The acid accelerated ruthenium-catalysed dihydroxylation. Scope and limitations

Article abstract of DOI:10.1039/b316546a

Recently, we discovered a significant rate acceleration in RuO ₄-catalysed dihydroxylations of olefins by addition of Broensted-acids resulting in a reduction of the catalyst loading to only 0.5 mol%. The present paper gives a full account on the optimisation protocol that led to the discovery of the beneficial influence of protic acids. A strong focus is set on the detailed description of the influence of different reaction parameters on both reactivity and selectivity. In the second part an intense investigation of scope and limitations will be presented. The results provided in this manuscript might lead to a deeper understanding of competing processes that influence the selectivity in RuO₄-catalysed dihydroxylations.

Full text of DOI:10.1039/b316546a

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The acid accelerated ruthenium-catalysed dihydroxylation.
Scope and limitations
Bernd Plietker,* Meike Niggemann and Anja Pollrich
Organische Chemie II, Fachbereich Chemie, Universität Dortmund, Otto-Hahn-Str. 6,
D-44221 Dortmund, Germany. E-mail: plietker@pop.uni-dortmund.de; Fax: ϩ49-231-7553884;
Tel: ϩ49-231-7554632
Received 22nd December 2003, Accepted 23rd February 2004
First published as an Advance Article on the web 24th March 2004
Recently, we discovered a significant rate acceleration in RuO4-catalysed dihydroxylations of olefins by addition of
Brönsted-acids resulting in a reduction of the catalyst loading to only 0.5 mol%. The present paper gives a full
account on the optimisation protocol that led to the discovery of the beneficial influence of protic acids. A strong
focus is set on the detailed description of the influence of different reaction parameters on both reactivity and
selectivity. In the second part an intense investigation of scope and limitations will be presented. The results provided
in this manuscript might lead to a deeper understanding of competing processes that influence the selectivity in
RuO4-catalysed dihydroxylations.
second part. The results presented in this paper lead to a
Introduction
more practical and understandable alternative dihydroxylation
The catalytic and stereoselective introduction of oxygen con-
method applicable to the oxidation of a variety of structural
taining functional groups represents a challenging problem in
diverse olefins.
organic synthesis.1 Among the so far known oxidations the di-
hydroxylation of C,C-double bonds occupies an important
place.2 The current success in the development of new and
Results and discussion
Overoxidation and formation of fission products are common
side reactions in ruthenium-catalysed dihydroxylations. Differ-
ent scenarios could account for these unwanted transform-
efficient olefinations via metathesis further underlines the use-
fulness of these oxygenation processes.3 Within the past twenty
years the osmium-catalysed dihydroxylation became a bench-
mark reaction when it comes to generality and selectivity.4 Due
ations (Fig. 2). Apart from a classical NaIO4-assisted glycol
to the pericyclic character of the stereoinducing step the double
cleavage of diol VI RuO4 I itself could react with VI in a
bond geometry is translated into the relative stereochemistry of
sequence of condensation–electrocyclic fragmentation. These
the two adjacent stereocentres. Thus, the question of diastereo-
options were ruled out by two simple control experiments. A
selectivity in the oxidation can be finally reduced to a stereo-
comparison of the reaction rate for the RuO4/NaIO4- and
NaIO4-assisted glycol cleavage of hydrobenzoin 2 indicated
that RuO4 accelerates the fission reaction, however, both
selective olefination. However, some problems are connected
with osmium-catalysed reactions.4 The catalyst is very expen-
sive, volatile and toxic. These three issues prevent a successful
application on an industrial scale. Different alternative oxidants
have been tried in order to circumvent the use of osmium. The
of these fragmentations are slow on the time scale of the
dihydroxylation (Fig. 1).6
isoelectronic ruthenium() oxide, prepared in situ from
inexpensive ruthenium() chloride, seems to be the most prom-
ising one (Scheme 1).5 Dihydroxylations under RuO4-catalysis
are in general very fast (Shing coined the reaction as “flash-
dihydroxylation”). However, due to the high redox potential of
the catalyst (EЊ (Os()/Os(): 1.020 V, Ru()/Ru(): 1.400
V) the reactions are often not very selective and difficult to
control.
Scheme 1 “Flash-dihydroxylation” of stilbene 1.
It is for that reason, that this transformation has been rarely
used in the past. The chemistry of highly oxidised transition
metals is in the centre of our current research. During our
investigations on ruthenium-catalysed oxidation processes we
discovered a significant rate acceleration of the dihydroxylation
using catalytic amounts of protic acids.6 The present paper pro-
vides a detailed description of our investigations on factors
influencing the selectivity and reactivity of the reaction. Apart
from this methodological information an intense screening of
scope, limitations and chemoselectivity will be provided in the
Fig. 1 Conversion–time-curve for the cleavage of hydrobenzoin 2.
Accordingly, aldehyde IV has to be formed via a side reaction
in the catalytic cycle (Fig. 2). In a proposed mechanism olefin II
adds to RuO4 I to give ester III, which can react in two different
ways. Apart from an oxidation to ruthenium()-species V an
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4
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Fig. 2 Proposed mechanism for the formation of fission products.
entropically favourable electrocyclic fragmentation results in
(Table 1). This is most likely due to an acceleration of the
the formation of aldehyde IV and RuO2. Furthermore, ruthen-
ate V can react in two competing ways. A hydrolysis furnishes
the desired diol VI while regenerating the catalytically active
RuO4 I, or an electrocyclic fragmentation leads to aldehyde IV.
Based upon the results of preliminary control experiments we
hypothesised the hydrolysis of ruthenate ester V to be the rate
limiting step in the dihydroxylation. If the hydrolysis is too
slow, the intermediate ruthenium species V reacts in the frag-
mentation pathway towards aldehyde IV. Hence, the strategy to
improve the selectivity for the dihydroxylation must include an
accelerated hydrolysis of ruthenate V.
NaIO4-assisted glycol cleavage. Methyl tert-butyl ether showed
a good selectivity, albeit the conversion stops at 50%.
These results are in line with observations reported by Yang
and Zhang recently, in which replacement of ethyl acetate and
acetonitrile by 1,2-dichloroethane resulted in the clean oxid-
ative cleavage of the C,C-double bond by the RuCl3/NaIO4-
system.8 Hence, water immiscible solvents like dichloromethane
stabilise the intermediate ruthenates III or V resulting in a
predominant electrocyclic fragmentation, while water miscible
solvents increase the activation of NaIO4 resulting in an
accelerated periodate-assisted glycol cleavage of product VI. At
this point no further investigations on the solvent effect was
performed. The original solvent combination5 of ethyl acetate,
acetonitrile and water in a ratio of 3 : 3 : 1 seems to be the
optimum.
Optimisation protocol
RuO4 is isoelectronic to OsO4, however, due to its position in
the periodic table of elements the redox potential is much
higher (vide supra). Another major difference is the stability of
ruthenium() oxide at different pH-values. Whereas OsO4 can
be used in alkaline solution, RuO4 is only stable up to pH 9.
Above this pH-value it reacts with the free hydroxide to give
perruthenate RuO4Ϫ.7 Hence, an optimisation protocol for this
dihydroxylation can only partially rely on the results of the
osmylation reactions. In osmium-catalysed dihydroxylations
the hydrolysis of the intermediate osmates represents the rate
limiting step.4 Sharpless and others investigated different
approaches to speed up the cleavage of metallo esters. From a
mechanistic point of view the hydrolysis starts with a nucleo-
philic addition of water towards the metal centre. One way to
improve this addition is the use of an organic solvent known to
be homogenous, mixable, with water. Different solvent combin-
ations and stoichiometries were tested, however, the original
solvent mixture of ethyl acetate/acetonitrile/water (3/3/1)
proved to be best. Different from the related osmylations a
homogenous mixture using acetone or tert-butanol as organic
solvents did not improve the conversion. Moreover, the selectiv-
ity for the dihydroxylated product 5 dropped significantly
Subsequently, the influence of higher temperatures on the
reaction course was investigated (Table 2). Thus, increasing the
temperature lead to a predominant formation of fission prod-
ucts. Apparently, the electrocyclic fragmentation is faster at ele-
vated temperature. Hence, an acceleration of the hydrolysis by a
simple variation of these reaction parameters was not possible.
