Catalytic enantioselective oxidation of aromatic hydrocarbons with D 4-symmetric chiral ruthenium porphyrin catalysts

Article abstract of DOI:10.1016/j.tetasy.2005.08.059

The [Ru^II(D₄-Por*)(CO)(MeOH)] (D ₄-H₂Por* = tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8- octahydro-1,4:5,8-dimethanoanthracen-9-yl]porphyrin) complex 1 is an effective catalyst for asymmetric hydroxylation of aromatic hydrocarbons with 2,6-dichloropyridine N-oxide (Cl₂pyNO) as terminal oxidant. Up to 76% ee was achieved for the catalytic hydroxylation of 4-ethyltoluene, 1,1-diethylindan and benzylcyclopropane. Both electron-donating and -withdrawing substituents were found to accelerate the catalytic oxidation reaction, and a large primary H/D kinetic isotope effect (k_H/k_D = 11 at 298 K) was observed for the catalytic ethylbenzene-d₁₀ oxidation. A mechanism involving rate-limiting hydrogen atom abstraction by reactive oxoruthenium species is postulated.

Full text of DOI:10.1016/j.tetasy.2005.08.059

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3520–3526
Catalytic enantioselective oxidation of aromatic hydrocarbons
with D4-symmetric chiral ruthenium porphyrin catalysts
Rui Zhang, Wing-Yiu Yu and Chi-Ming Che*
Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug
Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong
Received 3 August 2005; accepted 24 August 2005
Available online 14 November 2005
Abstract—The [RuII(D4-Por*)(CO)(MeOH)] (D4-H2Por* = tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoan-
thracen-9-yl]porphyrin) complex 1 is an effective catalyst for asymmetric hydroxylation of aromatic hydrocarbons with
2,6-dichloropyridine N-oxide (Cl2pyNO) as terminal oxidant. Up to 76% ee was achieved for the catalytic hydroxylation of
4-ethyltoluene, 1,1-diethylindan and benzylcyclopropane. Both electron-donating and -withdrawing substituents were found to
accelerate the catalytic oxidation reaction, and a large primary H/D kinetic isotope effect (kH/kD = 11 at 298 K) was observed
for the catalytic ethylbenzene-d10 oxidation. A mechanism involving rate-limiting hydrogen atom abstraction by reactive oxoruthe-
nium species is postulated.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
epoxyalcohols and epoxides in >90% ee through kinetic
resolution.6 By employing Mn(III)–salen complexes,
which had chiral binaphthyl units as catalyst, Katsuki
et al. reported the attainment of up to 90% ee for asym-
metric hydroxylation of 1,1-dimethylindan by PhIO.7
While JacobsenÕs catalytic system produced only 14%
ee for the same reaction, the atropochirality of the Kat-
sukiÕs catalyst system was suggested to be important for
the observed enantioselectivity.
Selective oxidation of saturated hydrocarbons presents a
major challenge in current chemical research.1 In biolo-
gical systems, alkanes are catalytically converted to alco-
hols by the cytochrome P-450 enzymes using dioxygen
under physiological conditions, and considerable effort
has been directed to the development of biomimetic
transition metal catalysts for stereo- and regioselective
organic oxidations.2,3 While significant progress has
been made in the transition metal-catalyzed enantio-
selective alkene epoxidations,4 attempts todevelpo
highly enantioselective alkane hydroxylations have been
met with limited success.
