12b as major enantiomer.
anionic micelles ensured a re-
markable increase in ee value
compared with organic chlori-
nated solvents. Conflicting be-
havior was observed with chiral
7936
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 7930 – 7939

Enantioselective Baeyer–Villiger Oxidation in Water
FULL PAPER
and were used without any further purification. meso-Cyclobutanones
were prepared following procedures reported in the literature.[33] Lactone
products were confirmed by 1H NMR spectroscopic analysis in compari-
son with reported assignments.[11a] Ligand 2g was prepared as reported in
the literature.[29] All the surfactants employed are commercial products
and were used as received.
cyclobutanones; the smaller compound, 7, gave better re-
sults with catalyst 1g, whereas 1g was nonselective for the
oxidation of the structurally similar substrate 10, for which
the best catalysts turned out to be atropisomeric 1a and 1b.
Overall, the use of surfactants in water for the BV reactions
studied implies the partition of all reaction components
(substrate, oxidant and catalyst) between the micelle, bulk
water, and the interphase between the two. As a conse-
quence, the lipophilicity of all species is crucial to rational-
ize their positioning in the micellar system, and as a general
observation, more hydrophilic substrates gave better results
in neutral surfactants whereas anionic micelles were pre-
ferred for more lipophilic substrates. Analogously, a general
increase in enantioselectivity was observed for more apolar
substrates in water–surfactant medium compared with reac-
tion in chlorinated solvent, with remarkable examples such
as those reported in Table 2. This demonstrates that water–
surfactant mixtures are viable media for PtII-mediated BV
oxidation reactions of cyclic ketones, as well as for other ox-
idation reactions studied recently.[22,23]
NMR spectroscopy experiments: The 2D-NOESY experiment was ac-
quired with a spectrum width of 10 ppm, a relaxation delay d1 of 1 s,
using 2000 data points in the t2 dimension and 512 data points in the t1 di-
mension, with subsequent weighting with the sine-bell function using 160
scans for each t1 increment. The mixing time d8 employed was 600 ms.
The 2D-DOSY spectrum was recorded with a Bruker AMX 300 spec-
trometer (1H=300.15 MHz) equipped with a PABBO BB-1H Z GRD
probe head. The pulse sequence used was ledbpgp2s 2D sequence for dif-
fusion measurements using stimulated echo and LED using bipolar gradi-
ent pulses with two spoil gradients. The duration of the magnetic field
pulse gradients (d) and diffusion time (D) were 1 and 75 ms, respectively.
The pulsed field gradients were incremented from 1 to 32 GcmÀ1. A
series of 32 spectra on 16000 data points were collected with 32 transi-
ents; the total measuring time was approximately 1 h. After Fourier
transformation and baseline correction, the diffusion dimension was pro-
cessed with the Bruker Xwin-NMR software package. In the experi-
ments, gradients were calibrated against the HOD diffusion constant at
258C (D2O (99.9% D) 19.0ꢃ10À10 m2 sÀ1). Spectra were measured at
258C with a 908 pulse duration of 8.3 ms and a relaxation delay of 5 s.
The general observation that the larger ee enhancements
moving from CH2Cl2 to the water–surfactant medium were
observed with SDS as the surfactant, especially for more
apolar substrates, could be interpreted in terms of tighter
binding of substrate and catalyst in the palisade created by
the alkyl chains of the surfactant. The entropic driving force
for this is the hydrophobic effect that tends to squeeze
apolar surfaces together to minimize their interaction with
water. Compared with other surfactants SDS contains rela-
tively shorter alkyl chains and, at the same time, relatively
polar head groups. Both of these properties favor close con-
tact between the catalyst and substrate, which are both
hosted in the core of the micelle. Such supramolecular con-
trol is not possible in common organic solvents, in which
there is a lower general order of the molecules around the
catalyst by means of simple solvation. A similar principle is
observed in several enzymes, in which the binding of sub-
strates and their juxtaposition in the hydrophobic active site
is driven by the hydrophobic effect.