At this point we sought for additives known to speed up the
hydrolysis of metallo esters. Sharpless used this strategy in
order to oxidise highly substituted or electron-poor olefins.4,9
Although the use of sulfonamides improved the hydrolysis
in osmylations an influence on both selectivity and reactivity
in ruthenium-catalysed dihydroxylations was not observed.10
AkashiЈs work on a faster hydrolysis in the osmylation reaction
by addition of tetra-n-alkyl ammonium acetates did not prove
useful for the related ruthenium-catalysed dihydroxylations.11
Moreover, the acetate inhibits the catalyst very efficiently. This
is in line with earlier observations on the influence of carb-
oxylates on RuO4-catalysed oxidations.12 We then investigated
the possibility to use an accelerated hydrolysis of the ruthenate
under slightly alkaline conditions. However, a further limitation
for an accelerated hydrolysis is given by the instability of
Table 1 Influence of solvent
Entrya
Solvent
5 : 3b
Conv. [%]b
1
2
3
4
5
CH2Cl2 (6 mL)/CH3CN (6 mL)/H2O (2 mL)
MTBE (6 mL)/CH3CN (6 mL)/H2O (2 mL)
acetone (6 mL)/ CH3CN (6 mL)/H2O (2 mL)
t-BuOH (6 mL)/ CH3CN (6 mL)/H2O (2 mL)
EtOAc (6 mL)/CH3CN (6 mL)/H2O (2 mL)
44 : 56
75 : 25
38 : 72
0 : 100
84 : 16
4
49
31
24
81
a All reactions were performed on a 1 mmol scale using 3.5 mol% RuCl3 (as a 0.1 M solution in H2O), 1.5 equiv. NaIO4 at 0 ЊC and stopped after
5 minutes by addition of 10 mL sat. Na2S2O3-solution. b Determined by GC-integration.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
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Table 2 Influence of temperature
Table 4 Influence of acid
Entrya
T [ЊC]
5 : 3b
Conv. [%]b
Entrya
Acid
5 : 3b
Conv. [%]b
1
2
3
4
0
5
10
20
84 : 16
79 : 21
71 : 29
39 : 61
81
88
94
99
1
2
3
4
5
6
7
8
9
—
HOAc
TFA
74 : 26
70 : 30
79 : 21
69 : 31
66 : 34
78 : 22
76 : 24
77 : 23
79 : 21
89 : 11
71 : 29
29
65
66
59
44
81
80
69
90
39
75
Benzoic acid
Citric acid
MeSO3H
p-TosOH
HCl
H2SO4
H3PO4
HNO3
a All reactions were performed as indicated in Table 1 in a solvent
system of EtOAc (6 mL)/CH3CN (6 mL)/H2O (2 mL). b Determined by
GC-integration.
10
11
Table 3 Influence of pH
a All reactions were performed on a 1 mmol scale using 0.5 mol% RuCl3
(as a 0.1 M solution in H2O), 1.5 equiv. NaIO4 and 5.0 mol% protic acid
(as a 1 M solution in water) at 0 ЊC in EtOAc (6 mL)/CH3CN (6 mL)/
H2O (2 mL) and stopped after 5 minutes by addition of 10 mL sat.
Na2S2O3-solution. b Determined by GC-integration.
Entrya
pHb
5 : 3b
Conv. [%]c
1
2
3
4
5
6
7
8
9
1
2
3
4
5
6
7
8
9
78 : 22
75 : 25
77 : 23
76 : 24
74 : 26
75 : 25
74 : 26
73 : 27
56 : 44
36 : 64
93
88
79
74
68
69
67
61
46
12
10
10
a All reactions were performed as indicated in Table 2. b The pH was
adjusted by addition of a certain amount of K2CO3 (pH > 7) or H2SO4
(pH < 7) to water. c Determined by GC-integration.
ruthenium() oxide under basic (pH > 9) conditions.7 In con-
trast to the osmylation inorganic bases like hydroxides or
organic bases like pyridine or tertiary nitrogen compounds
inhibit the reaction. Different buffer solutions have been tried,
however, due to the rather low solubility of NaIO4 in water the
reactions in the presence of buffer were usually sluggish and
very slow. Furthermore, the formation of black precipitates was
observed. It is for that reason, that the pH-value was adjusted
manually by addition of K2CO3 or 1 M H2SO4. As can be seen
from Table 3 the conversion increases with a decreasing pH.13
The selectivity is not affected.
Because of the accelerated hydrolysis further attempts to
lower the amount of catalyst while maintaining the total
amount of acid were performed. At pH = 1 the amount of
RuCl3 was reduced stepwise. The results are visualized in Fig. 3.
The addition of acid allowed a decrease in catalyst loading
down to only 0.5 mol%.
Fig. 4 Influence of acid concentration.
concentrations accelerate the reaction but lead to the formation
of side products, e.g. aldehydes.
The acidity of the aqueous phase is dependant on the
amount of water. Thus, keeping the amount of added acid con-
stant while dividing the total amount of solvent by a factor
of two increases the proton concentration. We were pleased
to find, that the selectivity and conversion was quantitative
within 3 minutes resulting in an isolated yield of 84% diol 4
(Scheme 2).
Scheme 2 Optimised conditions for the “flash-dihydroxylation”.
The effect of acid can be rationalised in analogy to the acid
catalysed cleavage of carboxylic acid esters by an activation of
the intermediate ruthenate V (Fig. 2) via coordination of a pro-
ton to one of the Ru–O-bonds (Fig. 5). The resulting electron-
deficient ruthenate VII should react fast with the incoming
water to give the desired diol VI and catalyst I. The concept of
an acid accelerated nucleophilic addition has recently been used
in the development of a direct RuO4-catalysed ketohydroxyl-
ation of olefins14 and mono oxidation of vic-diols15 under
slightly acidic conditions. In either of these three reactions the
Fig. 3 Conversion at different catalyst concentrations (pH = 1).
Up to this point sulfuric acid has been used as proton source.
The influence of other acid sources was investigated next
(Table 4). Carboxylic acids had a minor influence on the select-
ivity, however, under these conditions they did not inhibit the
catalytic system. Stronger Brönsted-acids showed a significant
influence (Table 4).
Increasing the amount of acid resulted in a fast conversion
paired with a good selectivity within 5 minutes (Fig. 4). With
regard to the scope and limitations the maximum amount
of added acid was chosen to be 20 mol% H2SO4. Higher acid
Fig. 5 Postulated activation of ruthenate VI by protonation.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
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Table 5 Dihydroxylation of mono- and 1,2-disubstituted olefins
Entrya
R1
R2
Product
H2SO4 [mol %]
Time [min]
Yield [%]b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Ph
Ph
C6H13
C4H9
Ph
Ph
CO2Me
H
C4H9
H
2
5
20
20
5
5
5
3
5
2
2
2
2
2
4
5
2
5
5
3
3
79
84
87
91
86
85
68
79
6
7
8
CN
9
20
10
20
20
20
20
20
10
20
20
20
20
20
CH2Ph
CH2Cl
CH2SO2Ph
CH2N3
CH2NHAc
C(O)Ph
CH2OBn
CH2OAc
10
11
12
13
14
15
16
17
18
19
20
21
94
65
79
59 (81)c
73
78
74
71
84
Cyclohexyl
CO2Et
CONEt2
CO2Me
CO2Et
4
3
2
96
a All reactions were performed on a 2 mmol scale using 0.5 mol% RuCl3 (as a 0.1 M solution in H2O), 1.5 equiv. NaIO4 at 0 ЊC in EtOAc (6 mL)/
CH3CN (6 mL)/H2O (2 mL) in the presence of the given amount of sulfuric acid. b Isolated yield. c Yield in brackets refers to the yield based on
recovered starting material.
presence of protons is essential for the outcome of the reaction.
However, the activation mechanism remains a postulate and
further investigations along these lines have to be performed.
Having in hand the optimised conditions we turned our
attention to the scope and limitations of the new acid acceler-
ated ruthenium-catalysed dihydroxylation.
RuO4.16 In order to get first information on the relative reac-
tivities in the ruthenium-catalysed dihydroxylation of double
vs. triple bonds, ester 24 (Scheme 4, eqn. (1)) and benzoate 26
(Scheme 4, eqn. (2)) were prepared and oxidised under standard
conditions (Scheme 4).
Scope and limitations
Scope. The acidic reaction media was expected to cause
incompatibilities with acid labile functional groups. A wide
variety of different olefins was prepared and dihydroxylated in
good to excellent yields. By varying the amount of added acid a
broad scope of functional groups is tolerated (Table 5). Minor
amounts of fission products are standard byproducts, which
can be removed conveniently via recrystallisation or chromato-
graphy.
Scheme 4 Oxidation of enynes 24 and 26.
Acid labile protecting groups like silyl ethers are not stable
under the reaction conditions (vide infra). However, allylic
halides (entry 8) known to be prone to hydrolysis as well as
esters (entries 2, 14, 17 and 18) or amides (entries 11 and 16) are
compatible with the acidic conditions. Apparently, the di-
hydroxylation of the double bond is too fast for any competing
side reaction. Byproducts resulting from an oxidation of activ-
ated C,H-bonds (benzylic C,H-bonds, entries 7 and 13; tertiary
C,H-bonds, entries 15–17) were not observed. The short reac-
tion time and low temperature allows even the dihydroxylation
of acetal 23 using 1 mol% ruthenium-catalyst (Scheme 3).
