Baeckvall J.-E. (ed.) Modern Oxidation Methods
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1.2
Environmentally Friendly Terminal Oxidants
1.2.1
Hydrogen Peroxide
Since the publication of the Upjohn procedure in 1976, the use of N-methylmorpho-
line N-oxide (NMO) based oxidants has become one of the standard methods for
osmium-catalyzed dihydroxylations. However, NMO has not been fully appreciated
in the asymmetric dihydroxylation for a long time since it was difficult to obtain
high enantiomeric excess (ee). This drawback was significantly improved by slow
addition of the alkene to the aqueous tert-BuOH reaction mixture, in which 97% ee
was achieved with styrene [15].
Although hydrogen peroxide was one of the first stoichiometric oxidants used in
osmium-catalyzed dihydroxylation [10a], it was not employed efficiently until re-
cently. When hydrogen peroxide is used as a reoxidant for transition metal catalysts,
a very common big disadvantage is that a large excess of H
2
O
2
is required to
compensate for the major unproductive peroxide decomposition to O
2
.
Recently, B
€
ackvall and coworkers were able to improve the H
2
O
2
reoxidation pro-
cess significantly by using N-methylmorpholine together with an electron transfer
mediator (ETM) as co-catalysts in the presence of hydrogen peroxide (Figure 1.1) [16].
Thus, a renaissance of both NMO and H
2
O
2
was brought about. The mechanism
of the triply catalyzed H
2
O
2
oxidation is shown in Scheme 1.2.
The oxidized electron transfer mediator (ETM
ox
), namely the peroxo complexes
of methyltrioxorhenium (MTO) and vanadyl acetylacetonate [VO(acac)
2
] and flavin
hydroperoxide, generated from its reduced form (Figure 1.1) and H
2
O
2
, recycles the
N-methylmorpholine (NMM) to N-methylmorpholine N-oxide (NMO), which in turn
reoxidizes the Os(VI) to Os(VIII). While the use of hydrogen peroxide as oxidant
without any electron transfer mediators is inefficient and nonselective, various
alkenes were oxidized to diols in good to excellent yields employing this mild triple
catalytic system (Scheme 1.2).
By using a chiral Sharpless ligand, high enantioselectivities were obtained. In the
flavin system, an increase in the addition time for alkene and H
2
O
2
has a positive
R
1
R
2
R
1
R
2
OH
OH
N
O
CH
3
O
N
O
CH
3
ETM
red
ETM
ox
OsO
4
OsO
3
H
2
O
H
2
O
2
Scheme 1.2 Osmium-catalyzed dihydroxylation of alkenes using H
2
O
2
as the terminal oxidant.
1.2 Environmentally Friendly Terminal Oxidants
j
3
effect on the enantioselectivity. For example, a-methylstyrene was oxidized with
the aid of flavin as the ETM to its corresponding vicinal diols in good yield (88%)
and excellent enantiomeric excess (99% ee) (Scheme 1.3).
B
€
ackvall and coworkers have shown that other tertiary amines can assume the role
of the N-methylmorpholine [16c]. They reported the first example of an enantiose-
lective catalytic redox process where the chiral tertiary amine ligand has two different
modes of operation. The primary function is to provide stereocontrol in the addition
of the substrate, and the secondary function is to reoxidize the metal through the
N-oxide [16c]. The results obtained with hydroquinidine 1,4-phthalazinediyl diether
(DHQD)
2
PHAL both as electron transfer mediator and chiral ligand in the osmium-
catalyzed dihydroxylation are comparable to those obtained employing NMM to-
gether with (DHQD)
2
PHAL. The proposed catalytic cycle for the reaction is depicted
in Scheme 1.4 [16c,e].
Flavin is an efficient electron transfer mediator, but is rather unstable. Several
transition metal complexes, such as vanadyl acetylacetonate, can also activate
hydrogen peroxide and are capable of replacing flavin in the dihydroxylation reaction
[16d,g]. The co-catalyst loading can hence be reduced from 5 mol% (flavin) to 2 mol%
[VO(acac)
2
or MTO] with comparable yield and ee. The introduction of ETM for the
oxidation of tertiary amine N-oxides significantly enhanced the efficiency of H
2
O
2
.
