Phase-transfer-catalyzed asymmetric alkylation of a-benzoyloxy-b-keto esters: Stereoselective construction of congested 2, 3-dihydroxycarboxylic acid esters

Article abstract of DOI:10.1002/asia.200900344

Highly enantioselective phase-transfer-catalyzed alkylation of tert-butyl 2-benzoyloxy-3-oxobutanoate was realized by the use of an N-spiro chiral quaternary ammonium salt, as a complementary approach to the asymmetric hydroxylation of α-alkyl-β-keto esters. The synthetic utility of the alkylated compounds is highlighted by the diastereoselective reduction and alkylation of the remaining ketone moiety to give various enantiomerically enriched congested 2, 3-dihydroxycarboxylic acid esters.

Full text of DOI:10.1002/asia.200900344

FULL PAPERS
DOI: 10.1002/asia.200900344
Phase-Transfer-Catalyzed Asymmetric Alkylation of a-Benzoyloxy-b-keto
Esters: Stereoselective Construction of Congested 2,3-Dihydroxycarboxylic
Acid Esters
Takuya Hashimoto,[a] Keigo Sasaki,[a] Kazuhiro Fukumoto,[a] Yuichi Murase,[a]
Naoyuki Abe,[a] Takashi Ooi,[b] and Keiji Maruoka*[a]
Dedicated to the 150th anniversary of Japan–UK diplomatic relations
Abstract: Highly enantioselective phase-transfer-catalyzed alkylation of tert-butyl
2-benzoyloxy-3-oxobutanoate was realized by the use of an N-spiro chiral quater-
Keywords: alkylation · asymmetric
nary ammonium salt, as a complementary approach to the asymmetric hydroxyl-
synthesis · diastereoselectivity · hy-
ation of a-alkyl-b-keto esters. The synthetic utility of the alkylated compounds is
droxylation · phase-transfer catal-
highlighted by the diastereoselective reduction and alkylation of the remaining
ysis
ketone moiety to give various enantiomerically enriched congested 2,3-dihydroxy-
carboxylic acid esters.
Introduction
Catalytic asymmetric a-hydroxylation of b-keto esters has
been developed in the past decade as an efficient means to
provide densely oxygenated chiral a-hydroxycarboxylic acid
derivatives, which are potentially valuable intermediates for
the synthesis of natural products and biologically active
compounds [Eq. (1)].[1] Examples include chiral Lewis acid
catalyzed a-hydroxylation using oxaziridine or dioxirane as
an oxygen source,[2] and organocatalytic a-hydroxylation
using hydroperoxides.[3] More recently, chiral Brønsted acid
catalyzed addition of nitrosobenzene to b-keto esters has ap-
peared as an alternative approach.[4]
Despite these advances, most of these methods are only
applicable to cyclic b-keto esters, and the use of acyclic b-
keto esters generally leads to either poor yields or modest
selectivity. In this context, we became interested in a com-
plementary strategy for the synthesis of enantiomerically en-
riched acyclic a-alkyl-a-hydroxy-b-keto esters by relying on
the phase-transfer-catalyzed asymmetric alkylation of acyclic
a-hydroxy-b-keto ester derivatives [Eq. (2)].[5] As the hy-
droxy moiety is incorporated into the a position of the b-
keto ester in advance and the subsequent alkylation under
phase-transfer conditions is set as a crucial asymmetric in-
duction step, a variety of enantioenriched compounds are
easily accessible just by changing the alkyl halides while an-
ticipating a similar level of enantioselectivity.
[a] Dr. T. Hashimoto, K. Sasaki, K. Fukumoto, Y. Murase, N. Abe,
Prof. Dr. K. Maruoka
Department of Chemistry
Graduate School of Science
Kyoto University
Sakyo, Kyoto, 606-8502 (Japan)
Fax : (+81)75-753-4041
E-mail: maruoka@kuchem.kyoto-u.ac.jp
We report herein the detailed study of this phase transfer
catalyzed asymmetric alkylation, building on the well-estab-
lished catalytic activity of binaphthyl-modified chiral quater-
nary ammonium bromides 1 under phase-transfer condi-
tions.[6] Diastereoselective transformation of the remaining
ketone moiety is also investigated to highlight the synthetic
utility of so-obtained a-alkyl-a-hydroxy-b-keto esters.
[b] Prof. Dr. T. Ooi
Department of Applied Chemistry
Graduate School of Engineering
Nagoya University
Chikusa, Nagoya 464-8603 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900344.
562
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Chem. Asian J. 2010, 5, 562 – 570

Table 1. Phase-transfer-catalyzed alkylation of tert-butyl 2-acyloxy-3-oxobutanoates with benzyl bromide.[a]
Results and Discussion
Phase-Transfer-Catalyzed
Asymmetric Alkylation of a-
Benzoyloxy-b-keto Esters
As a suitable substrate for our
synthetic plan, we focused on
the use of a-acyloxy-b-keto
esters, in view of the ease of
deprotection of the acyl moiety
after the reaction. These sub-
strates can be easily prepared
from the corresponding b-keto
ester in two steps by following
the procedure developed by
Wessjohann and co-workers
(Scheme 1).[7]
We commenced our study by
investigating asymmetric ben-
zylation of tert-butyl 2-benzoyl-
oxy-3-oxobutanoate (3a) cata-
lyzed by 1 mol% N-spiro
chiral quaternary ammonium
bromide 1a in the presence of
25% aqueous KOH in relation
to our extensive research on
the use of 1 for asymmetric
phase-transfer-catalyzed alky-
lation of various b-keto esters
(Table 1).[8] Gratifyingly, asym-
Entry
PTC
Base
R
T [8C], t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
2
1c
1c
1c
1c
1c
1c
1c
1c
25% KOH[d]
25% KOH
25% KOH
25% KOH
25% KOH
25% KOH
25% KOH
25% KOH
25% KOH
25% KOH
KOH[e]
Ph (3a)
Ph
Ph
Ph
Ph
Ph
4-ClC6H4 (3b)
4-MeOC6H4 (3c)
2-Np (3d)
tBu (3e)
Ph
0, 9
0, 9
0, 10
0, 9
72
72
76
83
66
79
79
68
63
57
91
49
95
79
60
85
62
35
90
89
87
89
77
90
89
94
0, 11
ꢀ20, 12
ꢀ20, 31
ꢀ20, 12
ꢀ20, 7
ꢀ20, 2
ꢀ20, 12
ꢀ20, 96
ꢀ40, 98
9
10
11
12
13
[f]
Cs2CO3
Ph
Ph
KOH[g]
[a] Performed with tert-butyl 2-acyloxy-3-oxobutanoate (0.20 mmol) and benzyl bromide (0.24 mmol) in the
presence of 1 mol% of catalyst (S,S)-1 or (S)-2 in toluene (2.0 mL) under the given reaction conditions.
[b] Yield of isolated product. [c] Determined by chiral HPLC analysis. [d] 25% aqueous KOH (0.50 mL).
[e] Powdered KOH (0.30 mmol). [f] Powdered Cs2CO3 (1.0 mmol). [g] Powdered KOH (1.0 mmol).
which the benzylated product was obtained in a highest ee
value of 85% (Table 1, entries 2–4). The use of phase-trans-
fer catalyst (S)-2, which has one binaphthyl unit, gave the
product in 66% yield and disappointingly low enantioselec-
tivity (Table 1, entry 5).[9] After setting (S,S)-1c as the opti-
mal catalyst, the reaction was then performed at lower tem-
perature, anticipating an increase of the enantioselectivity.
As expected, 4a was obtained in 90% ee by carrying out the
reaction at ꢀ208C (Table 1, entry 6).
Scheme 1. Reagents and conditions: a) N-bromosuccinimide, acetone,
74%; b) RCO2Na, DMF, 74% (R=Ph, R2 =Me).
metric benzylation proceeded smoothly at 08C to provide
the alkylated compound 4a in 72% yield with 79% ee
(Table 1, entry 1). Further experiments with the catalysts
(S,S)-1b–d revealed the highest efficiency for (S,S)-1c, with
At this stage, the relationship of acyl groups and ee values
was examined by using substrates bearing different acyl
groups. Whereas the attachment of other aryl groups did not
affect the selectivity (Table 1, entries 7–9), the use of piva-
loyloxy-substituted b-keto ester 3e led to the lower enantio-
selectivity (Table 1, entry 10). For substrates bearing smaller
acyl groups, rapid hydrolysis of the acyl moiety was a signifi-
cant problem, furnishing the alkylated compounds in low
yields (data not shown).
Abstract in Japanese:
As we observed some amounts of deacylated side product
derived from 4a in the experiments above (e.g., Table 1,
entry 6), we conducted the reaction under the influence of
solid KOH (1.5 equiv) to minimize such competitive side re-
actions (Table 1, entry 11). As a result, the benzylated com-
pound was obtained in 91% yield without affecting the
enantioselectivity.
