(S)-Threonine/α,α-(S)-diphenylvalinol-derived chiral ionic liquid: An immobilized organocatalyst for asymmetric syn-aldol reactions

Article abstract of DOI:10.1016/j.tet.2011.01.017

Chiral ionic liquids containing (S)-or (R)-threonine amide and α,α-(S)-diphenylvalinol units were synthesized In the presence of the (S)-threonine-derived catalyst reactions between ketones with secondary carbon atom(s) at the α-position with respect to the carbonyl group and aromatic (heteroaromatic) aldehydes afforded the corresponding syn-aldols in high yields (up to 99%) and with high diastereo-(syn/anti up to 97:3) and enantioselectivity (up to 99% ee), which was maintained over three reaction cycles.

Full text of DOI:10.1016/j.tet.2011.01.017

Tetrahedron 67 (2011) 1948e1954
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
(S)-Threonine/
a,
a-(S)-diphenylvalinol-derived chiral ionic liquid: an immobilized
organocatalyst for asymmetric syn-aldol reactions
*
Natalia A. Larionova, Alexandr S. Kucherenko, Dmitry E. Siyutkin, Sergei G. Zlotin
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prospect, 119991 Moscow, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2010
Received in revised form 9 December 2010
Accepted 6 January 2011
Available online 13 January 2011
Chiral ionic liquids containing (S)- or (R)-threonine amide and
a
,
a
-(S)-diphenylvalinol units were syn-
thesized In the presence of the (S)-threonine-derived catalyst reactions between ketones with secondary
carbon atom(s) at the -position with respect to the carbonyl group and aromatic (heteroaromatic) al-
a
dehydes afforded the corresponding syn-aldols in high yields (up to 99%) and with high diastereo-(syn/
anti up to 97:3) and enantioselectivity (up to 99% ee), which was maintained over three reaction cycles.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric syn-aldol reactions
Organocatalysis
Threonine amide
Chiral ionic liquid
Immobilized catalyst
1. Introduction
Asymmetric aldol reactions are widely used for the formation of
the carbonecarbon bonds in organic compounds.1 These reactions
are often carried out in the presence of chiral organocatalysts, in
particular (S)-proline,2 (S)-proline amide,3 sulfonylamides,4 pro-
line-containing di- and tripeptides5 and some others, with high
diastereo- and enantioselectivity. As a rule, the major reaction
products have anti-configuration, whereas syn-aldols are formed
exclusively in native aldolase catalyzed aldol reactions.6
Recently, it was found that some primary a
-amino acid-7 or pri-
Fig. 1. Known organocatalysts of syn-aldol reactions.
mary amine-derived8 organocatalysts direct, like enzymes, asym-
metric aldol reactions toward the formation of syn-products. Among
them, a-amino acid amides A, containing a chiral b-aminoalcohol
2. Results and discussion
fragment within the amide unit are the most efficient ones (Fig. 1).9
The synthesis of catalysts A, containing several chiral centers in
the molecule, is rather complicated and/or expensive, which makes
their regeneration desirable. Very recently, we discovered that the
modification of proline amides with ionic groups, in particular with
imidazolium cation and PFꢀ6 anion, opens up a convenient way to
their immobilization.10 It might be expected that application of this
To verify this hypothesis, we synthesized (2S,3R)-threonine 1a
and (2R,3S)-threonine 1b amides, bearing the -(S)-diphenylva-
linol fragment along with the ionic group. The synthetic scheme
included the reaction of commercially available N-Cbz-protected
amino acids 2a,b with a,a-(S)-diphenylvalinol in the presence of
ClCO2Et/Et3N, esterification of the corresponding amides 3a,b un-
der the action of 5-bromovaleric acid and DCC/DMAP, subsequent
reaction of esters 4a,b with methyl-1H-imidazole, followed by
metathesis of the anion in bromides 5a,b and deprotection (H2e5%
Pd/C) of the amino group in hexafluorophosphates 6a,b. Salts 1a
and 1b melt at 110 ꢁS and 96 ꢁS, respectively, and can be described
as chiral ionic liquids (Scheme 1).
a,a
approach to primary a-amino acid amides would lead to the de-
velopment of immobilized organocatalysts for syn-aldol reactions.
As far as we know, organocatalysts of this type have not been
prepared so far.
We studied the catalytic properties of (S)-threonine-derived
chiral salt 1a in a model aldol reaction between hydroxyacetone 7a
* Corresponding author. Tel.: þ7 499 137 13 53; fax: þ7 499 135 53 28; e-mail
address: zlotin@ioc.ac.ru (S.G. Zlotin).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.017

N.A. Larionova et al. / Tetrahedron 67 (2011) 1948e1954
1949
Scheme 1. Synthesis of (S)- or (R)-threonine-derived catalysts 1a,b modified with ionic groups.
(10 equiv) and 4-nitrobenzaldehyde 8a at ambient temperature in
CH2Cl2, THF, toluene, NMP, water or under neat conditions. The
amount of organocatalyst 1a was 15 mol % with respect to aldehyde
8a. Under the studied conditions syn-aldol 9a formed as the major
product (syn/anti>9:1). The enantiomeric excess of the compound
syn-9a was 92e96% ee irrespective of the solvent. However, the
product yield was influenced by the solvent nature: it was poor
(10e45%) in CH2Cl2, THF, NMP or water (Table 1, entries 1e4) and
rose to 99% in toluene or under neat conditions (Table 1, entries 5,
6). Lowering the temperature to 4 ꢁC or ketone 7a excess to 5 equiv
resulted in a decrease of the reaction rate but scarcely effected
selectivity (Table 1, entries 7, 8). The reaction between compounds
7a and 8a in the presence of (R)-threonine-derived organocatalyst
1b (15 mol %) under optimal conditions (PhMe, rt) gave the aldol
ent-9a in 99% yield (Table 1, entry 9), however, diastereo- (syn/anti
76/24) and enantioselectivity (ꢀ14% ff) were lower than in the
respective reaction catalyzed by the isomer 1a. The presence of the
primary amino acid fragment in catalysts 1a and 1b is crucial for the
syn-diastereoselectivity: anti-aldol 9a was the major product when
the reaction between compounds 7a and 8a was carried out in the
presence of immobilized catalyst 1c10c (15 mol %) bearing (S)-pro-
line instead of (S)-threonine unit (Table 1, entry 10).