The dihydroxylation occurred exclusively at the C,C-double
bond, the alkyne moiety was kept intact. The simple diastereo-
selectivity of the process is modest, but comparable to the selec-
tivities obtained in analogous osmium-catalysed oxidation
reactions. The dihydroxylation of a double bond is much faster
compared to the oxidation of a triple bond. Hence, apart from
functional groups like esters, chlorides, azides or amides
alkynes are tolerated as well.
Different cycloalkenes were oxidised under the optimised
conditions. The results are outlined in Table 6.
As mentioned above the hydrolysis is the rate limiting step.
Therefore, the dihydroxylation of cyclic olefins can be problem-
atic due to a favourable fast electrocyclic fragmentation caused
by the release of ring strain. Cyclic olefins are oxidised in
moderate to good yields. The moderate yields in the case of
cyclopentene and cyclohexene derivatives (entries 1 and 3)
might be due to the polarity of the final products. Furthermore,
allylic oxidation products and scission products were detected
in minor amounts. The oxidation of indene 29 (entry 2) is very
interesting since it clearly indicates that in this case the oxid-
ation of the double activated allylic and benzylic proton is slow
on the time scale of the oxidation reaction. Chiral cyclic alkenes
Scheme 3 Dihydroxylation of acetal 23.
Following these lines we investigated the oxidation of
substrates incorporating both an alkyne and alkene moiety.
Alkynes can be efficiently converted into 1,2-diketones using
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
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Table 6 Dihydroxylation of cycloalkenes
Time
[min]
Yield
[%]b
Entrya
1
Substrate
Product
3
61
2
5
75
Scheme 6 Limitations of the dihydroxylation.
however, acid labile groups like silyl ethers are not stable
under the reaction conditions. Apart from desilylation and
concomitant oxidation of the liberated hydroxy group a silyl
group migration is a competing side reaction leading to
different mono-, di- and even persilylated products in varying
amounts.
The most problematic side reaction still remains the electro-
cyclic fragmentation resulting in the formation of aldehydes.
This reaction is in particular problematic, if the resulting alde-
hyde is stabilised by a neighbouring group (e.g. aryl groups), or
if the scission product is thermodynamically favored due to the
release of ring strain. A lower temperature might suppress these
fragmentation processes, however, the presence of water does
not allow temperatures lower than Ϫ5 ЊC. Finally, highly sub-
stituted olefins are not very reactive towards dihydroxylation
reagents. Hence, stabilised tri- and tetrasubstituted olefins can
not be converted to the diols most likely due to the stability of
the intermediate ruthenate ester. Based upon our observations
these are the only limitations observed.
3
4
3
3
79
69
5
5
79
a All reactions were performed under the conditions listed in Table 4.
b Isolated yield.
Interestingly, phenanthrene 48 could not be converted to the
corresponding diol 50. Instead a mixture of fission product 49
and o-quinone 53 was obtained (Scheme 7). The formation of
53 might be explained by a fast overoxidation of the intermedi-
ate diol 50 to the corresponding ketol 51, which tautomerises
under the acidic reaction conditions to the o-hydroquinone
52. 52 is oxidised to the stable o-quinone 53 under the acidic
reaction conditions.
are oxidised in moderate to good stereoselectivities follow-
ing the Kishi-rules.17 Whereas the oxidation of allyl acetate
38 furnished anti- and syn-39 with high diastereoselectivity
(Scheme 5, eqn. (1)), as expected the homoallylic stereocentre in
40 had a smaller influence on the selectivity in 41 (Scheme 5,
eqn. (2)). The stereochemical assignments are based upon
NOE-measurements as shown below.
The results shown so far clearly underline the broad scope of
the acid-accelerated dihydroxylation protocol.
Scheme 7 Oxidation of phenanthrene 48.
The limitations do however emphasise the need for further
studies on this oxidation in order to develop protocols for the
dihydroxylation of these problematic substrates.
Summary
The present paper describes our investigations on the scope and
limitations of the acid accelerated RuO4-catalysed dihydroxyl-
ation protocol. A wide range of different olefins are oxidised in
good to excellent yields. The interplay of ruthenium- and acid
concentration allows the dihydroxylation of acid labile alkenes.
Due to the very short reaction times acid assisted side reaction
are often of minor importance. Hence, the acid accelerated
ruthenium-catalysed dihydroxylation is a less expensive and
toxic oxidation reaction that is suitable for the preparation of a
variety of racemic glycols.
Scheme 5 Dihydroxylation of chiral cyclic olefins 38 and 40.
Limitations. Although a broad scope of different olefins can
be dihydroxylated in good to excellent yields, certain limitations
do exist. A survey of problematic substrates is given in Scheme
6. The mechanistic scenario shown in Fig. 2 can serve as an
explanation. The acidic conditions speed up the hydrolysis,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
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(5R*,6R*)-Decane-5,6-diol (7).18 Following the general pro-
Experimental
cedure diol 7 (317 mg, 1.82 mmol, 91%) was obtained as a
colourless solid; mp 50 ЊC; Rf. 0.56 (5 : 1 pentane/ethyl acetate);
νmax(KBr)/cmϪ1 3409 (s), 2954 (s), 2932 (s), 2858 (m), 1465 (m),
1147 (m), 1073 (m); δH (400 MHz, CDCl3) 3.37–3.39 (2 H, m,
H-5 and H-6), 2.12 (2 H, s, OH ), 1.28–1.50 (12 H, m, CH2),
0.90 (6 H, t, J 7.1, CH3); δC (100 MHz, CDCl3) 74.5, 33.3, 27.7,
22.7, 14.1; m/z (EI) 176 (29%, Mϩ ϩ H2), 134 (43), 115 (100,
C7H15Oϩ), 105 (42), 92 (31).
Ethyl acetate and pentane were purified by distillation over
CaCl2 prior to use. RuCl3 was obtained from Aldrich. A stock
solution was prepared calculating with RuCl3(H2O)2 and dis-
solving the catalyst (2.44 g, 10 mmol) in 100 mL water (0.1 M).
The deep brown solution can be stored on the bench for weeks
without loss of activity. Flash-chromatography was done on
silica 60 (230–400 mesh). Infrared spectra (IR) were recorded as
a thin film between KBr-plates. The instrument used was a
Bruker IFS 66 FT-IR spectrophotometer. Proton (1H NMR,
400 MHz) and carbon (13C NMR, 100.6 MHz) nuclear mag-
netic resonance spectra were recorded in deuteriochloroform
and referenced to the solvent signal. The instrument used was a
Bruker DRX 400. All signal points are listed on a δ-scale in
ppm and coupling constants are in Hz. All commercially avail-
able starting materials were used without further purification.
(2R*)-Phenylethane-1,2-diol (8).18 Following the general pro-
cedure diol 8 (237 mg, 1.72 mmol, 86%) was obtained as a
colourless solid; mp 67 ЊC; Rf 0.23 (3 : 1 pentane/ethyl acetate);
νmax(KBr)/cmϪ1 3213 (s), 2933 (m), 1457 (s), 1100 (s), 1054 (s);
δH (400 MHz, CDCl3) 7.35–7.23 (5 H, m, aryl-H ), 4.76 (1 H,
dd, J 8.4, 3.6, H-2), 3.69 (1 H, dd, J 11.2, 3.6, CH2OH), 3.60
(1 H, dd, J 11.2, 8.0, CH2OH), 3.08 (2 H, s, OH ); δC (100 MHz,
CDCl3) 140.5, 128.6, 128.1, 126.2, 74.8, 68.1; m/z (EI) 138 (11%,
Mϩ), 107 (100, C7H7Oϩ), 91 (10), 79 (91), 77 (73).
General procedure for the dihydroxylation
In a 50 mL round-bottomed flask equipped with magnetic stir-
ring bar and overpressure valve NaIO4 (642 mg, 3 mmol) was
stirred in 1.5 mL H2O. 1 M H2SO4 (400 µL, 0.4 mmol) was
added. After all solids were dissolved the solution was cooled to
0 ЊC. A 0.1 M aqueous solution of RuCl3 (100 µL, 0.01 mmol)
was added and the mixture was stirred until the color turned
bright yellow. Ethyl acetate (6 mL) was added and stirring was
continued for 5 min. Acetonitrile (6 mL) was added and stirring
was continued for further 5 min. The olefin (2 mmol) was added
in one portion and the resulting slurry was stirred until all
starting material was consumed. The mixture was poured onto
15 mL sat. NaHCO3- and 20 mL sat. Na2S2O3-solution. Phases
were separated and the aqueous layer was extracted with ethyl
acetate (3 × 30 mL). After drying the combined organic layer
over Na2SO4 and evaporation of the solvent in vacuum the
crude product was purified by flash-chromatography.