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The use of Cs2CO3 as base resulted in poor reactivity,
leading to moderate conversion after prolonged reaction
time (Table 1, entry 12). Although a further increase of the
enantioselectivity could be achieved by conducting the reac-
tion at ꢀ408C at the expense of the reaction time and the
amount of base (Table 1, entry 13), we employed the reac-
tion conditions in Table 1, entry 11 for further investigations,
having practical aspects in mind.
slightly diminished ee value of 79% (Table 2, entry 12). The
use of a-benzoyloxy-b-keto ester 3g bearing propyl group as
R2, resulted in the further decrease of the enantioselectivity
(Table 2, entry 13). An attempt to extend this method in the
reaction with the malonate 3h having two different ester
moieties led to the formation of the alkylated compound
with moderate enantioselectivity (Table 2, entry 14).[10]
With the optimized conditions in hand, we surveyed the
scope and limitations of this asymmetric alkylation of a-ben-
zoyloxy-b-keto esters (Table 2). The use of substituted
Stereoselective Construction of Congested 2,3-
Dihydroxycarboyxlic Acid Esters
To underline the synthetic value of so-obtained enantioen-
riched a-hydroxy-b-keto esters, removal of the benzoyl
moiety and subsequent diastereoselective reduction of the
remaining ketone moiety were initially examined
(Scheme 2). As the benzoyl group could be easily cleaved
Table 2. Phase-transfer-catalyzed alkylation of a-benzoyloxy-b-keto
esters and alkyl halides.[a]
Entry
1
R1Br
R2
Yield [%][b]
91
ee [%][c]
Me (3a)
4a
4 f
90
2
3
4
5
Me
Me
Me
Me
86
91
79
92
92
91
89
88
Scheme 2. Deprotection and diastereoselective reduction.
4g
4h
4i
under the basic hydrolytic conditions, the reduction of the
ketone moiety was then implemented following the litera-
ture procedure.[11] Thus, treatment of the hydrolysis products
5 with the 1:1 mixture of NaBH4 and ZnCl2 gave the esters
6 bearing the 2,3-tertiary–secondary diol moiety in good
yields with uniformly high diastereoselectivity.[12]
6
Me
Me
Me
85
90
88
4j
4k
4l
91
91
90
7[d]
8
We then investigated the nucleophilic addition of
Grignard reagents to the ketone moiety to find an access to
the esters with highly congested vicinal tertiary–tertiary
diols.[13] In this regard, subjecting the deacylated compound
5j (see Scheme 2) to an excess of Grignard reagent fur-
nished the cis-2,3-dihydroxy esters 7a–d in good yields with
moderate to excellent diastereoselectivities (Scheme 3).[12]
Intriguingly, the stereochemical outcome could be invert-
ed by premixing Grignard reagent with ZnCl2 in a ratio of
2:1,[14] giving the opposite trans isomer 8 in greater than 1:20
diastereomeric ratio.[12] Such a phenomenon could only be
observed in the case of the reactions using vinyl and aryl
Grignard reagents.
9
Me
89
4m
87
10
11
Me
Me
41
29
4n
4o
83
61
12
Et (3 f)
Pr (3g)
OMe (3h)
88
40
94
4p
4q
4r
79
73
31
13
14[e]
[a] Performed with 3 (0.2 mmol) and R1Br (0.24 mmol) in the presence
of 1 mol% of catalyst (S,S)-1c and powdered KOH (0.3 mmol) in toluene
(2 mL) at ꢀ208C. [b] Yield of isolated product. [c] Determined by chiral
HPLC analysis or GC analysis. [d] Crotyl bromide used as a E/Z mixture
(5:1). [e] Performed at 08C.
benzyl bromides was initially evaluated. Irrespective of the
electronic properties of the aromatic rings, alkylated com-
pounds were obtained in good yields with the selectivity
ranging from 88% to 92% ee (Table 2, entries 1–5). Allylic
substrates were also suitable for this reaction, furnishing the
products in good yields and enantioselectivities (Table 2, en-
tries 6–10). Curiously, the reaction with propargyl bromide
led to the significant decrease of the enantiomeric excess
(Table 2, entry 11). Our focus then moved to the employ-
ment of other a-benzoyloxy-b-keto esters as nucleophiles.
Asymmetric benzylation of 2-benzoyloxy-3-oxopentanoate
3 f furnished the alkylated compound in 88% yield with
The relative as well as the absolute configurations of
these congested 2,3-dihydroxycarboyxlic acid esters were de-
Scheme 3. Diastereoselective addition of Grignard reagents.
564
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Chem. Asian J. 2010, 5, 562 – 570

Phase-Transfer-Catalyzed Asymmetric Alkylation of a-Benzoyloxy-b-keto Esters
microTOF instrument. Optical rotations were measured on a JASCO
termined unambiguously by X-ray crystallographic analyses
of the arylated compounds derived from 5g (Scheme 4 and
Figure 1).[15]
DIP-1000 digital polarimeter. For thin layer chromatography (TLC) anal-
ysis throughout this work, Merck precoated TLC plates (silica gel 60
GF254, 0.25 mm) were used. The products were purified by flash column
chromatography on silica gel 60 (Merck, 230–400 mesh). Toluene was
purchased from Wako Chemical Co. Other simple chemicals were pur-
chased and used as received. ZnCl2 was fused under vacuum prior to use.
Preparation of tert-butyl 2-benzoyloxy-3-oxobutanoate (3a): To a solu-
tion of tert-butyl 2-bromo-3-oxobutanoate (2.11 g, 8.9 mmol) DMF
(18 mL), prepared according to a literature method,[7] was added sodium
benzoate (1.93 g, 13.4 mmol), and the mixture was stirred at room tem-
perature for 2 h. The resulting solution was then diluted with water and
extracted with ethyl acetate. The organic layer was dried over Na2SO4
and concentrated in vacuo. The residue was purified by column chroma-
tography on silica gel (eluting with hexane/ethyl acetate=10:1) to give
3a as a white solid [74% (1.83 g)]. 1H NMR (400 MHz, CDCl3): d=8.13
(2H, m, ArH), 7.62 (1H, tt, J=1,5, 7.6 Hz, ArH), 7.48 (2H, app t, J=
7.6 Hz, ArH), 5.63 (1H, s, BzOCH), 2.42 (3H, s, CH3CO), 1.52 ppm (9H,
s, tBu); 13C NMR (100 MHz, CDCl3): d=197.9, 165.1, 163.4, 133.7, 130.1,
128.7, 128.5, 84.1, 78.6, 27.9, 27.3 ppm; IR (neat): n˜ =2980, 1726, 1603,
1452, 1366, 1256, 1148, 1113, 1069, 1026, 841, 779, 710 cmꢀ1; HRMS (ESI)
exact mass calcd for C15H18O5: m/z 301.1046 [M+Na]+, found: m/z
301.1047 [M+Na]+.
Scheme 4. Determination of the stereochemistry by X-ray crystallograph-
ic analyses.
tert-Butyl 2-benzoyloxy-3-oxopentanoate (3 f): 1H NMR (400 MHz,
CDCl3): d=8.13 (2H, m, ArH), 7.61 (1H, tt, J=1.5, 7.6 Hz, ArH), 7.48
(2H, app t, J=7.7 Hz, ArH), 5.64 (1H, s, BzOCH), 2.77 (2H, q, J=
7.3 Hz, CH2CH3), 1.51 (9H, s, tBu), 1.52 ppm (3H, t, J=7.3 Hz,
CH2CH3); 13C NMR (100 MHz, CDCl3): d=201.0, 165.2, 163.6, 133.7,
130.0, 128.7, 128.5, 83.9, 78.1, 33.3, 27.9, 7.3 ppm; IR (neat): n˜ =2980,
1601, 1452, 1261, 1236, 1125, 1109, 1026, 839, 710 cmꢀ1; HRMS (ESI)
exact mass calcd for C16H20O5: m/z 315.1203 [M+Na]+, found: m/z
315.1191 [M+Na]+.
Figure 1. ORTEP plots at 50% probability of 9 (left) and 10 (right).
tert-Butyl 2-benzoyloxy-3-oxohexanoate (3g): 1H NMR (400 MHz,
CDCl3): d=8.13 (2H, m, ArH), 7.61 (1H, tt, J=1.5, 7.4 Hz, ArH), 7.48
(2H, app t, J=7.7 Hz, ArH), 5.63 (1H, s, BzOCH), 2.72 (2H, t, J=
7.1 Hz, CH2CH2CH3), 1.70 (2H, m, CH2CH2CH3), 1.51 (9H, s, tBu),
0.96 ppm (3H, t, J=7.3 Hz, CH2CH2CH3); 13C NMR (100 MHz, CDCl3):
d=200.2, 165.1, 163.5, 133.7, 130.0, 128.7, 128.5, 83.9, 78.3, 41.7, 27.9,
16.6, 13.5 ppm; IR (neat): n˜ =2974, 1726, 1452, 1369, 1256, 1113, 1070,
1026, 841, 710 cmꢀ1; HRMS (ESI) exact mass calcd for C17H22O5: m/z
329.1359 [M+Na]+, found: m/z 329.1351 [M+Na]+.
Conclusions
In conclusion, we obtained a-alkyl-a-hydroxy-b-keto esters
with high enantioselectivities by employing the phase-trans-
fer-catalyzed asymmetric alkylation of a-benzoyloxy-b-keto
tert-Butyl methyl 2-(benzoyloxy)malonate (3h): To a stirred solution of
tert-butyl methyl malonate (338 mL, 2.0 mmol) and N-bromosuccinimide
(356 mg, 2.05 mmol) in benzene (5.0 mL) was added 2,2’-azobis(isobutyr-
onitrile) (32.8 mg, 0.20 mmol) at room temperature. The reaction mixture
was then heated at reflux for 4 h, poured into water, and extracted with
AcOEt. The combined extracts were washed with brine, dried over
Na2SO4, and concentrated in vacuo. To this residue were added DMF
(3 mL) and sodium benzoate (432 mg, 3.0 mmol) at room temperature.