Synthesis of the complexes: All work was carried out with the exclusion
of atmospheric oxygen under a dinitrogen atmosphere by using standard
Schlenk techniques. Solvents were dried and purified according to stan-
dard methods. The catalysts 1 f, 1g, and 1h are new complexes and were
synthesized through chlorine abstraction from the corresponding (2 f–h)–
PtCl2 complexes 3 f, 3g, and 3h, which were prepared by the treatment
of [PtCl2ACHTUNTRGNEU(GN cod)] (cod=1,5-cyclooctadiene) with the corresponding phos-
phine 2 f, 2g or 2h.
3 f: Ligand 2 f (1 equiv) was added to a solution of [PtCl2ACHTUNGTRENNUNG
(cod)][34]
(100 mg, 0.25 mmol) in dichloromethane (20 mL) at room temperature.
The reaction mixture was stirred for 2 h and then, after concentration,
the product was precipitated as a white solid using pentane. The product
was then filtered and dried under vacuum (138 mg, 93%). 1H NMR
(CDCl3, 258C, TMS): d=8.30 (dd, J=3.57 Hz, 2H; Ar), 8.02 (dd, J=
3.57 Hz, 2H; Ar), 2.38–2.16 (m, 6H; CH3), 1.19 (d, J=15.9 Hz, 18H;
tBu); 31P{1H} NMR (CDCl3, 258C, TMS): d=29.6 (s, 1J
ACTHNUTRGNE(NUG Pt,P)=3448 Hz);
elemental analysis calcd (%) for C18H28Cl2N2P2Pt: C 36.01, H 4.70;
found: C 36.11, H 4.66.
1 f: A 0.35m solution of AgOTf (2.05 equiv) in acetone was added to a
solution of 3 f (100 mg, 0.17 mmol) in acetone (20 mL) at room tempera-
ture. The reaction mixture was stirred for 2 h, then the AgCl formed was
filtered off. After concentration, the solution was treated with pentane to
give a white solid, which was filtered off and dried under vacuum (89 mg,
62%). 1H NMR (CDCl3, 258C, TMS): d=8.35 (dd, J=3.57 Hz, 2H; Ar),
8.13 (dd, J=3.57 Hz, 2H; Ar), 2.27 (d, J=12.4 Hz, 6H; CH3), 1.28 (d,
Experimental Section
1
J=17.6 Hz, 18H; tBu); 31P{1H} NMR (CDCl3, 258C, TMS): d=26.4 (s, J-
ACHUTNGRTEN(GUNN Pt,P)=3764 Hz); elemental analysis calcd (%) for C20H28F6N2O6P2PtS2:
C 29.03, H 3.41; found: C 29.09, H 3.36.
General: 1H and 31P{1H} NMR spectra were recorded at 298 K, unless
otherwise stated, on a Bruker AVANCE 300 spectrometer operating at
300.15 and 121.50 MHz, respectively. d values in ppm are relative to
SiMe4 and 85% H3PO4. 19F{1H} NMR spectra were recorded at 298 K on
a Bruker AC200 spectrometer operating at 188.25 MHz. d values in ppm
3g: Yield: 124 mg, 71%; 1H NMR (CDCl3, 258C, TMS): d=8.29 (d, J=
8.10 Hz, 1H; Ar), 8.10–7.95 (m, 2H; Ar), 7.79 (d, J=7.97 Hz, 1H; Ar),
7.63–7.34 (m, 8H; Ar), 7.33–7.17 (m, 3H; Ar), 7.12 (d, J=8.10 Hz, 1H;
Ar), 6.57 (d, 8.51 Hz, 1H; Ar), 3.5–2.5 (m, 4H; CH2); 31P{1H} NMR
1
are relative to CFCl3. All reactions were monitored by H NMR spectros-
(CDCl3, 258C, TMS): d=25.01 (s, 1J
ACTHNUTRGNEU(GN Pt,P)=3571 Hz); elemental analysis
calcd (%) for C56H42Cl2P2Pt: C 64.50, H 4.06; found: C 64.55, H 4.03.
