Methanesulfonamide: A cosolvent and a general acid catalyst in sharpless asymmetric dihydroxylations

Article abstract of DOI:10.1021/jo8026998

To obtain information about the effect that methanesulfonamide has in the hydrolysis step in Sharpless asymmetric dihydroxylation, a series of aliphatic and conjugated aromatic olefins were dihydroxylated with and without methanesulfonamide. The hypothesis in this study was that methanesulfonamide is a cosolvent that aids in the transfer of the hydroxide ions from the water phase to the organic phase. A plot of t90% versus the computational partition coefficient clog P of the intermediate osmate ester of nonterminal aliphatic olefins revealed that the polarity of the intermediate osmate ester has a significant effect on the reaction time and methanesulfonamide effect. The more polar the intermediate osmate ester, the faster is the reaction without methanesulfonamide and the smaller the accelerating methanesulfonamide effect. Methanesulfonamide had no accelerating effect in the asymmetric dihydroxylation of short chain terminal aliphatic olefins as a result of easier accessibility of terminal osmate ester groups to the water phase. A cosolvent hypothesis was found not to be valid in asymmetric dihydroxylations of conjugated aromatic olefins. In the reaction conditions used in Sharpless asymmetric dihydroxylation, weakly acidic methanesulfonamide was found to be a general acid catalyst that protonates the intermediate osmate esters of conjugated aromatic olefins in the hydrolysis step.

Full text of DOI:10.1021/jo8026998

Methanesulfonamide: a Cosolvent and a General Acid Catalyst in
Sharpless Asymmetric Dihydroxylations
Mikko H. Junttila and Osmo O. E. Hormi*
Department of Chemistry, UniVersity of Oulu, P.O. Box 3000, FIN-90014 Oulu, Finland
osmo.hormi@oulu.fi
ReceiVed December 9, 2008
To obtain information about the effect that methanesulfonamide has in the hydrolysis step in Sharpless
asymmetric dihydroxylation, a series of aliphatic and conjugated aromatic olefins were dihydroxylated
with and without methanesulfonamide. The hypothesis in this study was that methanesulfonamide is a
cosolvent that aids in the transfer of the hydroxide ions from the water phase to the organic phase. A plot
of t90% versus the computational partition coefficient clog P of the intermediate osmate ester of
nonterminal aliphatic olefins revealed that the polarity of the intermediate osmate ester has a significant
effect on the reaction time and methanesulfonamide effect. The more polar the intermediate osmate ester,
the faster is the reaction without methanesulfonamide and the smaller the accelerating methanesulfonamide
effect. Methanesulfonamide had no accelerating effect in the asymmetric dihydroxylation of short chain
terminal aliphatic olefins as a result of easier accessibility of terminal osmate ester groups to the water
phase. A cosolvent hypothesis was found not to be valid in asymmetric dihydroxylations of conjugated
aromatic olefins. In the reaction conditions used in Sharpless asymmetric dihydroxylation, weakly acidic
methanesulfonamide was found to be a general acid catalyst that protonates the intermediate osmate
esters of conjugated aromatic olefins in the hydrolysis step.
Introduction
to be an additive that accelerates the rate-limiting hydrolysis
step under the heterogeneous reaction conditions.2 For reasons
that were not understood then, addition of CH3SO2NH2 acceler-
ated the hydrolysis of osmate esters derived from 1,2-disubsti-
tuted and trisubstituted olefins but slowed the catalytic AD of
monosubstituted and 1,1-disubstituted olefins. So, today the
recommended procedure in Sharpless AD is to add 1 equiv of
CH3SO2NH2 per 1 equiv of olefin for the AD of nonterminal
olefins.
Reaction time can be significantly shorter in the presence of
CH3SO2NH2. It has been reported that in the absence of
CH3SO2NH2 trans-5-decene is only partially (70%) converted
to the corresponding diol after 3 days at 0 °C, whereas the diol
is isolated in 97% yield after only 10 h at 0 °C in the presence
During the early 1990s developments in Sharpless asymmetric
dihydroxylation (AD) led to a protocol that uses potassium
ferricyanide as the stoichiometric oxidant.1 Potassium ferricya-
nide was used in biphasic reaction conditions with which the
enantioselectivity-deteriorating secondary cycle was nearly
completely avoided. The turnover rate of the new catalytic cycle
depended on the rate of the hydrolysis of the intermediate
osmate(VI) ester. Methanesulfonamide (CH3SO2NH2) was found
(1) (a) Kwong, H.-L.; Sorato, C.; Ogino, Y.; Chen, H.; Sharpless, K. B.
Tetrahedron Lett. 1990, 31, 2999–3002. (b) Shibata, T.; Gilheany, D. G.;
Blackburn, B. K.; Sharpless, K. B. Tetrahedron Lett. 1990, 31, 3817–3820. (c)
Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV. 1994, 94,
2483–2547. (d) Zaitsev, A. B.; Adolfsson, H. Synthesis 2006, 11, 1725–1756.
(e) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; VCH Publishers: New York, 2000; pp 357-398. (f) Marko´, I. E.;
Svendsen, J. S. ComprehensiVe Asymmetric Catalysis I-III; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; pp 711-787.
(2) Sharpless, K. B.; Amberg, W.; Youssef, L. B.; Crispino, G. A.; Hartung,
J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang,
X.-L. J. Org. Chem. 1992, 57, 2768–2771.
3038 J. Org. Chem. 2009, 74, 3038–3047
10.1021/jo8026998 CCC: $40.75 2009 American Chemical Society
Published on Web 03/20/2009

Methanesulfonamide in Sharpless Dihydroxylations
of CH3SO2NH2.2 Under certain reaction conditions CH3SO2NH2
can be omitted also with nonterminal olefins. Mehltretter et al.
have reported that by providing the constant high pH value of
12.0, trans-5-decene can be dihydroxylated even faster than in
the presence of CH3SO2NH2.3 We have reported that nonter-
minal olefins react quickly without CH3SO2NH2 if sodium
chlorite (NaClO2) is used as the stoichiometric oxidant.4 NaClO2
oxidizes the osmate(VI) ester to the more reactive osmate(VIII)
ester prior hydrolysis.5 In addition, the pH of the reaction
medium stays at a high level since dihydroxylations with
NaClO2 do not consume any hydroxide ions. Sodium hypochlo-
rite (NaOCl) as the stoichiometric oxidant has provided similar
results.6 So far, there has not been a report to explain why
nonterminal olefins benefit from the addition of CH3SO2NH2
and why terminal olefins do not benefit, nor have there been
any other studies of the details of the CH3SO2NH2 effect in
Sharpless AD except for those mentioned above. Here we
present the first systematic study of the CH3SO2NH2 effect in
Sharpless asymmetric dihydroxylation.
FIGURE 1. t90% values of Sharpless ADs of nonterminal aliphatic
olefins with (b) and t90%M without (0) CH3SO2NH2 versus compu-
tational partition coefficient clog P’s of the intermediate osmate esters.
Our hypothesis for this study was that in an alkaline biphasic
tert-butanol/water solvent system CH3SO2NH2 aids in the
transfer of hydroxide ions from the water phase to the organic
phase. Therefore the accessibility of the osmate ester group in
the intermediate (the species that reacts during the hydrolysis
step) to the water phase is decisive in terms of the reaction time
and CH3SO2NH2 effect. The more polar the intermediate osmate
esters, the more water-soluble they are and the faster the rate-
limiting hydrolysis of the intermediate osmate esters will be.