After stirring for 4 h, the resulting mixture was poured into water and ex-
tracted with AcOEt. The combined extracts were washed with brine,
dried over Na2SO4, and concentrated in vacuo. The residue was purified
by column chromatography on silica gel (eluting with hexane/AcOEt=
10:1) to give 3h as a colorless oil (455 mg, 1.55 mmol, 77%). 1H NMR
(400 MHz, CDCl3): d=8.13 (2H, m, ArH), 7.60 (1H, tt, J=1.6, 7.6 Hz,
ArH), 7.47 (2H, t, J=8.0 Hz, ArH), 5.68 (1H, s, CHOBz), 3.86 (3H, s,
OCH3), 1.52 ppm (9H, s,tBu); 13C NMR (100 MHz, CDCl3) d 165.4,
165.1, 163.3, 133.7, 130.1, 128.6, 128.5, 84.0, 72.5, 53.0, 27.8 ppm; IR
ꢀ
esters as a key asymmetric C C bond forming step. The syn-
thetic application of the so-obtained alkylated compounds
allowed facile access to a variety of densely functionalized
2,3-dihydroxy esters in a highly diastereoselective fashion by
the judicious choice of the reaction conditions.
Experimental Section
General information: Infrared (IR) spectra were recorded on a Shimadzu
IRPrestige-21 spectrometer. H NMR spectra were measured on a JEOL
1
JNM-FX400 (400 MHz) spectrometer. Data are reported as follows:
chemical shifts in ppm from tetramethylsilane as an internal standard in
CDCl3, integration, multiplicity (s=singlet, d=doublet, t=triplet, q=
quartet, dd=doublet of doublets, tt=triplet of triplets, m=multiplet,
br=broad, app=apparent), coupling constants (Hz), and assignment.
13C NMR spectra were measured on a JEOL JNM-FX400 (100 MHz)
spectrometer with complete proton decoupling. Chemical shifts are re-
ported in ppm from the residual solvent as an internal standard. Analyti-
cal gas–liquid phase chromatography (GLC) was performed on Shimadzu
GC-14B instruments equipped with a flame ionization detector using an
Astec Chiraldex B-DM (30 mꢁ0.25 mm) column. High-performance
liquid chromatography (HPLC) was performed on Shimadzu 10 A instru-
ments at 220 nm using 4.6 nmꢁ25 cm Daicel Chiralpak and Chiralcel.
High-resolution mass spectrometry (HRMS) was performed on Brucker
(neat): n˜ =2982, 1769, 1730, 1236, 1150, 1113, 1024, 841, 748, 710 cmꢀ1
;
HRMS (ESI) exact mass calcd for C15H18NaO6: m/z 317.0996 [M+Na]+,
found: 317.0995 [M+Na]+.
General procedure for the catalytic asymmetric alkylation of tert-butyl 2-
benzoyloxy-3-oxoalkanoate under phase-transfer conditions (Table 2): To
a solution of phase transfer catalyst (S,S)-1c (2.2 mg, 0.002 mmol) and 3
(0.20 mmol) in toluene (2 mL) was added the corresponding alkyl halide
and the mixture was cooled to ꢀ208C. Freshly powdered KOH (19.8 mg,
0.3 mmol) was added to the mixture, and the reaction mixture was vigo-
rously stirred until the completion of the reaction. The mixture was then
Chem. Asian J. 2010, 5, 562 – 570
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565

K. Maruoka et al.
FULL PAPERS
poured into saturated aqueous NH4Cl and extracted with ethyl acetate.
The organic layer was dried over Na2SO4 and concentrated in vacuo. The
residue was purified by column chromatography on silica gel to give the
alkylated compound.
(2H, app t, J=8.1 Hz, ArH), 7.02 (2H, d, J=8.6 Hz, ArH), 6.99 (2H, d,
J=8.6 Hz, ArH), 3.60 (2H, s, ArCH2), 2.28 (3H, s, COCH3), 2.24 (3H, s,
ArCH3), 1.41 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=202.2,
165.4, 165.2, 136.7, 135.5, 131.2, 130.1, 129.8, 129.4, 129.0, 128.5, 89.1,
83.4, 38.4, 27.7, 27.5, 21.0 ppm; IR (neat): n˜ =2978, 2932, 1757, 1722,
1281, 1175, 1155, 1109, 1069, 1026, 841, 814, 712 cmꢀ1; HRMS (ESI) exact
mass calcd for C23H26O5: m/z 405.1672 [M+Na]+, found: m/z 405.1660
[M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-benzyl-3-oxobutanoate (4a): Prepared ac-
cording to the general procedure with benzyl bromide (28.5 mL,
0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course of 12 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4a as a colorless oil
[91% (67.6 mg), 90% ee]. Enantiomeric purity was determined by HPLC
analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1, flow rate=
0.5 mLminꢀ1, retention time; 22.3 min (major) and 25.0 min (minor)).
½aꢁ2D8 =ꢀ46.5 (c=1.0, CHCl3; 90% ee); 1H NMR (400 MHz, CDCl3): d=
8.00 (2H, m, ArH), 7.61 (1H, app t, J=7.6 Hz, ArH), 7.46 (2H, app t,
J=7.8 Hz, ArH), 7.21–7.22 (3H, m, ArH), 7.12 (2H, m, ArH), 3.65 (2H,
s, PhCH2), 2.25 (3H, s, COCH3), 1.40 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3): d=202.2, 165.3, 165.2, 134.4, 133.5, 130.2, 129.8,
129.3, 128.5, 128.3, 127.1, 89.0, 83.4, 38.8, 27.6, 27.4 ppm; IR (neat): n˜ =
2978, 2932, 1755, 1721, 1279, 1152, 1107, 1094, 1069, 1026 912, 845, 733,
700 cmꢀ1; HRMS (ESI) exact mass calcd for C22H24O5: m/z 391.1516
[M+Na]+, found: m/z 391.1516 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-(4-methoxylbenzyl)-3-oxobutanoate (4i):
Prepared according to the general procedure with 4-methoxybenzyl bro-
mide (34.6 mL, 0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course
of 7 h. The crude material was purified by column chromatography on
silica gel (eluting with hexane/ethyl acetate=10:1) to give 4i as a color-
less oil [92% (73.6 mg), 88% ee]. Enantiomeric purity was determined
by HPLC analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1,
flow rate=0.5 mLminꢀ1, retention time; 45.2 min (major) and 51.7 min
(minor)). ½aꢁ3D0 =ꢀ43.1 (c=1.0, CHCl3; 88% ee); 1H NMR (400 MHz,
CDCl3): d=8.01 (2H, m, ArH), 7.61 (1H, app t, J=7.4 Hz, ArH), 7.47
(2H, app t, J=8.1 Hz, ArH), 7.03 (2H, d, J=8.8 Hz, ArH), 6.76 (2H, d,
J=8.8 Hz, ArH), 3.75 (3H, s, OCH3), 3.58 (2H, s, ArCH2), 2.25 (3H, s,
COCH3), 1.41 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=202.3,
165.4, 165.1, 158.7, 133.5, 131.2, 129.8, 129.3, 128.5, 126.3, 113.7, 89.1,
83.3, 55.1, 38.0, 27.6, 27.5 ppm; IR (neat): n˜ =2978, 2934, 1755, 1514,
1281, 1248, 1177, 1153, 1111, 1096, 1069, 1026, 841, 731, 710 cmꢀ1; HRMS
(ESI) exact mass calcd for C23H26O6: m/z 421.1622 [M+Na]+, found: m/z
421.1611 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-(4-fluorobenzyl)-3-oxobutanoate (4 f): Pre-
pared according to the general procedure with 4-fluorobenzyl bromide
(30.0 mL, 0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course of
10 h. The crude material was purified by column chromatography on
silica gel (eluting with hexane/ethyl acetate=10:1) to give 4 f as a color-
less oil [86% yield (66.2 mg), 92% ee]. Enantiomeric purity was deter-
mined by HPLC analysis (Daicel Chiralpak AD-H, hexane/2-propanol=
100:1, flow rate=0.5 mLminꢀ1, retention time; 23.6 min (major) and
24.8 min (minor)). ½aꢁD29 =ꢀ46.7 (c=1.0, CHCl3; 92% ee); 1H NMR
(400 MHz, CDCl3): d=7.99 (2H, m, ArH), 7.62 (1H, app t, J=7.6 Hz,
tert-Butyl (R)-2-allyl-2-benzoyloxy-3-oxobutanoate (4j): Prepared ac-
cording to the general procedure with allyl bromide (51.9 mL, 0.6 mmol)
and 3a (55.7 mg, 0.20 mmol) over the course of 20 h. The crude material
was purified by column chromatography on silica gel (eluting with
hexane/ethyl acetate=10:1) to give 4j as a colorless oil [85% (53.9 mg),
91% ee]. Enantiomeric purity was determined after the reduction of the
olefin moiety (see below). ½aꢁ2D7 =ꢀ29.2 (c=1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): d=8.08 (2H, m, ArH), 7.56 (1H, tt, J=1.5, 7.6 Hz,
ArH), 7.47 (2H, app t, J=8.1 Hz, ArH), 5.73 (1H, m, CH=CH2), 5.10–
5.18 (2H, m, CH=CH2), 3.07 (2H, d, J=7.3 Hz, CH2CH=CH2), 2.41 (3H,
s, COCH3), 1.46 (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=200.8,
165.4, 164.9, 133.5, 130.5, 129.8, 129.3, 128.5, 120.0, 88.2, 83.5, 37.8, 27.7,
26.9 ppm; IR (neat): n˜ =3078, 2980, 2934, 1755, 1721, 1315, 1281, 1242,
1157, 1138, 1107, 1096, 1069, 1026, 991, 924, 840, 710 cmꢀ1; HRMS (ESI)
exact mass calcd for C18H22O5: m/z 341.1359 [M+Na]+, found: m/z
341.1366 [M+Na]+.