With 1.5 equivalents of commercially available aqueous 30% H
2
O
2
, good to excellent
yield can be achieved [16e]. Interestingly, an ETM, MTO, catalyzes oxidation of
the chiral ligand to its mono-N-oxide, which in turn can be used as the oxidant to
CH
3
H
3
C
OH
OH
2 mol% K
2
[OsO
2
(OH)
4
]
6 mol% (DHQD)
2
PHAL
5 mol% flavin
50 mol% NMM
88% yield
99%
ee
2 eq tetraethylammonium
acetate
1.5 eq H
2
O
2
tert-
BuOH / H
2
O, 0 °C
Scheme 1.3 Osmium-catalyzed dihydroxylation of a-methylstyrene using H
2
O
2
.
N
N
N
N
O
CH
3
O
CH
3
Et
H
O
H
3
C
H
3
C
O
O
CH
3
CH
3
O
V
O
Re
O
CH
3
O O
Flavin derivative
VO(acac)
2
MTO
Figure 1.1 Electron transfer mediators (ETMs).
4
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1 Recent Developments in Metal-catalyzed Dihydroxylation of Alkenes
generate Os
VIII
from Os
VI
. The system gives phenylethanediol diols in 71% yield
with 98% ee. This clearly confirms the role of the ETM in the regeneration of
N-oxides during the dihydroxylation process.
1.2.2
Hypochlorite
Apart from oxygen and hydrogenperoxide, bleach is the simplestand most economical
oxidant, and is widely used in industry without problems. This oxidant has only been
applied in the presence of osmium complexes in two patents in the early 1970s for the
oxidation of fatty acids [17]. In 2003 the first general dihydroxylation procedure of
various alkenes in the presence of sodium hypochlorite as the reoxidant was described
by our group [18]. Using a-methylstyrene as a model compound, 100% conversion and
98% yield of the desired 1,2-diol were demonstrated (Scheme 1.5).
N
MeO
N
O
NN
O
N
N
OMe
N
MeO
N
O
NN
O
N
N
OMe
O
N
MeO
N
O
NN
O
N
N
OMe
O
Os
O O
O
O
N
MeO
N
O
NN
O
N
N
OMe
O
Os
O O
O
O
R
N
MeO
N
O
NN
O
N
N
OMe
Os
O O
O
O
R
O
ETM
ox
ETM
red
H
2
O
2
H
2
O
OsO
4
R
R
HO OH
H
2
O
+OsO
4
Scheme 1.4 Catalytic cycle for the enantioselective dihydroxylation of alkenes using
(DHQD)
2
PHAL for oxygen transfer and as source of chirality.
CH
3 H
3
C
OH
OH
0.4 mol% K
2
[OsO
2
(OH)
4
]
1 mol% (DHQD)
2
PHAL
98% yield
77%
ee
2 eq K
2
CO
3
1.5 eq NaOCl
tert-
BuOH / H
2
O, 0°C
Scheme 1.5 Osmium-catalyzed dihydroxylation of a-methylstyrene using sodium hypochlorite.
1.2 Environmentally Friendly Terminal Oxidants
j
5
The efficacy of hypochlorite is significantly higher than that of other conventional
oxidants. The yield of 2-phenyl-1,2-propanediol reached 98% after only 1 h, while
literature protocols using NMO [19] or K
3
[Fe(CN)
6
] [7b] gave both in 90% yield at
0
C. The turnover frequency of the hypochlorite system was 242 h
1
, which is a
reasonable level for further industrial application [20]. Under the conditions shown
in Scheme 1.5 an enantioselectivity of only 77% ee was obtained, while 94% ee was
reported using K
3
[Fe(CN)
6
] as reoxidant [7b]. The lower enantioselectivity can be
explained by some involvement of the so-called second catalytic cycle with the
intermediate Os(VI) glycolate being oxidized to an Os(VIII) species prior to hydro-
lysis (Scheme 1.6) [21].
The enantioselectivity can be improved by applying a higher ligand concentration.
In the presence of 5 mol% (DHQD)
2
PHAL a good enantioselectivity (91% ee) was
observed for a-methylstyrene. Using tert-butylmethylether as organic co-solvent
instead of tert-butanol, 99% yield and 89% ee with only 1 mol% (DHQD)
2
PHAL
were reported for the same substrate. An increase in the concentration of the chiral
ligand in the organic phase could be an explanation of this increase in enantios-
electivity. Increasing the polarity of the water phase by using a 10% aqueous NaCl
R R
HO OH
Os
O
O
O
O
Os
O
O
O
O
R
R
Os
O
O
O
O
R
R
O
R R
HO OH
L
L
L
L
first
cycle
second
cycle
high
enantioselectivity
low
enantioselectivity
Os
O
O
O
O
R
R
R
R
O
low
ee
high
ee
H
2
O
H
2
O
NaOCl
NaCl
VIII
VIII
VI
VI
R
R
R
R
Scheme 1.6 The two catalytic cycles in asymmetric dihydroxylation.