Next, we applied catalyst 1a in asymmetric aldol reactions be-
tween hydroxyacetone (7a) and aromatic (heteroaromatic) alde-
hydes 8aej. In all the cases, the corresponding aldols 9aeo were
obtained. High yields (90e99%) were achieved after 24 h in the
reactions of aldehydes 8aef, bearing electron-withdrawing groups
on the aromatic ring (Table 2, entries 1e6) and in the reaction of
Table 1
Asymmetric aldol reactions between compounds 7a and 8a in the presence of organocatalysts 1a, 1b or 1c: optimization of reaction conditions
O
OH
4
O
OH
4
3
3
O
+
+
Me
Me
Ar
Ar
O
1a,c
OH
OH
1 (15 mol %)
+
Me
syn-9a (3R,4S)
O
anti-9a (3S,4S)
O
1b
solvent
OH
OH
OH
NO2
r.t., 15 h
7a (10 equiv.)
8a
3
3
4
4
Me
Me
Ar
Ar
OH
OH
O
N
O
ent-syn-9a (3S,4R)
ent-anti-9a (3R,4R)
4
O
i
Pr
N
N
HN
H3C
PF6
H
9: Ar = 4-NO2C6H4
Ph
Ph
1c
HO
Entry
Solvent
Catalyst
Yield of 9 %a
dr (syn/anti)b
ee (syn) %c
1
2
3
4
5
6
CH2Cl2
THF
NMP
H2O
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
9a, 45
9a, 10
9a, 10
9a, 9
93/7
93/7
92/8
93/7
90/10
93/7(80/20d)
94/6
92/8
76/24
24/76
96
94
92
94
neat
9a, 99
92
PhMe
PhMe
PhMe
PhMe
PhMe
9a, 99(91d)
9a, 75
94(80d)
93
7e
8f
9
9a, 80
ent-9a, 99
9a, 90
92
ꢀ14
10
70g
a
Total yield of a mixture of syn- and anti-isomers after column chromatography on silica gel.
b
c
d
e
f
3
3
4
1H NMR spectroscopic data (JH
4 syn 2.6 Hz, JH
anti 5.0 Hz).
eH
eH
HPLC (Daicel Chiralpak AD, Hexane/Isopropanol¼9:1, Flow rate¼0.5 mL/min, 254 nm): tR¼62.5 min (minore3S,4R-syn-9a), 93.0 min (majore3R,4S-syn-9a).
Data according to Ref. 9a.
The reaction was carried out at 4 ꢁS.
The amount of 7a was 5 equiv with respect to 8a.
The ee value of anti-9a is given.
g

1950
N.A. Larionova et al. / Tetrahedron 67 (2011) 1948e1954
Table 2
IL 1a-catalyzed asymmetric aldol reactions between compounds 7 and 8a
O
OH
4
O
O
OH
4
O
1a (15 mol %)
3
3
+
+
Ar
Ar
Ar
PhMe, rt, 24 h
R1
R2
R1
7a-d (10 equiv.)
7: R1 = H, R2 = OH (a), OMe (b), Me (c); R1 = R2 = OH (d)
R2
R1
R2
8a-j
anti-9a-o (3S,4S)
syn-9a-o (3R,4S)
Entry
9
R1
R2
Ar
Yield of 9 %b
dr (syn/anti)c
fe (syn) %d
1
2
3
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OMe
OMe
OMe
Me
OH
4-NO2C6H4
2-NO2C6H4
2-ClC6H4
99 (91e)
93/7 (80/20e)
94 (80e)
94 (92f, 91g, 85h)
97/3 (>95/5f, 99/1g, 97/3h)
97 (98f, 99g, 98h)
96 (91f, 99g)
97/3 (94/6f, 88/12g)
86/14
97 (97f, 92g)
4-FC6H4
99
92
5
4-MeO2CC6H4
4-OHCC6H4
4-MeOC6H4
3-PhOC6H4
2-Naphthyl
2-Thienyl
4-NO2C6H4
2-ClC6H4
2-Thienyl
95 (95f)
90
93/7 (93/7f)
80/20
95 (95f)
99
6
7i
8
79 (50g)
48
96/4 (94/6g)
94/6
96 (93g)
94
9
60
99
99
98
99
46
40
95/5
95/5
84/16
95/5
95/5
75/25
90/10
87
98
99
97
96
86
92
10
11
12
13
14i
15j
4-NO2C6H4
4-NO2C6H4
a
Unless otherwise specified, reactions were carried out with 7 (1.3 mmol), 8 (0.13 mmol), and the toluene (0.2 mL).
b
c
d
e
f
Total yield of a mixture of syn- and anti-isomers after column chromatography on silica gel.
1H NMR spectroscopic data.
HPLC data (Chiralcel AD, eluent n-hexane/i-PrOH 7/3, 0.7 mL/min, 254 nm) for purified compounds.
Data according to Ref. 9a.
Data according to Ref. 9c.
Data according to Ref. 8b.
Data according to Ref. 8a.
Reaction period was 50 h.
g
h
i
j
Dihydroxyacetone 7d was generated in situ from corresponding dimer in the presence of AcOH (15 mol %) and the reaction period was 60 h.
2-thiophene aldehyde 8j (Table 2, entry 10). Interestingly, only one
The feasibility of recycling of catalyst 1a was demonstrated in the
asymmetric aldol reaction between compounds 7a and 8a. After the
reaction completed, aldol 9a was extracted with diethyl ether and
replaced with fresh portions of starting compounds 7a and 8a in
toluene. Product yield andreactiondiastereo-and enantioselectivity
retained over three reaction cycles (Table 3). However, the reaction
period increased from 24 h in the first cycle to 4 and 7 days in the
second and in the third cycles, respectively, and in the fourth itera-
tion the yield of aldol 9a did notexceed 20% overaweek. The catalyst
deactivationwas not caused by its ‘washing out’ during the working-
up procedure. In contrast, the mass of recovered matter increased by
15e20% in each subsequent cycle presumably due to the formation
of by-products incorporating the catalyst. The reaction rate became
somewhat higher after the addition of AcOH (15 mol %). Hence, we
assume that the acid returned part of the poisoned catalyst to the
catalytic cycle.
of two aldehyde groups in terephthalaldehyde 8f took part in the
reaction (Table 2, entry 6). 4-Methoxybenzaldehyde (8g) and poly-
nuclear aromatic aldehydes 8h,i were found to be less active under
the conditions studied: yields of respective aldols 9h,i after 24 h
were 48e60% and the aldol 9g was obtained in 79% yield after 48 h
(Table 2, entries 7e9). The scope of the donor ketones is not limited
by hydroxyacetone 7a. Methoxyacetone (7b) also reacted with al-
dehydes 8 under the studied conditions yielding the respective
aldols 9kem in nearly quantitative yields (Table 2, entries 11e13).