In order to design effective chiral catalysts for enantio-
selective alkane hydroxylations, we decided to prepare
structurally well-defined chiral oxo-metal complexes
for stoichiometric asymmetric oxygen atom transfer
reactions.8 Previously, we showed that homochiral
trans-dioxoruthenium(VI) porphyrins such as [RuVI(D4-
Por*)O2]{D4-H2Por* = tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,
6,7,8-octahydro-1,4:5,8-dimethanoanthracen-9-yl]por-
phyrin, Fig. 1} can undergo enantioselective oxygen
atom transfer to alkenes.8 Subsequently, we reported
that [RuVI(D4-Por*)O2] is an effective catalyst for asym-
metric hydroxylation of ethylbenzene with 2,6-dichloro-
pyridine N-oxide (Cl2pyNO) as oxidant, and (S)-1-
phenylethanol was obtained in up to 76% ee.9 The use
of ruthenium porphyrins for catalytic organic oxidations
is well documented.10 We and others have reported
catalytic systems based on ruthenium porphyrin catalyst
for alkene epoxidations with Cl2pyNO as oxidant.8,10
In 1989, Groves et al. reported an asymmetric hydroxyl-
ation of ethylbenzene and derivatives using a chiral iron
porphyrin complex as catalyst and iodosylbenzene
(PhIO) as oxidant; the corresponding alcohols were
obtained in 19–72% yield and 40–72% ee.5 Later Jacob-
sen et al. reported that chiral [MnIII(salen)] complexes
derived from optically active diamines can effect cata-
lytic diastereoselective hydroxylation of racemic 1,2-
dihydronaphthalene oxide to afford optically active
*
Corresponding author. Tel.: +852 2859 2154; fax: +852 2857 1586;
e-mail: cmche@hku.hk
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.08.059

R. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 3520–3526
3521
48% ee, respectively, (entries 7 and 8). When 2-ethyl-
naphthalene was employed as a substrate, (S)-1-(2-
naphthyl)ethanol was obtained in 62% yield and 75%
ee (entry 9). This level of enantioselectivity is compara-
ble to the best results for the reported metal-catalyzed
asymmetric hydroxylation of ethylbenzenes.5–7
X
X = CO, Y = MeOH; 1 (RuII)
X = Y = O2-; 2 (RuVI
X = Y = Cl-; 3 (RuIV
N
N
N
Ru
)
)
N
Y
Cyclic alkanes such as indane and tetrahydronaphthal-
ene are poor substrates, and enantioselectivities of ca.
12% ee were obtained (entries 10 and 11). Assuming a
reactive O@Ru species as an intermediate, functionaliza-
tion of the two enantiotopic benzylic C–H bonds of the
cycloalkanes would generate two enantiomeric alcohols,
thereby accounting for the observed low ee for the
indane and tetrahydronaphthalene oxidation (Scheme 1).
However, with 1,1-diethylindane as substrate, the 1-cat-
alyzed oxidation reaction gave the (S)-alcohol in 76% ee
(entry 12).
Figure 1.
Groves et al. recently described that a perfluorinated
ruthenium porphyrin can catalyze alkane oxidation
using aromatic N-oxides with high product turnovers.10d
In conjunction to our earlier report,9 we herein report a
full account of the catalytic enantioselective alkane oxi-
dations by homochiral ruthenium porphyrin complexes.
O
Ru
2. Results and discussion
direction of
facial approach
HS
Treatment of ethylbenzene (0.5 mmol) with Cl2pyNO
(0.55 mmol) and a catalytic quantity (0.5 lmol) of either
[RuII(D4-Por*)(CO)(MeOH)] 1 or [RuVI(D4-Por*)O2] 2
in dry degassed benzene (5 mL) at room temperature
for 12 h afforded a mixture of (S)-1-phenylethanol
(62%) and acetophenone (37%) (Table 1, entry 1). The
enantiopurity of the phenylethanol was determined to
be 72% ee by chiral capillary GC analysis. However,
when the ethylbenzene oxidation was performed under
stoichiometric conditions: 2 (30 lmol), ethylbenzene
(1 mmol) in CH2Cl2 (containing 2% pyrazole as addi-
tive), (S)-1-phenylethanol was obtained in 32% yield
and 45% ee. Similar results [30% yield and 37% ee for
(S)-1-phenylethanol formation] were obtained with benz-
ene as solvent for the same transformation.
H’R
H’S
HR
HS
HR
OH
H’R
insertion to
C-H’R bond
insertion to
C-HS bond
H’S
OH
H’S
(R)-indanol
(S)-indanol
Scheme 1.
Subjecting benzylcyclopropane to the 1-catalyzed oxida-
tion, the corresponding benzyl alcohol and ketone were
formed in 28% and 70% yield, respectively (entry 13).
No ring opened products were detected by NMR or
GLC techniques. Using chiral capillary GC analysis,
the enantiopurity of the product alcohol was determined
tobe 76% ee.
