Enzymatic resolution of 1,1-dimethoxybut-3-en-2-ol and 1,1-dimethoxypent-4- en-2-ol, α-hydroxyaldehyde precursors for aldol-type reactions

Article abstract of DOI:10.1016/j.tetasy.2005.05.013

Hydroxyacetals 2 and 3 were resolved by acylation with vinyl acetate in the presence of lipases in organic media. The reverse reaction, the enzymatic hydrolysis of the corresponding acetates, was also highly stereoselective and provided the opposite enant

Full text of DOI:10.1016/j.tetasy.2005.05.013

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2081–2086
Enzymatic resolution of 1,1-dimethoxybut-3-en-2-ol and
,1-dimethoxypent-4-en-2-ol, a-hydroxyaldehyde precursors
for aldol-type reactions
1
a,
Robert Ch eˆ nevert, S e´ bastien Gravil and Jean Bolte
a,b
b
*
a
D e´ partement de Chimie, CREFSIP, Facult e´ des Sciences et de G e´ nie, Universit e´ Laval, Qu e´ bec (Qc), Canada G1K 7P4
b
´
Laboratoire de Synth e` se et Etude de Syst e` mes a` Int e´ r eˆ t Biologique, UMR 6504 du CNRS, Universit e´ Blaise-Pascal,
3177 Aubi e` re Cedex, France
6
Received 1 February 2005; revised 22 March 2005; accepted 6 May 2005
Abstract—Hydroxyacetals 2 and 3 were resolved by acylation with vinyl acetate in the presence of lipases in organic media. The
reverse reaction, the enzymatic hydrolysis of the corresponding acetates, was also highly stereoselective and provided the opposite
enantiomers.
ꢀ
2005 Elsevier Ltd. All rights reserved.
1. Introduction
hydes by hydrolysis of the acetal group or ozonolysis
of the double bond.
The development of methods for stereoselective carbon–
carbon bond formation using aldol-type reactions is a
1
major focus of interest in organic synthesis. Both chem-
2
2. Results and discussion
2.1. Substrate preparation
–5
5–8
ical
and enzymatic
aldol reactions with very high
levels of asymmetric induction have been reported.
Aldolases catalyze the reversible stereoselective addition
of an active methylene donor (dihydroxyacetone phos-
phate or DHAP, glycine, pyruvate, etc.) with an alde-
hyde acceptor. To date, DHAP-dependent aldolases
Hydroxyacetal 2 and 3 (Scheme 1) are readily available
by the addition of a Grignard reagent to dimethoxyacet-
aldehyde 1 (glyoxal dimethyl acetal). This compound is
commercially available but undergoes oligomerization
and we found it more convenient to prepare it by a
two-step method: first treatment of furan with bromine
8
are the most widely used aldolases in organic synthesis.
Transketolase catalyzes the condensation of a hydroxy-
acetyl group provided by decarboxylation of hydroxy-
pyruvic acid with a-hydroxyaldehydes to yield ketoses
of (2S,3R)-configuration. Lerner and Barbas et al. have
shown that it is possible to obtain catalytic antibodies
that catalyze stereoselective aldol reactions.
metric aldol reactions catalyzed by metal-free organo-
catalysts, such as proline, have received increased
attention recently. Chiral a-substituted aldehydes
are valuable substrates for Mannich, aldol, and related
C–C bond-forming reactions. Herein, we report the
enzymatic resolution of 1,1-dimethoxybut-3-en-2-ol
and 1,1-dimethoxypent-4-en-2-ol. These highly func-
tionalized compounds are easily transformed into alde-
6
OH
OAc
c
5
,9
MeO
MeO
MeO
MeO
Asym-
a
O
MeO
MeO
2
4
2
,10–12
H
b
1
3
OH
OAc
c
1
MeO
MeO
MeO
MeO
1
4
3
5
Scheme 1. Reagents: (a) CH
2
@CH–MgBr, THF; (b) CH
2
2
@CH–CH –
*
Corresponding author. Tel.: +1 418 656 3283; fax: +1 418 656
916; e-mail: robert.chenevert@chm.ulaval.ca
Br, In, H O or CH @CH–CH –MgBr, THF; (c) Ac O, DMAP,
pyridine.