Ethyl methylketone (7c) and 1,3-dihydroxyacetone (7d), which
was generated in situ from commercially available 1,3-di-
hydroxyacetone dimer in the presence of AcOH (15 mol %) were less
active in the studied reactions. Moderate yields of corresponding
aldols 9n,o were achieved after 50e60 h, however, the syn:anti
ratio and ee values of products 9n,o were rather high (Table 2,
entries 14, 15).
3 4
According to 1H NMR spectroscopic data (J
0e4 Hz,
Table 3
HeH syn
Recycling of the catalyst 1a in the reaction between compounds 7a and 8aa
3 4
J
¼5e10 Hz) the syn/anti diastereomeric ratio (dr) of aldols
HeH anti
Cycle
Time, db
Yield of 9a %
dr (syn/anti)
ee (syn) %
9aeo was high (ꢂ75:25) irrespective of the aldehyde structure.
Moreover, the ee values of the major syn-isomers were similar to or
even higher than those under the influence of the most efficient
1
2
3
4
1(1)
4 (2)
7 (5)
7
99 (98)
98 (96)
98 (94)
20
93/7 (92/8)
92/8 (91/9)
94/6 (92/8)
93/7
94 (92)
93 (92)
94 (91)
93
primary a
-amino acid-derived catalysts A.9 The absolute (3R,4S)-
configuration was assigned to the major enantiomers of aldols 9
based on HPLC-analysis of the product syn-9a [Chiralcel AD, eluent
n-hexane/i-PrOH 9/1, 0.5 mL/min, retention times: 62.5 min
(minore3S,4R), 93.0 min (majore3R,4S)] and comparison of the
a
Reactions were carried out under conditions specified in Table 2; After the
indicated time the catalyst was separated from the products by addition of ether
(see Experimental section) and reused.
b
Reaction period in the presence of AcOH (15 mol %) is given in brackets.
results with available HPLC-data for both enantiomers of this
7a,8a
compound.
This assignment was in accordance with optical
20
rotations of syn-aldols 9a ([
a]
20 þ39.0), 9b ([
a
]
20 ꢀ142.0), 9c ([
a]
D
D
D
The prepared compounds are valuable intermediates for the
synthesis of polyols with syn-configuration of hydroxy groups,
which are structural units of carbohydrates and some other natural
þ37.2), their signs were opposite to the reported rotation signs for
their (3S,4R)-antipodes8b under similar measurement conditions
(c 1, CH3OH).
compounds.11 The synthetic utility of syn-aldols
9
was

N.A. Larionova et al. / Tetrahedron 67 (2011) 1948e1954
1951
demonstrated by the reduction of the aldol 9b to the triol 10 with
sodium borohydride (Scheme 2). Despite of the absence of chiral
catalyst, the reaction was stereoselective affording all-syn-1-(2-
nitrophenyl)butane-1,2,3-triol 10 as the major product. The
(1S,2R,3R)-configuration was assigned to compound 10 based on
the configuration of starting aldol 9b and on the identity of its di-
astereomeric composition with the reported data.8a The 1S/1R-ratio
for compound 10 was 96/4 (1H NMR spectroscopic data) in accor-
dance with that in the aldol 9b.
with hexane/Et2O 3/1 (2ꢃ10mL). The resulting white solid was
dried in vacuo (0.5 Torr) at 50 ꢁC for 2 h to afford amides 3a or 3b.
Compound 3a: Yield 5.40
g (70%) as colorless solid, mp
26
120e122 ꢁS; [
a
]
ꢀ48.1 (c 1, CHCl3); 1H NMR (CDCl3)
d: 7.52 (m,
D
4H, Ar), 6.96e7.44 (11H, Ar, 1H, NH), 5.91 (d, J¼8.1 Hz, 1H, NH), 5.15
(m, 1H, CHO), 5.10 (s, 2H, CH2CO), 4.98 (d, J¼9.5 Hz, 1H, CHNHCO),
4.01 (d, J¼7.0 Hz, 1H, CHNH2), 1.88 (m, 1H, CH(CH3)2), 0.89 (d,
J¼7.0 Hz, 3H, OCHCH3), 0.84 (d, J¼7.0 Hz, 6H, CH(CH3)2); 13C NMR
(CDCl3) d: 170.4, 156.0, 146.3, 137.1, 128.3, 128.0, 127.8, 127.7, 127.0,
126.1, 125.4, 125.2, 80.9, 65.6, 65.4, 61.4, 57.7, 28.6, 22.9, 19.4, 17.9. IR
spectra (KBr, cmꢀ1): 3401, 3063, 2963, 1707, 1643, 1532, 1450, 1250,
1063, 747, 669. Elemental analysis calcd for C29H34N2O5: C, 71.00; H,
6.99; N, 5.71; found C, 71.12; H, 6.81; N, 5.82.
Compound 3b: Yield 5.6
g (73%) as colorless solid, mp
26
132e134 ꢁC; [
a
]
þ17.8 (c 1, CHCl3); 1H NMR (acetone-d6)
d: 8.06
D
(d, J¼8.0 Hz, 4H, Ar), 7.61e7.96 (11H, Ar), 7.58 (d, J¼8.0 Hz, NH), 6.60
(br, 1H, NH), 5.57 (m, 1H, CHO), 5.53 (m, 2H, CH2CO), 5.48 (m, 1H,
CHNHCO), 4.12 (m, 1H, CHNH2), 2.26 (m, 1H, CH(CH3)2), 1.51 (d,
J¼6.2 Hz, 3H, OCHCH3), 1.38 (d, J¼6.6 Hz, 6H, CH(CH3)2); 13C NMR
Scheme 2. Reduction of 9b to syn, syn-triol 10.
