Catalytic asymmetric dihydroxylation of C,C double bonds with osmium tetroxide using selenoxides as co-oxidants

Article abstract of DOI:10.1055/s-2001-12437

Asymmetric dihydroxylation of olefins has been achieved in good yields and ee's using potassium osmate dihydrate (K₂OsO₂(OH)₄, the pre-oxidant), (DHQD)₂PHAL (the chiral ligand), potassium carbonate (the base) and selenoxides (the co-oxidants). Both the yield and the ee proved to be pH dependent, the highest yield and ee being found at almost the same pH values. The rate of the reaction was found to be highly dependent upon the structure of the selenoxide used. Some representative examples involving aminoxides are presented for comparison.

Full text of DOI:10.1055/s-2001-12437

LETTER
501
Catalytic Asymmetric Dihydroxylation of C,C Double Bonds with Osmium
Tetroxide Using Selenoxides as Co-oxidants
Alain Krief,*,a Catherine Castillo-Colauxa,b
aLaboratoire de Chimie Organique de Synthèse, Département de Chimie, Facultés Universitaires Notre-Dame de la Paix, 61 rue de Bruxel-
les, B-5000 NAMUR, Belgium
bFonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture, 5 Rue d'Egmont, B-1000, Bruxelles, B-1050, Belgium
Fax +32(81)724536; E-mail: alain.krief@fundp.ac.be
Received 12 February 2001
Dedicated to Professor J. F. Normant at the occasion of his 65th birthday
bearing a thiophenyl group in the allylic position, using
Abstract: Asymmetric dihydroxylation of olefins has been
standardized conditions, which involve K2OsO2(OH)4
[0.014-0.022 mol equiv.], (DHQD)2PHAL [0.027-0.051
mol equiv.], K2CO3 [0.3 mol equiv.] and benzyl phenyl se-
achieved in good yields and ee’s using potassium osmate dihydrate
(K2OsO2(OH)4, the pre-oxidant), (DHQD)2PHAL (the chiral
ligand), potassium carbonate (the base) and selenoxides (the co-ox-
idants). Both the yield and the ee proved to be pH dependent, the lenoxide (1.1 mol equiv.) in aqueous tert-butyl alcohol [1-
1 in volume] (Scheme 1, Table 1).2a
The yields and ee’s observed4 are in all cases reasonably
highest yield and ee being found at almost the same pH values. The
rate of the reaction was found to be highly dependent upon the struc-
ture of the selenoxide used. Some representative examples involv-
high and close to those described using Sharpless AD-mix
reagent3 although longer reaction times are in some cases
required to reach similar yields. The amount of co-oxidant
is however lower (less than one third) and the benzyl phe-
nyl selenide obtained in quantitative yield, as the by-prod-
uct, can be easily recycled after oxidation.5
ing aminoxides are presented for comparison.
Key words: alkenes, dihydroxylation, glycolysation, selenoxides,
osmium tetroxide, oxidation
Some time ago, we described that benzyl phenyl selenox-
ide and p-methylselenoxy-benzoic acid, in aqueous tert-
butyl alcohol, are efficient co-oxidants in the asymmetric
dihydroxylation of the C,C double bond of -methyl sty-
rene using catalytic amounts of potassium osmate dihy-
drate (the pre-oxidant), (DHQD)2PHAL (the chiral
ligand) and potassium carbonate (the base) (Scheme 1,
Table 1).1,2a
Preliminary results, obtained on 1-phenyl cyclohexene
and gathered in Table 2, tend to show that rates and ee’s
are both pH dependent.6,7 The reaction is extremely slow
at pH under 9.5 (Table 2, entries a, b). Best yield is ob-
tained at pH 10.4 (Table 2, entry e) and best ee at pH 11.5
(Table 2, entry f). Work is in progress to confirm these
trends.
We were curious to know whether all selenoxides behave
similarly. We have, for that purpose, carried out a series
of dihydroxylations on -methyl styrene, under the condi-
tions described above, using some representative diaryl-,
alkyl aryl- and dialkyl-selenoxides as co-oxidants
(Scheme 1; R1 = Ph, R2 = Me, R3 = H; Figure).