ACTHNUTRGNEUNG
ArH), 7.47 (2H, app t, J=8.0 Hz, ArH), 7.08 (2H, dd, J=8.8 Hz, 4J(1 H,
19F)=5.6 Hz, ArH), 6.90 (2H, app t, J=8.8 Hz, ArH), 3.62 (2H, s,
ArCH2), 2.26 (3H, s, COCH3), 1.40 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3): d=202.1, 165.2, 165.1, 162.0 (d, 1J
ACHTUNGTRENNUNG
246.9 Hz), 133.7, 131.7 (d, 3J
(13C, 19F)=8.2 Hz), 130.2 (d, 4J
ACHUTGTNRENNUG CAHTUNGTRENNUNG
3.3 Hz), 129.8, 129.1, 128.6, 115.2 (d, 2J
AHCTUNGTRENNUNG
37.8, 27.6, 27.4 ppm; IR (neat): n˜ =2978, 2934, 1755, 1721, 1510, 1279,
1223, 1153, 1099, 1069, 1026, 841, 708 cmꢀ1; HRMS (ESI) exact mass
calcd for C22H23FO5: m/z 409.1422 [M+Na]+, found: m/z 409.1424
[M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-(4-bromobenzyl)-3-oxobutanoate (4g):
Prepared according to the general procedure with 4-bromobenzyl bro-
mide (60.0 mg, 0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course
of 10 h. The crude material was purified by column chromatography on
silica gel (eluting with hexane/ethyl acetate=10:1) to give 4g as a color-
less oil [91% (81.8 mg), 91% ee]. Enantiomeric purity was determined
by HPLC analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1,
flow rate=0.5 mLminꢀ1, retention time; 29.4 min (major) and 33.0 min
(minor)). ½aꢁ2D9 =ꢀ46.7 (c=1.0, CHCl3; 91% ee); 1H NMR (400 MHz,
CDCl3): d=7.99 (2H, d, J=7.4 Hz, ArH), 7.62 (1H, t, J=7.6 Hz, ArH),
7.45 (2H, app t, J=7.8 Hz, ArH), 7.34 (2H, d, J=8.3 Hz, ArH), 6.98
(2H, d, J=8.3 Hz, ArH), 3.61 (2H, s, ArCH2), 2.27 (3H, s, COCH3),
1.41 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=201.9, 165.1,
165.0, 133.7, 133.5, 131.9, 131.4, 129.7, 129.1, 128.6, 121.3, 88.8, 83.7, 37.9,
27.6, 27.3 ppm; IR (neat): n˜ =2978, 1755, 1724, 1489, 1369, 1281, 1153,
1107, 1094, 1070, 843, 712 cmꢀ1; HRMS (ESI) exact mass calcd for
C22H23BrO5: m/z 469.0621 [M+Na]+, found: m/z 469.0622 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-propyl-3-oxobutanoate: To a solution of
10% Pd/C (20 mg) in methanol (2 mL) was added 4j (23.0 mg,
0.083 mmol), and the flask was charged with H2. The reaction mixture
was then stirred for 2 h at room temperature under hydrogen atmosphere
(balloon) and filtered through celite. The filtrate was concentrated in
vacuo and passed through short pad of silica gel (eluting with hexane/
ethyl acetate=10:1) to give tert-butyl (R)-2-benzoyloxy-2-propyl-3-oxo-
butanoate as a colorless oil [97% (22.5 mg), 91% ee]. Enantiomeric
purity was determined by HPLC analysis (Daicel Chiralpak AD-H,
hexane/2-propanol=300:1, flow rate=0.5 mLminꢀ1
, retention time;
30.3 min (major) and 32.2 min (minor)). ½aꢁ2D8 =ꢀ21.6 (c=1.0, CHCl3;
91% ee); 1H NMR (400 MHz, CDCl3): d=8.09 (2H, m, ArH), 7.60 (1H,
tt, J=1.5, 7.6 Hz, ArH), 7.47 (2H, app t, J=8.1 Hz, ArH), 2.42 (3H, s,
CH3), 2.26 (2H, m, CH2CH2CH3), 1.46 (9H, s, tBu), 1.38 (2H, m,
CH2CH2CH3), 0.95 ppm (3H, t, J=7.3 Hz, CH2CH2CH3); 13C NMR
(100 MHz, CDCl3): d=201.2, 166.1, 165.0, 133.4, 129.9, 129.4, 128.5, 88.9,
83.3, 35.7, 27.7, 26.9, 17.0, 14.1 ppm; IR (neat): n˜ =2972, 2934, 2876, 1724,
1454, 1368, 1283, 1248, 1163, 1138, 1111, 1028, 845, 712 cmꢀ1; HRMS
(ESI) exact mass calcd for C18H24O5: m/z 343.1516 [M+Na]+, found: m/z
343.1529 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-(4-methylbenzyl)-3-oxobutanoate (4h):
Prepared according to the general procedure with 4-methylbenzyl bro-
mide (44.4 mg, 0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course
of 4 h. The crude material was purified by column chromatography on
silica gel (eluting with hexane/ethyl acetate=10:1) to give 4h as a color-
less oil [79% (60.5 mg), 89% ee]. Enantiomeric purity was determined
by HPLC analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1,
flow rate=0.5 mLminꢀ1, retention time; 24.1 min (major) and 28.2 min
(minor)). ½aꢁ2D8 =ꢀ42.3 (c=1.0, CHCl3; 89% ee); 1H NMR (400 MHz,
CDCl3): d=8.00 (2H, m, ArH), 7.60 (1H, tt, J=1.5, 7.6 Hz, ArH), 7.46
tert-Butyl (R)-2-benzoyloxy-2E-crotyl-3-oxobutanoate (5:1 E/Z mixture)
(4k): Prepared according to the general procedure with crotyl bromide
(5:1 E/Z mixture) (29.0 mL, 0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over
the course of 9 h. The crude material was purified by column chromatog-
raphy on silica gel (eluting with hexane/ethyl acetate=10:1) to give 4k
as a colorless oil [90% (60.1 mg, E/Z=5:1), 92% ee (for E isomer)].
566
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 562 – 570

Phase-Transfer-Catalyzed Asymmetric Alkylation of a-Benzoyloxy-b-keto Esters
Enantiomeric purity was determined after the hydrolysis of the benzoyl
group (see below). ½aꢁ3D1 =ꢀ25.2 (c=1.0, CHCl3; E/Z=5:1); 1H NMR
(400 MHz, CDCl3) (major isomer): d=8.08 (2H, m, ArH), 7.61 (1H, app
t, J=7.3 Hz, ArH), 7.47 (2H, app t, J=8.0 Hz, ArH), 5.56 (1H, m,
CH2CH=CH), 5.36 (1H, m, CH2CH=CH2), 2.98 (2H, d, J=7.3 Hz,
CH2CH=CH2), 2.39 (3H, s, COCH3), 1.46 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3) (major isomer): d=201.0, 165.6, 165.0, 133.4, 130.8,
129.8, 129.4, 128.5, 122.8, 88.4, 83.3, 36.9, 27.8, 27.0, 18.0 ppm; IR (neat):
n˜ =2978, 2934, 1755, 1724, 1315, 1283, 1260, 1157, 1128, 1107, 968, 843,
710 cmꢀ1; HRMS (ESI) exact mass calcd for C19H24O5: m/z 355.1516
[M+Na]+, found: m/z 355.1528 [M+Na]+.
843, 710 cmꢀ1; HRMS (ESI) exact mass calcd for C20H26O5: m/z 369.1672
[M+Na]+, found: m/z 369.1675 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-methallyl-3-oxobutanoate (4n): Prepared
according to the general procedure with methallyl bromide (60.5 mL,
0.60 mmol) and 3a (55.7 mg, 0.20 mmol) over the course of 20 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4n as a colorless oil
[41% (27.5 mg), 83% ee]. Enantiomeric purity was determined after the
hydrolysis of benzoyl group (see below). ½aꢁ2D9 =ꢀ24.9 (c=1.0, CHCl3;
83% ee); 1H NMR (400 MHz, CDCl3): d=8.08 (2H, m, ArH), 7.61 (1H,
tt, J=1.5, 7.6 Hz, ArH), 7.48 (2H, app t, J=8.1 Hz, ArH), 4.84 (1H, t,
J=1.4 Hz, C=CHH), 4.79 (1H, s, C=CHH), 3.12 (1H, d, J=15.2 Hz,
tert-Butyl (R)-2E-crotyl-2-hydroxy-3-oxobutanoate (5:1 E/Z mixture): To
a solution of 4k (5:1 E/Z mixture) (29.9 mg, 0.090 mmol) in CH3OH
(1.8 mL) was added 1n aq. NaOH (180 mL, 0.18 mmol), and the mixture
was stirred for 1 h at room temperature. The reaction solution was then
diluted with water and extracted with hexane. The organic layer was
dried over Na2SO4 and concentrated in vacuo. The residue was passed
through a short pad of silica gel (eluting with hexane/ethyl acetate=5:1)
to give tert-butyl (R)-2E-crotyl-2-hydroxy-3-oxobutanoate as a colorless
oil [84% (17.3 mg), 92% ee (for E isomer)]. Enantiomeric purity of E
isomer was determined by GLC analysis (Astec Chiraldex B-DM
(0.25 mmꢁ30 m) column, 1008C isotherm, retention time; 35.9 min
(minor) and 37.2 min (major)). ½aꢁ3D0 =ꢀ16.4 (c=1.0, CHCl3; 92% ee, E/
Z=5:1); 1H NMR (400 MHz, CDCl3) (major isomer): d=5.58 (1H, m,
CH2CH=CH), 5.33 (1H, m, CH2CH=CH2), 4.05 (1H, s, OH), 2.72 (1H,
dd, J=7.3, 14.4 Hz, CHHCH=CH2), 2.54 (1H, dd, J=7.1, 14.6 Hz,
CHHCH=CH2), 2.23 (3H, s, COCH3), 1.47 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3) (major isomer): d=204.3, 169.8, 130.2, 123.5, 83.72,
83.68, 38.0, 27.8, 24.8, 18.0 ppm; IR (neat): n˜ =3480, 2980, 2936, 1719,
1369, 1287, 1260, 1225, 1155, 1140, 1109, 970, 843 cmꢀ1; HRMS (ESI)
exact mass calcd for C12H20O4: m/z 251.1254 [M+Na]+, found: m/z
251.1250 [M+Na]+.