Also, as the intermediate osmate ester becomes more polar and
thus dissolves better in water, the accelerating effect of
CH3SO2NH2 will be smaller. As a measure of the polarity of
the intermediate osmate ester we used computational octanol/
water partition coefficient clog P.7
FIGURE 2. t90% values of Sharpless ADs of terminal aliphatic olefins
with (O) and t90%M without (9) CH3SO2NH2 versus computational
partition coefficient clog P’s of the intermediate osmate esters.
in reactions without CH3SO2NH2 and t90%M in the presence of
CH3SO2NH2.8 In Figure 1 are presented the t90% and t90%M
of nonterminal aliphatic olefins, and in Figure 2 are the t90%
and t90%M in ADs of terminal aliphatic olefins versus clog P’s
of the intermediate osmate esters. From Figure 1 it is quite
evident that even though the correlation between the t90% time
and clog P is not linear, the polarity and thus the solubility of
the intermediate osmate ester to water is a very significant factor
in the t90% of the AD of nonterminal aliphatic olefins. The
t90% is 1180 min in the AD of trans-5-decene, the compound
that has the least water-soluble osmate ester intermediate (clog
P ) 2.85), almost nine times higher than the t90% of 135 min
in the AD of trans-4-hexen-1-ol, which has the most water-
soluble osmate ester intermediate (clog P ) -0.25). Figure 1
shows that in the presence of CH3SO2NH2 the t90%M in the
AD of nonterminal aliphatic olefins is evened out. The difference
between the shortest and the longest t90% times decreases from
about 1050 to 40 min if CH3SO2NH2 is used. The rate
acceleration by CH3SO2NH2 is most effective with the olefins
that have the least water-soluble intermediate osmate esters. The
t90%M of 105 min in the AD of trans-5-decene is more than
11 times shorter, whereas the t90%M of 140 min in the AD of
trans-4-hexen-1-ol is slightly longer than the corresponding
t90%.
Results and Discussion
A qualitative indication of the hydroxide ion transfer to the
organic phase by CH3SO2NH2 in the AD was obtained by taking
aliquots from the organic tert-butanol phase of the alkaline
biphasic reaction mixture and adding the sample to a phenol-
phthalein indicator solution. The color of the indicator solution
changed from colorless to red only if CH3SO2NH2 was added
to the reaction mixture, indicating the presence of hydroxide
ions in the organic phase. The importance of the hydrogen
bonding ability of the organic solvent to the hydroxide ion
transfer by CH3SO2NH2 was revealed in an experiment where
protic tert-butanol was changed to aprotic tert-butyl methyl
ether. Aliquots from the tert-butyl methyl ether phase of the
alkaline biphasic reaction mixture did not change the color of
the phenolphthalein indicator solution even if CH3SO2NH2 was
added to the reaction mixture, indicating that there were not
hydroxide ions in the organic phase.
The common protocol of Sharpless AD was used in ADs of
several olefins, and t90% was measured for all of those olefins
(3) Mehltretter, G. M.; Do¨bler, C.; Sundmermeier, U.; Beller, M. Tetrahedron
Lett. 2000, 41, 8083–8087.
(4) Junttila, M. H.; Hormi, O. E. O. J. Org. Chem. 2004, 69, 4816–4820.
(5) Junttila, M. H.; Hormi, O. E. O. J. Org. Chem. 2007, 72, 2956–2961.
(6) (a) Mehltretter, G. M.; Bhor, S.; Klawonn, M.; Do¨bler, C.; Sundermeier,
U.; Eckert, M.; Militzer, H.-C.; Beller, M. Synthesis 2003, 2, 295–301. (b)
Sundermeier, U.; Do¨bler, C.; Beller, M. In Modern Oxidation Methods; Ba¨ckvall,
J.-E., Ed.; VCH Publishers: Weinheim, 2004; pp 1-20.
(7) http://www.chemaxon.com/demosite/marvin/index.html (method, weighted;
method weights, VG 1, KLOP 1, PHYS 1, User defined 0; Cl- concentration
(mol/dm3) 0.1; Na+K+ concentration (mol/dm3) 0.1; type log P).
From Figure 1 we draw a conclusion that if CH3SO2NH2 is
not used, the hydrolysis of the intermediate osmate esters takes
place in the water phase, rather than in the interphase of the
(8) Becker, H.; Sharpless, K. B. In Asymmetric Oxidation Reactions; Katsuki,
T., Ed.; Oxford University Press: New York, 2001; pp 81-104.
J. Org. Chem. Vol. 74, No. 8, 2009 3039

Junttila and Hormi
TABLE 1. Results from Sharpless ADs of Olefins with and without CH3SO2NH2
a Computational partition coefficient clog P’s of the intermediate osmate esters. b Enantiomeric excesses were determined by analyzing chiral GC data
(Lipodex E) of the TFA-derivatives of the diols or by analyzing the 1H NMR spectra of the bisMosher ester of the diol. c Configuration of the major
enantiomer was determined by comparing the optical rotation to literature values. d Enantiomeric excess was determined by comparing the optical
rotation to literature values. e Crude yield; we were not able to purify the product. f Reactions were performed at 0 °C. g 0.5 mmol of olefin.
water and organic phases. The most evident result in Figure 1
in favor of the hydrolysis taking place in the water phase is
that the smaller the clog P value is, i.e., the greater the amount
of intermediate osmate ester in the water phase, the faster the
AD. If the hydrolysis of the intermediate osmate ester took place
in the interphase, one could expect that the sterically more
hindered and, due to alkyl groups, more electron-rich trisub-
stituted olefins such as 1-methylcyclohexene and 2-methylhept-
2-ene would react more slowly than the sterically less hindered
and more electron-poor disubstituted trans-5-decene. Yet there
is a significant difference in t90% in favor of the trisubstituted
olefins. Also, if the hydrolysis of the intermediate osmate ester
took place in the interphase, it would be difficult to see why
disubstituted nonterminal olefins presented in Figure 1 would
react so differently in the presence of methanesulfonamide.
CH3SO2NH2 accelerates significantly the AD of disubstituted
trans-5-decene and decelerates slightly the AD of disubstituted
trans-4-hexen-1-ol. In fact, all of these observations support our
hypothesis that the accessibility of the osmate ester intermediate
to the water phase is decisive in terms of the reaction time and
also that the CH3SO2NH2 is aiding in the transfer of hydroxide
ions to the organic phase.
From Figure 2 one can see that in the case of terminal
aliphatic olefins there is no similar correlation between the t90%
3040 J. Org. Chem. Vol. 74, No. 8, 2009

Methanesulfonamide in Sharpless Dihydroxylations
SCHEME 1. Schematic Presentation of the Hydrolysis of
Intermediate Osmate Esters of trans-5-Decene and 1-Decene
with and without CH3SO2NH2
In addition to the different t90% values in the AD without
CH3SO2NH2, the CH3SO2NH2 effect on the t90%M in Sharpless
AD of trans-5-decene and 1-decene is different: in the presence
of CH3SO2NH2 the t90%M of 105 min in the AD of trans-5-
decene is about 1/11 of the t90% of 1180 min in the AD of
trans-5-decene without CH3SO2NH2, and the t90%M of 145 min
in the AD of 1-decene is almost two times longer than the t90%
of 75 min in the AD of 1-decene without CH3SO2NH2 (Table
1). CH3SO2NH2 accelerates considerably the AD of trans-5-
decene and decelerates the corresponding reaction of 1-decene.