copy. GLC data were measured on a Hewlett–Packard 5890 A gas chro-
matograph equipped with a FID detector (carrier gas He). All reactions
1g: Yield: 45.7 mg, 73%; 1H NMR (CDCl3, 258C, TMS): d=8.32 (d, J=
8.37 Hz, 1H; Ar), 8.10–7.95 (m, 2H; Ar), 7.80 (d, J=7.97 Hz, 1H; Ar),
7.63–7.35 (m, 8H; Ar), 7.31–7.18 (m, 3H; Ar), 7.12 (d, J=8.60 Hz, 1H;
Ar), 6.58 (d, J=8.60 Hz, 1H; Ar), 3.8–2.5 (m, 4H; CH2); 31P{1H} NMR
1
were monitored either by GC or by H NMR spectroscopy. Enantiomeric
excesses were determined by extraction of the reaction mixture with
ethyl acetate, drying, and dissolving the residue in hexane. The ee of the
solution was then analyzed as reported below. Elemental analyses were
performed by the Department of Analytical, Inorganic and Organometal-
lic Chemistry of the Universitꢀ di Padova.
(CDCl3, 258C, TMS): d=15.97 (s, 1J
ACTHNUTRGNEU(GN Pt,P)=3871 Hz); elemental analysis
calcd (%) for C58H42F6O6P2PtS2: C 54.85, H 3.33; found: C 54.78, H 3.40.
Substrates: Six-membered-ring meso ketones, chiral cyclobutanones 7
and 10, and hydrogen peroxide (35%) are commercial products (Aldrich)
3h: Yield: 105 mg, 71%; 1H NMR (CDCl3, 258C, TMS): d=8.30–7.28
(m, 12H; Ar), 2.30 (brs, 6H; CH3); 31P{1H} NMR (CDCl3, 258C, TMS):
Chem. Eur. J. 2009, 15, 7930 – 7939
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7937

A. Scarso, G. Strukul et al.
d=93.91 (s, 1J
C44H36Cl2N2O4P2Pt: C 53.67, H 3.68; found: C 53.62, H 3.71.
(Pt,P)=5605 Hz); elemental analysis calcd (%) for
R. A. Sheldon, Chem. Rev. 2004, 104, 4105–4124; c) M. Renz, B.
Meunier, Eur. J. Org. Chem. 1999, 737–750.
1h: Yield: 110 mg, 88%; 1H NMR (CD2Cl2, 258C, TMS): d=8.11–7.33
[4] C. Bolm, G. Schlingloff, K. Weickhardt, Angew. Chem. 1994, 106,
1944–1946; Angew. Chem. Int. Ed. Engl. 1994, 33, 1848–1849.
[5] A. Gusso, C. Baccin, F. Pinna, G. Strukul, Organometallics 1994, 13,
3442–3451.
(m, 12H; Ar), 2.35 (brs, 6H; CH3); 31P{1H} NMR (CDCl3, 258C, TMS):
d=63.11 (s, 1J
ACHTUNGTRENNUNG(Pt,P)=6269 Hz); elemental analysis calcd (%) for
C46H36F6N2O10P2PtS2: C 45.59, H 2.99; found: C 45.55, H 3.04.
[6] a) S. Xu, Z. Wang, X. Zhang, X. Zhang, K. Ding Angew. Chem.
2008, 120, 2882; Angew. Chem. Int. Ed. 2008, 47, 2840–2843;
Angew. Chem. Int. Ed. 2008, 47, 2840–2843; b) B. Wang, Y.-M.
Shen, Y. Shi, J. Org. Chem. 2006, 71, 9519–9521; c) S.-I. Murahashi,
S. Ono, Y. Imada, Angew. Chem. 2002, 114, 2472–2474; Angew.
Chem. Int. Ed. 2002, 41, 2366–2368.