6
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1 Recent Developments in Metal-catalyzed Dihydroxylation of Alkenes
solution showed a similar positive effect. Table 1.1 shows the results of the
asymmetric dihydroxylation of various alkenes with NaOCl as terminal oxidant.
Despite the slow hydrolysis of the sterically hindered Os(VI) glycolate, trans-5-
decene reacted smoothly to give the corresponding diol. This result is especially
impressive since addition of stoichiometric amounts of hydrolysis aids is usually
necessary in the dihydroxylation of most internal alkenes in the presence of other
oxidants.
Thus this hypochlorite-procedure is economical, productive, and easy to manage
for asymmetric dihydroxylation.
Table 1.1 Asymmetric dihydroxylation of different alkenes using NaOCl as the terminal oxidant.
a)
.
Entry Alkene Time
(h)
Yield
(%)
Selectivity
(%)
ee
(%)
ee (%)
Ref. [4b]
b)
ee (%)
Ref. [15]
c)
1 188 88 95 99 —
2
CH
3
293 99 95 97 98
3
CH
3
199 99 91 95 —
4
C
4
H
9
C
4
H
9
192 94 93 97 —
5 184 84 91 97 97
6
O
288 94 73 88 —
7
H
3
C
Si
H
3
C
H
3
C
287 9380
d)
——
8
C
6
H
13
297 97 73 ——
9
H
3
CO
H
3
CO
294 9634
d)
——
10
H
3
C
CH
3
H
3
C
297 >97 80
d)
92 46
a) Reaction conditions: 2 mmol alkene, 0.4 mol% K
2
[OsO
2
(OH)
4
], 5 mol% (DHQD)
2
PHAL, 10 mL
H
2
O, 10 mL tert-BuOH, 1.5 equiv. NaOCl, 2 equiv. K
2
CO
3
,0
C.
b) K
3
[Fe(CN)
6
] as oxidant.
c) NMO as oxidant.
d) 5 mol% (DHQD)
2
PYR instead of (DHQD)
2
PHAL.
1.2 Environmentally Friendly Terminal Oxidants
j
7
1.2.3
Chlorite
The pH of the system is of vital importance in osmium-catalyzed dihydroxylation
reactions [5, 6]. An additional base, which aids the hydrolysis of the osmium
glycolate, is usually present in the reci pe of the general procedure. In 2004 Hormi
and Junttila introduced sodium chlorite as the new reoxidant in asymmetric
dihydroxylation [22]. NaClO
2
acts as both an oxidant and a hydroxyl ion pump
in the system (Scheme 1.7). The pH value was maintained since each NaClO
2
provides the reaction with the necessary stoichiometric number of electrons and
hydroxide ions during the reaction profile. Various alkenes can be dihydroxylated
to the corresponding diols in good yield (63– 80%) with good enantioselectivity
(41–>99.5% ee) (Sc heme 1.8).
Kinetic studies showed that the dihydroxylation of styrene using NaClO
2
was twice
as fast as in the established Sharpless K
3
[Fe(CN)
6
] protocol. This higher reaction
rate can be attributed to the oxidation of an osmium(VI) mono(glycolate) to cor-
responding osmium(VIII) mono(glycolate) before hydrolysis. As the concentration
2 OsO
4
2 L ++
2 R
OOs
O
L
O
O
2
R
OOs
O
L
O
O
2
R
4 H
2
O
+++
+
24 KOH 2 K
2
[OsO
2
(OH)
4
]
+ 2 L
HO OH
R
2 K
2
[OsO
2
(OH)
4
] NaClO
2
2 K
2
[OsO
4
(OH)
2
]
2 H
2
ONaCl2K
2
[OsO
4
(OH)
2
]
2 OsO
4
4 KOH
+++
2 H
2
O
+
2 R
NaClO
2
+
+
2
HO OH
R
NaCl
Scheme 1.7 Essential steps for osmium-catalyzed dihydroxylation using NaClO
2
.