3. Conclusion
(CDCl3) d: 169.4, 154.2, 146.3, 137.1, 128.3, 128.0, 127.8, 127.8, 127.0,
In conclusion, we have synthesized for the first time an immo-
bilized organocatalyst for asymmetric syn-aldol reactions by in-
126.1, 125.4, 125.2, 81.3, 65.6, 65.4, 61.4, 57.7, 28.6, 22.9, 19.4, 17.9. IR
spectra (KBr, cmꢀ1): 3400, 3060, 2965, 1709, 1645, 1530, 1453, 1255,
1066, 749, 670. Elemental analysis calcd for C29H34N2O5: C, 71.00;
H, 6.99; N, 5.71; found C, 71.28; H, 6.84; N, 5.86.
corporating (S)-threonine and
chiral ionic liquid. In the presence of this catalyst ketones bearing
secondary carbon atom(s) at the -position with respect to the
a,a-(S)-diphenylvalinol units into
a
carbonyl group reacted with aromatic (heteroaromatic) aldehydes
affording the respective syn-aldols in high yields (up to 99%) and
with high diastereo- (syn/anti up to 97:3) and enantioselectivity (up
to 99% ee), which was maintained over 3 reaction cycles. The op-
timization of the catalyst structure aiming at the extension of its
operation period is currently under way in our laboratory.
4.2.2. 5-Bromopentanoic acid 2-benzyloxycarbonylamino-2-[1-(hy-
droxy-diphenyl-methyl)-2-methyl-propylcarbamoyl]-1-methyl-ethyl
esters (4a) and (4b). A mixture of amide 3a or 3b (5.0 g, 10.2 mmol),
5-bromovaleric acid (1.84 g, 10.2 mmol), DCC (2.10 g, 10.2 mmol),
and DMAP (cat.) in CH2Cl2 (30 mL) was stirred at 5 ꢁC for 12 h. The
precipitate was filtered off and washed with CH2Cl2 (3ꢃ5 mL). The
combined organic extracts were evaporated, the residue was pu-
rified by column chromatography on silica gel (eluent: n-hexane/
EtOAc 3/1) to afford ester 4a or 4b.
4. Experimental
4.1. General
Compound 4a: Yield 5.3 g (80%) as colorless oil, [
a
]
26 ꢀ21.25 (c 1,
D
CHCl3); Rf¼0.31; 1H NMR (CDCl3)
d: 7.60e7.15 (m, 15H, Ar), 6.75 (d,
NMR 1H and 13C spectra were recorded with Bruker AM 300
instrument in CDCI3, DMSO-d6 and acetone-d6. Chemical shifts of
1H and 13C were measured relative to Me4Si or CDCl3, respectively.
High resolution mass spectra (HRMS) were measured on a Bruker
microTOF II instrument using electrospray ionization (ESI).12 The
measurements were done in a positive ion mode (interface capil-
lary voltagee4500 V) or in a negative ion mode (3200 V); mass
range from m/z 50 to m/z 3000 Da; external or internal calibration
was done with Electrospray Calibrant Solution (Fluka). A syringe
J¼7.0 Hz, 1H, NH), 5.60 (d, J¼9.9 Hz, 1H, NH), 5.30e5.05 (s, 2H,
CH2CO, 1H, CH), 5.01 (d, J¼9.8 Hz, 1H, CH), 4.18 (m, 1H, CHNH2), 3.32
(t, J¼6.3 Hz, 2H, CH2Br), 2.60 (br, 1H, OH), 2.22 (m, 2H, CH2), 1.82 (m,
2H, CH2), 1.70 (m, 1H, CH; 2H, CH2), 1.80 (m, 2H, CH2; 1H, CH(CH3)2),
0.85e0.76 (m, 3H, OCHCH3; 6H, CH(CH3)2); 13C NMR (CDCl3)
d:
172.0, 168.8, 155.2, 147.4, 146.2, 137.1, 128.5e125.4 (Ar), 81.0, 69.5,
65.8, 58.9, 57.9, 34.7, 31.9, 28.7, 23.1, 23.0, 17.9, 16.6. IR spectra (KBr,
cmꢀ1): 3464, 3321, 3062, 2936, 1726, 1648, 1533, 1449, 1239, 1064,
747, 699. Elemental analysis calcd for C34H41BrN2O6: C, 62.48; H,
6.32; N, 4.29; found C, 62.23; H, 6.24; N, 4.41.
injection was used for solution in methanol (flow rate 3 mL/min).
Compound 4b: Yield 5.2 g (78%) as colorless oil, [
a
]
26 ꢀ21.45 (c 1,
Nitrogen was applied as a dry gas; interface temperature was set at
D
180 ꢁC. IR spectra (KBr pellets) were recorded with a Specord M82
CHCl3); Rf¼0.34; 1H NMR (acetone-d6)
d: 7.17e7.51 (15H, Ar). 7.14
20
instrument. Specific optical rotations [
a
]
were measured with
D
(d, J¼7.0 Hz, 1H, NH), 6.67 (d, J¼9.9 Hz, 1H, NH), 5.40 (m, 1H, CH),
5.32 (m, 1H, CHNH2), 5.0 (m, 2H, CH2CO), 4.12 (dd, J1¼4.9 Hz,
J2¼12.8 Hz, 1H), 3.35 (t, J¼6.3 Hz, 2H, CH2Br), 2.78 (br, 1H, OH), 1.86
(m, 1H, CH(CH3)2), 1.80 (m, 2H, CH2CH2), 1.63 (m, 2H, CH2CH2), 1.24
(d, J¼6.2 Hz, 3H, OCHCH3), 0.86 (m, 6H, CH(CH3)2); 13C NMR (CDCl3)
a Jasco DIP-360 instrument at 589 nm. Silica gels 0.060e0.200 and
0.035e0.070 nm (Acros) were used for column chromatography.
Solvents were purified by standard methods.
4.2. Catalysts preparation
d: 171.0, 168.6, 156.2, 146.1, 145.3, 128.6e125.3 (Ar), 82.2, 69.6, 67.3,
58.8, 58.0, 33.0, 31.9, 28.9, 23.3, 22.7, 17.4, 16.8. IR spectra (KBr,
cmꢀ1): 3466, 3319, 3060, 2933, 1728, 1650, 1530, 1451, 1242, 1065,
749, 701. Elemental analysis calcd for C34H41BrN2O6: C, 62.48; H,
6.32; N, 4.29; found C, 62.31; H, 6.19; N, 4.37.