[7] T. Uchida, T. Katsuki, Tetrahedron Lett. 2001, 42, 6911–6914.
[8] C. Bolm, T. K. Khanh Luong, G. Schlingloff, Synlett 1997, 1151–
1152.
Catalytic studies
General procedure for asymmetric BV oxidation with chiral complexes
1a–h: In a vial equipped with a screw-capped septum, the cyclic ketones
(0.25 mmol) were dissolved in water (0.5 mL) with the aid of the proper
amount of surfactant (1 mm in micelles). Complex 1a–h was added (1–
5 mol%) and the vial was heated at the desired temperature. 35% H2O2
(1 equiv) was then added in one portion and the resulting mixture was
vigorously stirred. The absence of diffusional problems was determined
by the independence of conversion versus time plots on the stirring rate.
The concentration of commercial 35% H2O2 solution was checked iodo-
metrically prior to use. The reaction progress was monitored by sampling
through the septum. Quenching of the reaction was performed by addi-
tion of solid NaCl to the sample. Conversion was determined by GC
analysis on a HP-5 column 1 mLminÀ1, carrier gas He.
[9] a) K. Ito, A. Ishii, T. Kuroda, T. Katsuki, Synlett 2003, 0643–0646;
b) A. V. Malkov, F. Friscourt, M. Bell, M. E. Swarbrick, P. Koc?ov-
´
sky, J. Org. Chem. 2008, 73, 3996–4003.
[10] C. Paneghetti, R. Gavagnin, F. Pinna, G. Strukul, Organometallics
1999, 18, 5057–5065.
[11] a) A. Watanabe, T. Uchida, R. Irie, T. Katsuki, Proc. Natl. Acad.
Sci. USA 2004, 101, 5737–5742; b) A. Watanabe, T. Uchida, K. Ito,
T. Katsuki, Tetrahedron Lett. 2002, 43, 4481–4485; c) C. Bolm, O.
Beckmann, Chirality 2000, 12, 523–525.
[12] K. Matsumoto, A. Watanabe, T. Uchida, K. Ogi, T. Katsuki, Tetrahe-
dron Lett. 2004, 45, 2385–2388.
[13] C. Bolm, O. Beckmann, A. Cosp, C. Palazzi, Synlett 2001, 1461–
1463.
Enantiomeric excess determination: Enantiomeric excesses of five-mem-
bered ring lactones derived from meso-cyclobutanones were analyzed by
GC: 4-phenyldihydrofuran-2(3H)-one: chiral GC column Lipodex B, He
1 mLminÀ1
, , tR =
1708C isotherm analysis, carrier He 1.0 mLminÀ1
24.8 min, 25.5 min; 4-cyclohexyldihydrofuran-2(3H)-one: chiral GC
column Lipodex B, 1708C isotherm analysis, carrier He 1.0 mLminÀ1
tR =25.6 min, 26.6 min.
,
Enantiomeric excesses of seven-membered ring lactones derived from
meso-cyclohexanones were analyzed as follows: 5-tert-butyloxepan-2-one:
GC column Lipodex B, He 1 mLminÀ1, 1808C isothermal analysis, tR =
7.35 min, 7.85 min; 5-phenyloxepan-2-one: GC column Lipodex B, He
1 mLminÀ1, 1908C isothermal analysis, tR =25. 5 min, 27.2 min 5-methyl-
oxepan-2-one: GC column Lipodex B, He 1 mLminÀ1, 1508C isothermal
analysis, tR =7.78 min, 8.47 min; 5-ethyloxepan-2-one: Chiral GC column
ASTEC g-TA, He 1 mLminÀ1, 1208C X 5 min, 58CminÀ1 up to 2008C,
tR =28.1 min, 28.6 min; 5-propyloxepan-2-one: chiral GC column ASTEC
g-TA, He 1 mLminÀ1, 1208C X 5 min, 58CminÀ1 up to 2008C, tR =
32.4 min, 32.8 min.