2
2
2
2
7
0
957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.05.013

2082
R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 16 (2005) 2081–2086
OH
OH
(CH
OAc
(CH
a
MeO
MeO
MeO
MeO
MeO
MeO
+
(
CH2)n
2
)
n
)
2 n
rac-2
rac-3
n = 0
n = 1
(S)-2
(S)-3
(R)-4
(R)-5
Scheme 2. Reagents: (a) vinyl acetate, enzyme.
1
5
in methanol followed by ozonolysis of the double
bond. Grignard addition of vinyl magnesium bromide
on 1 in THF provided 2 in moderate yield (both reagents
are freshly prepared for best yield). Compound 1 was
treated with allyl bromide and indium powder in water
preparative scale (entry 1). In the case of alcohol 3, all of
1
7
the active lipases showed good enantioselectivity (E
P29); among them Pseudomonas fluorescens lipase
(PFL) gave the best enantiomeric excesses and therefore
the highest E value (entry 5).
(Barbier reaction) to give homoallylic alcohol 3. Indium
metal is expensive and on preparative scale, 3 was pre-
pared by Grignard reaction of allyl magnesium bromide
with 1 in THF. The corresponding acetates 4 and 5
were prepared via the acetylation of 2 and 3 with acetic
anhydride in pyridine in the presence of dimethylamino-
pyridine (DMAP).
In general, the transesterification of racemic alcohols
and the hydrolysis of the corresponding racemic esters
are complementary and lead to opposite enantiomers
of both alcohol and ester. The results of the enzymatic
hydrolysis of acetates 4 and 5 in a phosphate buffer at
pH 7 are shown in Table 2. Among the lipases tested
for the hydrolysis of racemic 4, CAL-B retained the high
enantioselectivity already observed in the acylation reac-
tion but lipase from Pseudomonas sp. also showed high
enantiodiscrimination. Both lipases from Pseudomonas
cepacia and lipoprotein lipase (LPL) displayed high
enantioselectivity toward racemic 5. In regard to the ee
of the product and the remaining substrate as well as
the rate of conversion (50% in 10 h), LPL was the en-
zyme of choice for the resolution on preparative scale.
1
6
2
.2. Enzymatic kinetic resolutions
We examined both the acylation (transesterification) of
alcohols 2 and 3 (Scheme 2) and the hydrolysis of esters
4
and 5 (Scheme 3) in the presence of commercially
available lipases under various conditions. The reactions
were monitored by gas chromatography on a chiral
phase column allowing the simultaneous determination
of conversion (c) and enantiomeric excesses (ee) of both
product and remaining substrate. The results of the li-
pase-catalyzed acylation of substrates 2 and 3 using
vinyl acetate as acyl donor and solvent are summarized
in Table 1. Candida antarctica lipase B (CAL-B) not
only showed the best performance in the analytical runs,
but also gave excellent results for the acylation of 2 on a
2.3. Determination of absolute configurations
The absolute configurations of 2 and 3 were determined
by correlation with 1,2-diols 6 and 7 of known absolute
configurations (Scheme 4). Thus, hydrolysis of the acetal
function in acetonitrile/water in the presence of lithium
OAc
OAc
(CH
OH
(CH
a
MeO
MeO
MeO
MeO
MeO
+
(CH2)n
2
)
n
)
2 n
MeO
(
rac)-4
n = 0
n = 1
(S)-4
(S)-5
(R)-2
(R)-3
(rac)-5
Scheme 3. Reagents: (a) phosphate buffer, pH 7.0, enzyme.
Table 1. Enzymatic resolution of 2 and 3 using various lipases under esterification conditions
a
b
b
Entry
Substrate
Enzyme
Time
ee (%)
c (%)
E value
Alcohol
Acetate
1
2
3
4
5
6
7
8
2
2
2
2
3
3
3
3
CAL-B
PSL
PCL
36 h
14 h
3 d
93
88
49
38
92
87
54
99
95
71
71
73
94
91
91
62
50
55
41
34
50
49
37
62
>100
16
9.5
9.2
>100
60
PFL
PFL
3 d
24 h
20 h
3 d
PCL
CAL-B
PSL
36
29
3 d
a
CAL-B (C. antarctica lipase B), PSL (Pseudomonas sp. lipase), PCL (P. cepacia lipase), PFL (P. fluorescens lipase).