4.2.1. 2-Hydroxy-1-{[1-(hydroxy-diphenyl-methyl)-2-methyl-pro-
pylcarbamoyl]-propyl}-carbamic acid benzyl esters (3a) and (3b). A
solution of ethylchloroformate (1.51 mL, 15.8 mmol) in THF (10 mL)
was added dropwise to a stirred solution of (S)- or (R)-N-(carbo-
benzyloxy)threonine 2a or 2b (4.0 g, 15.8 mmol) and Et3N (2.21 mL,
4.2.3. 1-(4-{2-Benzyloxycarbonylamino-2-[1-(hydroxy-diphenyl-
methyl)-2-methyl-propylcarbamoyl]-1-methyl-ethoxycarbonyl}-butyl)-
3-methyl-3H-imidazol-1-ium bromides (5a) and (5b). A mixture of
compound 4a or 4b (5.00 g, 7.65 mmol) and 1-methyl-1H-imidazole
(2.46 g, 30 mmol) was heated at 80 ꢁC for 5 min, cooled to 20 ꢁC and
washed thoroughly with Et2O (5ꢃ10 mL). The residue was dissolved
in MeOH (3 mL), then Et2O (30 mL) was added to the solution.
15.8 mmol) in THF (20 mL) at 0 ꢁC for 15 min. After 30 min,
a,a-(S)-
diphenylvalinol (16.0 mmol, 3.6 g) was gradually added (15 min) to
the mixture. The resulting solution was stirred at 0 ꢁC for 1 h, kept
at ambient temperature for 16 h and then diluted with ethyl acetate
(30 mL). By-product Et3N$HCl was filtered off, the filtrate was
evaporated under reduced pressure and the residue was washed

1952
N.A. Larionova et al. / Tetrahedron 67 (2011) 1948e1954
The separated oil was dried under reduced pressure (0.5 Torr) for 1 h
to afford bromides 5a or 5b.
filtrate was evaporated under reduced pressure (40 Torr) and the
residue was dried in vacuo (0.5 Torr) for 2 h to afford catalyst 1a or 1b.
Compound 5a: Yield 4.8 g (85%) as highly hydroscopic yellow
Catalyst 1a: Colorless solid, yield 3.5 g (97%), mp 110e112 ꢁC;
26
26
solid, [
a
]
ꢀ33.2 (c 1, CHCl3); 1H NMR (CDCl3)
d
: 10.04 (s, 1H,
[a
]
ꢀ32.0 (c 1, CH3OH); 1H NMR (acetone-d6)
d: 9.08 (s, 1H,
D
D
NCHN), 8.09e6.98 (m, 17H, Ar; 1H, NH), 5.98 (d, J¼8.2 Hz, 1H, NH),
5.02e4.90 (m, 2H, CH2; 1H, CH; 1H, CH), 4.47 (m, 1H, CH), 4.16 (m,
2H, CH2), 3.96 (s, 3H, CH3), 2.26 (m, 2H, CH2), 1.87 (m, 2H, CH2; 1H,
CH), 1.53 (m, 2H, CH2), 0.98 (d, J¼7.5 Hz, 3H, OCHCH3), 0.78 (d,
NCHN), 7.76 (s, 2H, NCHCHN), 7.70 (s, 2H, NCHCHN), 7.60 (m, 4H,
Ar), 7.44e7.03 (8H, Ar and NH), 5.12 (br, 1H, CHO), 5.00 (dd,
J1¼6.23 Hz, J2¼2.2 Hz, 1H, CHNHCO), 4.37 (t, J¼7.30 Hz, 2H,
NCH2CH2), 4.21 (m, 1H, CHNH2), 4.06 (s, 3H, NCH3), 2.93 (br, 1H,
OH), 2.34 (t, J¼7.00 Hz, 2H, CH2CO), 2.04 (m, 2H, CH2CH2), 1.96 (m,
1H, CH(CH3)2), 1.64 (m, 2H, CH2CH2), 0.94 (d, J¼6.60 Hz 3H,
OCHCH3), 0.77 (dd, J1¼6.60 Hz, J2¼2.5 Hz, 6H, CHCH3); 13C NMR
J¼6.4 Hz, 6H, CH(CH3)2); 13C NMR (CDCl3)
d: 171.7, 168.9, 155.9,
147.2, 146.0, 136.9, 136.5, 128.3e122.2 (Ar), 80.8, 69.4, 65.4, 58.8,
57.8, 48.4, 35.8, 34.5, 28.6, 22.7, 21.7, 17.8, 16.1. IR spectra (KBr,
cmꢀ1): 3391, 3063, 2958, 1721, 1664, 1525, 1450, 1238, 1169, 1064,
749, 702. Elemental analysis calcd for C38H47BrN4O6: C, 62.04; H,
6.44; N, 7.62; found C, 62.22; H, 6.35; N, 7.49.
(CDCl3) d: 171.9, 170.5, 147.4, 146.6, 128.1, 127.8, 126.2, 125.7, 125.4,
123.7, 122.4, 81.1, 71.00, 59.1, 57.6, 48.6, 35.8, 32.9, 28.9, 28.6, 23.0,
22.03, 18.07. IR spectra (KBr, cmꢀ1): 3413, 2962, 1637, 1522, 1450,
1171, 843, 751, 707, 558. Elemental analysis calcd for
C30H41F6N4O4P: C 54.05; H 6.20; N 8.40; P 4.65. Found C 54.28; H
6.11; N 8.17; P 4.89. HRMS: C30H41N4O4 calcd 521.3122, found
Compound 5b: Yield 4.5 g (80%) as highly hydroscopic yellow
26
solid, [
a]
ꢀ38.84ꢁ (c 1.6, CHCl3); 1H NMR (CDCl3)