This reaction, whose conditions are related to those de-
scribed earlier by Sharpless3 who used either potassium
ferricyanate (K3Fe(CN)6) or N-methyl morpholine N-ox-
ide (NMO) as co-oxidants, was nevertheless described for
a single olefin and its scope and limitations were not avail-
able.1 We have now successfully extended it to a wide
range of aromatic and aliphatic olefins as well as to those
R1
m eq K2OsO2(OH)4, n eq (DHQD)2PHAL , co-oxidant, R2
R3
R3
R1
R2
base, aq t-BuOH
OH
OH
Scheme 1
OH
OH
K2OsO2(OH)4, (DHQD)2PHAL, 1.1 equiv. PhSe(O)CH2Ph,
aq t-BuOH, buffered solution, 20 °C, 24 h
Ph
Ph
Scheme 2
Synlett 2001 No. 4, 501–504 ISSN 0936-5214 © Thieme Stuttgart · New York

502
A. Krief, C. Castillo-Colaux
Table 1 AD reaction on C,C double bonds using SeOAD2a method.
LETTER
Table 2 Dependence of the yields and ee’s of the diols obtained
from the SeOAD of 1-phenyl cyclohexene on the pH of the medium.
with entry c) and this is particularly the case when the aryl
group bears electron withdrawing groups (Table 3, com-
pare entry g with entries b and c). Surprisingly, the pres-
ence of an electron donating group on the phenyl group
does not seem to affect the rate of the dihydroxylation re-
action (Table 3, compare entry b with entry c). Similar re-
sults have been obtained when the reaction is carried out
on 1-phenyl cyclohexene.8
The re-oxidation of Os (VI) to Os (VIII) can take place ei-
ther on the glycolate or on the free osmium (VI) salt by di-
rect attack of the oxygen of the selenoxide on the osmium
atom followed by lost of the selenide. Apparently it is not
the “nucleophilicity” of the oxygen atom of the selenoxide
but the ability of the selenides to be kicked off which is the
rate limiting step of this reaction. We are currently trying
to generalize these observations.
We found that the nature of the selenoxide greatly influ-
ences the rate of the reaction but not its enantioselectivity
(Table 3). It is much faster when carried out with diaryl
selenoxides rather than with the related aryl methylselen-
oxides (Table 3, compare entry d with entry a and entry e
We have then studied the amine oxide promoted AD reac-
tion under the AD3,9 and SeOAD1 conditions which are
significantly different from those described in the original
reports.3,10,11
Synlett 2001, No. 4, 501–504 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Catalytic Asymmetric Dihydroxylation of C,C Double Bonds with Osmium Tetroxide
503
R1
R3
R3
R1
R2
R2
0.01 eq K2OsO2(OH)4, 0.017 eq (DHQD)2PHAL,
[0.3 eq K2CO3 or 0.3 eq KHCO3 or without additive], 1.7
eq NMO, aq t-BuOH, 20 °C
OH
OH
Scheme 3
The reactions have been systematically carried out by
adding at once K2OsO2(OH)4 (0.01 equiv.) and
(DHQD)2PHAL (0.017 equiv.) to a mixture of the olefin,
NMO (1.7 equiv.) and K2CO3 (0.3 equiv., 0.015 M aque-
ous solution) in aqueous tert-butyl alcohol (1/1 v/v,
Scheme 3, Table 4, entry K2CO3).2b These results have
been compared with those obtained when the reaction is
carried out (i) in the presence of potassium hydrogenocar-
bonate (0.3 mol equiv., Table 4, entry KHCO3) or (ii) in
neutral media (Table 4, entry Neutral).
Yield in diol
100
80
60
40
20
Table 4 Asymmetric dihydroxylation of C,C double bonds using
NMO in the presence of K2CO3 or KHCO3.