Previously we reported that [RuIV(D4-Por*)Cl2] 3 is a
highly effective catalyst for enantioselective alkene epox-
idation using Cl2pyNO as oxidant.8f In this work, we
found that 3 is equally effective as 1 and 2 for asymmet-
ric ethylbenzene oxidation, and comparable results were
obtained. Unless otherwise noted, 1 was chosen here-
after as the catalyst for the rest of our study because
of sample availability.
Previously, we reported that homochiral D2-symmetric
[RuVI(D2-Por*)O2] can effect asymmetric epoxidation
8e
of trans-alkenes in up to80% ee.
Herein, we found
that neither [RuVI(D2-Por*)O2] nor [RuII(D2-Por*)(CO)-
(MeOH)] exhibited comparable enantioselectivity for
catalytic ethylbenzene oxidation. For example, treat-
ment of ethylbenzene (0.5 mmol) with Cl2pyNO
(0.55 mmol) and [RuVI(D2-Por*)O2] (0.5 mmol) in
degassed benzene afforded (S)-1-phenylethanol in only
13% ee with only 4% substrate conversion. Recently,
Gross et al. reported that an isostructural chiral D2-sym-
metric ruthenium porphyrin complex containing four
diaryl-substituted threitol units catalyzed oxidation of
tertiary alkanes with 38% ee.8d
At higher temperature (40 ꢁC), the 1-catalyzed ethylbenz-
ene oxidation proceeded faster without compromising
the enantioselectivity (70% ee), albeit with a lower alco-
hol yield (45%). Benzene was found to be the solvent of
choice; polar solvents such as CH2Cl2 gave a lower
enantioselectivity of 62% for the asymmetric ethylbenz-
ene oxidation.
As shown in Table 1, para-substituted ethylbenzenes
(Y = H, F, Cl, Br, Me and MeO) are alsoeffective sub-
strates for the 1-catalyzed asymmetric hydroxylation,
and the corresponding 1-arylethanols were produced in
comparable ee of 62–76% (entries 2–6). However, the
analogous catalytic oxidation of 2- and 3-ethyltoluenes
furnished their corresponding alcohols in 38% and
By competitive experiments, a primary kinetic isotope
effect (kH/kD) = 11.2 (298 K) was established for the 1-
catalyzed oxidation of ethylbenzene-d10. This indicates
that the rate-limiting step involves substantial C–H
bond cleavage.11 Similarly, the electronic effect on the
catalytic oxidation of para-substituted ethylbenzenes

3522
R. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 3520–3526
Table 1. Ruthenium-catalyzed asymmetric alkane oxidation
Entry
1
Substrate
Product
Time (h)
% Conv
Alcohol yield %a
% ee (abs. config.)
Ketone yield %a
OH
12
12b
13
10b
62
67b
72 (S)
62 (S)b
37
32
OH
2
3
4
5
6
30
10
18
8
20
11
23
14
15
72
60
28
63
65
76 (S)
72 (S)
74 (S)
74 (S)
62 (S)
24
38
70
36
32
Me
F
Me
F
OH
OH
OH
Cl
Br
Cl
Br
OH
8
MeO
Me
MeO
Me
7
OH
16
22
20
6
5
12
15
54
42
90
60
62
65
60
38 (S)
48 (S)
75 (S)
12 (S)
12 (S)
10
40
38
34
40
OH
8
Me
Me
OH
9
OH
10
11
OH
2
OH
12
13
3
36
30
70
28
76 (S)
76 (S)
30
70
Et
Et
Et
Et
OH
18
Reaction conditions: A mixture of alkane (0.5 mmol), [RuII(D4-Por*)(CO)(MeOH)] (0.5 lmol) and Cl2pyNO (0.55 mmol) was stirred in dry C6H6
(5 mL) for 12 h at room temperature. Aliquots were analyzed by chiral capillary GC equipped with either J & W scientific Cyclodex B or B-PM chiral
column for quantification and ee determination.
a % Yield were based on the amount of alkane consumed.
b In CH2Cl2.
(Y = H, F, Cl, Br, Me and MeO) was alsoexamined.