(2S*,3R*)-2,3-Dihydroxy-3-phenylpropanenitrile (9).20 Fol-
lowing the general procedure diol 9 (277 mg, 1.70 mmol, 85%)
was obtained as a colourless oil; Rf 0.53 (1 : 1 pentane/ethyl
acetate); νmax(film)/cmϪ1 3421 (s), 2904 (m), 2361 (m), 1699 (m),
1496 (s), 1455 (s), 1197 (m), 1078 (s); δH (400 MHz, CDCl3)
7.49–7.41 (5 H, m, aryl-H ), 4.87 (1 H, d, J 6.0, H-2), 4.47 (1 H,
dd, J 6.5, 6.5, H-3), 3.40 (1 H, d, J 6.9, OH ), 3.07 (1 H, s, OH );
δC (100 MHz, CDCl3) 137.0, 129.5, 129.0, 126.9, 118.0, 74.8,
66.4; m/z (EI) 163 (1%, Mϩ), 105 (100, C7H5Oϩ), 91 (6), 77 (43).
(1R*,2R*)-1,3-Diphenylpropane-1,2-diol (10).21 Following
the general procedure diol 10 (310 mg, 1.36 mmol, 68%) was
obtained as a colourless solid; mp 83 ЊC; Rf 0.32 (3 : 1 pentane/
ethyl acetate); νmax(KBr)/cmϪ1 3434 (s, br), 3252 (s, br), 2916
(m), 2897 (m), 1604 (w), 1495 (s), 1453 (s), 1040 (s), 1020 (s);
δH (400 MHz, CDCl3) 7.37–7.16 (10 H, m, aryl-H ), 4.52 (1 H,
d, J 6.3, H-1), 3.93 (1 H, ddd, J 9.0, 6.3, 4.0, H-2), 2.72 (1 H, dd,
J 13.8, 4.0, CH2), 2.63 (1 H, dd, J 13.8, 9.0, CH2), 2.29 (2 H, s,
OH ); δC (100 MHz, CDCl3) 141.0, 138.1, 129.5, 128.8, 128.73,
128.70, 128.3, 127.0, 126.7, 39.6; m/z (EI) 228 (1%, Mϩ), 121
(14), 108 (100, C7H8Oϩ), 91 (40), 79 (46), 77 (35).
(1R*,2R*)-1,2-Diphenyl-ethane-1,2-diol (2).18 Following the
general procedure diol 2 (338 mg, 1.58 mmol, 79%) was
obtained as a colourless solid; mp 150 ЊC; Rf. 0.36 (3 : 1 penta-
ne/ethyl acetate); νmax(KBr)/cmϪ1 3499 (s), 3395 (s), 2895 (m),
1452 (m), 1198 (s), 1044 (s), 777 (s), 705 (s), 696 (s), 519 (m);
δH (400 MHz, CDCl3) 7.16–7.23 (6 H, m, aryl-H ), 7.08–7.10
(4 H, m, aryl-H ), 4.67 (2 H, s, H-1 and H-2), 3.02 (2 H, s, OH);
δC (100 MHz, CDCl3) 139.9, 128.0, 127.9, 127.0, 79.2; m/z (EI)
214 (1%, Mϩ), 108 (92, C7H8Oϩ), 107 (100, C7H7Oϩ), 105 (72,
C7H5Oϩ), 79 (95, C6H7ϩ), 77 (100, C6H5ϩ).
(1R*,2S*)-3-Chloro-1-phenyl-propane-1,2-diol (11).22 Follow-
ing the general procedure diol 11 (295 mg, 1.58 mmol, 79%) was
obtained as a colourless oil; Rf. 0.26 (3 : 1 pentane/ethyl acet-
ate); νmax(film)/cmϪ1 3394 (s), 1454 (m), 1197 (m), 1058 (m), 764
(m), 702 (m); δH (400 MHz, CDCl3) 7.31–7.37 (5 H, m, aryl-H ),
4.69 (1 H, d, J 6.8, H-1), 3.87 (1 H, ddd, J 6.8, 5.6, 4.0, H-2),
3.53 (1 H, dd, J 11.6, 4.0, CH2), 3.45 (1 H, dd, J 11.6, 5.6, CH2);
δC (100 MHz, CDCl3) 139.9, 128.8, 128.6, 126.7, 75.5, 74.8,
46.2; m/z (EI) 150 (8%, Mϩ Ϫ Cl), 107 (100, C7H7Oϩ), 91 (16),
79 (81), 51 (16).
(2S*,3R*)-2,3-Dihydroxy-3-phenyl-propionic acid methyl
ester (5).19 Following the general procedure diol 5 (339 mg, 1.68
mmol, 84%) was obtained as a white solid; mp 79 ЊC. Rf 0.30
(4 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1 3495 (s), 3378 (s),
3086 (m), 3062 (m), 3038 (m), 3007 (m), 2954 (s), 2931 (m), 1732
(s), 1493 (s), 1458 (s), 1324 (s), 1308 (s), 1104 (s), 1083 (s);
δH (400 MHz, CDCl3) 7.22–7.38 (5 H, m, aryl-H ), 4.94 (1 H, d,
J 3.3, H-3), 4.28 (1 H, d, J 3.3, H-2), 3.70 (3 H, s, CH3), 3.49
(2 H, s, OH ); δC (100 MHz, CDCl3) 173.2, 140.0, 128.4, 128.2,
126.3, 75.0, 74.5, 52.7; m/z (EI) 196 (2%, Mϩ), 119 (30,
C4H7O4ϩ), 107 (100, C7H7Oϩ), 105 (54, C7H5Oϩ), 90 (96,
C7H6ϩ), 79 (92, C6H7ϩ), 77 (85, C6H5ϩ).
(1S*,2R*)-1-Phenyl-3-(phenylsulfonyl)propane-1,2-diol (12).
Following the general procedure diol 12 (549 mg, 1.88 mmol,
94%) was obtained as a colourless solid; (found: C, 61.69; H,
5.48. C15H16O4S requires: C, 61.62; H, 5.52%); mp 133 ЊC; Rf.
0.48 (3 : 2 pentane/ethyl acetate); νmax(KBr)/cmϪ1 3521 (s), 3064
(w), 3028 (w), 2976 (w), 2942 (w), 2925 (w), 1168 (s), 1147 (m),
1084 (m); δH (400 MHz, CDCl3) 7.80–7.84 (2 H, m, aryl-H ),
7.49–7.65 (3 H, m, aryl-H ), 7.20–7.30 (5 H, m, aryl-H ), 4.56
(1 H, d, J 6.0, H-1), 4.24 (1 H, ddd, J 9.4, 6.0, 2.0, H-2), 3.25
(1 H, dd, J 14.6, 9.4, CH2), 3.21 (1 H, dd, J 14.6, 0.2, CH2), 2.60
(2 H, s, OH ); δC (100 MHz, CDCl3) 139.2, 139.0, 134.2, 129.5,
128.9, 128.7, 128.0, 126.9, 70.5, 58.8, 37.1; m/z (EI) 310 (42%,
Mϩ ϩ H2O), 275 (100, C15H15O3Sϩ), 132 (27); HRMS
(FABϩLR, C15H16O4S). Calc. 292.0769, found. 292.0774.
(2R*)-Octane-1,2-diol (6).18 Following the general procedure
diol 6 (254 mg, 1.74 mmol) was obtained as a colourless oil
(yield: 87%); Rf. 0.33 (7 : 1 pentane/ethyl acetate); νmax(film)/
cmϪ1 3341 (s), 2922 (s), 2858 (s), 1466 (s), 1072 (s), 1040 (s);
δH (400 MHz, CDCl3) 3.73–3.66 (1 H, m, H-2), 3.63 (1 H, dd,
J 11.0, 2.8, CH2OH), 3.41 (1 H, dd, J 11.0, 7.8, CH2OH), 2.76
(2 H, s, OH ), 1.51–1.20 (10 H, m, CH2), 0.87 (3 H, t, J 6.9,
CH3); δC (100 MHz, CDCl3) 72.5, 66.9, 33.3, 31.9, 29.4, 25.7,
22.7, 14.2; m/z (EI) 145 (1%, Mϩ Ϫ H), 115 (40), 97 (95), 69
(30), 55 (100, C4H7ϩ).