In Scheme 1 is presented a rationalization for their different
behavior in Sharpless AD without CH3SO2NH2 and in the
presence of CH3SO2NH2. If CH3SO2NH2 is not used, the
hydroxide ions required in the hydrolysis step are in the water
phase, into which the nonterminal osmate ester can not enter
as easily as the terminal osmate ester in 1-decene. If
CH3SO2NH2 is used, then hydroxide ions resides in both the
water and the organic phase and therefore the rate-limiting
hydrolysis step can occur quickly regardless of the position of
the osmate ester group. Hydroxide ions, attached to the
CH3SO2NH2, are less nucleophilic than the free hydroxide ions.
A consequence of the decrease in nucleophilicity of the
hydroxide ion in the presence of CH3SO2NH2 is the slight
increase in t90% in the AD of 1-decene and other aliphatic
olefins that react quickly without CH3SO2NH2.
in ADs without CH3SO2NH2 and clog P’s of the intermediate
osmate esters, as there is with the nonterminal aliphatic olefins.
Quite surprisingly the major difference in reaction times in the
AD of terminal olefins is due to the elongation of the carbon
chain. There is a significant change in reaction time after the
carbon chain is longer than 13 carbons. The t90% in the AD of
1-hexadecene is more than six times longer than the t90% in
the AD of other terminal aliphatic olefins except for 1-tet-
radecene (Table 1). As it was with the nonterminal aliphatic
olefins, CH3SO2NH2 evens out the reaction times in the AD of
terminal aliphatic olefins. The difference between the t90% in
the AD of 1-hexadecene and 2-methylheptene decreases from
630 to 45 min if CH3SO2NH2 is used (Table 1). Again, the most
significant CH3SO2NH2 rate-accelerating effect is with the
olefins that are slowest to react in the AD without CH3SO2NH2,
and also the addition of CH3SO2NH2 has no significant
accelerating effect or retards slightly the reaction times in the
AD of those terminal aliphatic olefins that react quickly without
CH3SO2NH2.
1-Hexadecene is a terminal olefin, yet the CH3SO2NH2 effect
in the AD of 1-hexadecene resembles more the CH3SO2NH2
effect in the AD of nonterminal olefins than the CH3SO2NH2
effect in the AD of other terminal olefins (Figure 2). The t90%
of 685 min in the AD of 1-hexadecene without CH3SO2NH2
and the CH3SO2NH2 effect (t90%/t90%M ) 6.23) are similar
to those of ADs of nonterminal olefins such as trans-5-decene.
We believe that there are two factors that prevent the terminal
osmate ester group in 1-hexadecene and other long chain
terminal olefins to react in a similar manner as other terminal
olefins: (1) as the size of the molecule increases, the probability
that the molecule, originally in the organic phase, approaches
the water phase in a way that the hydrophilic osmate ester group
can enter the water phase becomes smaller, and (2) as the size
of the hydrophobic part of the molecule increases, the time that
the osmate ester group spends in the water phase, if it gets there,
becomes shorter than the time required for the hydrolysis to
take place. The hydrophilicity of the terminal osmate ester group
is the same in the osmate esters of 1-hexadecene 1 and 1-decene
2, but there is a significant difference in the hydrophobicity of
the water-insoluble part of the molecule: clog P’s are 6.05 and
3.67, respectively. The more hydrophobic the water-insoluble
part of the terminal olefin, the stronger it pulls the osmate ester
group from the water phase into the organic phase. We think
that there is a certain limit, after which the hydrophobic part of
the molecule starts to increase the reaction time by decreasing
the time that the osmate ester group spends in the water phase,
so that there is not enough time for hydrolysis to take place. In
the case of terminal straight chain olefins, that limit seems to
be clogP > 5.2 (n-C12H28) for the hydrophobic part of the
molecule.
Osmate esters of trans-5-decene and 1-decene have almost
the same clog P’s (2.85 and 2.76, respectively), but their t90%
values in Sharpless AD without CH3SO2NH2 differ significantly
(1200 and 75 min). In Scheme 1 is presented the major
difference in the hydrolysis step in Sharpless ADs of terminal
and nonterminal aliphatic olefins. The osmate ester group is
highly hydrophilic: clog P of the osmate ester of ethylene is
-0.50. In aliphatic terminal olefins, the osmate ester end of the
chain is extremely hydrophilic and in the biphasic reaction
conditions can easily enter the water phase. So, the hydrolysis
of the terminal osmate ester group in 1-decene takes place
quickly in alkaline water phase as presented in Scheme 1. In
nonterminal olefins the hydrophilic osmate ester group is
between hydrophobic groups, which diminishes the accessibility
of the osmate ester group to the water phase. Therefore the t90%
is much longer in the AD of nonterminal trans-5-decene.
Nonterminal olefins can also react quickly without CH3SO2NH2
if the whole molecule is hydrophilic and has easy access to the
water phase, as is the case in the AD of trans-4-hexen-1-ol (clog
P ) -0.25 for the intermediate osmate ester).
Ethyl-trans-2-octenoate 3 is a nonterminal olefin, yet its t90%
in Sharpless AD without CH3SO2NH2 does not fit the curve
presented in Figure 1. The clog P of 1.68 of the osmate ester
of ethyl-trans-2-octenoate is almost the same as the clog P of
1.67 for the osmate ester of 2-methylhept-2-ene 4, yet the t90%
of 110 min in the AD of ethyl-trans-2-octenoate is almost five
J. Org. Chem. Vol. 74, No. 8, 2009 3041

Junttila and Hormi
times shorter than the t90% of 530 min in the AD of
2-methylhept-2-ene. The t90% in the AD of ethyl-trans-2-
octenoate is even shorter than the t90% of 135 min in the AD
of trans-4-hexen-1-ol 5 (clog P ) -0.25). Also the CH3SO2NH2
effect is different in the AD of ethyl-trans-2-octenoate than it
is in the AD of 2-methylhept-2-ene: CH3SO2NH2 has no effect
on the t90% in the AD of ethyl-trans-2-octenoate, whereas in
the AD of 2-methylhept-2-ene the t90%M is one-fourth of the
t90%. It seems that ethyl-trans-2-octenoate reacts almost as if
it is a terminal olefin. In the osmate ester of ethyl-trans-2-
octenoate 6, despite the ethyl group, the osmate ester and ester
groups form an almost as highly hydrophilic end (clog P )
-0.39) to the molecule as there is in terminal osmate esters 1
and 2 (clog P ) -0.50). Hydrophilicity of the osmate ester of
trans-4-hexen-1-ol 7 is smaller (clog P ) -0.26), and therefore
a slightly slower AD occurs with trans-4-hexen-1-ol.
