Heterogeneous asymmetric aminohydroxylation of alkenes using a silica gel-supported bis-cinchona alkaloid

Article abstract of DOI:10.1039/a806959j

Excellent enantioselectivities of up to > 99% ee have been achieved in the heterogeneous asymmetric aminohydroxylation of trans-cinnamate derivatives using silica gel-supported (QN)₂PHAL [SGS-(QN)₂PHAL 1]; the dark brown 1·Os complex

Full text of DOI:10.1039/a806959j

Heterogeneous asymmetric aminohydroxylation of alkenes using a silica
gel-supported bis-cinchona alkaloid
Choong Eui Song,*a Chun Rim Oh,a Sung Woo Lee,a Sang-gi Lee,a Laetitia Canalib and David C. Sherringtonb
a Division of Applied Science, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul,
130-650, Korea. E-mail: s1673@kistmail.kist.re.kr
b Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral
Street, Glasgow, UK G1 1XL
Received (in Cambridge, UK) 7th September 1998, Accepted 5th October 1998
Excellent enantioselectivities of up to > 99% ee have been
achieved in the heterogeneous asymmetric aminohydroxyl-
ation of trans-cinnamate derivatives using silica gel-sup-
ported (QN)2PHAL [SGS-(QN)2PHAL 1]; the dark brown
1·Os complex, recovered by simple filtration after reaction,
could be reused without any loss of enantioselectivity.
(DHQ)2PHAL. No trace amounts of osmium could be found in
all filtrates examined. These results encouraged us to examine
the efficiency of 1 in the heterogeneous AA reactions. We report
here our preliminary findings.
The heterogeneous AA reactions of trans-cinnamate deriva-
tives using 1 were carried out either with EtOCONH2/ButOCl/
NaOH1d or AcNHBr/LiOH1e as the oxidant/nitrogen source
under the same reaction conditions adopted for the analogous
homogeneous process (Scheme 1). The results are summarized
in Table 1. The data show that all reactions examined using 1
exhibited excellent enantioselectivities. Generally, the amide-
based AA reactions (Table 1, entries 4 and 6) gave higher yields
and ees ( > 99% ee) than those employing the carbamate-based
chemistry (entries 1–3). In particular, the AA reactions at 4 °C
with amide as oxidant gave similar chemical yields (71–76%)
and ees ( > 99% ee) to those obtained in homogeneous AA
reactions.1e It is noteworthy that when these reactions were
carried out at room temperature, the chemical yields were
significantly decreased (ca. 30–40% yield), whereas the ees
were maintained. The reactions always stopped after ca. 50%
conversion, and the pH of the mixture at the end of the reactions
was about 5–6. It is probable that Hoffmann rearrangement3 of
the N-bromoacetamide is a significant concurrent reaction at
this temperature.
Highly efficient methods for osmium-catalyzed asymmetric
aminohydroxylation (AA) of alkenes in the presence of
(DHQ)2PHAL or (DHQD)2PHAL ligands have been dis-
covered recently by Sharpless and co-workers.1 Initially, the
catalytic AA reaction exploited TsNClNa (Chloramine-T) as
the oxidant/nitrogen source.1a,b Subsequently, with the develop-
ment of new procedures which utilize carbamates-1d and amide-
derived oxidants,1e the substrate scope and selectivity has been
greatly improved. The resulting chiral b-amino alcohol group is
an important structural element in many biologically active
molecules as well as the starting point in the design of many
chiral ligands.
Recently, we prepared silica gel-supported (QN)2PHAL
[SGS-(QN)2PHAL 1],2 which with OsO4 yielded excellent
MeO
OMe
Si
O
O
O
O
Silica
gel
Silica
gel
S
Si
S
N
N
N
N
O
O
O
H
H
MeO
OMe
O
Ligand 1,
K2OsO2(OH)4
R3
NH
O
N
N
OR2
R3C(O)NHX, [OH]–
solvent
OR2
R1
OH
R1
enantioselectivities in asymmetric dihydroxylation of alkenes
( > 99% ee for trans-stilbene). Moreover the catalytic system,
the SGS-(QN)2PHAL 1–osmium complex, could be reused
after simple filtration without any significant loss of enantio-
selectivity. UV analysis of the filtrate of the simple mixture of
ligand 1 and OsO4 in ButOH–H2O (1:1) in several molar ratios
(1:1, 2:1, 4:1 etc.) showed that the binding affinity of 1 to OsO4
is much greater than that of the homogeneous analogue
3a R1 = H, R2 = Me, R3 = OEt
b R1 = OMe, R2 = Me, R3 = OEt
c R1 = NO2, R2 = Me, R3 = OEt
d R1 = H, R2 = Pri, R3 = Me
2a R1 = H, R2 = Me
b R1 = OMe, R2 = Me
c R1 = NO2, R2 = Me
d R1 = H, R2 = Pri
e R1 = OMe, R2 = Pri, R3 = Me
e R1 = OMe, R2 = Pri
Scheme 1
Table 1 Heterogeneous catalytic AA reaction using SGS-(QN)2PHAL 1a
Entry
Substrate Oxidant
Solvent
t/h
Yield (%)b
Ee (%)c Configurationc
1
2
3
2a
2b
2c
2d
2d
2e
2e
2e
EtOCONClNa
PriOH–H2O
PriOH–H2O
12
12
12
7
7
9
40
43
52
71
30
76
32
81
88
92
92
> 99
> 99
> 99
> 99
> 99
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
EtOCONClNa
EtOCONClNa
AcNBrLi
AcNBrLi
AcNBrLi
CH3CN–H2O
ButOH–H2O
ButOH–H2O
ButOH–H2O
ButOH–H2O
ButOH–H2O
4
5d
6
7d
8e
AcNBrLi
AcNBrLi
9
7
a
In all cases 4 mol% K2OsO2(OH)4 and 5 mol% ligand were used. The reactions in entries 1–3 were carried out at 10 °C under the same reaction
conditions as those reported in ref. 1(d). The reactions in entries 4–7 were carried out at 4 °C under the same reaction conditions as those reported in ref. 1(e).
b Isolated yields by column chromatography. c The ees and absolute configuration were determined by chiral HPLC analysis.† d Reaction was carried out
with 1·Os complex recovered from the reaction in entries 4 and 6 respectively without further addition of K2OsO2(OH)4. e Reaction was carried out with 1·Os
complex recovered from the reaction in entry 6 with the addition of small amounts of K2OsO2(OH)4 (2 mol%).
Chem. Commun., 1998, 2435–2436
2435