Conversion c and ee for alcohol and acetate, determined by chiral GC.
b

R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 16 (2005) 2081–2086
2083
Table 2. Enzymatic resolution of 4 and 5 using various lipases under hydrolysis conditions
a
b
b
Entry
Substrate
Enzyme
Time
ee (%)
c (%)
E value
Alcohol
Acetate
1
2
3
4
5
6
7
8
9
4
4
4
4
4
5
5
5
5
5
CAL-B
PSL
LPL
CE
30 h
5 h
94
>99
78
92
78
26
31
40
96
89
85
53
54
50
44
25
36
51
50
49
54
45
46
>100
>100
10
1 d
1 d
55
38
4.6
3.2
PLE
LPL
PCL
PLE
PFL
CE
1 h
10 h
3 d
98
91
>100
63
16
10 m
3 d
72
66
8.2
7.5
1
0
1 d
63
a
CAL-B (C. antarctica lipase B), PSL (Pseudomonas sp. lipase), LPL (lipoprotein lipase), CE (cholesterol esterase), PLE (porcine liver esterase), PCL
P. cepacia lipase), PFL (P. fluorescens lipase).
Conversion c and ee for alcohol and acetate, determined by chiral GC.
(
b
OH
OH
MeO
5
O
a
a
H
OH
L
H
OH
MeO
MeO
HO
OMe
C H
6
O
O
M
F3C
OMe
O
H
(
R)-2
2
6
A
B
C
Figure 1. (A) KazlauskasÕ model; M: medium substituent; L: large
substituent. (B) (R)-2 corresponding to the model. (C) MosherÕs ester
of 2.
OH
OH
MeO
MeO
HO
3
7
OH
OH
O
Scheme 4. Reagents: (a) (i) LiBF
4
, CH
3
CN/H
2
4 2
O; (ii) NaBH , H O.
MeO
MeO
a, b
MeO
MeO
OH OH
1
8
tetrafluoroborate followed by reduction of the inter-
mediate aldehyde by NaBH in water in a one-pot pro-
2
8
4
cedure yielded the corresponding diols 6 and 7. In both
the transesterification and hydrolysis reactions, the (R)-
compound was the fast reacting enantiomer yielding the
Scheme 5. Reagents and conditions: (a) (i) O
Me S; (b) transketolase, lithium hydroxypyruvate, thiamine pyrophos-
3
, CH
2
Cl
2
, ꢀ78 ꢁC; (ii)
2
2
phate, MgCl , tris buffer, pH 7.5.
(R)-product and leaving the (S)-compound unreacted in
enantiomerically pure form.
tors (thiamine pyrophosphate and magnesium chloride)
in the tris buffer provided 4-keto-D-arabinose dimethyl
acetal 8. This compound may be used as a key inter-
mediate in the synthesis of diverse pentoses.
The configuration assignment confirmed that the cata-
lytic preference of the lipases is in accordance with
2
5
1
9,20
empirical models
(Fig. 1). These models imply that
the enantiodiscrimination of secondary alcohols by lip-
ases is dominated by steric interactions. It is interesting
to note that the MosherÕs method using NMR analysis
of MTPA (a-methoxy-a-(trifluoromethyl)phenylacetic
acid) ester of 2 produced the correct assignment of the
3. Experimental
3.1. General
2
1–23
absolute configuration.
NMR spectra were recorded on Varian Inova AS400
spectrometer (400 MHz). Infrared spectra were recorded
on a Bomem MB-100 spectrometer. Optical rotations
were measured using a JASCO DIP-360 digital polari-
meter (c as gram of compound per 100 mL). Flash
column chromatography was carried out using 40–
63 lm (230–400 mesh) silica gel. The enantiomeric
excesses (ee) were determined by GC analysis on a
Chiraldex G-TA (c-cyclodextrin trifluoroacetyl) capil-
lary column (20 m · 0.25 mm, film thickness 0.125 lm)
using racemic compounds as references. C. antarctica
lipase B (Chirazyme L-2) was obtained from Boehringer
Mannheim. PSL (Pseudomonas sp. Lipase), CE (Choles-
terol esterase), and PLE (Porcine liver esterase) were
Finally, to show the usefulness of the title compounds
we used compound 2 in an enzymatic aldol reaction cat-
alyzed by transketolase (TK) (Scheme 5). Although TK
is an enantioselective enzyme, which only accepts a-
hydroxyaldehydes with an (R)-configuration, it is more
convenient to run the reaction with optically pure sub-
strates instead of racemates in order to avoid enzyme
inhibition by the S isomer and to facilitate the purifica-
tion procedure. The aldehyde substrate was prepared
by ozonolysis and reductive workup with dimethyl sul-
fide, and used directly in the biotransformation. The
reaction of the aldehyde with lithium hydroxypyruvate
in the presence of transketolase and the required cofac-
2
4

2084
R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 16 (2005) 2081–2086
from Sigma, and PFL (P. fluorescens) was from Fluka.