FIGURE 3. Computational partition coefficient clog P’s of the
intermediate osmate esters of conjugated aromatic olefins versus t90%/
t90%M of the Sharpless ADs of corresponding olefins.
completely different effect in the AD of 2-methylhept-2-ene than
it has in the AD of 2-methylheptene. The t90%M of 135 min in
the AD of 2-methylhept-2-ene in the presence CH3SO2NH2 is
one-fourth the t90% of 530 min in the AD without CH3SO2NH2,
and the t90%M of 65 min in the AD of 2-methylheptene with
CH3SO2NH2 is slightly higher than the corresponding t90% of
55 min without CH3SO2NH2. In other words, CH3SO2NH2
accelerates significantly the AD of nonterminal 2-methylhept-
2-ene and decelerates slightly the AD of terminal 2-methyl-
heptene. It is difficult, if not even impossible, to see why steric
crowding or electronic effects would have such a different effect
in the t90% and t90%M values of 2-methylhept-2-ene and
2-methylheptene. What has already been said about the acces-
sibility of the osmate ester group in the intermediate to the water
phase applies also here. As a result of easier accessibility of
the osmate ester group to water phase, the rate-determining
hydrolysis of the intermediate osmate ester occurs more quickly
if the osmate ester group is in the terminal position, as it is in
2-methylheptene. Hydroxide ion attached to CH3SO2NH2, being
a weaker nucleophile than free hydroxide ion, accelerates the
Sharpless AD of aliphatic olefins if the osmate ester group in
the intermediate is predominantly in the organic phase, as it is
in the case of AD of the nonterminal 2-methylhept-2-ene.
Our hypothesis of the CH3SO2NH2 effect in Sharpless AD
applied well with ADs of aliphatic olefins. ADs of conjugated
aromatic olefins seem not to be as straightforward as ADs of
aliphatic olefins. In Figure 3 are presented the results from the
ADs of conjugated aromatic olefins. The x-axis is the compu-
tational partition coefficient clog P of the intermediate osmate
esters, and the y-axis is the t90% in ADs without CH3SO2NH2
divided by the t90%M in ADs with CH3SO2NH2. If t90%/t90%M
> 1, then CH3SO2NH2 accelerates the AD of that particular
olefin, and if t90%/t90%M < 1, then CH3SO2NH2 decelerates
the AD. From Figure 3, one can see clearly that the polarity of
the intermediate osmate ester is not a factor that determines the
effect that CH3SO2NH2 has on the reaction times in ADs of
conjugated aromatic olefins, as in ADs of nonterminal aliphatic
olefins. In our series of conjugated aromatic olefins, the ADs
of olefins that have the most and the least polar intermediate
osmate esters benefit from the addition of CH3SO2NH2. In
between those two olefins, there is a series of both terminal
and nonterminal conjugated aromatic olefins for which
CH3SO2NH2 has a decelerating effect on their t90% in ADs. It
seems that polarity of the intermediate osmate ester can be used
to predict the reaction time and CH3SO2NH2 effect in Sharpless
AD of conjugated aromatic olefins only if the molecules are
alike, such as the ethyl ester and octyl ester of cinnamic acid.
The pair of 2-methylhept-2-ene 4 and 2-methylheptene 8 gives
an excellent example of the importance the position of the
double bond in olefin to the reaction time in Sharpless AD. In
the absence of CH3SO2NH2, the t90% of 55 min in the AD of
terminal 2-methylheptene is almost 1/10 the t90% of 530 min
in the AD of nonterminal 2-methylhept-2-ene. One could say
that the difference in t90% can be attributed to the larger steric
crowding in the osmate ester of nonterminal 2-methylhept-2-
ene than in the osmate ester of terminal 2-methylheptene or
that the osmate ester of 2-methylhept-2-ene is less electrophilic
because there are more electron-donating alkyl groups than there
are in 2-methylheptene. We think that steric crowding and
electronic effects due to alkyl groups have only minor effect in
the t90% in the AD of 2-methylhept-2-ene and 2-methylheptene.
The steric crowding or the electronic effects are not changed if
hydrolysis aid CH3SO2NH2 is used, yet the CH3SO2NH2 has a
3042 J. Org. Chem. Vol. 74, No. 8, 2009

Methanesulfonamide in Sharpless Dihydroxylations
The intermediate osmate ester of the octyl ester of cinnamic
acid (clog P ) 3.91) is less polar than the corresponding
intermediate of the ethyl ester of cinnamic acid (clog P ) 1.46),
which correlates with a longer reaction time and stronger
CH3SO2NH2 effect as it does also with nonterminal aliphatic
olefins.
chloride 12 is not. The same interaction plays a vital role in
Sharpless asymmetric epoxidation of allylic alcohols.9 The
intramolecular electron donation effect can be seen in the t90%
values in the AD of cinnamyl alcohol and ethyl ester of cinnamic
acid without CH3SO2NH2. The t90% of 295 min in the AD of
cinnamyl alcohol and the t90% of 200 min in the AD of ethyl
ester of cinnamic acid are more than twice the t90% of 95 min
in the AD of cinnamyl chloride, even though their osmate ester
intermediates are more polar.
Another striking difference in ADs of conjugated aromatic
olefins compared to aliphatic olefins is that CH3SO2NH2 does
not necessarily accelerate the ADs of those olefins that are the
slowest to react in the absence of CH3SO2NH2. For instance,
the osmate ester intermediate of indene is one of the highest
polarity in our series of conjugated aromatic olefins, yet its t90%
) 550 min in the AD without CH3SO2NH2 is the second longest,
and in the presence of CH3SO2NH2, its t90%M ) 630 min is
the longest. Another difference in the AD of conjugated aromatic
olefins compared to AD of aliphatic olefins is that CH3SO2NH2
does not even out the t90% values in the AD of conjugated
aromatic olefins as much as it does in the AD of aliphatic olefins.
The difference in t90% and t90%M values between the fastest
and the slowest ADs of conjugated aliphatic olefins without
CH3SO2NH2 is 1090 min and with CH3SO2NH2 540 min. The
corresponding differences in t90% and t90%M values in ADs
of aliphatic olefins are 1125 and 80 min.
Interestingly, our results seem to show that CH3SO2NH2 has
an accelerating effect in ADs of aromatic conjugated olefins
only if there is an electron-withdrawing group, such as a hydroxy
or an ester group, attached to the carbon next to the double
bond and to a lesser extent if there is a halogen attached to the
carbon next to the double bond (Figure 3). A plausible
rationalization for the observed phenomenon is that the osm-
ate esters of unfunctionalized conjugated aromatic olefins are
less electrophilic than the corresponding esters of functionalized
olefins. Aromatic group(s) and alkyl group(s) donate electron
density toward the osmate ester group and thus make it less
reactive toward nucleophiles, and if the hydroxide ion nucleo-
phile is weakened by the interaction with CH3SO2NH2, the
reaction is even slower. Regardless of the polarity of the
intermediate osmate ester or the substitution pattern of the olefin,
in our study CH3SO2NH2 decelerated the ADs of all unfunc-
tionalized conjugated aromatic olefins starting from indene,
which has the most polar intermediate, to trans-stilbene, which
has the least polar intermediate. However, if there is an allylic
electron-withdrawing group in the olefin, such as chlorine, the
electrophilicity of the osmate ester group is increased and
CH3SO2NH2 does not decelerate the AD of that olefin, as is the
case for instance in the AD of cinnamyl chloride. Unfortunately,
as convincing as this explanation may appear, it does not stand
a more detailed analysis of the results.