d: 9.97 (s, 1H,
D
NCHN), 7.88 (d, J¼10.6 Hz, 1H, NH), 7.90e6.92 (m, 17H, Ar), 6.44 (d,
J1¼7.7 Hz,1H, NH), 5.17 (m, 1H, CH), 5.05 (s, 2H, CH2CO), 5.01 (m, 1H,
CH,), 4.44 (m, 1H, CH), 4.17 (m, 2H, CH2), 3.82 (s, 3H, CH3), 2.29 (m,
2H, CH2), 1.83 (m, 2H, CH2; 1H, CH), 1.53 (m, 2H, CH2), 1.20 (d,
J1¼6.0 Hz, 3H, CH3), 1.01 (d, J1¼6.6 Hz, 3H, OCHCH3), 0.80 (d,
521.3116. HRMS: C30H41N4O4 calcd 521.3122, found 521.3102.
26
Catalyst 1b: Yield 3.5 g (97%), mp 96e98 ꢁC [
a
]
D
ꢀ11.1 (c 1,
CH3OH); 1H NMR (DMSO-d6)
d: 9.08 (s, 1H, NCHN), 7.70 (s, 2H,
NCHCHN), 7.68 (s, 2H, NCHCHN), 7.47 (m, 4H, Ar), 7.34e7.00 (8H, Ar
and NH), 4.85 (m,1H, CHO), 4.53 (d, J¼5.10 Hz,1H, CHNHCO), 4.16 (t,
J¼6.80 Hz, 2H, NCH2CH2), 3.90 (m, 1H, CHNH2), 3.84 (s, 3H, NCH3),
2.17 (t, J¼7.10 Hz, 2H, CH2CO), 1.75 (m, 3H, CH2CH2, CH(CH3)2), 1.44
(m, 2H, CH2CH2), 0.85 (d, J¼6.40 Hz 3H, OCHCH3), 0.66 (d,
J¼6.80 Hz, 3H, CHCH3), 0.57 (d, J¼5.50 Hz, 3H, CHCH3); 13C NMR
J1¼6.3 Hz, 3H, CH(CH3)2); 13C NMR (CDCl3)
d: 171.9, 169.0, 156.3,
147.5, 145.0, 134.5, 128.6e122.1 (Ar), 82.0, 70.1, 66.7, 58.6, 49.3, 36.6,
33.3, 29.2, 28.9, 23.0, 21.0, 18.3, 16.4. IR spectra (KBr, cmꢀ1): 3390,
3060, 2959, 1723, 1665, 1528, 1451, 1240, 1170, 1062, 752, 701. Ele-
mental analysis calcd for C38H47BrN4O6: C, 62.04; H, 6.44; N, 7.62;
found C, 62.31; H, 6.29; N, 7.81.
(CDCl3) d: 172.1, 169.5, 145.4, 144.3, 124.6, 126.4, 126.2, 123.9, 122.8,
122.6, 122.4, 82.3, 72.2, 60.3, 58.6, 50.7, 35.8, 32.9, 28.9, 28.4, 23.5,
21.0, 16.3. IR spectra (KBr, cmꢀ1): 3411, 2963, 1638, 1520, 1452, 1174,
845, 750, 704, 560. Elemental analysis calcd for C30H41F6N4O4P: C
54.05; H 6.20; N 8.40; P 4.65. Found C 53.77; H 6.35; N 8.61; P 4.72.
HRMS: C30H41N4O4 calcd 521.3122, found 521.3117.
4.2.4. 1-(4-{2-Benzyloxycarbonylamino-2-[1-(hydroxy-diphenyl-
methyl)-2-methyl-propylcarbamoyl]-1-methyl-ethoxycarbonyl}-bu-
tyl)-3-methyl-3H-imidazol-1-ium hexafluorophosphates (6a) and
(6b). A solution of KPF6 (1.1 g, 5.44 mmol) in water (10 mL) was
added to a stirred solution of bromide 5a or 5b (4.0 g, 5.44 mmol) in
water (10 mL). The precipitate was filtered off, washed with water
(3ꢃ10 mL) and dried under reduced pressure (0.5 Torr) for 1 h.
4.3. General procedure for the aldol reaction
Compound 6a: Yield 4.2 g (96%), colorless solid, mp 156e157 ꢁS;
Ketone 7 (1.30 mmol) and aldehyde 8 (0.13 mmol) and AcOH
(0.02 mmol, if specified) were added to a suspension of the catalyst
1a, 1b or 1c (0.02 mmol) in toluene (0.2 mL). The reaction mixture
was stirred at ambient temperature for the indicated time (TLC-
monitoring) (Tables 1e3). The solvent was evaporated under re-
duced pressure and the residue was extracted with Et2O (3ꢃ1 mL).
The combined extracts were evaporated in vacuo affording aldols 9,
which were purified by column chromatography on silica gel.
Yields of compounds 9 are given in Tables 1e3. Optical rotations
and 1H NMR data of compounds 9aec,9a,c 9e,9c 9g,8b 9k,13 9l,13 9n,8e
and 9o8b were identical to reported in the literature. Characteristics
of newly synthesized compounds are given below.
26
[
a]
ꢀ28.1 (c 1, CHCl3); 1H NMR (CDCl3)
d: 9.10 (s, 1H, NCHN),
D
8.10e6.90 (m, 17H, Ar; 1H, NH), 6.01 (d, J¼8.0 Hz, 1H, NH),
5.01e4.87 (m, 2H, CH2; 1H, CH; 1H, CH), 4.46 (m, 1H, CH), 4.20 (m,
2H, CH2), 3.96 (s, 3H, CH3), 2.26 (m, 2H, CH2), 1.87 (m, 2H, CH2; 1H,
CH), 1.53 (m, 2H, CH2), 0.98 (d, J¼7.0 Hz, 3H, OCHCH3), 0.78 (d,
J¼6.3 Hz, 6H, CH(CH3)2); 13C NMR (CDCl3)
d: 170.1, 166.3, 155.9,
147.2, 146.0, 136.9, 136.5, 126.3e120.1 (Ar), 81.0, 70.3, 65.2, 57.8,
56.4, 43.1, 33.4, 34.6, 28.4, 21.4, 22.3, 17.6, 16.0. IR spectra (KBr,
cmꢀ1): 3411, 3167, 2961, 1723, 1656, 1524, 1450, 1239, 1170, 1065,
844, 749, 703, 558. Elemental analysis calcd for C38H47PF6N4O6: C,
57.00; H, 5.92; N, 7.00; found C, 56.92; H, 5.81; N, 7.11.