CHHC
ACHTUNGTERNNUG(CH3)C=CH2), 3.08 (1H, d, J=15.2 Hz, CHHCACHTUNGTRENNUNG
2.42 (3H, s, COCH3), 1.74 (3H, s, CH2CACHTUNGTRENNNUG
tBu); 13C NMR (100 MHz, CDCl3): d=201.1, 165.5, 164.9, 139.4, 133.5,
129.8, 129.3, 128.5, 116.2, 88.7, 83.5, 40.6, 27.7, 26.7, 23.4 ppm; IR (neat):
n˜ =2978, 2934, 1757, 1722, 1452, 1369, 1356, 1315, 1281, 1153, 1107, 1096,
1070, 1026, 902, 845, 710 cmꢀ1
; HRMS (ESI) exact mass calcd for
C19H24O5: m/z 355.1516 [M+Na]+, found: m/z 355.1502 [M+Na]+.
tert-Butyl (R)-2-hydroxy-2-methallyl-3-oxobutanoate: To a solution of 4n
(22.1 mg, 0.066 mmol) in CH3OH (1.3 mL) was added 1n aq. NaOH
(140 mL, 0.14 mmol) and the mixture was stirred for 1 h at room tempera-
ture. The reaction solution was then diluted with water and extracted
with hexane. The organic layer was dried over Na2SO4 and concentrated
in vacuo. The residue was passed through a short pad of silica gel (eluting
with hexane/ethyl acetate=5:1) to give tert-butyl (R)-2-hydroxy-2-meth-
allyl-3-oxobutanoate as a colorless oil [66% (10.0 mg), 83% ee]. Enantio-
meric purity was determined by GLC analysis (Astec Chiraldex B-DM
(0.25 mmꢁ30 m) column, 808C isotherm, retention time; 81.1 min
(major) and 83.5 min (minor)). ½aꢁ3D0 =ꢀ16.2 (c=1.0, CHCl3; 83% ee);
1H NMR (400 MHz, CDCl3): d=4.87 (1H, s, C=CHH), 4.79 (1H, s, C=
CHH), 4.08 (1H, s, OH), 2.82 (1H, d, J=14.6 Hz, CHHC
2.62 (1H, d, J=14.6 Hz, CHHC(CH3)C=CH2), 2.24 (3H, s, COCH3), 1.76
(3H, s, CH2C
(CH3)C=CH2), 1.48 ppm (9H, s, tBu); 13C NMR (100 MHz,
ACHTUGNTRNEN(UNG CH3)C=CH2),
AHCTUNGTRENNUNG
tert-Butyl (R)-2-benzoyloxy-2E-cinnamyl-3-oxobutanoate (4l): Prepared
according to the general procedure with cinnamyl bromide (47.3 mg,
0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course of 9 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4l as a colorless oil
[88% (69.8 mg), 90% ee]. Enantiomeric purity was determined by HPLC
analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1, flow rate=
0.5 mLminꢀ1, retention time; 30.1 min (major) and 36.3 min (minor)).
½aꢁ3D0 =ꢀ30.4 (c=1.0, CHCl3; 90% ee); 1H NMR (400 MHz, CDCl3): d=
8.08 (2H, m, ArH), 7.60 (1H, m, ArH), 7.46 (2H, app t, J=8.1 Hz,
ArH), 7.18–7.27 (5H, m, ArH), 6.47 (1H, d, J=15.9 Hz, PhCH=CH),
6.09 (1H, dt, J=7.6, 15.9 Hz, PhCH=CH), 3.22 (2H, d, J=7.6 Hz,
PhCH=CHCH2), 2.42 (3H, s, COCH3), 1.45 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3): d=200.9, 165.4, 165.0, 136.8, 134.9, 133.5, 129.9,
129.2, 128.53, 128.47, 127.5, 126.2, 121.9, 88.4, 83.6, 37.1, 27.8, 27.0 ppm;
IR (neat): n˜ =2978, 2932, 1753, 1721, 1369, 1356, 1356, 1152, 1105, 1096,
1069, 1026, 966, 843, 743, 710, 692 cmꢀ1; HRMS (ESI) exact mass calcd
for C24H26O5: m/z 417.1672 [M+Na]+, found: m/z 417.1683 [M+Na]+.
AHCTUNGTRENNUNG
CDCl3): d=204.3, 170.0, 140.4, 115.0, 87.0, 83.9, 41.7, 27.8, 24.7,
23.9 ppm; IR (neat): n˜ =3482, 2980, 2932, 1719, 1456, 1371, 1288, 1153,
1125, 1022, 897, 839, 772 cmꢀ1
; HRMS (ESI) exact mass calcd for
C12H20O4: m/z 251.1254 [M+Na]+, found: m/z 251.1256 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-propargyl-3-oxobutanoate (4o): Prepared
according to the general procedure with propargyl bromide (45.2 mL,
0.60 mmol) and 3a (55.7 mg, 0.20 mmol) over the course of 24 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4o as a colorless oil
[29% (18.4 mg), 61% ee]. Enantiomeric purity was determined by HPLC
analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1, flow rate=
0.5 mLminꢀ1, retention time; 22.7 min (minor) and 26.6 min (major)).
½aꢁ3D0 =ꢀ32.9 (c=1.0, CHCl3; 61% ee); 1H NMR (400 MHz, CDCl3): d=
8.12 (2H, m, ArH), 7.63 (1H, app t, J=7.6 Hz, ArH), 7.50 (2H, t, J=
8.1 Hz, ArH), 3.36 (1H, dd, J=2.7, 17.8 Hz, CHHCCH), 3.29 (1H, dd,
J=2.7, 17.6 Hz, CHHCCH), 2.49 (3H, s, COCH3), 1.98 (1H, app t, J=
2.7 Hz, CH2CCH), 1.46 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3):
d=200.8, 164.8, 164.3, 133.7, 129.9, 129.0, 128.6, 86.9, 84.0, 77.5, 71.6,
27.6, 26.9, 23.4 ppm;IR (neat): n˜ =3287, 2980, 2934, 1753, 1724, 1368,
1281, 1242, 1155, 1098, 1070, 839, 710 cmꢀ1; HRMS (ESI) exact mass
calcd for C18H20O5: m/z 339.1203 [M+Na]+, found: m/z 399.1204
[M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-prenyl-3-oxobutanoate (4m): Prepared ac-
cording to the general procedure with prenyl bromide (28.2 mL,
0.24 mmol) and 3a (55.7 mg, 0.20 mmol) over the course of 10 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4m as a colorless oil
[89% (61.9 mg), 87% ee]. Enantiomeric purity was determined by HPLC
analysis (Daicel Chiralpak AD-H, hexane/2-propanol=100:1, flow rate=
0.5 mLminꢀ1, retention time; 15.7 min (major) and 16.8 min (minor)).
½aꢁ3D1 =ꢀ22.6 (c=1.0, CHCl3; 87% ee); 1H NMR (400 MHz, CDCl3): d=
8.08 (2H, m, ArH), 7.60 (1H, tt, J=1.5, 7.4 Hz, ArH), 7.47 (2H, app t,
tert-Butyl (R)-2-benzoyloxy-2-benzyl-3-oxopentanoate (4p): Prepared ac-
cording to the general procedure with benzyl bromide (28.5 mL,
0.24 mmol) and 3 f (58.5 mg, 0.20 mmol) over the course of 4 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4p as a colorless oil
[88% (67.5 mg), 79% ee]. Enantiomeric purity was determined after the
cleavage of the benzoyl group (see below). ½aꢁ3D2 =ꢀ37.3 (c=1.0, CHCl3;
79% ee); 1H NMR (400 MHz, CDCl3): d=7.98 (2H, m, ArH), 7.61 (1H,
app t, J=7.6 Hz, ArH), 7.46 (2H, app t, J=8.0 Hz, ArH), 7.20 (3H, m,
ArH), 7.07 (2H, m, ArH), 3.66 (2H, s, PhCH2), 2.72 (1H, dq, J=7.1,
18.8 Hz, CHHCH3), 2.37 (1H, dq, J=7.3, 19.0 Hz, CHHCH3), 1.40 (9H,
s, tBu), 1.01 ppm (3H, t, J=7.1 Hz, CH2CH3); 13C NMR (100 MHz,
J=7.8 Hz, ArH), 5.09 (1H, app t, J=7.6 Hz, CH=C
(1H, dd, J=7.6, 15.1 Hz, CHHCH=C), 2.98 (1H, dd, J=7.1, 15.1 Hz,
CHHCH=C), 2.40 (3H, s, COCH3), 1.67 (3H, s, CH=C(CH3)CH3), 1.58
(3H, s, CH=C
(CH3)CH3), 1.45 ppm (9H, s, tBu); 13C NMR (100 MHz,
ACHTUGNTREN(UNNG CH3)CH3), 3.06
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
CDCl3): d=201.2, 165.8, 165.1, 136.6, 133.4, 129.8, 129.4, 128.5, 115.9,
88.4, 83.2, 32.5, 27.7, 27.0, 25.9, 17.9 ppm; IR (neat): n˜ =2978, 2932, 1755,
1721, 1452, 1369, 1354, 1315, 1281, 1246, 1153, 1107, 1096, 1069, 1026,
Chem. Asian J. 2010, 5, 562 – 570
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
567