Why is it then that hydroxide ion attached to CH3SO2NH2,
being less nucleophilic than free hydroxide ion, seems to
accelerate more the hydrolysis of more electron-rich and thus
less nucleophilic osmate esters? A plausible explanation is that
the hydrolysis pathway is different in the AD of conjugated
aromatic olefins that have electron-rich osmate ester intermedi-
ates. In Scheme 2 is presented two possible reaction pathways:
(A) general acid-catalyzed and (B) nucleophilic attack of
hydroxide ion pathway. CH3SO2NH2 is a weak acid (pKa )
10.8) and thus capable of protonating the electron-rich inter-
mediate osmate ester in the rate-limiting hydrolysis step as
presented in Scheme 2.10 AD of the ethyl ester of cinnamic
acid and, to our surprise, also AD of trans-methyl styrene in
the presence of CH3SO2NH2 were found to follow pseudo-zero-
order kinetics with respect to the olefin as presented in Figure
4. Aliphatic 1-decene, trans-5-decene, and 2-methylhept-2-ene
followed pseudo-first-order kinetics with respect to the olefin
in the presence of CH3SO2NH2 (Figure 5). Clearly, in the
presence of CH3SO2NH2, the mechanism of the hydrolysis step
in the AD of conjugated aromatic olefins is different from the
mechanism of hydrolysis step in the AD of aliphatic olefins.
Usually zero-order kinetics is associated with catalytic reactions
where catalyst is saturated with the substrate. In AD of conjugate
aromatic olefins the pseudo-zero-order kinetics is due to the
osmate ester intermediate being saturated with the proton-
donating catalyst CH3SO2NH2. At pH 10.8 the concentration
of the intermediate osmate ester is less than 1/100 the
concentration of CH3SO2NH2. Experiments performed at el-
evated alkaline conditions support the proposed general acid-
catalyzed reaction mechanism. When the pH of the reaction
mixture was elevated from 10.7 to 11.9 and maintained there
during the reaction with 12 M NaOH, the ADs of the ethyl
The electron-withdrawing nature of the alcohol, ester, and
halogen groups cannot account for all of results that we see in
Figure 3 and Table 1, for instance, why, whether the
CH3SO2NH2 is used or not, cinnamyl alcohol and the ethyl ester
of cinnamic acid react more slowly in ADs than cinnamyl
chloride does and why the CH3SO2NH2 effect is more significant
in ADs of cinnamyl alcohol and ethyl ester of cinnamic acid
than it is in the AD of cinnamyl chloride, even though their
intermediate osmate esters are more polar than the intermediate
osmate ester of the cinnamyl chloride. Allylic alcohol in
cinnamyl alcohol 9 and allylic ester groups in esters of cinnamic
acid 10 and 11 are capable of donating electron density
intramolecularly toward the electron-poor osmium center in the
osmate ester intermediate, whereas the halogen in cinnamyl
(9) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric Synthesis, 2nd
ed.; Ojima, I., Ed.; VCH Publishers: New York, 2000; pp 231-280.
(10) Trepka, R. D.; Harrington, J. K.; Belisle, J. W. J. Org. Chem. 1974, 39,
1094–1098.
J. Org. Chem. Vol. 74, No. 8, 2009 3043

Junttila and Hormi
SCHEME 2. Two Proposed Reaction Pathways of the
Hydrolysis Step in Sharpless AD in the Presence of
CH3SO2NH2
FIGURE 5. Pseudo-first-order fittings of asymmetric dihydroxylations
of (0) 1-decene, (∆) 2-methylhept-2-ene, and (b) trans-5-decene.
SCHEME 3. Resonance Structures of the
Methanesulfonamide-Hydroxide Ion Pair
of the intermediate osmate ester. In the so-called secondary
cycle, a second olefin reacts with the intermediate osmate ester
without enantioselection.1e The slower the hydrolysis of the
intermediate osmate ester, the more olefins react through the
secondary cycle. In Table 1 are presented the enantioselectivities
of our ADs with and without CH3SO2NH2. In our series of
olefins it is always so that CH3SO2NH2 improves enantioselec-
tivity if it accelerates the AD and decreases enantioselectivity
if it decelerates the AD. The differences in enantioselectivities
between ADs with and without CH3SO2NH2, even though the
rate acceleration can be quite significant, are only small, varying
from 0 to 4 percentage units. The small differences are due to
the fact that the secondary cycle is slow in ADs if potassium
ferricyanide is used as the stoichiometric oxidant.1e
The indirect evidence from the different ADs and the actual
finding of hydroxide ions in the organic tert-butanol phase if
CH3SO2NH2 is present have conclusively shown that CH3-
SO2NH2 is a cosolvent that aids in the solvation of hydroxide
ions to the organic tert-butanol phase. Consequently, there has
to be such an interaction between the hydroxide ion and
CH3SO2NH2 that delocalizes sufficiently the negative charge
on the hydroxide ion. The most obvious such intermolecular
interaction would be hydrogen bonding, but since the tert-
butanol is also capable of forming hydrogen bonds with
hydroxide ions, hydrogen bonding cannot account for the
interaction that explains the CH3SO2NH2 effect in Sharpless ADs
of aliphatic olefins. In Scheme 3 is presented our proposal of
the more efficient delocalization of the negative charge on
hydroxide ion. In our proposal CH3SO2NH2 and the hydroxide
ion form a resonance-stabilized six-membered ring intermediate.
The structure presented in Scheme 3 is held together by both
hydrogen bonding and resonance. In this structure the negative
charge is delocalized so that a protic solvent such as tert-butanol
can solvate it.
ester of cinnamic acid and trans-methyl styrene were almost
two times slower than the ADs performed at lower pH. At
elevated alkaline conditions CH3SO2NH2 is in ionized form and
therefore not capable of donating a proton to the intermediate
osmate ester. It is known from the literature that at elevated
alkaline conditions the AD of aliphatic trans-5-decene is faster
than at lower pH and CH3SO2NH2 can even be omitted if highly
alkaline conditions are maintained during the reaction.3
Enantioselectivity of the Sharpless AD depends partly on the
reaction rate, which is usually the same as the hydrolysis rate
There are actually two nucleophilic sites in the structure
presented in Scheme 3 (shown by arrows). If nucleophilicities
of the hydroxide ion and deprotonated methanesulfonamide are
FIGURE 4. Pseudo-zero-order fittings of asymmetric dihydroxylations
of (() trans-methyl styrene and (0) ethyl ester of cinnamic acid.
3044 J. Org. Chem. Vol. 74, No. 8, 2009

Methanesulfonamide in Sharpless Dihydroxylations
TABLE 2. Results from Sharpless ADs of trans-5-Decene and the
Ethyl Ester of Cinnamic Acid in the Presence of Different Additives
estimated by their pKaH values (15.7 and 10.8, respectively) it
is obvious that hydroxide ion is more nucleophilic, but in a
structure presented in Scheme 3 one can not deduce the reactive
site on the basis of pKaH values. Decisive in terms of the reactive
nucleophilic site is the location of the negative charge and
availability of the free electron pair that forms the bond to the
electrophilic osmium in osmate ester. The free electron pair on
the amide nitrogen is shielded by the neighboring methyl group,
double-bonded oxygen and its free electron pairs, and the
hydrogen attached to the nitrogen. All of these shielding effects
are missing in the two free electron pairs on hydroxide ion
oxygen.