CH
3 H
3
C
OH
OH
Kmol%0.4
2
[OsO
2
(OH)
4
]
(DHQD)mol%1
2
PHAL
yield73%
93%
ee
NaCleq10
NaClOeq0.5
2
tert-
BuOH H/
2
°C0O,
Scheme 1.8 Osmium-catalyzed dihydroxylation of a-methylstyrene using NaClO
2
.
8
j
1 Recent Developments in Metal-catalyzed Dihydroxylation of Alkenes
of the more electrophilic osmium(VIII) mono(glycolate) is increased, the rate-
limiting hydrolysis step is accelerated [23].
1.2.4
Oxygen or Air
Several groups have reported the oxidation of alkenes in the presence of OsO
4
and
oxygen. However mainly nonselective oxidation reactions take place in these
systems [24]. The breakthrough came in 1999 when Krief et al. published a reaction
system consisting of oxygen, cat alytic amounts of OsO
4
, and selenides for
the a symmetric dihydroxylation of a-methylstyrene under irradiation of visible
light in the presence of a sensitizer (Scheme 1.9) [25]. In t his system, the selenides
are oxidized t o th eir oxides by singl et oxygen and the selenium oxides are t hen
able to re-oxidize osmium (VI) to osmium (VIII). The reaction works w ith yields
and ees similar to those in Sharpless AD. Potassium carbonate is used in only
onetenthoftheamountpresentintheADmix,andaircanbeusedinsteadof
pure oxygen.
A wide range of aromatic and aliphatic alkenes were demonstrated in this
system [26]. It was shown that both yield and enantioselectivity are in fluenced by
the pH of the reaction medium. The procedure was also applied to practical syntheses
of natural product derivatives [27]. This version of the AD reaction not only uses a
more ecological co-oxidant, but also requires much less material: 87 mg of material
(catalyst, ligand, base, reoxidant) is required to oxidize 1 mmol of the same alkene
instead of 1400 mg when AD mix is used.
In 1999 the first AD reaction using molecular oxygen without any secondary
electron transfer mediator was published [28]. Osmium(VI) was readily reoxidized
to osmium(VIII) in this system. We demonstrated that the osmium-catalyzed
dihydroxylation of aliphatic and aromatic alkenes proceeds efficiently in the presence
of dioxygen under ambient conditions. This dihydroxylation procedure constitutes
a significant advancement compared to other re-oxidation procedures (Table 1.2,
entry 7).
For a bet ter comparison, a mode l reaction of the dihydroxylation of a-methyl-
styrene was examined using different stoichiometric oxidants. The yield of the
1,2-diol remained good to very good (73– 99%), independently of the oxidant used.
CH
3
H
3
C
OH
OH
1.25 mol% K
2
[O sO
2
(OH)
4
]
2.3 mol% (DHQD)
2
PHAL
30 m ol% K
2
CO
3
tert-
BuOH / H
2
O, 20°C
8 mol% PhSeCH
2
Ph
0.3 mol% Rose Bengal
1barO
2
,h
ν
,24h
93% yield
97%
ee
Scheme 1.9 Osmium-catalyzed dihydroxylation using
1
O
2
and benzyl phenyl selenide.
1.2 Environmentally Friendly Terminal Oxidants
j
9
The b est enantioselectivities (94–99% ee) we re obtained with hydroquinidine
1,4-phthalazinediyl diether ((DHQD)
2
PHAL) as the ligand at 0– 12
C(Table1.2,
entries1,3,and4).
The dihydroxylation process with oxygen is clearly the most ecologically favorable
procedure (Table 1.2, entry 7) if the production of waste from a stoichiometric
Table 1.2 Comparison of the dihydroxylation of a-methylstyrene in the presence of different
oxidants.
Entry Oxidant Yield
(%)
Reaction
conditions
ee
(%)
TON Waste
(oxidant)
(kg/kg diol)
Ref.
