Cinchona alkaloid ester derivatives as ligands in the asymmetric dihydroxylation and aminohydroxylation of alkenes

Article abstract of DOI:10.1016/j.mencom.2010.03.013

Cinchona alkaloid ester derivatives were adopted to asymmetric dihydroxylation and asymmetric aminohydroxylation reactions in excellent yields and enantiomeric excesses.

Full text of DOI:10.1016/j.mencom.2010.03.013

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 104–105
Cinchona alkaloid ester derivatives as ligands in the asymmetric
dihydroxylation and aminohydroxylation of alkenes
a
a
a
b
a
Hui Chen, Qiao Feng Wang, Xiao Li Sun, Jing Luo and Ru Jiang*
a
b
Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, P. R. China.
Fax: +82 29 8477 6945; e-mail: jiangru@fmmu.edu.cn
Shannxi Institute for Food and Drug Control, Xi’an 710061, P. R. China
DOI: 10.1016/j.mencom.2010.03.013
Cinchona alkaloid ester derivatives were adopted to asymmetric dihydroxylation and asymmetric aminohydroxylation reactions in
excellent yields and enantiomeric excesses.
The catalytic asymmetric dihydroxylation (AD) and asym-
CbzHN
OH
metric aminohydroxylation (AA) of olefins using cinchona
alkaloid derivatives as ligands have become a useful and
R5
H
R4
H
1
–5
reliable transformation in organic synthesis. High regio- and
stereoselectivity for a broad range of substrates are the most
outstanding characteristics of these reactions. To date, many
ligands have been tested and a few superior structural types
H
R5
H
A
K2OsO2(OH)4, ligand
+
PrOH–H2O (1:1, v/v)
R4
HO
H
R4
NHCbz
+
–
CbzNHNa Cl
5
R
6
–9
have been identified, and our group had developed ligands
H
1
0–13
for the AD and AA reactions.
B
Here, we synthesized a range of analogues using phthaloyl
or pyridyl spacer groups between two chiral moieties14 (the
following alkaloid moieties were used: quinine a and its pseudo-
enantiomer quinidine c and their dihydro analogues hydroquinine
b and hydroquinidine d, which afforded a set of ligands capable
Scheme 2 The AA reactions.
†
The synthesis of cinchona alkaloid ester derivatives. Into a solution
of 2 mmol of cinchona alkaloid in 10 ml of anhydrous CH Cl , 2 ml of
anhydrous Et N was added at 0 °C and the mixture was stirred. A solution
2
2
3
of performing the transformation across a broad range of alkene
of dicarbonyl dichloride (0.2 g, 1 mmol) in CH2Cl2 was slowly added for
10 min using a dropping funnel. After 1 h, the reaction mixture was
warmed to room temperature and stirred for 2 h. Upon completion of the
reaction as indicated by TLC, the mixture was poured into 10 ml of water;
substrates by asymmetric AD and AA reactions) (Figure 1).†
R1
R1
the organic layer was separated and washed with a saturated NH Cl solu-
4
tion and then with water. The organic solution was dried by anhydrous
N
N
O
O
MgSO and evaporated in vacuo, followed by purification by flash chro-
4
matography on silica gel (EtOAc–EtOH–Et N, 7:3:0.5).
3
R2
R2
15
Typical procedure for the AD reactions
.
A ligand (0.05 mmol), K Fe(CN)6
3
(
0.99 g, 3 mmol), K CO (0.42 g, 3 mmol) and OsO (0.005 mmol) were
2
3
4
t
dissolved in 10 ml of Bu OH–water (1:1, v/v) at room temperature. For
,2-disubstituted olefins, MeSO NH (0.095 g, 1 mmol) was added. The
N
N
1
3
2
Quinyl (QN):
R = vinyl, R = OMe
Quinidyl (QD):
R = vinyl, R = OMe
solution was cooled to 0 °C and the olefin (1 mmo1) was added. The mix-
ture was stirred at 0 °C usually for 12 h. In the workup, Na SO (0.8 g)
1
2
1
2
2
3
Dihydroquinyl (DHQN):
R = Et, R = OMe
Dihydroquinidyl (DHQD):
was slowly added, and the suspension was warmed to room temperature
with vigorous stirring. Ethyl acetate (20 ml) was added, and the aqueous
layer was further extracted with ethyl acetate (2×5 ml). If MeSO NH was
1
2
1
2
R = Et, R = OMe
3
2
used, the combined organic layers were washed with 20 ml of 2 M aqueous
NaOH. Then, the combined organic layers were dried over MgSO and
concentrated. The crude product was purified by flash chromatography
on silica gel to afford the diol.
Typical procedure for the AA reactions.16 An aqueous solution of
sodium hydroxide (0.122 g in 7.5 ml of water) was added to a solution
of benzyl carbamate (0.469 g, 3.1 mmo1) in 4 ml of propan-1-ol at room
temperature. Then, tert-butyl hypochlorite (0.35 ml, 3.05 mmol) and a
solution of ligand (0.05 mmol) in 3.5 ml of propan-1-ol were succes-
sively added to the mixture. The solution was sonicated to ensure homo-
geneity. A substrate olefin (1 mmol) and then potassium osmate dihydrate
4
O
O
O
O
a R = QN
b R = DHQN
c R = QD
N
R
R
R
R
1
a–d
2a–d
d R = DHQD
Figure 1 The structure of ester derivatives.
The asymmetric AD reaction (Scheme 1) gave good results
for eight substrates furnishing the chiral diol products in good
yields 94–99% (Table 1) with satisfying enantioselectivities.
(
0.414 mg, 0.04 mmol) were added to the reaction mixture. The mixture
was stirred at ambient temperature for 5 h and the reaction was controlled
by TLC. Then, propan-1-ol was distilled off from the reaction solution under
reduced pressure and the rest was extracted with diethyl ether (2×15 ml).
R2
R1
R3
H
K3Fe(CN)6, OsO4,
MeSO2NH2, ligand
HO
R2
R1
OH
R3
H
t
Bu OH–H2O (1:1, v/v)
The combined organic extract was washed with brine, dried with MgSO and
4
K2CO3
concentrated under reduced pressure to give the crude product, which was
purified by flash chromatography on silica gel to afford the amino alcohols.
Scheme 1 The AD reactions.
©
2010 Mendeleev Communications. All rights reserved.
– 104 –