0
00:00
01:00
02:00
03:00
04:00
05:00
06:00
Reaction time
Ph-Se(O)Me
p-NO2-Ph-Se(O)Me
p-Cl-Ph-Se(O)Me
Ph-Se(O)Ph
p-MeO-Ph-Se(O)Me
Bn-Se(O)Me
Ph-Se(O)Bn
Figure Relative rate of AD of -methyl styrene under SeOAD con-
ditions involving different selenoxides performed in the presence of
K2CO3 (% of diol formed versus reaction time in hour).
Table 3 Half-time reaction and ee values of the diol resulting from
the SeOAD reaction on -methyl styrene, and involving different se-
lenoxides as co-oxidant.
We found (Table 4, entries K2CO3) that the ee’s are in
general reasonably high but often significantly lower than
those obtained when selenoxides are used (Table 1). The
yields, however, proved to be highly dependent upon the
structure of the olefin and this was not observed with the
SeOAD method. Performing the reaction at a lower pH
provides the diols faster and in better yields but with poor-
er ee’s (Table 4, entries KHCO3 or Neutral).
In conclusion, we have found that the SeOAD and NMO-
AD reactions behave differently under closely related
conditions although in many cases they are both pH de-
pendent. The results involving the SeOAD are close to
those originally described when AD-mix3 is used instead
whereas, except for a few cases (Table 4) the NMO-AD
reaction has not yet reached this level.12
a These results have been determined by chiral HPLC (Chiralcel, OC)
on the monobenzoate of the corresponding diol obtained after com-
pletion of the AD reaction.
Synlett 2001, No. 4, 501–504 ISSN 0936-5214 © Thieme Stuttgart · New York

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A. Krief, C. Castillo-Colaux
LETTER
sodium perborate or sodium percarbonate. Our results will be
reported in due course (b) Krief, A. in "Comprehensive
Organometallic Chemistry II", Abel, E. W.; Stone, F. G. A.;
Wilkinson, G.; McKillop, A. Eds, Pergamon: Oxford 1995,
11, 516-569 (c) J. Reich, in “Oxidation in Organic Chemistry”
Trahanovsky, W. S.; Wasserman, H. H. Eds., Academic Press:
New York 1978, 5 (d) Krief, A. Tetrahedron 1980, 36, 2531
(e) Sharpless, K. B.; Gordon, K. M.; Lauer, R. F.; Patrick, D.
W.; Singer, S. P.; Young, M. W. Chem. Scr. 1975, 8, 9.
(6) Buffered solutions used : pH 7.5: KH2PO4 / K2HPO4; pH 8.4,
9.0, 9.56: Na2B4O7 / HCl (1M); pH 10.65, 11.5: KHCO3 /
K2CO3; pH 12.1: Na2HPO4 / Na3PO4, the initial pH of the
aqueous solution of K2CO3 was 11.4 slightly increases at the
end of the reaction.
(7) The AD reaction has been already performed in buffered
solutions : (a) Kolb, H. C.; Bennani, Y. L.; Sharpless, K. B.
Tetrahedron: Asymmetry 1993, 4, 133-141 (b) Vanhessche, K.
P. M.; Wang, Z.-M.; Sharpless, K. B. Tetrahedron Lett. 1994,
35, 3469-3472 (c) Doebler, C.; Mehlretter, G.; Beller, M.
Angew. Chem., Int. Ed. 1999, 3026-3028 (d) Mehltretter, G.
M.; Döbler, C; Sundermeier, U.; Beller, M. Tetrahedron Lett.
2000, 41, 8083-8087 (e) Döbler, C; Mehltretter, G. M.;
Sundermeier, U.; Beller, M. J. Am. Chem. Soc. 2000; 122,
10289-10297.
(8) These results will be reported in the full paper.
(9) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G.; J.
Hartung, Jeong K.-S; Kwong, H.-L; Morikawa, K.; Wang,
Z.-M.; Zu, D.; Zhang, X.-L J. Org. Chem. 1992, 57, 2768.