1K
3
[Fe(CN)
6
]900
C94
a)
450 8.1
c)
[7b]
K
2
[OsO
2
(OH)
4
]
t
BuOH/H
2
O
2 NMO 90 0
C33
b)
225 0.88
d)
[19]
OsO
4
Acetone/H
2
O
3 PhSeCH
2
Ph/O
2
89 12
C96
a)
222 0.16
e)
[25a]
PhSeCH
2
Ph/air 87 K
2
[OsO
2
(OH)
4
]93
a)
48 0.16
e)
t
BuOH/H
2
O
4 NMM/Flavin/H
2
O
2
88 RT 99
a)
44 0.33
f)
[16a]
OsO
4
Acetone/H
2
O
5 NMM/VO(acac)
2
/
H
2
O
2
86 RT — 43 0.25
g)
[16d]
OsO
4
Acetone/H
2
O
6 MTO/H
2
O
2
85 RT 64
a)
43 0.041
h)
[16e]
OsO
4
Acetone/H
2
O
7O
2
96 50
C80
a)
192 — [28a]
K
2
[OsO
2
(OH)
4
]
t
BuOH/aq. buffer
8 NaOCl 99 0
C91
a)
247 0.58
i)
[18]
K
2
[OsO
2
(OH)
4
]
t
BuOH/H
2
O
9 NaClO
2
73 0
C93
a)
183 0.26
i)
[22]
K
2
[OsO
2
(OH)
4
]
t
BuOH/H
2
O
a) Ligand: Hydroquinidine 1,4-phtalazinediyl diether.
b) Hydroquinidine p-chlorobenzoate.
c) K
4
[Fe(CN)
6
].
d) N-Methylmorpholine (NMM).
e) PhSe(O)CH
2
Ph.
f) NMO/Flavin-OOH.
g) NMO/VO
2
(acac)
2
.
h) MTO(O).
i) NaCl.
10
j
1 Recent Developments in Metal-catalyzed Dihydroxylation of Alkenes
reoxidant is considered. With the use of K
3
[Fe(CN)
6
] as oxidant, approximately
8.1 kg of iron salts per kg of product are formed. However, in the case of the Krief
(Table 1.2, entry 3) and B
€
ackvall procedures (Table 1.2, entry 4) as well as in the
presence of NaOCl (Table 1.2, entry 8) some by-products also arise because of the use
of co-catalysts and co-oxidants. It should be noted that only salts and by-products
formed from the oxidant were included in the calculation. Other waste products were
not considered. Nevertheless, the calculations presented in Table 1.2 give a rough
estimation of the environmental impact of the reaction.
Since the use of pure molecular oxygen on a larger scale might lead to safety
concerns, it is even more advantageous to use air as the oxidizing agent. In fact, all
current bulk oxidation processes, such as the oxidation of BTX (benzene, toluene,
xylene) aromatics or alkanes to carboxylic acids, and the conversion of ethylene to
ethylene oxide, use air but not pure oxygen as the oxidant [29]. The results of using air
and pure oxygen have been compared in the dihydroxylation of a-methylstyrene as a
model reaction (Scheme 1.10 and Table 1.3) [30].
CH
3
+
1
2
OH
OH
H
3
C
+
K
2
[OsO
2
(OH)
4
]
ligand
H
2
/O
t
2.5:1BuOH
air°C,50
H
2
OO
2
Scheme 1.10 Osmium-catalyzed dihydroxylation of a-methylstyrene.
Table 1.3 Dihydroxylation of a-methylstyrene with air.
a)
.
Entry Pressure
(atm)
c)
Cat.
(mol%)
Ligand L/Os [L]
(mmol/l)
Time
(h)
Yield
(%)
Selectivity
(%)
ee
(%)
1 1 (pure O
2
) 0.5 DABCO
d)
3 : 1 3.0 16 97 97 —
2 1 (pure O
2
) 0.5 (DHQD)
2
PHAL
e)
3 : 1 3.0 20 96 96 80
3 1 0.5 DABCO 3.1 3.0 24 24 85 —
4 1 0.5 DABCO 3.1 3.0 68 58 83 —
5 5 0.1 DABCO 3 : 1 0.6 24 41 93 —
6 9 0.1 DABCO 3 : 1 0.6 24 76 92 —
7 20 0.5 (DHQD)
2
PHAL 3 : 1 3.0 17 96 96 82
8 20 0.1 (DHQD)
2
PHAL 3 : 1 0.6 24 95 95 62
9 20 0.1 (DHQD)
2
PHAL 15 : 1 3.0 24 95 95 83
10
b)
20 0.1 (DHQD)
2
PHAL 3 : 1 1.5 24 94 94 67
11
b)
20 0.1 (DHQD)
2
PHAL 6 : 1 3.0 24 94 94 78
12
b)
20 0.1 (DHQD)
2
PHAL 15 : 1 7.5 24 60 95 82
a) Reaction conditions: K
2
[OsO
2
(OH)
4
], 50
C, 2 mmol alkene, 25 mL buffer solution (pH 10.4),
10 mL tert-BuOH.
b) 10 mmol alkene, 50 mL buffer solution (pH 10.4), 20 mL tert-BuOH.
c) The autoclave was purged with air and then pressurized to the given value.
d) 1,4-Diazabicyclo[2.2.2.]octane.
e) Hydroquinidine 1,4-phthalazinediyl diether.