The structure presented in Scheme 3 explains not only the
solvation of hydroxide ions in tert-butanol but also the different
effects CH3SO2NH2 has on the reaction times in Sharpless AD
of structurally diverse olefins. There is a water-like substructure
in the structure presented in Scheme 3. The water-like sub-
structure, which is less nucleophilic than hydroxide ion but more
nucleophilic than a water molecule, reacts as a nucleophile in
the rate-limiting hydrolysis of the aliphatic intermediate osmate
esters. If the osmate ester group in the intermediate has easy
access to the water phase, then in the presence of CH3SO2NH2
the overall reaction is usually slower because the reactive
nucleophile is weaker than the free hydroxide ion. If the osmate
ester in the intermediate has no easy access to the water phase,
CH3SO2NH2 accelerates the reaction by providing the organic
phase with a nucleophile, albeit a weaker one than a naked
hydroxide ion.
If the structure presented in Scheme 3 exists, one would
expect to see differences in the chemical shifts of nitrogen in
CH3SO2NH2 acidic and in alkaline conditions. Bagno et al. have
reported a small +8 ppm shift in the 14N signal of CH3SO2NH2
when conditions were changed from 0.1 M HCl to 1 M NaOH.11
Kricheldorf has reported a similar +11 ppm shift in the 15N
signal of CH3SO2NH2 when the pH of the media was changed
from 1.0 to 12.3.12 One could argue that the deshielding of the
nitrogen nucleus in alkaline conditions is due to the double bond
formation between nitrogen and sulfur. Results from the NMR
experiments do not explicitly confirm the structure presented
in Scheme 3 but do not rule it out either. Results from the NMR
studies are in favor of some resonance taking place in
CH3SO2NH2 in alkaline conditions.
a With no additive t90% ) 1180 min. b With no additive t90% ) 200
min. c CH3(CH2)15N(CH3)3Br.
therefore the AD of the ethyl ester of cinnamic acid is slower
in the presence of N-methyl methanesulfonamide than in the
presence of methanesulfonamide. In fact, in the presence of
N-methyl methanesulfonamide, the AD of ethyl ester of cin-
namic acid is even slower than with no additives. Interaction
between the hydroxide ion and N-methyl methanesulfonamide
decreases the nucleophilicity of hydroxide ion compared to
naked hydroxide ion so that even if the hydrolysis of osmate
ester intermediate is not acid-catalyzed, the hydrolysis by
nucleophilic attack of hydroxide ion to the osmate ester
intermediate is slower in the presence of N-methyl methane-
sulfonamide than without.
We were interested in to know if Sharpless ADs in the
presence of other sulfonamides would support our results, and
conclusions presented. In Table 2 are presented the t90%M of
ADs of trans-5-decene and the ethyl ester of cinnamic acid in
the presence of methanesulfonamide, N-methyl methanesulfona-
mide, N,N-dimethyl methanesulfonamide, and butanesulfona-
mide. Even though N-methyl methanesulfonamide is capable
of forming a similar structure as presented for methanesulfona-
mide in Scheme 3, N-methyl methanesulfonamide does not
accelerate the AD of trans-5-decene nearly as efficiently as
methanesulfonamide. Compared with methanesulfonamide the
electron-donating methyl group in N-methyl methanesulfona-
mide destabilizes the resonance stabilization shown in Scheme
3. The charge distribution of hydroxide ion is not as efficient
in the presence of N-methyl methanesulfonamide as it is in the
presence of methanesulfonamide, which leads to poorer solubil-
ity of hydroxide ions in the organic phase. N-Methyl methane-
sulfonamide is a weaker acid than methanesulfonamide, and
N,N-Dimethyl methanesulfonamide does not have amide
protons, so it is not capable of forming the structure presented
in Scheme 3. As expected, N,N-dimethyl methanesulfonamide
does not accelerate the AD of trans-5-decene (Table 2). Also,
as a result of the lack of an acidic proton, N,N-dimethyl
methanesulfonamide does not accelerate the AD of the ethyl
ester of cinnamic acid. However, there is interaction between
hydroxide ion and N,N-dimethyl methanesulfonamide because
reaction times are longer in the presence of N,N-dimethyl
methanesulfonamide than with no additive.
Butanesulfonamide (clog P ) -0.06) is less hydrophilic than
methanesulfonamide (clog P ) -1.54), but contrary to what
one might expect, butanesulfonamide is not as efficient in
transferring hydroxide ions to the organic phase as is methane-
sulfonamide (Table 2). Reaction time in the AD of trans-5-
decene is almost four times longer in the presence of butane-
sulfonamide than in the presence of methanesulfonamide;
probably a smaller amount of cosolvent in the water layer
increases reaction time. The most surprising result was the huge
increase in reaction time in the AD of the ethyl ester of cinnamic
(11) Bagno, A.; Comuzzi, C. Eur. J. Org. Chem. 1999, 287–295.
(12) Kricheldorf, H. R. Angew. Chem. 1978, 6, 489–490.
J. Org. Chem. Vol. 74, No. 8, 2009 3045

Junttila and Hormi
SCHEME 4. Hydrolysis of the Osmate Ester via Os-Amide
Intermediate
phase. We have already shown that hydroxide ions can be found
in the organic phase if methanesulfonamide is added to the
reaction mixture. As a charge neutral compound methane-
sulfonamide dissolves in organic phase but it is significantly
poorer nucleophile than deprotonated methanesulfonamide and
also poorer nucleophile than hydroxide ion even if hydroxide
ion is attached to methanesulfonamide. In fact, if nucleophilicity
is estimated by their pKaH values methanesulfonamide is poorer
nucleophile than water.15 If we estimate nucleophilicity of the
hydroxide ion and nucleophilicity of the deprotonated meth-
anesulfonamide from their pKaH values (15.7 and 10.8 cor-
respondingly), we can assume that the nucleophilicity of the
hydroxide ion attached to methanesulfonamide and nucleophi-
licity of the deprotonated methanesulfonamide are probably quite
similar. Even though deprotonated methanesulfonamide can
delocalize its charge via resonance, it is highly hydrophilic (clog
P ) -2.48) and does not dissolve in organic phase easily.
Delocalization of the negative charge on deprotonated meth-
anesulfonamide can take place in a similar way as presented in
Scheme 3. Instead of hydroxide ion, deprotonated methane-
sulfonamide forms a resonance stabilized pair with water
molecule, which is an identical structure as presented for
methanesulfonamide-hydroxide ion pair in Scheme 3. Even
though the acceleration of hydrolysis step in Sharpless AD can
in principle take place via Os-amide intermediate if deprotonated
methanesulfonamide acts as a nucleophile, we think that the
most plausible explanation for the rate acceleration is the
cosolvent effect of the methanesulfonamide.
acid in the presence of butanesulfonamide. With butanesulfona-
mide reaction time was more than three times longer than the
reaction time with no additives and more than five times longer
than the reaction time with methanesulfonamide. The AD of
ethyl ester of cinnamic acid in the presence of butanesulfona-
mide followed pseudo-zero-order kinetics with respect to olefin.
Therefore we believe that reaction is general acid-catalyzed as
is the AD of ethyl ester of cinnamic acid in the presence of
methanesulfonamide. Acid strengths of butanesulfonamide and
methanesulfonamide are the same, so the difference in reaction
times rises probably from the different hydrophilicities of the
additives. It seems that in biphasic reaction conditions butane-
sulfonamide and the intermediate osmate ester do not meet
efficiently enough so that a fast reaction is obtained.