(1R*,2R*)-3-Azido-1-phenylpropane-1,2-diol (13). Following
the general procedure diol 13 (251 mg, 1.30 mmol, 65%) was
obtained as a yellow oil; (found: C, 55.88; H, 5.78. C9H11N3O2
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
1121

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requires: C, 55.95; H, 5.74%); Rf 0.31 (3 : 2 pentane/ethyl acet-
ate); νmax(film)/cmϪ1 3394 (s), 3087 (w), 3064 (w), 3032 (w), 2924
(w), 2103 (s), 1083 (m), 1043 (m); δH (400 MHz, CDCl3) 7.18–
7.43 (5 H, m, aryl-H ), 4.72 (1 H, dd, J 6.7, 1.8, H-1), 3.88 (1 H,
m, H-2), 3.55 (1 H, dt, J 11.5, 3.5, H-3), 3.38 (1 H, ddd, J 11.5,
5.7, 2.7, H-3), 3.08 (2 H, s, OH ); δC (100 MHz, CDCl3) 140.1,
128.9, 128.7, 126.7, 75.24, 75.20, 53.1; m/z (EI) 193 (44%, Mϩ ϩ
H), 177 (23), 147 (15), 106 (100, C7H6Oϩ); HRMS (FABϩLR,
C9H11N3O2). Calc. 193.0851, found. 193.0832.
1.83 (1 H, m, cyclohexyl-H ), 1.78–1.61 (4 H, m, cyclohexyl-H ),
1.53–1.43 (m, 4H, cyclohexyl-H ), 1.27–0.96 (2 H, m, cyclo-
hexyl-H ); δC (100 MHz, CDCl3) 171.6, 75.6, 69.4, 66.9, 40.3,
29.6, 28.5, 26.5, 26.2, 26.1, 21.0; m/z (EI) 199 (15%, Mϩ ϩ H Ϫ
H2O), 160 (9), 129 (29), 117 (100, C5H9O3ϩ), 101 (10), 75 (17);
HRMS (FABϩLR, C11H21O4). Calc. 217.1440, found. 217.1427.
(2S*,3R*)-3-Cyclohexyl-N,N-diethyl-2,3-dihydroxypropan-
amide (19). Following the general procedure diol 19 (345 mg,
1.42 mmol, 71%) was obtained as a colourless solid; (found: C,
64.11; H, 10.33. C13H25NO3 requires: C, 64.16; H, 10.36%); mp
149 ЊC; Rf 0.63 (3 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1
3290 (s), 2933 (s), 2854 (s), 1700 (s), 1683 (s), 1465 (s), 1114 (m),
1049 (m); δH (400 MHz, CDCl3) 5.15 (1 H, s, H-2), 3.83 (4 H, m,
CH2), 3.46 (1 H, m, H-3), 2.13–2.04 (2 H, m, cyclohexyl-H ),
1.98 (1 H, d, cyclohexyl-H ), 1.89–1.76 (6 H, m, CH3), 1.72–1.60
(4 H, m, cyclohexyl-H ), 1.41–1.13 (4 H, m, cyclohexyl-H );
δC (100 MHz, CDCl3) 154.9, 52.5, 51.8, 32.8, 30.0, 29.6, 29.5,
(1R*,3R*)-N-(2,3-Dihydroxy-3-phenyl-propyl)-acetamide
(14). Following the general procedure diol 14 (331 mg, 1.58
mmol, 79%) was obtained as a colourless oil; (found: C, 63.09;
H, 7.28. C11H15NO3 requires: C, 63.14; H, 7.23%); Rf. 0.18
(ethyl acetate); νmax(film)/cmϪ1 3319 (s), 2930 (m), 1653 (s), 1558
(s), 1453 (s), 1295 (m), 1102 (s), 1047 (s); δH (400 MHz, CDCl3)
7.26–7.33 (5 H, m, aryl-H ), 5.29 (1 H, s, NH ), 4.48 (1 H, d,
J 6.0, H-3), 3.57–3.94 (2 H, s, OH ), 3.75 (1 H, m, H-2), 3.28
(1 H, m, CH2), 3.13 (1 H, m, CH2), 1.90 (3 H, s, CH3); δC (100
MHz, CDCl3) 173.3, 141.9, 130.1, 129.6, 128.1, 76.4, 76.2, 43.9,
24.4; m/z (EI) 207 (4%, Mϩ Ϫ H2), 136 (69), 107 (94), 91 (18), 77
(100, C6H5ϩ); HRMS (FABϩLR, C11H16NO3). Calc. 210.1130,
found. 210.1122.
29.0, 25.9, 25.9, 25.8, 25.4, 25.1; m/z (EI) 199 (100%, Mϩ
Ϫ
C2H4O), 181 (31), 155 (19), 117 (21), 99 (23).
(2S*,3R*)-Methyl
3-cyclohexyl-2,3-dihydroxypropanoate
(20). Following the general procedure diol 20 (340 mg, 1.68
mmol, 84%) was obtained as a colourless solid; (found: C,
59.34; H, 9.01. C10H18O4 requires: C, 59.39; H, 8.97%); mp
82 ЊC; Rf 0.87 (3 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1 3330
(s), 2927 (s), 2851 (m), 1733 (s), 1628 (s), 1576 (m), 1446 (m),
1246 (m), 1115 (m), 1039 (m); δH (400 MHz, CDCl3) 4.30 (1 H,
s, H-2), 3.82 (3 H, s, CH3), 3.55 (1 H, d, J 8.7, H-3), 2.09–2.01
(1 H, m, cyclohexyl-H ), 1.82–1.64 (2 H, m, cyclohexyl-H ),
1.63–1.54 (2 H, m, cyclohexyl-H ), 1.40–1.18 (4 H, m, cyclo-
hexyl-H ), 1.16–0.96 (2 H, m, cyclohexyl-H ); δC (100 MHz,
CDCl3) 174.9, 71.1, 52.9, 40.5, 33.9, 29.5, 29.2, 26.4, 26.0, 25.9;
m/z (EI) 200 (2%, Mϩ Ϫ H2), 146 (44), 90 (100, C7H6ϩ), 55 (17);
HRMS (FABϩLR, C10H19O4). Calc. 203.1283, found. 203.1309.
(2S*,3R*)-2,3-Dihydroxy-1,3-diphenyl-propan-1-one (15).23
Following the general procedure diol 15 (286 mg, 1.18 mmol,
59%) was obtained as a colourless solid; mp 117 ЊC; Rf. 0.15
(3 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1 3434 (s), 3065 (w),
2929 (m), 2857 (w), 1694 (s), 1598 (m), 1579 (m), 1450 (m), 1284
(s), 1227 (s), 1113 (s); δH (400 MHz, CDCl3) 7.41–7.78 (10 H, m,
aryl-H ), 6.36 (1 H, d, J 8.0, H-3), 5.01 (1 H, d, J 8.0, H-2);
δC (100 MHz, CDCl3) 189.7, 130.7, 130.6, 130.1, 129.1, 128.9,
128.7, 128.6, 128.5, 88.7, 87.8; m/z (EI) 224 (1%, Mϩ Ϫ H2O),
207 (100, Mϩ Ϫ C15H13Oϩ), 179 (30), 165 (14), 131 (37), 103
(38), 77 (74).
(1R*,2R*)-3-Benzyloxy-1-phenyl-propane-1,2-diol (16).5 Fol-
lowing the general procedure diol 16 (386 mg, 1.46 mmol, 73%)
was obtained as a colourless solid; mp 61 ЊC; Rf. 0.28 (3 : 1
pentane/ethyl acetate); νmax(KBr)/cmϪ1 3415 (s), 3031 (w), 3030
(w), 2876 (w), 1495 (m), 1118 (s), 1026 (s), 737 (s), 700 (s);
δH (400 MHz, CDCl3) 7.31–7.36 (10 H, m, aryl-H ), 4.72 (1 H,
d, J 5.5, H-2), 4.54 (1 H, d, J 12.0, phenyl-CH2), 4.47 (1 H, d,
J 12.0, phenyl-CH2), 3.83 (1 H, m, H-2), 3.50 (1 H, dd, J 9.5,
3.0, H-3), 3.42 (1 H, dd, J 9.5, 5.5 Hz, H-3), 3.11 (s, 1H, OH),
2.83 (s, 1H, OH); δC (100 MHz, CDCl3) 141.9, 139.1, 130.0,
129.9, 129.5, 129.4, 129.3, 128.1, 76.3, 76.2, 75.1, 72.5; m/z (EI)
258 (1%, Mϩ), 150 (11), 121 (10), 108 (68), 91 (100, C7H7ϩ), 77
(81).