Both electron-donating and -withdrawing substituents
were found to accelerate the catalytic reactions. This
result is incompatible with a mechanism involving either
rate-limiting carbocation or cation radical formation.
Figure 2 depicts a dual Hammett correlation analysis
of the relative rate constants (logkrel) using the substitu-
ent constants rþp and rJꢀJ, a linear correlation (R = 0.99)
was established: log krel ¼ 0:78rꢀJJ À 0:71rpþ. The term
rꢀJJ is a carboradical substituent constant developed by
Jiang and Ji to measure the spin delocalization effect
oꢀf the benzylic radical transition state.12 The
qJJ=qþp ¼ 1:1 reflects that both spin delocalization and
polar effects are equally important with respect to their
influence tothe transition state energy.
It is well documented that dioxoruthenium(VI) porphy-
rins are potent oxidants for alkenes and alkanes.13
Herein, we have examined the stoichiometric reactions
of 2 with a series of substituted ethylbenzenes and
related compounds for a better understanding of the
nature of the active species involved in the catalytic
ethylbenzene oxidation. As noted in earlier sections,
the stoichiometric ethylbenzene oxidation by 2 produced
1-phenylethanol in only 45% ee, which is appreciably
lower than the 72% ee value observed for the catalytic
reactions. Likewise, the stoichiometric oxidation of
other substituted ethylbenzenes also gave <60% ee.
Using UV–vis spectrophotometry, we have undertaken
a kinetic study on the stoichiometric oxidation of ethyl-

R. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 3520–3526
3523
tion with rþp and rJꢀJ for the second-order rate constants
(logkrel) has been established: log krel ¼ þ0:56rꢀJJÀ
0:36rþp ; the reaction constants (qJꢀJ and qþp ) are compara-
ble tothose ( qꢀJJ ¼ 0:78; qþp ¼ À0:71) for the catalytic
reaction. These findings suggest that the transition states
of the catalytic and stoichiometric ethylbenzene oxida-
tions are similar, presumably proceeding via a hydrogen
atom abstraction mechanism.
0.8
0.6
0.4
0.2
0.0
-OMe
slope = 1
R = 0.99
k
-Me
The nature of the active species for the 1-catalyzed
alkane oxidation was further scrutinized using cis-deca-
lin as a mechanistic probe. When cis-decalin was treated
with 1 (1 mol %) and Cl2pyNO in dry benzene, cis-9-
decalol was formed exclusively in >98% yield without
any trans-alcohol being detected. Herein, we found that
dioxoruthenium(VI) complex 2 did not effectively oxi-
dize cis-decalin under similar conditions. Yet by using
[RuVI(TMP-b-Br8)O2] [H2TMP-b-Br8 = meso-tetrakis-
(2,4,6-trimethylphenyl)-b-octabromoporphyrin] as an
oxidant, the cis-decalin oxidation proceeded non-stereo-
selectively and both cis- and trans-9-decalol were
obtained in a ratio of 80:20. The disparate results for
the catalytic and stoichiometric decalin oxidations
raises doubts about the involvement of dioxoruthe-
nium(VI) complexes for the 1-catalyzed asymmetric
hydroxylation.
-Cl
-F
-H
0.0
0.2
0.4
0.6
0.8
+
+0.78 σJJ – 0.71 σp
Figure 2. Dual parameter Hammett correlation plot for the 1-
catalyzed ethylbenzene oxidation.
benzene by 2 in 1,2-dichloroethane [containing 2%
pyrazole (Hpz)] at 313 K (Fig. 3). Under pseudo-first-
order conditions, that is, [alkane] ꢁ [Ru], an experimen-
tal rate law: rate = kobs [Ru] (where kobs = pseudo-
first-order rate constant) was established. The second-
order rate constant was evaluated to be (7.7 0.4) ·
10À4 dm3 molÀ1 sÀ1. For the stoichiometric oxidation
of ethylbenzene-d5, the second-order rate constant was
determined tobe (0.87 0.1) · 10À4 dm3 molÀ1 sÀ1 at
313 K, which then translates to a primary kinetic isotope
effect (kH/kD) = 8.9. This KIE for the stoichiometric
reaction is comparable to the related value (kH/
kD = 11) for the catalytic reaction.