K. Maruoka et al.
FULL PAPERS
CDCl3): d=205.2, 165.4, 165.1, 134.6, 133.5, 130.2, 129.8, 129.5, 128.5,
128.2, 127.1, 89.2, 83.3, 38.9, 33.0, 27.7, 7.3 ppm; IR (neat): n˜ =2978, 2938,
1757, 1720, 1601, 1452, 1369, 1281, 1155, 1111, 1093, 1026, 953, 845,
710 cmꢀ1; HRMS (ESI) exact mass calcd for C23H26O5: m/z 405.1672
[M+Na]+, found: m/z 405.1666 [M+Na]+.
m, ArH), 4.02 (1H, s, OH), 3.36 (1H, d, J=14.4 Hz, PhCHH), 3.13 (1H,
d, J=14.2 Hz, PhCHH), 2.24 (3H, s, CH3), 1.43 ppm (9H, s, tBu);
13C NMR (100 MHz, CDCl3): d=204.0, 169.7, 135.1, 130.3, 128.1, 127.0,
84.2, 84.1, 40.0, 27.7, 24.9 ppm; IR (neat): n˜ =3480, 2980, 1717, 1456,
1369, 1281, 1219, 1150, 1119, 837, 746, 700 cmꢀ1; HRMS (ESI) exact mass
calcd for C15H20O4: m/z 287.1254 [M+Na]+, found: m/z 287.1247
[M+Na]+.
tert-Butyl (R)-2-allyl-2-hydroxy-3-oxobutanoate (5j): ½aꢁ3D0 =ꢀ20.3 (c=
1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.72 (1H, m, CH2CH=
CH2), 5.12–5.19 (2H, m, CH2CH=CH2), 4.08 (1H, s, OH), 2.79 (1H, dd,
J=7.3, 14.4 Hz, CH2CH=CHH), 2.62 (1H, dd, J=7.1, 14.4 Hz, CH2CH=
CHH), 2.23 (3H, s, CH3CO), 1.47 ppm (9H, s, tBu); 13C NMR (100 MHz,
CDCl3): d=204.1, 169.7, 131.2, 119.4, 83.9, 83.4, 39.1, 27.8, 24.7 ppm; IR
(neat): n˜ =3483, 2980, 2928, 1721, 1369, 1287, 1244, 1150, 1016, 922, 841,
772, 673 cmꢀ1; HRMS (ESI) exact mass calcd for C11H18O4: m/z 237.1097
[M+Na]+, found: m/z 237.1098 [M+Na]+.
tert-Butyl (R)-2-benzyl-2-hydroxy-3-oxopentanoate: To a solution of 4p
(57.3 mg, 0.15 mmol) in CH3OH (2.0 mL) was added 1n aq. NaOH
(300 mL, 0.30 mmol), and the mixture was stirred for 1 h at 08C. The re-
action solution was then diluted with water and extracted with hexane.
The organic layer was dried over Na2SO4 and concentrated in vacuo. The
residue was passed through a short pad of silica gel (eluting with hexane/
ethyl acetate=5:1) to give tert-butyl (R)-2-benzyl-2-hydroxy-3-oxopenta-
noate as a colorless oil [94% (39.2 mg), 79% ee]. Enantiomeric purity
was determined by HPLC analysis (Daicel Chiralpak AD-H, hexane/2-
propanol=30:1, flow rate=0.5 mLminꢀ1
, retention time; 18.1 min
(minor) and 21.7 min (major)). ½aꢁ3D1 =ꢀ54.8 (c=1.0, CHCl3; 79% ee);
1H NMR (400 MHz, CDCl3): d=7.18–7.33 (5H, m, ArH), 4.01 (1H, s,
OH), 3.36 (1H, d, J=14.2 Hz, PhCHH), 3.14 (1H, d, J=14.4 Hz,
PhCHH), 2.72 (1H, dq, J=7.3, 18.6 Hz, CH3CHH), 2.48 (1H, dq, J=7.3,
18.6 Hz, CH3CHH), 1.42 (9H, s, tBu), 1.05 ppm (3H, t, J=7.1 Hz,
CH3CH2); 13C NMR (100 MHz, CDCl3): d=206.9, 169.9, 135.2, 130.4,
128.1, 127.0, 84.1, 84.0, 40.3, 30.6, 27.8, 7.8 ppm; IR (neat): n˜ =3478, 2978,
1717, 1454, 1369, 1279, 1260, 1219, 1153, 1113, 839, 748, 700 cmꢀ1; HRMS
(ESI) exact mass calcd for C16H22O4: m/z 301.1410 [M+Na]+, found: m/z
301.1402 [M+Na]+.
25
tert-Butyl (R)-2-(4-bromobenzyl)-2-hydroxy-3-oxobutanoate (5g): ½aꢁD
=
ꢀ64.0 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.38 (2H, d, J=
8.8 Hz, ArH), 7.13 (2H, d, J=8.8 Hz, ArH), 4.04 (1H, s, OH), 3.29 (1H,
d, J=14.4 Hz, ArCHH), 3.08 (1H, d, J=14.4 Hz, ArCHH), 2.22 (3H, s,
COCH3), 1.43 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=203.7,
169.6, 134.1, 132.0, 131.2, 121.1, 84.5, 83.8, 39.4, 27.8, 24.8; IR (neat): n˜ =
3487, 2978, 1719, 1487, 1369, 1288, 1151, 1121, 1072, 1013, 841 cmꢀ1
;
HRMS (ESI) exact mass calcd for C15H19BrNaO4: m/z 365.0359
[M+Na]+, found: m/z 365.0374 [M+Na]+.
tert-Butyl (R)-2-benzoyloxy-2-benzyl-3-oxohexanoate (4q): Prepared ac-
cording to the general procedure with benzyl bromide (28.5 mL,
0.24 mmol) and 3g (61.3 mg, 0.20 mmol) over the course of 12 h. The
crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4q as a colorless oil
[40% (30.7 mg), 73% ee]. Enantiomeric purity was determined by HPLC
analysis (Daicel Chiralcel OD-H, hexane/2-propanol=300:1, flow rate=
0.5 mLminꢀ1, retention time; 18.0 min (major) and 20.5 min (minor)).
½aꢁ2D8 =ꢀ34.5 (c=1.0, CHCl3; 73% ee); 1H NMR (400 MHz, CDCl3): d=
7.98 (2H, m, ArH), 7.61 (1H, app t, J=7.6 Hz, ArH), 7.46 (2H, app t,
J=7.8 Hz, ArH), 7.19 (3H, m, ArH), 7.07 (2H, m, ArH), 3.69 (1H, d,
J=14.6 Hz, PhCHH), 3.65 (1H, d, J=14.7 Hz, PhCHH), 2.70 (1H, m,
COCHH), 2.32 (1H, m, COCHH), 1.57 (2H, m, CH2CH2CH3), 1.40 (9H,
s, tBu), 0.86 ppm (3H, t, J=7.3 Hz, CH2CH2CH3); 13C NMR (100 MHz,
CDCl3): d=204.3, 165.3, 165.1, 134.6, 133.5, 130.3, 129.8, 129.5, 128.6,
128.2, 127.1, 89.3, 83.3, 41.3, 38.7, 27.7, 16.5, 13.5 ppm;IR (neat): n˜ =2974,
1720, 1452, 1369, 1281, 1155, 1107, 1026, 845, 710 cmꢀ1; HRMS (ESI)
exact mass calcd for C24H28O5: m/z 419.1829 [M+Na]+, found: m/z
419.1845 [M+Na]+.
tert-Butyl (2R,3R)-2-benzyl-2,3-dihydroxybutanoate (6a): To a solution
of ZnCl2 (27.2 mg, 0.2 mmol) in THF (1.0 mL) was added NaBH4
(7.6 mg, 0.2 mmol), and the mixture was stirred at room temperature for
1 h. After cooling the mixture to ꢀ788C, THF (1.0 mL) solution of 5a
(26.4 mg, 0.1 mmol) was added dropwise. The reaction was stirred for 1 h
at the same temperature. The reaction mixture was then poured into sa-
turated aqueous NH4Cl and extracted with ethyl acetate. The combined
organic layers were dried over Na2SO4 and concentrated in vacuo. The
residue was passed through a short pad of silica gel (eluting with hexane/
ethyl acetate=4:1) to give 6a as a colorless oil [89% (23.8 mg), d.r.