(1S*,2S*)-Diethyl 2,3-dihydroxysuccinate (21).24 Following
the general procedure diol 21 (396 mg, 1.92 mmol, 96%) was
obtained as a colourless oil; Rf 0.44 (3 : 2 pentane/ethyl acetate);
νmax(film)/cmϪ1 3470 (s), 2984 (s), 2939 (m), 2910 (m), 2876 (w),
1745 (s), 1129 (s), 1089 (s); δH (400 MHz, CDCl3) 4.49 (2H, s,
H-2 and H-3), 4.23 (4 H, q, J 7.0, CH2), 3.55 (2 H, s, OH ), 1.25
(6 H, t, J 7.0, CH3); δC (100 MHz, CDCl3) 171.6, 72.2, 62.3,
14.0; m/z (EI) 207 (5%, Mϩ ϩ Hϩ), 134 (30), 132 (62), 104 (100,
C4H6O3ϩ), 87 (49), 76 (100), 59 (100, C2H3O2ϩ).
(1S*,2R*)-1-(5,5-Dimethyl-1,3-dioxan-2-yl)-2-phenylethane-
1,2-diol (23). Following the general procedure diol 23 (267 mg,
1.06 mmol, 53%) was obtained as a colourless solid; (found: C,
66.68; H, 8.02. C14H20O4 requires: C, 66.65; H, 7.99%); mp
126 ЊC; Rf 0.84 (3 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1
3447 (s, br), 3362 (s, br), 2955 (m), 2871 (m), 1495 (m), 1473
(m), 1396 (m), 1091 (s), 1030 (s); δH (400 MHz, CDCl3) 7.41–
7.24 (5 H, m, aryl-H ), 4.99 (1 H, d, J 3.2, H-1), 4.46 (1 H, d,
J 3.2, H-3), 3.68 (2 H, d, J 10.8, CH2), 3.64 (1 H, dd, J 3.2, H-3),
3.43 (2 H, d, J 10.8, CH2), 3.18 (1 H, s, OH ), 2.60 (1 H, s, OH ),
1.20 (3 H, s, CH3), 0.72 (3 H, s, CH3); δC (100 MHz, CDCl3)
140.7, 128.5, 127.8, 126.6, 101.2, 77.3, 75.5, 72.5, 31.3, 30.6,
23.1, 21.8; m/z (EI) 252 (3%, Mϩ), 207 (27), 194 (13), 117 (31),
91 (100, C7H7ϩ); HRMS (FABϩLR, C14H20NaO4). Calc.
275.1259, found. 275.1235.
Acetic acid (2R*,3R*)-2,3-dihydroxy-3-phenyl-propyl ester
(17).5 Following the general procedure diol 17 (328 mg, 1.56
mmol, 78%) was obtained as a colourless oil; Rf. 0.38 (1 : 1
pentane/ethyl acetate); νmax(film)/cmϪ1 3418 (s), 3032 (w), 2900
(w), 1723 (s), 1381 (m), 1244 (s), 704 (s); δH (400 MHz, CDCl3)
7.28–7.38 (5 H, m, aryl-H ), 4.58 (1 H, d, J 6.4, H-3), 4.04 (1 H,
m, H-2), 3.91 (2 H, m, CH2), 2.86 (2 H, br. s., OH ), 2.02 (3 H, s,
CH3); δC (100 MHz, CDCl3) 140.1, 128.8, 128.5, 127.2, 126.7,
74.6, 74.1, 65.3, 20.9; m/z (EI) 212 (11%, Mϩ ϩ H2), 105 (100,
C7H5Oϩ), 91 (7), 77 (29).
(2R*,3R*)-3-Cyclohexyl-2,3-dihydroxypropyl acetate (18).
Following the general procedure diol 18 (320 mg, 1.48 mmol,
74%) was obtained as a colourless solid; (found: C, 61.14; H,
9.36. C11H20O4 requires: C, 61.09; H, 9.32%); mp 88 ЊC; Rf 0.65
(1 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1 3358 (s), 2923 (s),
2855 (m), 1736 (s), 1449 (w), 1384 (w), 1250 (s), 1124 (m), 1042
(s); δH (400 MHz, CDCl3) 4.19 (1 H, dd, J 11.5, 4.5, H-1), 4.11
(1 H, dd, J 11.5, 7.0, H-1), 3.95–3.85 (1 H, m, H-3), 3.21 (1 H,
dd, J 6.9, 3.0, H-2), 2.27 (2 H, s, OH ), 2.07 (3 H, s, CH3), 1.91–
(2S*,3R*)-2,3-Dihydroxy-5-phenylpent-4-ynoic acid ethyl
ester (25). Following the general procedure diol 25 (344 mg,
1.72 mmol, 86%) was obtained as a colourless oil; (found: C,
66.71; H, 5.97. C13H14O4 requires: C, 66.66; H, 6.02%); Rf 0.14
(3 : 1 pentane/ethyl acetate); νmax(film)/cmϪ1 3404 (s, br), 2360
(s), 2340 (s), 1735 (s), 1276 (m), 1114 (s), 1053 (m); δH (400
MHz, CDCl3) 7.36–7.47 (2 H, m, aryl-H ), 7.21–7.36 (3 H, m.
aryl-H ), 4.89 (1 H, d, J 2.5, H-2), 4.39 (1 H, d, J 2.5, H-3), 4.32
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
1122

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(2 H, q, J 7.5, CH2), 3.47 (1 H, s, OH ), 2.98 (1 H, s, OH ), 1.32
(3 H, t, J 7.5, CH3); δC (100 MHz, CDCl3) 173.2, 133.3, 130.2,
129.7, 123.5, 87.6, 77.6, 75.2, 65.9, 64.0, 15.6; m/z (EI) 234 (3%,
Mϩ), 143 (9), 131 (100, C9H7Oϩ), 115 (35), 104 (89), 76 (63).
HRMS (FABϩLR, C13H14O4). Calc. 234.0892, found. 234.0897.
(2S*,3S*)-2,3-Dihydroxycyclohexanone (36).5 Following the
general procedure diol 36 (179 mg, 1.38 mmol, 69%) was
obtained as a colourless solid; mp 52 ЊC; Rf 0.25 (3 : 2 pentane/
ethyl acetate); νmax(KBr)/cmϪ1 3405 (s), 2949 (m), 1718 (s), 1140
(m), 1107 (m) 1075 (m); δH (400 MHz, CDCl3) 4.35–4.39 (1 H,
m, H-2), 4.13 (1 H, dd, J 3.3, 1.2, H-3), 3.49 (2 H, s, OH ), 2.49
(1 H, dq, J 13.6, 2.3, CH2), 2.32 (1 H, dt, J 13.6, 1.2, CH2), 2.03–
2.14 (2 H, m, CH2), 1.75–1.82 (2 H, m, CH2); δC (100 MHz,
CDCl3) 210.2, 77.5, 72.8, 39.1, 29.0, 21.2; m/z (EI) 130 (37%,
Mϩ), 112 (61), 86 (79), 83 (76), 73 (80), 69 (55), 58 (67), 57 (92),
55 (100, C3H3Oϩ).
Benzoic acid 1-(1,2-dihydroxy-2-phenyl-ethyl)-3-phenyl-prop-
2-ynyl ester (27). Following the general procedure diol 27 was
obtained as a diastereomeric mixture (syn-27/anti-27, 1.4 : 1.0
(1H NMR-integration)) as a colourless oil (395 mg, 1.06 mmol,
53%), that was separated via flash-chromatography.
Diastereomer 1: (1S*,2R*,3R*)-benzoic acid (1,2-dihydroxy-
2-phenyl-ethyl)-3-phenyl-prop-2-ynyl ester (anti-27). (164 mg,
0.44 mmol, 22%); (found: C, 77.38; H, 5.38. C24H20O4 requires:
C, 77.40; H, 5.41%); Rf 0.21 (3 : 1 pentane/ethyl acetate);
νmax(film)/cmϪ1 3421 (s), 3063 (m), 3033 (m), 2927 (m), 1726 (s),
1601 (m), 1491 (m), 1452 (m), 1267 (s), 1112 (m), 1069 (m), 1026
(m); δH (400 MHz, CDCl3) 7.97 (2 H, d, J 8.0, aryl-H ), 7.62–
7.16 (13 H, m, aryl-H ), 5.87 (1 H, d, J 5.5, H-3), 5.11 (1 H, d,
J 4.8, H-1), 4.13 (1 H, dd, J 5.1, 5.1, H-2), 3.26 (2 H, s, OH );
δC (100 MHz, CDCl3) 165.6, 140.5, 133.5, 132.1, 130.0, 129.1,
128.8, 128.5,128.4, 128.3, 126.8, 121.8, 87.7, 83.8, 77.0, 73.7,
66.2.