(10) This reaction has been previously performed with the
"bystander" methoxyquinoleine [such as dihydroquinidine
4-chlorobenzoate (DHQD)CLB] ligand in an acetone-water
mixture as the solvent (a) Jacobsen, E. N.; Marko, I.; Mungall,
W. S.; Schroder, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988,
110, 1968-1970 (b) Lohray, B.; Kalantar, T. H.; Kim, B. M.;
Park, C. Y.; Shibata, T.; Wai, J. S. M.; Sharpless, K. B.
Tetrahedron Lett. 1989, 30, 2041-2044 (c) Jacobsen, E.N.;
Marko, I.; France, M. B.; Svendsen, J. S.; Sharpless, K. B. J.
Am. Chem. Soc. 1989, 110, 737-739.
References and Notes
(1) (a) Krief, A.; Castillo-Colaux, C. Tetrahedron Lett. 1999, 40,
4189-4192 (b) This work has been in part reported by AK at
ICOS 13 (Warsaw, July 2000).
(2) Typical experiments (a) The SeOAD-method1:
Dihydroquinidine phthalazine [(DHQD)2PHAL; 55.2 mg;
0.015 mol equiv.] and potassium osmate dihydrate
[K2OsO2(OH)4; 27.5 mg; 0.03 mol equiv.] were added at once
at room temperature, to a vigorously stirred suspension of
benzyl phenyl selenoxide (1.45 g; 1.1 equiv.), potassium
carbonate (207 mg; 0.3 equiv.) and the olefin (5 mmol) in tert-
butyl alcohol/water (100 mL; 1/1). The heterogeneous slurry
was stirred vigorously at the same temperature until the TLC
(SiO2) revealed the absence of the starting olefin. The reaction
was quenched by addition of sodium metabisulfite (1.5 g) then
stirred for an additional 0.5 h. The mixture was extracted
several times with ethyl acetate or CH2Cl2, dried over MgSO4
and evaporated to dryness to deliver after purification by flash
chromatography (SiO2, AcOEt/pentane) the pure diol and
benzyl phenyl selenide in typically excellent yields. The
ligand was not eluted under these conditions. (b) NMO-
K2CO3 method : Potassium osmate dihydrate (18.4 mg, 0.01
equiv.) and the dihydroquinidine phthalazine (66.2 mg 0.017
equiv.) were added, at once and at room temperature, to a
vigorously stirred suspension of N-methylmorpholine N-
oxide (1.027 g, 1.7 equiv.), potassium carbonate (207 mg; 0.3
equiv.) and the olefin (5 mmoles) in of a tert-butanol-water
solution (100 mL, 1/1 v/v). The resulting mixture was stirred
vigorously at the same temperature until the TLC (SiO2)
revealed the absence of the starting olefin. The reaction was
quenched by addition of sodium metabisulfite (1.5 g) and then
stirred for an additional 0.5 h at room temperature. The
mixture was extracted several times with ethyl acetate or
dichloromethane, dried over magnesium sulfate then
concentrated to dryness. Purification of the crude mixture was
performed as described above.
(3) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483-2547 and references cited.
(11) Wai, J. S. M.; Marko, I.; Svendsen, J. S.; Finn, M. G.;
Jacobsen, E. N.; Sharpless, K. B. J. Am. Chem. Soc. 1989, 111,
1123-1125.
(12) The authors warmly thank Prof. K. B. Sharpless and Dr V. V.
Fokin for their critical refereeing of our original papers.
(4) Determination of most of the ee’s disclosed in this paper has
been carried out by comparing the optical rotations of the diols
obtained to the reported data.3 HPLC has, however, been used
on the diol derived from 1-phenyl cyclohexene and on the
monobenzoate of the diol derived from -methyl styrene.
(5) (a) Selenides have been oxidized by several oxidants. 1,5b-e We
are presently carrying out this reaction using catalytic
amounts of selenides and performing their in situ oxidation by
singlet oxygen, hydrogen peroxide, organic hydroperoxides,
Article Identifier:
1437-2096,E;2001,0,04,0501,0504,ftx,en;G00301ST.pdf
Synlett 2001, No. 4, 501–504 ISSN 0936-5214 © Thieme Stuttgart · New York