Mendeleev Commun., 2010, 20, 104–105
Table 1 The results of asymmetric dihydroxylation.a
binding pocket, and an aromatic olefin inside such a pocket would
experience not only parallel stacking but also attractive edge-
to-face interactions, which may lead to even further stabiliza-
tion of the transition state. This hypothesis may also account
ee (%)
Yield
Entry Olefin
(
%)
19
1
a 1b 1c 1d 2a 2b 2c 2d
for the extraordinary enantioselectivities since chirality transfer
based on such effects should be very efficient. This mechanism
demonstrated that the type of aromatic ring was inessential,
and the carbon or nitrogen atom in the bridging group had no
influence on the enantioselectivity.
Ph
O
1
2
94–96 98 97 98 99 99 97 98 99
94–97 97 98 97 99 98 99 98 99
Ph
Ph
OEt
The catalytic asymmetric reaction of alkenes with osmium
tetroxide or potassium osmate dihydrate in the presence of bis-
cinchona alkaloid derivatives has provided a remarkable tool
by which optically pure diols or amino alcohols can be easily
obtained in high yields and with excellent enantioselectivities.
O
3
95–97 97 99 98 99 98 97 99 98
94–98 91 93 92 91 93 94 92 90
Ph
Ph
OPri
4
5
96–99 92 91 93 94 94 92 92 93
94–99 93 94 94 94 95 94 94 95
This work was supported by the National Natural Science
Foundation of China (grant nos. 20972189, 20672141 and
Ph
Ph
6
7
8
30901883).
2-Allyloxynaphthalene 96–98 99 98 98 99 97 98 99 98
Bun
95–98 89 88 90 91 91 89 90 91
Bun
Online Supplementary Materials
aDetermined by chiral HPLC.
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2010.03.013.
Table 2 The results of asymmetric aminohydroxylation.a
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1
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1
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1
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ester catalysts 1a–d were similar to those of pyridyl ester
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derived from different cinchona alkaloid exhibited parallel asym-
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ethyl substitution in the structure of cinchona alkaloids had no
influence on the asymmetric induce. The ester derivatives have
the same excellent asymmetric induction as the previously
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4
5
1
1
7
18
reported, such as (DHQD) PHAL and (DHQD) PDZ, and
2
2
the result suggested average C symmetry with respect to an
2
axis through the plane of the aromatic ring and, therefore, a
preferred anti-arrangement of the two alkaloid units. The two
alkaloid units and aromatic bridging group systems set up a
Received: 10th November 2009; Com. 09/3416
–
105 –