Diastereomer 2: (1R*,2S*,3R*)-benzoic acid (1,2-dihydroxy-
2-phenyl-ethyl)-3-phenyl-prop-2-ynyl ester (syn-27). (231 mg,
0.62 mmol, 31%); (found: C, 77.41; H, 5.40. C24H20O4 requires:
C, 77.40; H, 5.41%); νmax(film)/cmϪ1 3409 (s), 3063 (m), 2033
(m), 2928 (m), 1732 (s), 1601 (m), 1491 (m), 1452 (m), 1266 (s),
1107 (m), 1069 (m), 1026 (m); δH (400 MHz, CDCl3) 8.04 (2 H,
d, J 7.6, aryl-H ), 7.64–7.15 (13 H, m, aryl-H ), 5.70 (1 H, d,
J 4.1, H-3), 4.93 (1 H, d, J 6.1, H-1), 4.14 (1 H, dd, J 6.1, 4.1,
H-2), 3.28 (2 H, s, OH ); δC (100 MHz, CDCl3) 165.4, 139.7,
133.6, 132.2, 130.0, 129.4, 129.2, 128.9, 128.6, 128.6, 128.4,
126.9, 121.8, 88.3, 82.9, 76.7, 74.2, 66.5.
(3S*,4S*)-3,4-Dihydroxychroman-2-one (37). Following the
general procedure diol 37 (285 mg, 1.58 mmol, 79%) was
obtained as a colourless solid; (found: C, 59.97; H, 4.52.
C9H8O4 requires: C, 60.00; H, 4.48%); mp 142 ЊC; Rf 0.58 (1 : 1
pentane/ethyl acetate); νmax(KBr)/cmϪ1 3431 (s), 3308 (s), 2887
(w), 1774 (s), 1487 (m), 1461 (s), 1158 (s), 1129 (s), 1113 (s),
1066 (s); δH (400 MHz, (CD3)2CO) 7.45–7.39 (2 H, m, aryl-H ),
7.20 (1 H, t, J 7.5, aryl-H ), 7.07 (1 H, d, J 8.1, aryl-H), 4.92–
4.87 (2 H, m, OH ), 4.79 (1 H, d, J 6.0, H-3), 4.69 (1 H, dd, J 6.0,
3.4, H-2); δC (100 MHz, (CD3)2CO) 170.1, 152.0, 131.2, 130.3,
125.3, 117.3, 71.6, 70.1; m/z (EI) 180 (15%, Mϩ), 123 (100,
C7H7O2ϩ), 105 (25), 95 (29), 77 (46); HRMS (FABϩLR,
C9H8NaO4). Calc. 203.0320, found. 203.0349.
(1S*,2S*,3S*)-2,3-Dihydroxycyclohexyl acetate (anti-39).5
Following the general procedure diol 39 was obtained as a
diastereomeric mixture (syn-39/anti-39, 1.0 : 32.3 (1H NMR-
integration)) as a colourless oil (254 mg, 1.46 mmol, 73%), that
was separated via flash-chromatography (3 : 2 pentane/ethyl
acetate).
Diastereomer 1: (1S*,2S*,3S*)-2,3-dihydroxycyclohexyl acet-
ate (anti-39). (246 mg, 1.41 mmol, 71%); Rf 0.19 (3 : 2 pentane/
ethyl acetate); νmax(film)/cmϪ1 3442 (s), 2942 (w), 2870 (w), 1732
(s), 1066 (m), 1042 (m); δH (400 MHz, CDCl3) 4.95 (1 H, ddd,
J 9.7, 4.3, H-1), 4.03 (1 H, ddd, J 4.3, 2.8, H-2), 3.52 (1 H, dd,
J 8.5, 3.0, H-3), 3.30 (2 H, s, OH ), 2.01 (3 H, s, CH3), 1.88–1.94
(1 H, m, H-6), 1.78–1.85 (1 H, m, H-4), 1.62–1.71 (1 H, m, H-5),
1.45–1.51 (1 H, m, H-5), 1.38–1.44 (1 H, m, H-4), 1.26–1.36
(1 H, m, H-6); δC (100 MHz, CDCl3) 172.0, 77.1, 74.4, 70.1,
30.1, 29.2, 21.5, 18.3; m/z (EI) 114 (48%, Mϩ-CH4O2), 96 (50),
70 (100, C4H6Oϩ), 57 (74).
Diastereomer 2: (1S*,2R*,3R*)-2,3-dihydroxycyclohexyl
acetate (syn-39). (8 mg, 0.05 mmol, 2%); Rf 0.09 (3 : 2 pentane/
ethyl acetate); νmax(film)/cmϪ1 3442 (s), 2942 (w), 2870 (w), 1732
(s), 1066 (m), 1042 (m); δH (400 MHz, CDCl3) 4.70 (1 H, ddd,
J 10.5, 4.8, 2.5, H-1), 4.02 (1 H, s, H-2), 3.60 (1 H, ddd, J 10.3,
4.8, 2.8, H-3), 2.88 (2 H, s, OH ), 2.02 (3 H, s, CH3), 1.55–1.74 (4
H, m, CH2), 1.15–1.28 (2 H, m, CH2); δC (100 MHz, CDCl3)
170.6, 74.0, 71.3, 70.8, 28.1, 24.6, 21.6, 19.5; m/z (EI) 114 (68%,
Mϩ Ϫ CH4O2), 96 (42), 70 (100, C4H6Oϩ), 57 (44).
(1S*,2R*)-1-Methyl-cyclopentane-1,2-diol (33).25 Following
the general procedure diol 33 (142 mg, 1.22 mmol, 61%) was
obtained as a colourless solid; mp 23 ЊC; Rf 0.17 (3 : 1 pentane/
ethyl acetate); νmax(KBr)/cmϪ1 3454 (s), 3394 (s), 3307 (s), 2970
(s), 2869 (m), 1465 (m), 1414 (m), 1373 (m), 1339 (m), 1165 (s),
1145 (s), 1122 (s); δH (400 MHz, CDCl3) 3.56 (1 H, dd, J 7.0,
H-2), 2.10 (2 H, s, OH ), 1.97–1.89 (1 H, m, CH2), 1.88 (3 H, m,
CH2), 1.62–1.46 (2 H, m, CH2), 1.29 (3 H, s, CH3); δC (100
MHz, CDCl3) 87.1, 86.3, 37.2, 30.0, 25.9, 19.4; m/z (EI) 115
(23%, Mϩ Ϫ H), 98 (100, Mϩ Ϫ H2O), 82 (68), 67 (81), 55 (35).
(1S*,2S*)-Indane-1,2-diol (34).26 Following the general pro-
cedure diol 34 (225 mg, 1.50 mmol, 75%) was obtained as a
colourless solid; mp 107 ЊC; Rf 0.32 (5 : 1 pentane/ethyl acetate);
νmax(KBr)/cmϪ1 3523 (m), 3440 (s), 3334 (s, br), 2951 (w), 2924
(m), 1579 (w), 1460 (w), 1431 (w), 1319 (s), 1153 (s), 1105 (s);
δH (400 MHz, CDCl3) 7.41–7.93 (1 H, m, aryl-H ), 7.26–7.09 (3
H, m, aryl-H ), 4.97 (1 H, d, J 5.0, H-1), 4.46 (1 H, dd, J 9.0, 5.0,
H-2), 3.08 (1 H, dd, J 16.3, 5.8, H-3), 2.92 (1 H, dd, J 16.3, 3.5,
H-3), 2.65 (2 H, s, OH ); δC (100 MHz, CDCl3) 142.1, 140.3,
129.0, 127.4, 125.6, 125.2, 76.1, 73.6, 38.8; m/z (EI) 146 (73%,
Mϩ Ϫ 2 H2), 107 (83), 91 (62), 79 (81), 69 (59), 60 (100,
C2H4O2ϩ).
3,4-Dihydroxy-cyclohexanecarbonitrile (41). Following the
general procedure diol 41 was obtained as an inseparable
diastereomeric mixture (syn-41/anti-41, 1.0 : 3.3 (1H NMR-
integration)) as a colourless oil (254 mg, 1.46 mmol, 73%);
(found: C, 59.52; H, 7.86. C7H11NO2 requires: C, 59.56; H,
7.85%); Rf 0.18 (diethyl ether); νmax(KBr)/cmϪ1 3447 (s), 2954
(m), 2246 (m), 1635 (m), 1073 (m).
Diastereomer 1: (1R*,3S*,4R*)-3,4-dihydroxy-cyclohexane-
carbonitrile (anti-41). δH (400 MHz, CDCl3) 4.05 (1 H, m, H-1),
3.78 (1 H, m, H-3), 2.92 (1 H, m, H-4), 2.12–2.19 (1 H, m, CH2),
2.05 (2 H, s, OH ), 1.91–1.98 (1 H, m, CH2), 1.73–1.81 (3 H, m,
CH2), 1.57–1.62 (1 H, m, CH2); δC (100 MHz, CDCl3) 122.3,
69.5, 67.9, 32.8, 31.4, 27.2; m/z (EI) 140 (2%, Mϩ Ϫ H), 114
(17), 96 (35), 85 (84), 69 (100, C5H9ϩ), 54 (88).