PCL (P. cepacia lipase) and LPL (lipoprotein lipase
J = 10.0 Hz, 1H), 5.29 (d, J = 17.0 Hz, 1H), 5.31 (m,
1
3
1H), 5.84 (m, 1H); C NMR (100 MHz, CDCl ) d
3
2
duced and purified as previously described.
00S) were a gift from Amano. Transketolase was pro-
2
20.8, 54.3, 55.2, 72.8, 104.2, 118.2, 131.9, 169.6; HRMS
(CI, NH ) calcd for C H O (M+NH ) : 192.1236.
Found: 192.1227.
6
+
3
8
14
4
4
3
.2. 1,1-Dimethoxybut-3-en-2-ol 2
1
3
.4.2. 1-(Dimethoxymethyl)but-3-enyl acetate 5.
H
To a solution of vinylmagnesium bromide (0.1 mol) in
THF (freshly prepared from magnesium and a commer-
cial 5 M solution of vinyl bromide in THF) cooled to
NMR (400 MHz, CDCl ) d 1.98 (s, 3H), 2.22 (m, 1H),
3
2.37 (m, 1H), 3.30 (s, 3H), 3.32 (s, 3H), 4.21 (d,
J = 5.0 Hz, 1H), 4.97 (m, 3H), 5.66 (m, 1H); C NMR
1
3
0
ꢁC under dry atmosphere was added dropwise a solu-
tion of dimethoxy acetaldehyde in tert-butylmethyl ether
45%, 26 mL, 0.1 mol). The mixture was stirred at room
(100 MHz, CDCl ) d 20.7, 33.8, 54.0, 55.0, 71.2, 103.8,
3
117.5, 132.3, 169.9; HRMS (CI, NH ) calcd for
3
+
C H O (M+NH ) : 206.1392. Found: 206.1398.
(
9
16
4
4
temperature for 12 h and then the reaction quenched by
the addition of a satd aq NH Cl solution. The aqueous
3.5. Enzymatic acylation of alcohol 2
4
phase was extracted with ethyl acetate and the combined
organic phases washed with brine, dried over MgSO4,
and evaporated. The crude product was purified by flash
To a solution of alcohol 2 (1.38 g, 10.4 mmol) in vinyl
acetate (35 mL) was added C. antarctica lipase (1.40 g)
and the mixture stirred at rt. The reaction course was
monitored by chiral GC and when the conversion
reached 50% (36 h), the reaction was quenched by filtra-
tion of the enzyme and the solvent evaporated. Chroma-
tography of the residue with EtOAc/petroleum ether
(10:90) afforded (S)-2 (457 mg, 33%, ee = 93%) and
(R)-4 (782 mg, 43%, ee = 95%).
chromatography (cyclohexane/EtOAc, 75:25) to give a
colorless oil (7.1 g, 55%): H NMR (400 MHz, CDCl )
1
3
d 2.51 (br s, 1H), 3.37 (s, 3H), 3.40 (s, 3H), 4.08 (m,
1
1
1
5
H), 4.13 (d, J = 5.0 Hz, 1H), 5.20 (d, J = 10.0 Hz,
H), 5.37 (d, J = 17.0 Hz, 1H), 5.86 (dd, J = 17.0 and
1
3
0.0 Hz, 1H); C NMR (100 MHz, CDCl ) d 54.5,
3
4.9, 72.1, 106.5, 116.7, 135.5; HRMS (CI, NH ) calcd
3
+
for C H O (M+NH ) : 150.1130. Found: 150.1126.