Conclusions
Branco et al. have reported recently Sharpless AD in the
presence of different surfactants.13 In Table 2 are presented
results from our experiments with N-cetyl-N,N,N-trimethylam-
moniumbromid surfactant. Reaction time in the AD of aliphatic
trans-5-decene is significantly decreased by adding surfactant
into the reaction mixture. Still surfactant is not nearly as efficient
as a rate-accelerating additive in the AD as is methanesulfona-
mide. Reaction time is more than 2.5 times longer in the
presence of surfactant than it is in the presence of methane-
sulfonamide. Either the nucleophilicity of the hydroxide ion is
reduced more if surfactant is used or surfactant does not assist
the transfer of hydroxide ions to organic phase as effectively
as methanesulfonamide does. Surfactant had no effect in reaction
time in the AD of ethyl ester of cinnamic acid. In the AD of
more hydrophobic octyl ester of cinnamic acid surfactant did
not show any better results since the t90%/t90%M was 1.13.
Under the alkaline reaction conditions used in Sharpless AD,
there is in addition to hydroxide ions other nucleophiles present.
One could argue that the rate acceleration is due to that
methanesulfonamide or deprotonated methanesulfonamide reacts
as a nucleophile toward the osmium center in the intermediate
osmate ester prior hydrolysis as presented in Scheme 4. Similar
reaction takes place in Sharpless asymmetric aminohydroxyla-
tion between N-halogenated sulfonamides and the azaglycolates
prior hydrolysis.14 Due to the increased polarity the supposed
Os-amide intermediate migrates into the water phase and a faster
hydrolysis would occur. Which one of the nucleophiles reacts
with the osmate ester depends on the nucleophilicity of the
species and which one of the species can be found in the organic
The CH3SO2NH2 effect in Sharpless AD was found in our
study to be two different effects: a general acid-catalyzed
hydrolysis and a cosolvent of hydroxide ion. Electron-rich
osmate ester intermediates of conjugate aromatic olefins are
protonated by acidic CH3SO2NH2 in the hydrolysis step.
CH3SO2NH2 accelerates the AD of aliphatic olefins by aiding
in the transfer of nucleophilic hydroxide ions to the organic
phase. A simple rule to divide olefins to terminal and nonter-
minal, when one considers whether to add CH3SO2NH2 to
accelerate the Sharpless AD, was in our study founded not to
be valid. There were ADs of both terminal and nonterminal
olefins that benefited from the addition of CH3SO2NH2. There
were also ADs of both terminal and nonterminal olefins that, if
CH3SO2NH2 had any effect on their reaction times, were
decelerated if CH3SO2NH2 was added to the reaction mixture.
The accessibility of the osmate ester group in the intermediate
osmate ester to the water phase was the most significant factor
in the reaction time in the AD of aliphatic olefins and also in
the CH3SO2NH2 effect. Sharpless ADs of conjugated aromatic
olefins was not as straightforward as for aliphatic olefins. If one
wants to play safe, one can use CH3SO2NH2 in every Sharpless
AD since the decelerating effect of CH3SO2NH2 in most cases
is not very significant.
Experimental Section
General Procedure for the Determination of the t90% and
t90%M Times. A 50 mL three-necked flask was equipped with a
magnetic stirring bar, pH electrode, and thermometer. The flask
(13) Branco, L. C.; Ferreira, F C.; Santos, J. L.; Crespo, J. G.; Afonso,
C. A. M. AdV. Synth. Catal. 2008, 350, 2086–2098.
(14) Bodkin, J. A.; McLeod, M. D. J. Chem. Soc., Perkin Trans. 1 2002,
2733–2746.
(15) The pKaH of N-methylmethanesulfonamide is-6.0, and the pKaH of N,N-
dimethylmethanesulfonamide is-5.5. Laughlin, R. G. J. Am. Chem. Soc. 1967,
89, 4268–4271. The pKaH of water is-1.7.
3046 J. Org. Chem. Vol. 74, No. 8, 2009

Methanesulfonamide in Sharpless Dihydroxylations
was charged with 1 mmol of olefin, 7.7 mg (0.1 mmol, 1 mol%)
of ligand (DHQD)2PHAL, 0.414 g (3 mmol) of K2CO3 and 0.990
g (3 mmol) of K3[Fe(CN)6]. If CH3SO2NH2 was used, the amount
was 95 mg (1 mmol). Reagents were dissolved in 10 mL of t-BuOH/
H2O (1:1) mixture. The reactions were initiated by adding 1.5 mg
(0.04 mmol, 0.4 mol%) of K2OsO4 ·2H2O. The reactions were
performed at room temperature. The reactions were followed by
monitoring the consumption of olefin. Aliquots of 20 µL were
withdrawn from the reaction mixture after periods of time. The
reaction was quenched by diluting the sample with a mixture
containing 20 µL of a 60 mM solution of Na2SO3 and 100 µL of
0.02 M 1-phenylethanol (standard) in EtOAc. The sample was dried
with Na2SO4 prior to analysis with GC. After all olefin had been
consumed, 0.8 g (6.3 mmol) of Na2SO3 was added, and the reaction
mixture was stirred for 30 min. The reaction mixture was extracted
in 50 mL separating funnel with 3 × 5 mL of EtOAc. If
CH3SO2NH2 was used, the combined organic layers were extracted
with 5 mL of 2 M NaOH. The combined organic layers were dried
with Na2SO4 and filtered, and the solvent was removed on a rotary
evaporator. The crude products were purified by flash chromatog-
raphy using EtOAc/n-hexane or EtOAc/MeOH as the eluent.
Reaction Order. The general AD procedure was used with minor
change in the reactions where reaction order was determined: pH
of the reaction medium was kept constant by adding 12 M NaOH
via syringe during the reaction and in high pH reaction elevated
with 12 M NaOH and kept constant by adding 12 M NaOH via
syringe during the reaction.
1.45 (m, 3H), 1.19 (m, 1H), 0.96 (d, J ) 6.2 Hz, 3H); HRMS m/z
found 157.0848, calcd 157.0841 (C6H14O3Na).
1
Decane-5,6-diol. H NMR (200 MHz, CDCl3) δ 3.42 (m, 2H),
2.00 (d, J ) 4.5 Hz, 2H), 1.42 (m, 12H), 0.92 (t, J ) 6.5 Hz, 6H);
HRMS m/z found 197.1523, calcd 197.1517 (C10H22O2Na).
Ethyl 2,3-dihydroxyoctanoate. 1H NMR (200 MHz, CDCl3) δ
4.30 (q, J ) 7.3 Hz, 2H), 4.09 (m, 1H), 3.89 (q, J ) 6.9 Hz, 1H),
3.05 (d, J ) 5.0 Hz, 1H), 1.87 (d, J ) 9.1 Hz, 1H), 1.58 (br, 3H),
1.41 (br, 5H) 1.33 (t, J ) 7.1 Hz, 3H), 0.90 (t, J ) 6.3 Hz, 3H);
HRMS m/z found 227.1268, calcd 227.1259 (C10H20O4Na).
1
Indane-1,2-diol. H NMR (200 MHz, CDCl3) δ 7.44 (m, 1H),
7.29 (m, 3H), 5.03 (dd, J ) 5.1, 7.4 Hz), 4.54 (m, 1H), 3.15 (dd,
J ) 5.7, 16.4 Hz, 1H), 2.97 (dd, J ) 3.7, 16.3 Hz, 1H), 2.43 (d, J
) 7.4, 1H), 2.36 (d, J ) 6.1 Hz, 1H); HRMS m/z found 173.0576,
calcd 173.0578 (C9H10O2Na).