Moreover, we employed cumene as another probe sub-
strate toevaluate the mechanism of the catalytic and
the stoichiometric reactions. Under the 1-catalyzed con-
ditions [cumene (0.5 mmol), Cl2pyNO (0.55 mmol) and
1 (0.5 lmol)], cumyl alcohol was formed in 80% yield
along with a small amount of acetophenone (9%). How-
ever, under the stoichiometric conditions, we found
that the reaction of cumene with 2 gave cumyl alcohol
and acetophenone in 20% and 40% yield, respectively.
Taken together the results of cis-decalin and cumene
oxidations, the observed stereoretention and high
Analogous to the catalytic reactions, both electron-
donating and -withdrawing substituents promote the
stoichiometric ethylbenzene oxidation. Linear correla-
Figure 3. UV–vis spectral trace for the stoichiometric ethylbenzene oxidation by [RuVI(D4-Por*)O2] (2) in 1,2-dichloroethane (with 2% pyrazole) at
313 K.

3524
R. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 3520–3526
Table 2. Competitive cycloalkane oxidations using the ÔRuIV(D4-Por*)Cl2] + Cl2pyNOÕ system
Entry
1
Alkanes
% Conversion
60
Products (% yield)a
Relative reactivityb
1
Cyclohexane + cyclohexane-d12
Cyclohexanol (35%)
Cyclohexanone (60%)
Cyclohexanol-d12 (35%)
Cyclohexanone-d10 (60%)
1.4
0.24 (kH/kD = 4.2)
2
Cyclooctane + cyclohexane
14.2
2.4
Cyclooctanol (53%)
Cyclooctanone (38%)
Cyclohexanol (30%)
Cyclohexanone (62%)
1
0.17
3
4
Cyclooctane + cis-decalin
11.8
Cyclooctanol (50%)
Cyclooctanone (35%)
cis-9-Decalol (92%)
1
13.0
8.2
8.7
1
Cyclooctane + adamantane
Cyclooctanol (54%)
Cyclooctanone (32%)
Adamantanol (92%)
36.8
24.1
Reaction conditions: To a 1:1 mixture of cycloalkanes (1 mmol) and Ru catalyst (1 lmol) was added Cl2pyNO (1.1 mmol) under argon, and the
mixture was stirred at room temperature for 36 h. Aliquots were taken and analyzed by GC–MS for product identification and quantitation.
a % Yield were based on the amount of alkane consumed.
b Calculated from alkane conversion; statistical factor corrected.
alcohol-to-ketone ratio for the catalytic reaction implies
a more efficient radical recombination step subsequent
to the hydrogen atom abstraction step.14
intermediates that were responsible for catalytic alkane
oxidation by aromatic N-oxides.10 It is not unreasonable
to assume that an oxoruthenium(V) species would
behave differently from trans-dioxoruthenium(VI)
complexes.11a,13 Indeed, our earlier work on asymmetric
alkene epoxidation also revealed similar disparities in
stereoretention for cis-alkene oxidation under the catal-
ytic and stoichiometric conditions.8
The participation of free radical intermediates for the 1-
catalyzed alkane oxidation has also been evaluated
using cyclohexane as substrate. However, 3 was chosen
tobe the catalyst because of its higher activity than
1
for the cyclohexene oxidation. As shown in Table 2,
cyclohexane was oxidized to a mixture of cyclohexanol
(35%) and cyclohexanone (60%; entry 1), and a primary
kinetic isotope effect (KIE) of 4.2 was registered based
on a competitive experiment (entry 1). Apparently, the
reaction involves the formation of the cyclohexyl radi-
cal, since trace (ca. 1%) cyclohexyl chloride was detected
when the oxidation was carried out in the presence of
CCl4. Furthermore, the reaction rate was largely
reduced by the addition of a free-radical scavenger
(hydroquinone).
3. Conclusion
A catalytic protocol based on a homochiral D4-symmet-
ric ruthenium porphyrin catalyst and Cl2pyNO as termi-
nal oxidant has been developed for enantioselective
hydroxylation of aromatic hydrocarbons. Results from
the mechanistic study and product analysis are consis-
tent with a mechanism involving hydrogen atom
abstraction. The 1-catalyzed alkane oxidations exhibit
moderate-to-good enantioselectivity and high stereo-
retention of the alcohol products.