6
12
3
4
3
.6. Enzymatic acylation of alcohol 3
3
.3. 1,1-Dimethoxypent-4-en-2-ol 3
To a solution of alcohol 3 (937 mg, 6.4 mmol) in vinyl
acetate (25 mL) was added P. fluorescens lipase
(1.00 g) and the mixture was stirred at rt. The reaction
course was monitored by chiral GC and when the con-
version reached 50% (24 h), the reaction was quenched
by filtration of the enzyme and the solvent evaporated.
Chromatography of the residue with EtOAc/petroleum
ether (10:90) provided alcohol (S)-3 (349 mg, 37%,
ee = 92%) and acetate (R)-5 (526 mg, 44%, ee = 94%).
To a stirred solution of allylmagnesium bromide in dry
THF (1 M, 10 mL, 10 mmol) at 0 ꢁC was added drop-
wise a solution of dimethoxy acetaldehyde in tert-
butylmethyl ether (45%, 2.9 mL, 11 mmol, 1.1 equiv).
The solution was stirred at rt for 12 h under a dry atmo-
sphere. The reaction was quenched by the addition of a
satd aq NH Cl solution. The organic layer was decanted
4
off and the aqueous layer extracted with ethyl acetate.
The combined organic layers were washed with brine,
dried over MgSO , and concentrated. The crude product
3.7. Enzymatic hydrolysis of acetate 4
4
was purified by flash chromatography (cyclohexane/
EtOAc, 75:25) to give a colorless oil (910 mg, 62%):
Ester 4 (459 mg, 2.64 mmol) was suspended in a buffered
aqueous solution (20 mL, phosphate pH 7.0). C. antarc-
tica lipase (450 mg) was added and the pH maintained at
its initial value by the addition of 0.1 M aqueous NaOH.
The reaction was monitored by chiral GC and stopped
at the 50%-of-hydrolysis point. The aqueous mixture
was extracted with EtOAc and the organic layer dried
over MgSO4 and concentrated. Chromatography of
the residue with EtOAc/petroleum ether (10:90) gave
alcohol (R)-2 (94 mg, 27%, ee = 92%) and acetate (S)-4
1
H NMR (400 MHz, CDCl ) d 2.05 (br s, 1H), 2.20
3
(
(
1
m, 1H), 2.37 (m, 1H), 3.41 (s, 3H), 3.43 (s, 3H), 3.65
m, 1H), 4.15 (d, J = 6.0 Hz, 1H), 5.07 (d, J = 15.0 Hz,
1
3
H), 5.12 (d, J = 8.0 Hz, 1H), 5.86 (m, 1H); C NMR
(
100 MHz, CDCl ) d 36.2, 54.7, 54.9, 70.4, 106.2,
3
1
17.1, 134.5; HRMS (CI, NH ) calcd for C H O
3 7 14 3
+
(
M+NH ) : 164.1287. Found: 164.1293.
4
3
.4. Preparation of diacetates 4 and 5: general procedure
(165 mg, 36%, ee = 94%).
To a stirred solution of alcohol 2 or 3 (12.1 mmol) in
pyridine (10 mL) were added acetic anhydride (3 equiv)
and a catalytic amount of DMAP, after which the solu-
tion was stirred overnight at rt under a dry atmosphere.
The solution was diluted with ether, washed with brine,
3.8. Enzymatic hydrolysis of acetate 5
Ester 3 (524 mg, 2.79 mmol) was suspended in a buffered
aqueous solution (10 mL, phosphate pH 7.0). Lipopro-
tein lipase LPL 200S (500 mg) was added and the pH
maintained at its initial value by the addition of 0.1 M
aqueous NaOH. The reaction was monitored by chiral
GC and stopped at the 50%-of-hydrolysis point. The
aqueous mixture was extracted with EtOAc and the or-
dried over MgSO , and evaporated. The crude product
4
was purified by flash chromatography (hexanes/EtOAc,
9
:1) to give acetates 4 or 5 as colorless oils (75–80%).
1
3
.4.1. 1-(Dimethoxymethyl)prop-2-enyl acetate 4.