(1S*,2R*)-1-Methyl-cyclohexane-1,2-diol (35).27 Following
the general procedure diol 35 (195 mg, 1.58 mmol, 79%) was
obtained as a colourless solid; mp 67 ЊC; Rf 0.78 (3 : 1 pentane/
ethyl acetate); νmax(KBr)/cmϪ1 3326 (s), 2991 (m), 2938 (s), 2881
(s), 2860 (s), 1716 (m), 1458 (m), 1444 (m), 1405 (m), 1370 (m),
1151 (s), 1087 (s), 1063 (s); δH (400 MHz, CDCl3) 3.27 (1 H, t,
J 5.7, H-2), 2.34 (2 H, s, OH ), 1.79–1.72 (1 H, m, CH2), 1.68–
1.54 (5 H, m, CH2), 1.41–1.30 (2 H, m, CH2), 1.22 (3 H, s, CH3);
δC (100 MHz, CDCl3) 82.5, 72.2, 37.2, 37.0, 29.0, 22.0; m/z (EI)
129 (15%, Mϩ Ϫ H), 112 (100, Mϩ Ϫ H2O), 96 (97), 81 (91), 71
(44), 55 (36).
Diastereomer 2: (1S*,3S*,4R*)-3,4-dihydroxy-cyclohexane-
carbonitrile (syn-41). (164 mg, 0.44 mmol, 22%); δH (400 MHz,
CDCl3) 3.91 (1 H, m, H-3), 3.65 (1 H, m, H-4), 2.52 (1 H, m,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 1 1 6 – 1 1 2 4
1123

View Article Online
4 (a) H. Becker and K. B. Sharpless, in Asymmetric Oxidation
H-1), 2.06 (2 H, s, OH ), 1.91–2.08 (2 H, m, CH2), 1.76–1.81
(3 H, m, CH2), 1.55 (1 H, m, CH2); δC (100 MHz, CDCl3) 121.9,
69.5, 68.3, 32.8, 28.6, 25.5, 23.4; m/z (EI) 140 (10%, Mϩ Ϫ H),
114 (27), 96 (53), 84 (42), 69 (100, C5H9ϩ), 54 (76).
Reactions, ed. T. Katsuki, Oxford University Press, New York, 2001,
p. 81; (b) K. Morikawa, J. Park, P. G. Andersson, T. Hashiyama and
K. B. Sharpless, J. Am. Chem. Soc., 1993, 115, 8463.
5 (a) T. K. M. Shing, V. W.-F. Tai and E. K. W. Tam, Angew. Chem.,
1994, 106, 2408; T. K. M. Shing, V. W.-F. Tai and E. K. W. Tam,
Angew. Chem., Int. Ed. Engl., 1994, 33, 2312; (b) T. K. M. Shing,
E. K. W. Tam, V. W. F. Tai, I. H. F. Chung and Q. Jiang, Chem. Eur.
J., 1996, 2, 50.
6 B. Plietker and M. Niggemann, Org. Lett., 2003, 5, 3353.
7 (a) V. S. Martin, J. M. Palazon and C. M. Rodriguez, in Oxidizing
and Reducing Agents – Handbook of Reagents for Organic Synthesis,
ed. S. D. Burke and R. L. Danheiser, Wiley-VCH, Weinheim-New
York, 1999, p. 346; (b) J. L. Courtney, in Organic Synthesis by
Oxidation with Metal Compounds, ed. W. J. Mijs and C. R. H. I. de
Jonge, Plenum Press, New York, London, 1986, p. 445.
8 D. Yang and C. Zhang, J. Org. Chem., 2001, 66, 4814.
9 K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crsipino,
J. Hartung, K.-S. Jeong, H.-L. Kwong, K. Morikawa, Z.-M. Wang,
D. Xu and X.-L. Zhang, J. Org. Chem., 1992, 57, 2768.
10 In contrast to our results a rate acceleration in RuO4-catalysed
dihydroxylation using methanesulfonyl amide was observed by:
T. K. M. Shing and E. K. W. Tam, Tetrahedron Lett., 1999, 40, 2179.
11 (a) K. B. Sharpless and K. Akashi, J. Am. Chem. Soc., 1976, 98,
1986; (b) K. Akashi, R. E. Palermo and K. B. Sharpless, J. Org.
Chem., 1978, 43, 2063.
Oxidation of phenanthrene (48). Following the general pro-
cedure a mixture of 51 (yellowish solid, 151 mg, 0.72 mmol,
36%) and 53 (yellowish solid, 171 mg, 0.82 mmol, 41%) was
obtained.
1,1Ј-Biphenyl-2,2Ј-dicarbaldehyde (49).28 Mp 61 ЊC; Rf 0.73
(7 : 1 pentane/ethyl acetate); νmax(KBr)/cmϪ1 3445 (m), 3376
(m), 3079 (w), 3056 (w), 3029 (w), 2834 (m), 2749 (m), 2729 (m),
1693 (s), 1593 (s), 1392 (m), 1248 (m), 1195 (m), 1164 (s);
δH (400 MHz, CDCl3) 9.82 (2 H, s, CHO), 8.02 (2 H, d, J 7.6,
aryl-H ), 7.65 (2 H, td, J 7.5, 1.4, aryl-H ), 7.58 (2 H, t, J 7.5,
aryl-H ), 7.33 (2 H, d, J 7.5, aryl-H ); δC (100 MHz, CDCl3)
236.1, 141.4, 135.8, 133.6, 131.9, 129.0, 128.7; m/z (EI) 210 (7%,
Mϩ), 181 (100, Mϩ Ϫ CHO), 152 (67), 126 (9), 76 (18).
Phenanthrene-9,10-dione (53).29 Mp 148 ЊC; Rf 0.84 (7 : 1
pentane/ethyl acetate); νmax(KBr)/cmϪ1 3446 (m), 3065 (w), 1674
(s), 1591 (s), 1451 (m), 1294 (s), 1282 (s); δH (400 MHz, CDCl3)
8.17 (2H, dd, J 7.9, 1.3, aryl-H ), 8.00 (2 H, d, J 7.9, aryl-H ),
7.70 (2 H, td, J 7.4, 1.3, aryl-H ), 7.45 (2 H, t, J 7.4, aryl-H ),
1.55 (2 H, s, OH ); δC (100 MHz, CDCl3) 236.1, 136.2, 131.2,
130.7, 129.7, 127.5, 124.1; m/z (EI) 208 (20%, Mϩ), 180 (100,
Mϩ Ϫ CO), 152 (56), 126 (12), 76 (17).
12 P. H. J. Carlsen, T. Katsuki, V. S. Martin and K. B. Sharpless, J. Org.
Chem., 1981, 46, 3936.
13 Recently, Sharpless reported the beneficial influence of citric acid on
osmium-catalysed dihydroxylations: P. Dupau, R. Epple, A. A.
Thomas, V. V. Fokin and K. B. Sharpless, Adv. Synth. Catal., 2002,
344, 421.
14 B. Plietker, J. Org. Chem., 2003, 68, 7123.
15 B. Plietker, Org. Lett., 2004, 6, 289.
Acknowledgements
16 R. Zibuck and D. Seebach, Helv. Chim. Acta, 1988, 71, 237.
17 (a) J. K. Cha, W. J. Christ and Y. Kishi, Tetrahedron, 1984, 40, 2247;
(b) J. K. Cha and N.-S. Kim, Chem. Rev., 1995, 95, 1761.
18 C. Döbler, G. M. Mehltretter, U. Sundermeier and M. Beller, J. Am.
Chem. Soc., 2000, 122, 10289.
19 M. Fujita, D. Laine and S. V. Ley, J. Chem. Soc., Perkin Trans. 1,
1999, 1647.
The authors thank Prof. Dr. N. Krause for generous support.
B. P. thanks the Fonds der Chemischen Industrie for a
Liebig fellowhip. Further financial support by the Deutsche
Forschungsgemeinschaft and the Fonds zur Förderung des
wissenschaftlichen Nachwuchses im Fachbereich Chemie der
Universität Dortmund is gratefully acknowledged.
20 F. Effenberger, M. Hopf, T. Ziegler and J. Hudelmayer, Chem. Ber.,
1991, 124, 1651.
21 W. A. Bonner and E. K. Raunio, J. Org. Chem., 1966, 31, 291.
22 K. P. Vanhessche, Z.-M. Wang and K. B. Sharpless, Tetrahedron
Lett., 1994, 35, 3469.
23 A. Clerici and O. Porta, J. Org. Chem., 1989, 54, 2872.
24 D. H. G. Crout, V. S. B. Gaudet and K. O. Hallinan, J. Chem. Soc.,
Perkin Trans. 1, 1993, 805.
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