We also investigated the competitive oxidation of cyclo-
octene/cycloalkanes in CH2Cl2 at 298 K using the
Ô3 + Cl2pyNOÕ protocol. The relative reactivities per H
atom (normalized) follow the order: adamantane
(24.1) > cis-decalin (8.7) > cyclooctane (1) > cyclohex-
ane (0.2). This reactivity pattern is parallel with the C–
H bond strength that a 2ꢁ C–H bond is stronger than
a 3ꢁ C–H bond. The employment of such competitive
experiments todistinguish between radical and Gif
chemistry has been proposed.15 It is apparent that the
ÔRu-porphyrin/Cl2pyNOÕ system in this work behaves
differently from the Gif system towards alkane oxida-
tion. The substantial increase in the reactivity from
cyclohexane to adamantane is consistent with the stabil-
ity of the alkyl radicals generated through H-atom
abstraction, that is, 3ꢁ C–H bonds are weaker than the
2ꢁ C–H bonds.
4. Experimental
4.1. General experimental
The alkanes employed herein were obtained commer-
cially and purified either by distillation or crystalliza-
tion, and their purities verified by GLC prior to use.
Solvents were of analytical grade and purified by
distillation over CaH2 or sodium/benzophenone. 2,6-
Dichloropyridine N-oxide was prepared by the literature
method.16 The synthesis and characterization of
[RuII(D4-Por*)(CO)(MeOH)] 18b and [RuVI(D4-Por*)O2]
28b were reported elsewhere.
4.2. Preparation of dichlororuthenium(IV) porphyrin
[RuIV(D4-Por*)Cl2] 3
With regard to the nature of the active species for the 1-
catalyzed ethylbenzene oxidation, Groves et al. pro-
posed some highly reactive oxoruthenium(V) porphyrin
A solution of [RuII(D4-Por*)(CO)(MeOH)] (10 mg,
8 lmol) in CCl4 (20 mL) was refluxed overnight, fol-

R. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 3520–3526
3525
krel ¼ kY=kH ¼ logðY f =Y iÞ= logðHf =HiÞ
where Yf and Yi are the final and initial quantities of the
substituted ethylbenzene; Hf and Hi are the final and ini-
tial quantities of ethylbenzene.
lowed by evaporation of the solvent and subsequent
washing with MeOH. The transformation of [RuII-
IV
(D4-Por*)(CO)(MeOH)] to[Ru (D4-Por*)Cl2] resulted
in a color change from orange to dark red-brown,
accompanied by a shift of the Soret band (kmax from
414 to411 nm in CH 2Cl2). Its 1H NMR spectrum shows
broad signals and the occurrence of one paramagneti-
cally shifted pyrrole proton signal at À52.3 ppm (in
CDCl3, 500 MHz), which are characteristic of dihalo-
genoruthenium(IV) porphyrins. Magnetic susceptibility
measurements for 3 by Evans Method gave leff of 3.1 lB
at 298 K, consistent with two unpaired electrons in the
ground state. Yield >95%. 1H NMR (500 MHz, CDCl3,
TMS): d 5.93 (s, 4H, phenyl-H), 5.71 (s, 8H), 4.62 (s,
8H), 2.52 (d, 8H), 2.15 (br, 8H), 1.99 (br, 8H), 1.88
(br, 8H), 1.72 (br, 16), À52.3 (s, 8H, pyrrole-H). IR
(KBr, cmÀ1): 1010 (oxidation state marker band). ESI-
MS m/z: 1314 (M+), 1280 (M+ÀCl). UV–vis (CH2Cl2)
4.6. Determination of primary kinetic isotope effect
(kH/kD) for catalytic oxidation of ethylbenzene and
ethylbenzene-d5
A solution containing ethylbenzene (0.5 mmol), 4-chlo-
roethylbenzene (0.5 mmol), 2,6-dichlorobenzene (0.1
mmol, as the internal standard), and Cl2pyNO
(0.55 mmol) was prepared. Another solution, using eth-
ylbenzene-d5 instead of ethylbenzene, was also added.