H
NMR (400 MHz, CDCl ) d 2.08 (s, 1H), 3.37 (s, 3H),
ganic layer dried over MgSO and concentrated. Chro-
4
matography of the residue with EtOAc/petroleum
3
3
.38 (s, 3H), 4.28 (d, J = 5.0 Hz, 1H), 5.24 (d,

R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 16 (2005) 2081–2086
2085
ether (10:90) gave alcohol (R)-3 (123 mg, 30%,
ee = 98%) and acetate (S)-5 (214 mg, 41%, ee = 96%).
3. Arya, P.; Qin, H. Tetrahedron 2000, 56, 917.
4
5
6
. Denmark, S. E.; Stavenger, R. A. Acc. Chem. Res. 2000,
3
3, 432.
. Machajewski, T. D.; Wong, C. H. Angew. Chem., Int. Ed.
000, 39, 1352.
3.9. Determination of absolute configurations by chemical
correlation: general procedure
2
. (a) Hecquet, L.; Demuynck, C.; Schneider, G.; Bolte, J. J.
Mol. Catal. B: Enzym. 2001, 11, 771; (b) Turner, N. J.
Curr. Opin. Biotechnol. 2000, 11, 527.
A solution of 2 or 3 (2 mmol, from enzymatic acylation)
and LiBF (2 mmol) in CH CN/H O (95:5, 3.6 mL) was
4
3
2
7. Silvestri, M. G.; Desantis, G.; Mitchell, M.; Wong, C. H.
Top. Stereochem. 2003, 23, 267.
8. (a) Breuer, M.; Hauer, B. Curr. Opin. Biotechnol. 2003, 14,
570; (b) Fessner, W. D.; Helaine, V. Curr. Opin. Biotech-
nol. 2001, 12, 574.
stirred at rt for 5 days. The solvent was evaporated and
the residue dissolved in water (10 mL). NaBH (2 mmol)
4
was added and the reaction mixture stirred at rt for 1 h.
The reaction mixture was extracted with EtOAc (contin-
uous extractor). The organic phase was dried over
9
. List, B.; Shabat, D.; Zhong, G.; Turner, J. M.; Li, A.; Bui,
T.; Anderson, J.; Lerner, R. A.; Barbas, C. F. J. Am.
Chem. Soc. 1999, 121, 7283.
MgSO and concentrated. The crude product was puri-
4
fied by flash chromatography (EtOAc/cyclohexane,
70:30) to give 6 or 7 as colorless oils. Analytical data
were in agreement with the published values for but-3-
1
0. Northrup, A. B.; Macmillan, D. W. C. J. Am. Chem. Soc.
002, 124, 6798.
2
1. Jarvo, E. R.; Miller, S. J. Tetrahedron 2002, 58, 2481.
2. List, B. Tetrahedron 2002, 58, 5573.
1
1
1
2
7
28
ene-1,2-diol 6 and pent-4-ene-1,2-diol 7.
3. For a recent exemple related to the title compounds, see:
Radha Krishna, P.; Kannan, V.; Sharma, G. V. M. J. Org.
Chem. 2004, 69, 6467.
0
3
.10. (3S,4S)-1,3,4-Trihydroxy-5,5 -dimethoxypentanone
8
1
4. For asymmetric syntheses of related acids, esters or diols,
see: (a) Dallanoce, C.; De Amici, M.; Carrea, G.; Secundo,
F.; Castellano, S.; De Micheli, C. Tetrahedron: Asymmetry
Ozone was passed through a solution of alcohol 2
(
color persisted. The excess ozone was purged with
407 mg, 3.1 mmol) in CH Cl at ꢀ78 ꢁC until a blue
2
2
2
000, 11, 2741; (b) Wang, D.; Wang, Z. G.; Wang, M. W.;
Chen, Y. J.; Liu, L.; Zhu, Y. Tetrahedron: Asymmetry
999, 10, 327; (c) Czapla, A.; Chajewski, A.; Kiegiel, K.;
argon, Me S (260 lL, 3.6 mmol) was added, and the
2
1
mixture stirred at ꢀ78 ꢁC for 1 h and then at rt over-
night. The solvent was evaporated. To a solution of
the crude aldehyde in tris buffer (15.4 mL) were added
thiamine pyrophosphate (14.2 mg, 0.031 mmol), MgCl2
Bauer, T.; Wielogorski, Z.; Urbanczyk-Lipkowska, Z.;
Jurczak, J. Tetrahedron: Asymmetry 1999, 10, 2101; (d)
Macritchie, J. A.; Silcock, A.; Willis, C. L. Tetrahedron:
Asymmetry 1997, 8, 3895; (e) Pearson, W. H.; Cheng, M.