Compound 6b: Yield 4.25
g (97%), colorless solid, mp
168e169 ꢁS; [
a
]
D
26 ꢀ36.1 (c 1, CHCl3); 1H NMR (CDCl3)
d: 9.09 (s, 1H,
4.3.1. (3R,4S)-4-(4-fluorophenyl)-3,4-dihydroxybutan-2-one
20
NCHN), 8.11e6.90 (m, 17H, Ar; 1H, NH), 5.98 (d, J¼8.0 Hz, 1H, NH),
5.01e4.87 (m, 2H, CH2; 1H, CH; 1H, CH), 4.31 (m, 1H, CH), 4.18 (m,
2H, CH2), 4.01 (s, 3H, CH3), 2.26 (m, 2H, CH2), 1.87 (m, 2H, CH2; 1H,
CH), 1.53 (m, 2H, CH2), 0.98 (d, J¼7.0 Hz, 3H, OCHCH3), 0.78 (d,
(9d). Colorless oil; [
d
a]
þ26.3 (c 1, MeOH); 1H NMR (CDCl3):
D
¼7.41 (m, 2H, Ar), 7.08 (t, J¼9.2 Hz, 2H, Ar), 5.0 (d, J¼3.6 Hz, 1H,
CHOH), 4.37 (d, J¼3.3 Hz, 1H, CHOH), 2.19 (s, 3H, CH3) ppm; 13C
NMR (CDCl3) d: 207.1, 160.5, 136.5, 128.9, 115.7, 95.6, 73.4, 18.4. IR
J¼6.3 Hz, 6H, CH(CH3)2); 13C NMR (CDCl3)
d: 169.1, 165.3, 156.7,
spectra (KBr, cmꢀ1): 3459, 1716, 1511, 1450, 1384, 1097, 1307, 1097,
146.3, 145.6, 137.5, 136.5, 125.3e122.1 (Ar), 82.0, 70.8, 66.0, 58.8,
56.7, 44.8, 34.1, 34.8, 28.1, 21.2, 22.4, 17.63, 15.6. IR spectra (KBr,
cmꢀ1): 3412, 3166, 2963, 1727, 1655, 1521, 1452, 1241, 1172, 1068,
850, 746, 702, 560. Elemental analysis calcd for C38H47PF6N4O6: C,
57.00; H, 5.92; N, 7.00; found C, 56.88; H, 5.80; N, 7.13.
758, 669. HPLC (Chiralcel AD, n-hexane/i-PrOH¼9/1, flow
rate¼1.0 mL/min,
l
¼254 nm, t1 (minor)¼11.2 min, t2 (major)¼
12.7 min). Elemental analysis calcd for C10H11FO3: C, 60.60; H, 5.59;
found C, 60.84; H, 5.71.
4.3.2. 4-((1S,2R)-1,2-dihydroxy-3-oxobutyl)benzaldehyde
20
4.2.5. 1-(4-{2-Amino-2-[1-(hydroxy-diphenyl-methyl)-2-methyl-
propylcarbamoyl]-1-methyl-ethoxycarbonyl}-butyl)-3-methyl-3H-
imidazol-1-ium hexafluorophosphates (1a) and (1b). The obtained
colorless solid 6a,b (4.2 g, 5.00 mmol) was dissolved in CH3OH
(100 mL) and 5% Pd/C (300 mg) was added to the solution. The
resulting suspension was stirred under H2 (1 bar) for 2 h, filtered, the
(9f). Colorless oil; [
CDCl3)
a]
þ32.4 (c 1, MeOH); 1H NMR (300 MHz,
D
d
: 10.03 (s, 1H, CHO), 7.92 (d, J¼8.0 Hz, 2H, Ar), 7.61 (d,
J¼8.0 Hz, 2H, Ar), 5.17 (d, J¼2.5 Hz, 1H, CHOH), 4.41 (d, J¼2.7 Hz, 1H
CHOH), 2.17 (s,1H, CH3); 13C NMR (CDCl3)
d: 208.5,191.9,148.9,135.1,
129.4e126.5 (Ar), 80.4, 79.4, 73.1, 67.8, 25.9. IR spectra (KBr, cmꢀ1):
3460, 1703, 1609, 1419, 1360, 1307, 1064, 844, 668. HPLC (Chiralcel

N.A. Larionova et al. / Tetrahedron 67 (2011) 1948e1954
1953
AD, n-hexane/i-PrOH¼9/1, flow rate¼1.0 mL/min,
l
¼254 nm, t1
eluent EtOAc/n-hexane 1:1) to afford the compound 10 (33 mg,
(minor)¼15.5 min, t2(major)¼16.7 min). Elemental analysiscalcd for
80%) as colorless oil.8a
C11H12O4: C, 63.45; H, 5.81; found C, 63.31; H, 5.89.
Acknowledgements
4.3.3. (3R,4S)-3,4-Dihydroxy-4-(3-phenoxyphenyl)butan-2-one
(9h). Colorlessoil;[
a
]
20þ23.1(c1,MeOH);1HNMR(CDCl3)
d:7.22e6.25
D
Financial supports by the President of the Russian Federation
(grant for young Ph.D. No. MK-7437.2010.3) and by the Russian
Foundation of Basic Research (grants No. 09-03-00384 and 09-
03-12164) are gratefully acknowledged. In addition, we are
grateful to Department of Structural Studies of Zelinsky Institute
of Organic Chemistry (Moscow) for recording high resolution
mass spectra.
(9H,Ar),4.86(d,J¼3.2Hz,1H,CHOH),4.50(d,J¼3.1Hz,1H,CHOH),2.08(s,3H,
CH3)ppm;13CNMR(CDCl3)
d:207.1,156.1,155.3,140.5,128.2,128.4,121.6,
120.4,117.3,116.1,95.5,73.5,18.4.IRspectra(KBr,cmꢀ1):3465,1706,1489,
1359,1250,1085,756,694.HPLC(ChiralcelAD,n-hexane/i-PrOH¼9/1,
flow rate¼1.0 mL/min, ¼254 nm, t1 (minor)¼15.1 min, t2(major)¼
l
18.4min).ElementalanalysiscalcdforC16H16O4:C,70.57;H,5.92;foundC,
70.73;H,6.07.
Supplementary data
4.3.4. (3R,4S)-3,4-Dihydroxy-4-(naphthalen-2-yl)butan-2-one
(9i). Colorless oil; [
a]
20 þ32.7 (c 1, MeOH); 1H NMR (CDCl3)
d: 7.88
D
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.01.017.