Catalyst 1a (0.5 lmol) was added to both solutions,
and the mixtures stirred for 12 h at 298 K. The amounts
of ethylbenzene before and after the reactions were
determined by GLC analysis. The kH/kD value was
determined by using the following equations:
k
max/nm (loge): 411 (5.12), 517 (4.03). leff (EvanÕs meth-
od) = 3.14 lB (solid, room temperature).
kH=kCl ¼ logðHf =HiÞ= logðClf =CliÞ
kD=kCl ¼ logðDf =DiÞ= logðClf =CliÞ
ðiÞ
ðiiÞ
4.3. General procedure for hydroxylation of alkanes by
[RuVI(D4-Por*)O2]
then, kH/kD = [Eqs. (i)/(ii)]
Toa degassed CH 2Cl2 solution (2 mL) containing
alkane (1 mmol) and pyrazole (0.3 mmol) was added
[RuVI(D4-Por*)O2] (15–30 lmol) under an argon atmo-
sphere. The reaction mixture was stirred at room tem-
perature overnight. The completion of the reaction
was indicated by the disappearance of the Soret band
of the starting dioxoruthenium(VI) complex. The ruthe-
nium-containing product was removed by filtration over
an alumina column using dichloromethane as the eluant,
and the filtrate was analyzed by gas chromatography
equipped with a chiral capillary column (J&W Scientific
Cyclodex-B or B-PM). Internal standard method was
employed to quantify the products. The product yields
were based on the amount of the oxidant used. Absolute
configurations were determined by comparing retention
times with the chiral authentic samples.
Clf and Cli are the final and initial quantities of the 4-
chloroethylbenzene; Df and Di are the final and initial
quantities of ethylbenzene-d5. Hf and Hi are the final
and initial quantities of ethylbenzene.
4.7. Kinetics measurements
Kinetic measurements were performed on a Hewlett-
Packard 8453A Diode Array Spectrophotometer inter-
faced with an IBM-compatible PC and equipped with
a Lauda RM6 circulating water bath by using standard
1.0-cm quartz cuvettes. The temperature of solutions
during kinetic experiments was maintained tobe within
0.2 ꢁC.
The rate constants of alkane oxidation by [RuVI-
(Por*)O2] were measured by monitoring the decrease
of the Soret absorption band under the condition that
the/alkane concentrations were at least 100-fold in
excess of [RuVI(Por*)O2]. The pseudo-first-order rate
constants (kobs) were obtained by non-linear least-
squares fits of (Af À At) totime ( t) according to the
following equation:
4.4. General procedure for catalytic asymmetric hydr-
oxylation by Cl2pyNO
To a mixture of alkane (0.5 mmol) and Cl2pyNO
(0.55 mmol) in dry, degassed benzene (5 mL) was added
the catalyst (0.5 lmol), and the solution stirred under an
argon atmosphere at room temperature unless otherwise
noted. The aliquot was analyzed by GLC for product
identification and quantification by the internal stan-
dard method. The product yields were based on the
amount of alkanes consumed.
ðAf À AtÞ ¼ ðAf À AiÞ expðÀkobstÞ
where Af and Ai are the final and initial absorbance,
respectively, and At is the absorbance measured at time
t. Kinetic data over 4 half-lives (t1/2) were used for the
least-squares fitting. Second-order rate constants, k2,
were obtained from the linear fit of kobs values tothe
concentration of alkanes.
4.5. Determination of the relative reactivities (krel) for
catalytic hydroxylation of para-substituted ethylbenzenes
A CH2Cl2 solution containing ethylbenzene (0.5 mmol),
substituted ethylbenzene (0.5 mmol) and Cl2pyNO
(0.55 mmol) was prepared. Catalyst (0.5 lmol) was
added and the solution stirred for 12 h. The amount of
arylalkanes before and after the reactions were deter-
mined by GLC. The relative reactivities were determined
by the following equation:
Acknowledgements
We acknowledge the support of The University of Hong
Kong (University Development Fund), The Areas of
Excellence Scheme (AoE P10/01) administered by the

3526
R. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 3520–3526
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University Grants Committee of HKSAR and the Hong
Kong Research Grants Council (HKU7384/02P).
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