>20:1]. ½aꢁ2D8 =ꢀ12.1 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=
7.23–7.27 (5H, m, ArH), 3.98 (1H, m, CHOH), 3.42 (1H, s, OH), 2.90
(2H, s, PhCH2), 2.06 (1H, d, J=10.5 Hz, CHOH), 1.39 (9H, s, tBu),
1.31 ppm (3H, d, J=6.6 Hz, CH3CH); 13C NMR (100 MHz, CDCl3): d=
173.5, 135.8, 130.2, 128.0, 126.8, 83.4, 80.5, 71.9, 40.9, 27.9, 17.4 ppm; IR
(neat): n˜ =3480, 2978, 2934, 1722, 1395, 1369, 1279, 1258, 1221, 1155,
1128, 1053, 999, 895, 841, 739, 700 cmꢀ1; HRMS (ESI) exact mass calcd
for C15H22O4: m/z 289.1410 [M+Na]+, found: m/z 289.1389 [M+Na]+.
tert-Butyl (2R,3R)-2-allyl-2,3-dihydroxybutanoate (6j): ½aꢁ3D0 =+31.5 (c=
1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.74 (1H, m, CH2CH=
CH2), 5.10–5.16 (2H, m, CH2CH=CH2), 3.90 (1H, dq, J=6.6, 10.2 Hz,
CH3CH(OH)), 3.49 (1H, s, OH), 2.31–2.41 (2H, m, CH2CH=CH2), 2.04
(1H, d, J=10.3 Hz, CH3CH(OH)), 1.49 (9H, s, tBu), 1.23 ppm (3H, d,
J=6.6 Hz, CH3CH(OH)); 13C NMR (100 MHz, CDCl3): d=174.0, 131.9,
118.9, 83.2, 79.6, 71.4, 39.6, 23.0, 17.2 ppm; IR (neat): n˜ =3495, 2980,
2936, 1724, 1641, 1393, 1371, 1283, 1238, 1152, 1109, 997, 918, 845, 756,
675 cmꢀ1; HRMS (ESI) exact mass calcd for C11H20O4: m/z 239.1254
[M+Na]+, found: m/z 239.1255 [M+Na]+.
tert-Butyl methyl (R)-2-(benzoyloxy)-2-benzylmalonate (4r): Prepared
according to the general procedure with benzyl bromide (28.5 mL,
0.24 mmol) and 3h (58.8 mg, 0.20 mmol) over the course of 3 h at 08C.
The crude material was purified by column chromatography on silica gel
(eluting with hexane/ethyl acetate=10:1) to give 4r as a colorless oil
[94% (72.4 mg), 31% ee]. Enantiomeric purity was determined by HPLC
analysis (Daicel Chiralpak OD-H, hexane/isopropyl alcohol=50:1, flow
rate=0.5 mLminꢀ1
, retention time; 13.5 min (minor) and 16.0 min
(major)). ½aꢁ2D3 =+1.9 (c=1.0, CHCl3; 31% ee); 1H NMR (400 MHz,
CDCl3): d=8.03 (2H, m, ArH), 7.58 (1H, app t, J=7.6 Hz, ArH), 7.44
(2H, t, J=7.6 Hz, ArH), 7.26–7.20 (5H, m, ArH), 3.79 (3H, s, OCH3),
3.66 (2H, s, ArCH2), 1.42 ppm (9H, s,tBu); 13C NMR (100 MHz, CDCl3):
d=167.2, 165.0, 164.7, 134.2, 133.4, 130.3, 130.0, 129.3, 128.4, 128.2, 127.3,
83.6, 83.5, 52.9, 39.8, 27.7 ppm; IR (neat): n˜ =1753, 1724, 1452, 1369,
1283, 1250, 1209, 1153, 1107, 1055, 843, 712, 702 cmꢀ1; HRMS (ESI) exact
mass calcd for C22H24O6: m/z 407.1465 [M+Na]+, found: m/z 407.1474.
tert-Butyl (2R,3R)-2-allyl-2,3-dihydroxy-3-methylpentanoate (7a): To a
1.0m solution (0.50 mL, 0.50 mmol) of ethylmagnesium bromide in dieth-
yl ether was added tert-butyl (R)-2-allyl-2-hydroxy-3-oxobutanoate
(21.4 mg, 0.10 mmol) at room temperature. The mixture was stirred for
2 h at the same temperature, and then the reaction was quenched with
1n HCl and extracted with hexane. Organic extracts were dried over
Na2SO4 and concentrated in vacuo. The residue was then purified by
column chromatography on silica gel (eluding with hexane/ethyl ace-
tate=10:1) to give 7a as a colorless oil [49% (12.0 mg), d.r.=5.2:1].
½aꢁ2D8 =+30.7 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3) (major
isomer): d=5.76 (1H, m, CH=CH2), 5.09–5.15 (2H, m, CH=CH2), 3.58
(1H, s, OH), 5.61 (2H, d, J=7.1 Hz, CH2CH=CH2), 1.68 (2H, m,
CHHCH3), 1.49 (9H, s, tBu), 1.27 (1H, m, CHHCH3), 1.22 (3H, s, CH3),
0.95 ppm (3H, t, J=7.6 Hz, CH2CH3); 13C NMR (100 MHz, CDCl3)
(major isomer): d=173.9, 132.9, 118.6, 83.6, 81.6, 75.4, 37.3, 28.6, 28.0,
tert-Butyl (R)-2-benzyl-2-hydroxy-3-oxobutanoate (5a): To a solution of
4a (32.0 mg, 0.088 mmol) in CH3OH (2 mL) was added 1n aq. NaOH
(180 mL, 0.18 mmol), and the mixture was stirred for 2 h at 08C. The re-
action solution was then diluted with water and extracted with hexane.
The organic layer was dried over Na2SO4 and concentrated in vacuo. The
residue was passed through a short pad of silica gel (eluting with hexane/
31
ethyl acetate=5:1) to give 5a as a colorless oil [80% (18.4 mg)]. ½aꢁD
=
ꢀ62.6 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.22–7.26 (5H,
568
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 562 – 570

Phase-Transfer-Catalyzed Asymmetric Alkylation of a-Benzoyloxy-b-keto Esters
20.0, 7.6 ppm; IR (neat): n˜ =3493, 3076, 2978, 2932, 1713, 1460, 1395,
1369, 1271, 1236, 1144, 1090, 1047, 999, 916, 843 cmꢀ1; HRMS (ESI) exact
mass calcd for C13H24O4: m/z 267.1567 [M+Na]+, found: m/z 267.1558
[M+Na]+.
37.6, 28.0, 22.6 ppm; IR (neat): n˜ =3491, 2980, 2932, 1715, 1369, 1273,
1238, 1142, 1096, 1072, 999, 922, 843, 756, 671 cmꢀ1; HRMS (ESI) exact
mass calcd for C13H22O4: m/z 265.1410 [M+Na]+, found: m/z 265.1400
[M+Na]+.
23
tert-Butyl (2R,3S)-2-allyl-2,3-dihydroxy-3-phenylbutanoate (8d): ½aꢁD
=
tert-Butyl (2R,3R)-2-allyl-2,3-dihydroxy-3-methylhex-5-enoate (7b):
½aꢁ2D9 =+55.3 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.93 (1H,
m, CH=CH2), 5.75 (1H, m, CH=CH2), 5.04–5.16 (4H, m, CH=CH2, CH=
CH2), 3.58 (1H, s, OH), 2.66 (1H, s, OH), 2.61 (2H, m, CH2CH=CH2),
2.46 (1H, dd, J=6.6, 14.4 Hz, CHHCH=CH2), 2.04 (1H, dd, J=8.0,
13.9 Hz, CHHCH=CH2), 1.51 (9H, s, tBu), 1.24 ppm (3H, s, CH3);
13C NMR (100 MHz, CDCl3): d=173.7, 134.0, 132.7, 118.8, 118.0, 83.8,
81.4, 75.1, 41.2, 37.3, 28.0, 21.4 ppm; IR (neat): n˜ =3509, 3076, 2978, 2934,
1717, 1639, 1369, 1273, 1238, 1144, 1096, 1051, 999, 916, 843 cmꢀ1; HRMS
(ESI) exact mass calcd for C14H24O4: m/z 279.1567 [M+Na]+, found: m/z
279.1556 [M+Na]+.