C. J. Org. Chem. 1986, 51, 3746; (f) Wong, C. H.; Matos,
J. R. J. Org. Chem. 1985, 50, 1992.
(
(
4.4 mg, 0.046 mmol), and lithium hydroxypyruvate
396 mg, 3.6 mmol). The mixture was adjusted to
1
5. Makin, S. M.; Telegina, N. I. I. Gen. Chem. USSR 1962,
3
pH 7.5 by the addition of aq NaOH and the reaction ini-
tiated by the addition of transketolase (100 U). The
solution was stirred at rt for 24 h and then quenched
by addition of MeOH (40 mL). The mixture was stirred
for 1 h, the solids collected by centrifugation, and the
solvents evaporated. The crude product was purified
by flash chromatography (CH Cl /MeOH, 90:10) to give
2, 1082.
1
6. For related syntheses, see: (a) Kobori, Y.; Myles, D. C.;
Whitesides, G. M. J. Org. Chem. 1992, 57, 5899; (b)
Parrain, J. L.; Beaudet, I.; Cintrat, J. C.; Duch eˆ ne, A.;
Quintard, J. P. Bull. Soc. Chim. Fr. 1994, 131, 304; (c)
Stamboli, A.; Amouroux, R.; Chastrette, M.; Mattioda,
G.; Blanc, A. J. Organomet. Chem. 1986, 307, 139; (d) Liu,
K. C.; Pederson, R. L.; Wong, C. H. J. Chem. Soc., Perkin
Trans. 1 1991, 2669; (e) Fessner, W. D.; Goße, C.;
Jaeschke, G.; Eyrish, O. Eur. J. Org. Chem. 2000, 125.
7. A lipase-catalyzed acylation of 3 was reported but ee of
the remaining substrate and absolute configurations were
not determined: Kim, M. J.; Lim, I. T.; Choi, G. B.;
Whang, S. Y.; Ku, B. C.; Choi, J. Y. Bioorg. Med. Chem.
Lett. 1996, 6, 71.
2
2
23
8
as a colorless oil (223 mg, 37%): ½aꢁ ¼ ꢀ20.5 (c 0.98,
D
1
MeOH); H NMR (400 MHz, CD OD) d 3.43 (s, 1H),
3
3
J = 2.0 Hz, 1H), 4.43 (d, J = 7.3 Hz, 1H), 4.45 (d,
.44 (s, 1H), 3.89 (dd, J = 7.3 and 2.0 Hz, 1H), 4.34 (d,
1
1
3
J = 19.3 Hz, 1H), 4.53 (d, J = 19.3 Hz, 1H); C NMR
100 MHz, CD OD) d 54.7, 55.8, 67.8, 73.0, 77.0,
(
3
1
05.5, 213.5; HRMS (EI) calcd for C H O
7 14 6
+
(
MꢀCH O ) : 145.0501. Found: 145.0500.
5
2
1
1
2
2
2
2
2
8. Lipshutz, B. H.; Harvey, D. F. Synth. Commun. 1982, 12,
2
67.
9. Kazlauskas, R. J.; Weissfloch, A. N. E.; Rappaport, A. T.;
Cuccia, L. A. J. Org. Chem. 1991, 56, 2656.
0. Burgess, K.; Jennings, L. D. J. Am. Chem. Soc. 1991, 113,
Acknowledgments
6
129.
1. Seco, J. M.; Qui n˜ o a´ , E.; Riguera, R. Chem. Rev. 2004, 104,
7.
The authors would like to thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support.
1
2. Seco, J. M.; Qui n˜ o a´ , E.; Riguera, R. Tetrahedron: Asym-
metry 2001, 12, 2915.
3. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95,
512.
4. Crestia, D.; Demuynck, C.; Bolte, J. Tetrahedron 2004, 60,
2417.
25. Williams, D. T.; Jones, J. K. N.; Dennis, N. J.; Ferrier, R.
J.; Overend, W. G. Can. J. Chem. 1965, 43, 955.
26. Hecquet, L.; Demuynck, C.; Bolte, J. J. Mol. Catal. B:
Enzym. 2001, 6, 797.
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