[14] a) C. Bolm, J.-C. Frison, Y. Zhang, W. D. Wulff, Synlett 2004, 1619–
1621; b) J.-C. Frison, C. Palazzi, C. Bolm, Tetrahedron 2006, 62,
6700–6706; c) C. Bolm, O. Beckmann, T. Kꢅhn, C. Palazzi, W.
Adam, P. Bheema Rao, C. R. Saha-Mçller, Tetrahedron: Asymmetry
2001, 12, 2441–2446; d) C. Bolm, O. Beckmann, C. Palazzi, Can. J.
Chem. 2001, 79, 1593–1597.
[15] a) G. Strukul, A. Varagnolo, F. Pinna, J. Mol. Catal. A 1997, 117,
413–423; b) R. Gavagnin, M. Cataldo, F. Pinna, G. Strukul, Organo-
metallics 1998, 17, 661–667; c) A. Brunetta, G. Strukul, Eur. J.
Inorg. Chem. 2004, 1030–1038; d) R. A. Michelin, E. Pizzo, P. Sgar-
bossa, A. Scarso, G. Strukul, A. Tassan, Organometallics 2005, 24,
1012–1017; e) V. Conte, B. Floris, P. Galloni, V. Mirruzzo, D. Sordi,
A. Scarso, G. Strukul, Green Chem. 2005, 7, 262–266; f) P. Sgarbos-
sa, A. Scarso, E. Pizzo, S. Mazzega Sbovata, R. A. Michelin, G. Stru-
kul, M. Mozzon, F. Benetollo, J. Mol. Catal. A 2006, 243, 202–206;
g) P. Sgarbossa, A. Scarso, R. A. Michelin, G. Strukul, Organometal-
lics 2007, 26, 2714–2719; h) G. Greggio, P. Sgarbossa, A. Scarso,
R. A. Michelin, G. Strukul, Inorg. Chim. Acta 2008, 361, 3230–3236.
[16] Only one example is known regarding asymmetric BV oxidation of
cyclohexanones, with a CuII chiral metal catalyst displaying ee values
up to 26%: Y. Peng, X. Feng, K. Yu, Z. Li, Y. Jiang, C.-H. Yeung, J.
Organomet. Chem. 2001, 619, 204–208.
Enantiomeric excesses of five-membered ring lactones were determined
as follows: 8 and 9: chiral HPLC analysis on a Chiracel OD-H column,
hexane/iPrOH 99:1 from 0 to 30 min, then up to hexane/iPrOH 98.5:1.5
at 35 min with constant composition until 60 min, flow 1.0 mLminÀ1, (+)-
(1R,5S)-8a tR =23.8 min, (À)-(1S,5R)-8b tR =26.4 min; 9: (À)-(1R,5R)-9a
tR =21.7 min, (+)-(1S,5S)-9b tR =22.4 min; 11 and 12: chiral HPLC anal-
ysis on a Chiracel OD-H column, hexane/iPrOH 99:1 from 0 to 15 min,
then up to hexane/iPrOH 96.5:3.5 at 20 min with constant composition
until 60 min, flow 1.2 mLminÀ1
,
(+)-(1R,5S)-11a tR =29.1 min, (À)-
(1S,5R)-11b tR =34.3 min; (À)-(1R,5R)-12a tR =28.0 min, (+)-(1S,5S)-
12b tR =31.1 min.
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Acknowledgments
The authors thank MIUR, the Universitꢄ Caꢁ Foscari di Venezia, Univer-
sitꢀ degli Studi di Padova, Universitꢀ degli Studi di Sassari and “Consor-
zio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materia-
li” for support. G.S. thanks Johnson-Matthey for the loan of platinum.
We thank L. Sperni for GC-MS analysis and Dr. M. Bertoldini for chiral
GC analysis.
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Received: February 3, 2009
Published online: April 29, 2009
Chem. Eur. J. 2009, 15, 7930 – 7939
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7939