+35.5 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.55 (2H, m,
ArH), 7.22–7.32 (3H, m, ArH), 5.73 (1H, m, CH=CH2), 5.08–5.14 (2H,
m, CH=CH2), 3.62 (1H, s, OH), 3.48 (1H, s, OH), 2.71 (1H, dd, J=8.3,
13.9 Hz, CHHCH=CH2), 2.63 (1H, app ddt, J=1.4, 6.2, 13.9 Hz,
CHHCH=CH2), 1.60 (3H, s, CH3), 1.27 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3): d=173.4, 144.3, 132.5, 127.5, 127.1, 126.3, 119.0, 84.3,
81.3, 76.9, 38.4, 27.7, 23.9 ppm; IR (neat): n˜ =1731, 1387, 1371, 1283,
1229, 1144, 1096, 1007 cmꢀ1; HRMS (ESI) exact mass calcd for C17H24O4:
m/z 315.1567 [M+Na]+, found: m/z 315.1560 [M+Na]+.
tert-Butyl (2R,3S)-2-(4-bromobenzyl)-2,3-dihydroxy-3-phenylbutanoate
(10): ½aꢁ2D4 =ꢀ30.6 (c=1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.56
(2H, m, ArH), 7.22–7.37 (5H, m, ArH), 7.12 (2H, m, ArH), 3.90 (1H, s,
OH), 3.28 (1H, d, J=13.5 Hz, ArCHH), 3.28 (1H, s, OH), 3.09 (1H, d,
J=13.8 Hz, ArCHH), 1.67 (3H, s, CH3), 1.07 ppm (9H, s, tBu); 13C NMR
(100 MHz, CDCl3): d=172.7, 144.2, 135.3, 132.4, 130.9, 127.6, 127.2,
126.4, 120.7, 84.6, 81.9, 77.3, 38.9, 27.5, 23.7 ppm; IR (neat): n˜ =1732,
1487, 1373, 1285, 1269, 1207, 1144, 1072, 1013 cmꢀ1; HRMS (ESI) exact
mass calcd for C21H25BrO4: m/z 443.0828 [M+Na]+, found: m/z 443.0844
[M+Na]+.
tert-Butyl (2R,3R)-2-allyl-2,3-dihydroxy-3-methylpent-4-enoate (7c):
½aꢁ3D0 =+22.4 (c=1.0, CHCl3; 91% ee); 1H NMR (400 MHz, CDCl3)
(major isomer): d=5.91 (1H, dd, J=11.0, 17.3 Hz, CH=CH2), 5.74 (1H,
m, CH2CH=CH2), 5.36 (1H, dd, J=1.4, 17.3 Hz, CH=CHH), 5.09–5.18
(3H, m, CH=CHH, CH2CH=CH2), 3.49 (1H, s, OH), 2.92 (1H, s, OH),
2.62 (1H, dd, J=8.6, 14.2 Hz, CHHCH=CH2), 2.52 (1H, m, CHHCH=
CH2), 1.50 (9H, s, tBu), 1.35 ppm (3H, s, CH3); 13C NMR (100 MHz,
CDCl3) (major isomer): d=173.5, 140.1, 132.6, 118.8, 114.4, 84.0, 80.8,
76.0, 37.4, 28.0, 23.1 ppm; IR (neat): n˜ =3493, 3078, 2980, 2934, 1717,
1641, 1369, 1275, 1144, 1090, 997, 920, 845 cmꢀ1; HRMS (ESI) exact mass
calcd for C13H22O4: m/z 265.1410 [M+Na]+, found: m/z 265.1412
[M+Na]+.
25
tert-Butyl (2R,3R)-2-allyl-2,3-dihydroxy-3-phenylbutanoate (7d): ½aꢁD
=
+22.5 (c=1.0, CHCl3; 91% ee); 1H NMR (400 MHz, CDCl3): d=7.52
(2H, m, ArH), 7.32 (2H, m, ArH), 7.26 (1H, m, ArH), 5.67 (1H, m,
CH2CH=CH2), 5.05–5.10 (2H, m, CH2CH=CH2), 3.61 (1H, s, OH), 3.54
(1H, s, OH), 2.75 (1H, ddd, J=0.7, 8.5, 14.0 Hz, CHHCH=CH2), 2.31
(1H, ddt, J=1.5, 5.8, 13.9 Hz, CHHCH=CH2), 1.66 (3H, s, CH3),
1.44 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=173.4, 142.9,
132.4, 127.4, 127.1, 126.9, 118.9, 84.3, 81.5, 76.8, 38.2, 27.9, 25.0 ppm; IR
(neat): n˜ =1717, 1369, 1271, 1238, 1140, 1101, 997, 914, 841 cmꢀ1; HRMS
(ESI) exact mass calcd for C17H24O4: m/z 315.1567 [M+Na]+, found: m/z
315.1565 [M+Na]+.
Acknowledgements
This work was partially supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
[1] For a general review, see: J. Christoffers, A. Baro, T. Werner, Adv.
Synth. Catal. 2004, 346, 143.
[2] a) P. Y. Toullec, C. Bonaccorsi, A. Mezzetti, A. Togni, Proc. Natl.
Acad. Sci. USA 2004, 101, 5810; b) C. Bonaccorsi, M. Althaus, C.
Becker, A. Togni, A. Mezzetti, Pure Appl. Chem. 2006, 78, 391; c) T.
Ishimaru, N. Shibata, J. Nagai, S. Nakamura, T. Toru, S. Kanemasa,
J. Am. Chem. Soc. 2006, 128, 16488; d) A. M. R. Smith, D. Billen,
K. K. Hii, Chem. Commun. 2009, 3925.
[3] a) S. F. McCann, G. D. Annis, R. Shapiro, D. W. Piotrowski, G. P.
Lahm, J. K. Long, K. C. Lee, M. M. Hughes, B. J. Myers, S. M. Gris-
wold, B. M. Reeves, R. W. March, P. L. Sharpe, P. Lowder, W. E.
Barnette, K. D. Wing, Pest. Manag. Sci. 2001, 57, 153; b) M. R. Aco-
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[4] M. Lu, D. Zhu, Y. Lu, X. Zeng, B. Tan, Z. Xu, G. Zhong, J. Am.
Chem. Soc. 2009, 131, 4562.
[5] For recent review articles on phase-transfer catalysis, see: a) T. Ooi,
K. Maruoka, Angew. Chem. 2007, 119, 4300; Angew. Chem. Int. Ed.
2007, 46, 4222; b) T. Hashimoto, K. Maruoka, Chem. Rev. 2007, 107,
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[6] For a preliminary communication, see: T. Hashimoto, K. Sasaki, K.
Fukumoto, Y. Murase, T. Ooi, K. Maruoka, Synlett 2009, 661.
[7] G. Scheid, W. Kuit, E. Ruijter, R. V. A. Orru, E. Henke, U. Born-
scheuer, L. A. Wessjohann, Eur. J. Org. Chem. 2004, 1063; the au-
thors describe the sodium hydride mediated alkylation of a-acyloxy-
b-keto esters.
[8] a) T. Ooi, T. Miki, M. Taniguchi, M. Shiraishi, M. Takeuchi, K. Mar-
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2006, 348, 1539.
tert-Butyl (2R,3R)-2-(4-bromobenzyl)-2,3-dihydroxy-3-(4-(trifluorome-
thyl)phenyl)butanoate (9): ½aꢁ2D4 =+3.5 (c=1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): d=7.76 (2H, d, J=8.2 Hz, ArH), 7.61 (2H, d, J=
8.2 Hz, ArH), 7.33 (2H, d, J=8.2 Hz, ArH), 7.02 (2H, d, J=8.5 Hz,
ArH), 3.86 (1H, s, OH), 3.50 (1.0H, s, OH), 3.27 (1H, d, J=13.5 Hz,
ArCHH), 2.50 (1.0H, d, J=13.8 Hz, ArCHH), 1.66 (3H, s, CH3),
1.33 ppm (9H, s, tBu); 13C NMR (100 MHz, CDCl3): d=172.9, 146.7,
3
134.7, 132.5, 131.0, 129.4 (q, 2JCꢀF =32.2 Hz), 127.8, 124.4 (q, JCꢀF
=
4.1 Hz), 124.3 (q, 1JCꢀF =272.0 Hz), 120.9, 85.5, 81.7, 38.9, 27.8, 25.6 ppm
(one peak overlaps with CDCl3); IR (neat): n˜ =1721, 1327, 1260, 1163,
1123, 1070, 1015, 851 cmꢀ1
; HRMS (ESI) exact mass calcd for
C22H24BrF3O4: m/z 513.0685 [M+Na]+, found: m/z 513.0675 [M+Na]+.
tert-Butyl (2R,3S)-2-allyl-2,3-dihydroxy-3-methylpent-4-enoate (8c): To a
solution of ZnCl2 (40.9 mg, 0.30 mmol) in THF (0.50 mL) was added a
1.0m solution (0.60 mL, 0.60 mmol) of vinylmagnesium bromide in THF
at room temperature, and the mixture was then stirred for 1 h. To the
mixture was added tert-butyl (R)-2-allyl-2-hydroxy-3-oxobutanoate
(21.4 mg, 0.10 mmol) at room temperature. The reaction mixture was
stirred for 2 h at the same temperature, and then the reaction was
quenched with 1n HCl and extracted with hexane. Organic extracts were
dried over Na2SO4 and concentrated in vacuo. The residue was then puri-
fied by column chromatography on silica gel (eluding with hexane/ethyl
acetate=10:1) to give 8c as a colorless oil [84% (20.6 mg), d.r.>20:1].
½aꢁ3D2 =ꢀ3.8 (c=1.0, CHCl3; 91% ee); 1H NMR (400 MHz, CDCl3): d=
6.12 (1H, dd, J=11.0, 17.6 Hz, CH=CH2), 5.73 (1H, m, CH2CH=CH2),
5.38 (1H, dd, J=1.7, 17.6 Hz, CH=CHH), 5.14 (1H, dd, J=1.7, 10.7 Hz,
CH=CHH), 5.09–5.14 (2H, m, CH2CH=CH2), 3.55 (1H, s, OH), 2.94
(1H, s, OH), 2.62 (1H, dd, J=8.3, 14.4 Hz, CHHCH=CH2), 2.53 (1H, m,
CHHCH=CH2), 1.48 (9H, s, tBu), 1.27 ppm (3H, s, CH3); 13C NMR
(100 MHz, CDCl3): d=173.6, 140.6, 132.5, 118.9, 113.6, 84.1, 80.4, 75.9,
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[15] CCDC 740881 (9) and CCDC 740880 (10) contain the supplementa-
ry crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif. See Supporting Informa-
tion for details.
1
[12] Determined by H NMR analysis of the crude material.
Received: August 6, 2009
[13] M. Hatano, K. Ishihara, Synthesis 2008, 1647.
Published online: December 10, 2009
570
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 562 – 570