(m, 4H, Ar), 7.51 (m, 4H, Ar), 5.20 (d, J¼3.3 Hz, 1H, CHOH), 4.49 (d,
J¼3.3 Hz, 1H, CHOH), 2.18 (s, 1H, CH3); 13C NMR (CDCl3)
d: 207.1,
133.5e127.2 (Ar), 93.0, 75.6, 19.2. IR spectra (KBr, cmꢀ1): 3429, 1715,
1384, 1360, 1171, 1056, 758, 669. HPLC (Chiralcel AD, n-hexane/i-
References and notes
PrOH¼7/3, flow rate¼0.7 mL/min, ¼254 nm, t1(minor)¼7.3 min,
l
1. (a) Guillena, G.; Najera, C.; Ramon, D. J. Tetrahedron: Asymmetry 2007, 18,
2249e2293; (b) Laina Geary, M.; Philip Hultin, G. Tetrahedron: Asymmetry 2009,
20, 131e173; (c) Mlynarski, J.; Paradowska, J. Chem. Soc. Rev. 2008, 37,
1502e1511; (d) Notz, W.; Tanaka, F.; Barbas, C. F., III. Acc. Chem. Res. 2004, 37,
580e591; (e) Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37, 570e579; (f)
Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107,
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Catal. 2009, 351, 33e57.
2. (a) List, B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc. 2000, 122,
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MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 6798e6799; (g) Cordova, A.
Tetrahedron Lett. 2004, 45, 3949e3952.
3. (a) Tang, Z.; Jiang, F.;Cui, X.; Gong, L. Z.; Mi, A. Q.; Jiang, Y. Z.; Wu, Y. D. PNAS 2004,16,
5755e5760; (b) Jia, Y. N.; Wu, F. C.; Ma, X.; Zhu, G. J.; Da, C. S. Tetrahedron Lett. 2009,
50, 3059e3062; (c) Xu, X. Y.; Wang, Y. Z.; Cuna, L. F.; Gong, L. Z. Tetrahedron:
Asymmetry 2007,18, 237e242; (d) Russo, A.; Botta, G.; Lattanzi, A. Tetrahedron 2007,
63, 11886e11892; (e) Maya, V.; Raj, M.; Singh, V. K. Org. Lett. 2007, 9 (13),
2593e2595; (f) Guillena, G.; Hita, M. C.; Najera, C. Tetrahedron: Asymmetry 2006,17,
1493e1497.
t2(major)¼10.2 min). Elemental analysis calcd for C14H14O3: C,
73.03; H, 6.13; found C, 73.28; H, 6.26.
4.3.5. (3R,4S)-3,4-Dihydroxy-4-(thiophen-2-yl)butan-2-one
20
(9j). Pale-yellow oil; [
a
]
þ42.4 (c 1, MeOH); 1H NMR (CDCl3)
d:
D
7.31 (m, 1H, Ar), 7.13 (m, 1H, Ar), 6.98 (m, 1H, Ar), 5.28 (d, J¼2.75 Hz,
1H, CHOH), 4.42 (d, J¼2.75 Hz, 1H, CH, CHOH), 2.25 (s, 3H, CH3); 13
C
NMR (300 MHz, CDCl3) d: 207.5, 205.3, 143.6, 127.1e124.7 (Ar), 80.8,
70.8, 69.0, 29.8, 25.3. IR spectra (KBr, cmꢀ1): 3460, 1711, 1531, 1359,
1230, 1160, 1063, 750, 685. HPLC (Chiralcel AD, n-hexane/i-
PrOH¼9/1, flow rate¼1.0 mL/min, ¼254 nm, t1(minor)¼7.7 min,
l
t2(major)¼8.1 min). Elemental analysis calcd for C8H10O3S: C, 51.60;
H, 5.41; found C, 51.49; H, 5.52.
4.3.6. (3R,4S)-4-Hydroxy-3-methoxy-4-thiophen-2-yl-butan-2-one
20
(9m). Pale-yellow oil; [
a
]
D
þ38.4 (c 1, MeOH); 1H NMR (CDCl3)
d:
7.31(m, 1H, Ar), 7.05 (m, 1H, Ar), 6.99 (m, 1H, Ar), 5.17 (d, J¼3.3 Hz,
4. (a) Wu, Y.; Zhang, Y.; Yu, M.; Zhao, G.; Wang, S. Org. Lett. 2006, 8, 4417e4420; (b)
Wang, X. J.; Yan Zhao, Y.; Liu, J. T. Org. Lett. 2007, 9, 1343e1345.
1H, CHOH), 3.81 (d, J¼3.3 Hz, 1H, CHOH), 3.49 (s, 3H, CH3), 2.21 (s,
3H, CH3); 13C NMR (CDCl3)
d: 207.3, 146.3, 126.3, 125.5, 124.5, 102.4,
5. (a) Kofoed, J.; Nielsen, J.; Reymond, J. L. Bioorg. Med. Chem. Lett. 2003, 2445e2447;
(b) Tang, Z.; Yang, Z. H.; Cun, L. F.; Gong, L. Z.; Mi, A. Q.; Jiang, Y. Z. Org. Lett. 2004, 6,
2285e2287; (c) Andreae, M. R. M.; Davis, A. P. Tetrahedron: Asymmetry 2005, 16,
2487e2492; (d) Zou, W.; Ibrahem, I.; Dziedzic, P.; Sunden, H.; Cordova, A. Chem.
Commun. 2005, 4946e4948; (e) Lei, M.; Shi, L.; Li, G.; Chen, S.; Fang, W.; Ge, Z.;
Cheng, T.; Li, R. Tetrahedron 2007, 63, 7892e7898; (f) Dziedzic, P.; Zou, W.; Hafren,
J.; Cordova, A. Org. Biomol. Chem. 2006, 4, 38e40; (g) Akagawa, K.; Sakamoto, S.;
Kudo, K. Tetrahedron Lett. 2005, 46, 8185e8187.
80.0, 51.5, 19.2. IR spectra (KBr, cmꢀ1): 3462, 1704, 1529, 1360, 1223,
1165, 1060, 755, 690. HPLC (Chiralcel AD, n-hexane/i-PrOH 7/3, flow
rate¼0.7 mL/min,
l
¼254 nm, t1(minor)¼10.4 min, t2(major)¼
13.8 min). Elemental analysis calcd for C9H12O3S: C, 53.98, H, 6.04;
found C, 54.16, H, 5.95.
6. (a) Wong, C. H.; Bryan, M. C.; Nyffeler, P. T.; Liu, H.; Chapman, E. Pure Appl.
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4.5. Synthesis of (1S,2R,3R)-1-(2-nitrophenyl)butane-1,2,3-
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Sodium borohydride (63.4 mg, 1.67 mmol) was added to a so-
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purified by column chromatography on silica gel (0.060e0.200 nm,
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