1
1-Phenylethane-1,2-diol. H NMR (200 MHz, CDCl3) δ 7.37
(m, 5H), 4.85 (dt, J ) 3.6, 7.9 Hz, 1H), 3.73 (m, 2H), 2.49 (d, J )
3.3 Hz, 1H), 2.04 (dd, J ) 4.8, 7.3 Hz, 1H); HRMS m/z found
161.0574, calcd 161.0578 (C8H10O2Na).
1
1,2-Diphenylethane-1,2-diol. H NMR (200 MHz, d-acetone)
δ 7.15 (m, 10H), 4.65 (br, 2H), 4.59 (br, 1H); HRMS m/z found
237.0889, calcd 237.0891 (C14H14O2Na).
1-Phenylpropane-1,2-diol. 1H NMR (200 MHz, CDCl3) δ 7.36
(m, 5H), 4.40 (dd, J ) 3.2, 7.4 Hz, 1H), 3.89 (m, 1H), 2.59 (d, J
) 3.4 Hz, 1H), 2.46 (d, J ) 3.4 Hz, 1H), 1.08 (d, J ) 6.3 Hz, 3H);
HRMS m/z found 175.0739, calcd 175.0735 (C9H12O2Na).
Ethyl 2,3-Dihydroxy-3-phenylpropanoate. 1H NMR (200 MHz,
CDCl3) δ 7.38 (m, 5H), 5.02 (dd, J ) 3.1, 7.1 Hz, 1H), 4.38 (dd,
J ) 3.1, 5.9 Hz, 1H), 4.28 (q, J ) 7.2 Hz, 2H), 3.11 (d, J ) 5.8
Hz, 1H), 2.74 (d, J ) 7.2 Hz, 1H), 1.29 (t, J ) 7.2 Hz, 3H); HRMS
m/z found 233.0806, calcd 233.0790 (C11H14O4Na).
1
Hexadecane-1,2-diol. H NMR (200 MHz, CDCl3) δ 3.67 (m,
2H), 3.45 (m, 1H), 1.97 (d, J ) 4.3 Hz, 1H), 1.84 (dd, J ) 5.2, 6.3
Hz, 1H), 1.44 (m, 2H), 1.26 (m, 24H), 0.89 (t, J ) 6.2 Hz, 3H);
HRMS m/z found 281.2464, calcd 281.2457 (C16H34O2Na).
Tetradecane-1,2-diol. 1H NMR (200 MHz, CDCl3) δ 3.67 (m,
2H), 3.45 (m, 1H), 1.97 (d, J ) 4.3 Hz, 1H), 1.84 (dd, J ) 5.2, 6.3
Hz, 1H), 1.44 (m, 2H), 1.26 (m, 20H), 0.89 (t, J ) 6.2 Hz, 3H);
HRMS m/z found 253.2154, calcd 253.2144 (C14H30O2Na).
Decane-1,2-diol. 1H NMR (200 MHz, CDCl3) 3.67 (d, J ) 11.0
Hz, 2H), 3.44 (dd, J ) 8.0, 10.8 Hz, 1H), 2.14 (br, 1H), 2.05 (br,
1H), 1.43 (br, 4H), 1.28 (br, 10H), 0.88 (t, J ) 6.0 Hz, 3H); HRMS
m/z found 197.1519, calcd 197.1517 (C10H22O2Na).
Octyl 2,3-Dihydroxy-3-phenylpropanoate. 1H NMR (200 MHz,
CDCl3) δ 7.38 (m, 5H), 5.00 (dd, J ) 3.1, 6.9 Hz, 1H), 4.37 (dd,
J ) 3.3, 5.7 Hz), 4.20 (t, J ) 6.7 Hz, 2H), 3.16 (d, J ) 5.9 Hz,
1H), 2.81 (d, J ) 7.1 Hz, 1H), 1.63 (br, 2H), 1.29 (br, 12H), 0.90
(t, J ) 6.0 Hz, 3H); HRMS m/z found 317.1731, calcd 317.1729
(C17H26O4Na).
3-Chloro-1-phenylpropane-1,2-diol. 1H NMR (200 MHz,
CDCl3) δ 7.40 (br, 5H), 4.77 (d, J ) 6.6 Hz, 1H), 3.92 (dd, J )
5.8, 9.7 Hz, 1H), 3.60 (dd, J ) 3.9, 11.5 Hz, 1H), 3.42 (dd, J )
5.8, 11.5 Hz, 1H), 2.77 (br, 2H); HRMS m/z found 209.0354, calcd
209.0345 (C9H11O2NaCl).
1
Octane-1,2-diol. H NMR (200 MHz, CDCl3) δ 3.67 (m, 2H),
3.45 (m, 1H), 1.97 (d, J ) 4.1 Hz, 1H), 1.84 (dd, J ) 5.2, 6.3 Hz,
1H), 1.44 (m, 2H), 1.26 (m, 20H), 0.89 (t, J ) 6.2 Hz, 3H); HRMS
m/z found 169.1198, calcd 169.1204 (C8H18O2Na).
1
1-Phenylpropane-1,2,3-triol. H NMR (200 MHz, d-acetone)
1
δ 7.33 (m, 5H), 4.69 (dd, J ) 4.3, 5.2 Hz, 1H), 4.30 (d, J ) 4.3
Hz, 1H), 3.89 (d, J ) 4.8 Hz, 1H), 3.63 (m, 2H), 3.45 (m, 2H);
HRMS m/z found 191.0685, calcd 191.0684 (C9H12O3Na).
2-Methylheptane-1,2-diol. H NMR (200 MHz, CDCl3) 3.50
(d, J ) 10.9 Hz, 1H), 3.41 (d, J ) 10.8 Hz, 1H), 1.81 (br, 1H),
1.61 (br, 1H), 1.47 (m, 2H), 1.32 (m, 6H), 1.18 (s, 3H), 0.90 (t, J
) 6.9 Hz, 3H); HRMS m/z found 169.1201, calcd 169.1204
(C8H18O2Na).
Supporting Information Available: Example of the t90%
and t90%M measurements, experimental procedures for the
synthesis of derivatives for determinations of enantiomeric
1
2-Methylheptane-2,3-diol. H NMR (200 MHz, CDCl3) 3.37
(d, J ) 8.8 Hz, 1H), 2.10 (br, 1H), 1.04 (br, 1H), 1.54 (m, 2H),
1.35 (m, 4H), 1.22 (s, 3H), 1.17 (s, 3H), 0.93 (t, J ) 6.8 Hz, 3H);
HRMS m/z found 169.1212, calcd 169.1204 (C8H18O2Na).
1-Methylcyclohexane-1,2-diol. 1H NMR (200 MHz, CDCl3) δ
3.42 (m, 1H), 1.89-1.19 (br, 10H), 1.26 (s, 3H); HRMS m/z found
153.0902, calcd 153.0891 (C7H14O2Na).
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excesses, H NMR spectra of the isolated products, H NMR
spectra of the bisMosher esters of the isolated products, and
chiral GC chromatograms of the TFA derivatives of the isolated
products. This material is available free of charge via the Internet
at http://pubs.acs.org.
Hexane-1,4,5-triol. 1H NMR (200 MHz, d-DMSO) 4.35 (t, J )
5.0 Hz, 1H), 4.27 (d, J ) 4.8 Hz, 2H), 3.38 (m, 3H), 3.15 (br, 1H),
JO8026998
J. Org. Chem. Vol. 74, No. 8, 2009 3047