1.2 Environmentally Friendly Terminal Oxidants
j
11
The dihydroxylation of a-methylstyrene in the presence of 1 atm of pure
dioxygen proceeded smoothly (Table 1.3, entries 1–2), with the best results being
obtained at pH 10.4. In the presence of 0.5 mol% K
2
[OsO
2
(OH)
4
]/1.5 mol%
DABCO or 1.5 mol% (DHQD)
2
PHAL at pH 10.4 and 50
C, full conversion was
achieved after 16 h or 20 h depending on the ligand. Though the total yiel d and
selectivity of th e react ion are excellent (97% and 96% respectively), the total
turnover freq uency of the catalyst is comparatively low (TOF ¼ 10–12 h
1
). In the
presence of the c hiral c inchona l igand (DHQD)
2
PHAL, an ee of 80% was observed.
Sharpless et al . reported an enantioselect ivity of 94% for the dihydroxylation of
a-methylstyrene with (DHQD)
2
PHAL as the ligand using K
3
[Fe(CN)
6
]asthe
reoxidantat0
C [31]. Studies of the ceiling ee at 50
C (88% ee) showed that the
main dif ference in the enantioselect ivity stems from the higher reaction tempera-
ture. Using air instead of pure dioxygen gas gave only 24% of the corresponding
diol afte r 24 h (TOF ¼ 1h
1
; Table 1.3, entry 3). Although the reaction is slow, it is
important to note that the catalyst stayed active as the product continuously
formed up t o 58% yield a fter 68 h (Table 1.3, entry 4). It is noteworthy that the
chemoselectivity of the dihydroxylation does not significantly decrease after
prolonged reaction time. At 5–20 atm air pre ssure, the turnover frequency of the
catalyst improved (Table 1.3, entries 5–11).
Full conversion of a-methylstyrene was achieved at an air pressure of 20 atm in
the presence of 0.1 mol% of osmium, which corresponds to a turnover frequency
of 40 h
1
(Table 1.3, entries 8–11). It is apparent that by increasing the oxygen
pressure it is possible to redu ce the osmium catalyst loading by a factor of 5. A
decrease in the amount of osmium catalyst and ligand led to a decrease in the
enantioselectivity from 82% to 62% ee. T his can easily be explained by the
participation of the nonstereoselective osmium glycolat e as the active catalyst.
The enantioselectivity can be resumed wh en higher concentration of the chiral
ligand is applied (Table 1.3, entry 7 a nd 9). While the reaction at higher substrate
concentration (10 mmol instead of 2 mmol) proceeded only sluggishly at 1 atm of
pure oxygen; full conversion was ach ieved after 24 h at 20 atm of air (Table 1.3,
entries 10, 11 and Table 1.4, entries 17, 18). It is interesting that under air
atmosphere t he chemoselectivit y of the dihydroxylation remained excellent
(92–96%).
As dep icted in Table 1.4, v arious alkenes gave the corresponding diol s in
moderate to good yields (55–97%) with air. The enantiosele ctivities varied from
63–98% ee depending on the substrat e. As the main side reaction is the oxidative
cleavage of the C¼C double bond and the yield decreases with respect to time, the
chemoselectivity of the re action patently relates to the sensitivity of the produce d
diol toward further oxidation. Thus, t he oxidat ion of trans-stilbene in the biphasic
mixture water/tert-butanol at pH 10.4, 50
C, and 20 atm air pressure gave no
hydrobenzoin, but gave benzaldehyde in 84% yield (Table 1.4, entry 9). Interest-
ingly, changing the solvent to isobutyl methyl ketone (Table 1.4, entry 12) made it
possible to obtain hydrobenzoin in high yield (89%) and enantioselectivity (98% ee)
at pH 10.4.
12
j
1 Recent Developments in Metal-catalyzed Dihydroxylation of Alkenes