the chiral ligand, which is a current intrinsic limitation of
catalytic AA and AD reactions.
In conclusion, we have achieved excellent ees for the
heterogeneous catalytic AA of alkenes using a silica gel-
supported bis-cinchona alkaloid 1. Moreover, the recovered
dark brown-coloured 1·Os complex can be reused without any
loss of enantioselectivity. We have also determined the Os
content of this complex by XPS analysis. Further studies are
currently in progress to increase the product yield, and the
recovery of both the chiral ligand and the osmium.
This research was supported by a grant (MOST 2N17410)
from the Ministry of Science and Technology in Korea.
Notes and references
† Determination of enantiomeric excesses: For 3a: Chiralcel AD, PriOH–
hexane (10:90), 0.7 ml min21; 25.0 min (2R,3S), 29.6 min (2S,3R). For 3b:
Chiralcel AD, PriOH–hexane (10:90), 0.7 ml min21; 36.1 min (2R,3S), 54.0
min(2S,3R). For 3c: Chiralcel AD, PriOH–hexane (10:90), 1 ml min21; 26.9
min (2R,3S), 43.2 min (2S,3R). For 3d: Chiralcel AD, PriOH–hexane
(20:80), 1 ml min21; 6.9 min (2R,3S), 10.9 min (2S,3R). For 3e: Chiralcel
AD, PriOH–hexane (20:80), 1 ml min21; 9.6 min (2R,3S), 16.7 min
(2S,3R).
1 (a) G. Li, H. T. Chang and K. B. Sharpless, Angew. Chem., Int. Ed. Engl.,
1996, 35, 451; (b) G. Li and K. B. Sharpless, Acta Chem. Scand., 1996,
50, 649; (c) J. Rudolph, P. C. Sennhenn, C. P. Vlaar and K. B. Sharpless,
Angew. Chem., Int. Ed. Engl., 1996, 35, 2810; (d) G. Li, H. H. Angert and
K. B. Sharpless, Angew. Chem., Int. Ed. Engl., 1996, 35, 2813; (e) M.
Bruncko, G. Schlingloff and K. B. Sharpless, Angew. Chem., Int. Ed.
Engl., 1997, 36, 1483; (f) K. L. Reddy and K. B. Sharpless, J. Am. Chem.
Soc., 1998, 120, 1207; (g) K. L. Reddy, K. R. Dress and K. B. Sharpless,
Tetrahedron Lett., 1998, 39, 3667; (h) P. O’Brien, A. O. Simon and D. D.
Parker, Tetrahedron Lett., 1998, 39, 4099.
2 (a) C. E. Song, J. W. Yang and H. J. Ha, Tetrahedron: Asymmetry, 1997,
8, 841; (b) For the preparation of chiral monomer, C. E. Song, J. W. Yang,
H. J. Ha and S. G. Lee, Tetrahedron: Asymmetry, 1996, 7, 645; (c) SGS-
(QN)2PHAL 1 was prepared as reported in ref. 2(a) using silica gel
Merck-60 (230–400 mesh) instead of Li Chrosorb SI 60 (Merck, 5 mm).
The content of alkaloid in 1 was determined by nitrogen analysis (0.21
mmol of alkaloid per gram).
Fig. 1 XPS-spectra of the 1-Os complex recovered after reaction, entry 4 (a)
and entry 6 (b).
The efficiency with which the catalyst can be recycled has
also been examined. The dark brown-coloured 1·Os complex
was recovered by simple filtration after each reaction (entries 4
and 6), which is not possible in a homogeneous process. XPS
(X-Ray Photoelectron Spectroscopy)-analysis (Fig. 1) of the
samples shows clearly that these recovered complexes contain
osmium. However, the recovery yields were not high enough
( < 50%). The rest of the osmium was obviously lost to the
mother liquor. The AA reactions were repeated with these
samples without further addition of osmate salt. As shown in
entries 5 and 7, the required amino alcohols 3d,e were obtained
in 30 and 32% yield with > 99% ee, respectively. Moreover, the
addition of small amounts of osmium to the recovered catalyst
regenerated completely the reaction conditions (entry 8). These
results indicate the viability of the repetitive use of osmium and
3 A. W. Hoffmann, Ber. Dtsch. Chem. Ges., 1881, 14, 2725; E. S. Wallis
and J. F. Lane, Org. React., 1967, 3, 267.
Communication 8/06959J
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Chem Commun., 1998, 2435–2436