Synthesis of α-diazo-β-hydroxyesters through a one-pot protocol by phase-transfer catalysis: Application to enantioselective aldol-type reaction and diastereoselective synthesis of α-amino-β-hydroxyester derivatives

Article abstract of DOI:10.1016/j.tet.2005.11.028

The one-pot synthesis of α-diazo-β-hydroxyesters from sodium azide under phase-transfer-catalyzed conditions has been achieved. This protocol includes three different chemical transformations promoted by a single catalyst in each step to give products in good to excellent yields. The reaction was applied to a catalytic asymmetric aldol-type reaction using α-diazoesters with aldehydes in the presence of a chiral quaternary ammonium salt and gave products with up to 81% ee. The diastereoselective transformation of the products to chiral α-amino-β-hydroxyester derivatives is also described.

Full text of DOI:10.1016/j.tet.2005.11.028

Tetrahedron 62 (2006) 1390–1401
Synthesis of a-diazo-b-hydroxyesters through a one-pot protocol
by phase-transfer catalysis: application to enantioselective
aldol-type reaction and diastereoselective synthesis of
a-amino-b-hydroxyester derivatives
*
Kazuya Hasegawa, Shigeru Arai and Atsushi Nishida
*
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Received 21 October 2005; accepted 15 November 2005
Available online 20 December 2005
Abstract—The one-pot synthesis of a-diazo-b-hydroxyesters from sodium azide under phase-transfer-catalyzed conditions has been
achieved. This protocol includes three different chemical transformations promoted by a single catalyst in each step to give products in good
to excellent yields. The reaction was applied to a catalytic asymmetric aldol-type reaction using a-diazoesters with aldehydes in the presence
of a chiral quaternary ammonium salt and gave products with up to 81% ee. The diastereoselective transformation of the products to chiral a-
amino-b-hydroxyester derivatives is also described.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
the aldol-type reaction of a-diazoesters with aldehydes has
been investigated.4,5 Since the starting a-diazoesters and the
precursor, tosyl azide are both readily available under PTC
conditions,6 we expected that all three sequences could be
promoted by a single phase-transfer catalyst without
isolation of any explosive intermediates.
Phase-transfer-catalyzed reactions are some of the most
environmentally-friendly processes in synthetic organic
chemistry due to their simplicity, mild conditions and high
cost performance.1 Particularly, chiral quaternary
ammonium salts have been recognized as powerful
asymmetric phase-transfer catalysts (PTCs) since Dolling
and O’Donnell independently reported their pioneering
studies.2 In this paper, we report the PTC-promoted one-pot
synthesis of a-diazo-b-hydroxyesters from sodium azide,
acetoacetate and aldehydes in the presence of a single
catalyst without isolation of intermediates. The application
to enantioselective carbon–carbon bond-forming reactions
and the diastereoselective synthesis of a-amino and
a-hydrazino-b-hydroxyesters is also described in detail.3
First, we investigated a three-step protocol using tosyl
chloride, t-butyl acetoacetate 1a and benzaldehyde 3a in the
presence of tetrahexylammonium bromide (THAB,
10 mol%) as a PTC. The results are summarized in
Table 1. The azidation of tosyl chloride (first step) in
CH2Cl2 proceeded quantitatively (rt, 1 h), however, diazo-
transfer (second step) with aqueous 11% NaOH at rt was
slow (85 h). Subsequent aldol-type reaction (third step) with
3a (5 equiv) gave the desired product 4a in 70% yield (entry
1). Ethylester 1b was more reactive in diazo-transfer step
and the reaction was completed within 9 h, and the aldol-
type reaction gave 5a in 87% (entry 2). The solvent
influenced the rate of diazo-transfer, for example, the
reaction in diethyl ether enabled rapid conversion in diazo-
transfer and 5a was obtained in 82% yield through three
steps (entry 3). Although a longer reaction time was
required, benzylester 1c was also transformed to 2c in
25 h and subsequent C–C bond formation gave 6 in 51%
overall yield (entry 4).
2. Resullts and discussion
2.1. One-pot synthesis of a-diazo-b-hydroxyesters
a-Diazo-b-hydroxyesters are useful as a potential source of
amino alcohols or acids and their facile preparation using
Keywords: Aldol-type reaction; a-Diazo-b-hydroxyester; a-Amino-b-
hydroxyester.
Next, we applied this three-step protocol to various
aldehydes under optimized conditions (Table 2). The
*
Corresponding authors. Tel.: C81 432902908; fax: C81 432902909;
e-mail: arai@p.chiba-u.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.11.028

K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
Table 1. One-pot syhthesis of a-diazo-b-hydroxyesters under PTC conditions
1391
Entry
1
Solvent
Time1 (h)
Time2 (h)
Yield (%)
1
2
3
4
1a: RZt-Bu
1b: RZEt
1b: RZEt
1c: RZBn
CH2Cl2
CH2Cl2
Et2O
85
9
1.5
25
3
3
3
7
4a: 70
5a: 87
5a: 82
6: 51
Et2O
Table 2. One-pot reaction using various aldehydes
Entry
3: Aldehyde
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
3b: RZ4-MeO–C6H4
3c: RZ4-CF3–C6H4
3d: RZ1-Napthyl
3e: RZPh(CH2)2
3f: RZi-Bu
3g: RZi-Pr
3h: RZc-Hex
3i: RZt-Bu
2
12
3
3
20
3
5b: 73
5c: 76
5d: 80
5e: 86a
5f: 82
5g: 75
5h: 75
5i: 73
4
18
a Three equivalent of 3e was used.
aromatic aldehydes shown in entries 1–3 were smoothly
transformed into the corresponding adducts 5b–d in yields
of 73–80%. In the case of aliphatic aldehydes including
sterically hindered substrate such as 3i, the reactions also
proceeded without any significant self-condensation with a
range of 73–86% yield (entries 4–8).
aldol-type reaction using a-diazoester has been reported.7
Initially, we surveyed this reaction using cinchoninium salts
(A–C9e) (Table 3). Although the enantioselectivities were
poor, an N-anthracenyl group gave better results at 0 8C
(entry 2). Moreover, a secondary hydroxy group was found
to be essential in asymmetric induction, suggesting that
hydrogen bonding between the catalyst and substrates is
important (entry 2 vs 3). Since the cinchonidinium salt (PTC
D) gave a slightly better result, the reaction conditions were
further optimized using catalyst D (Table 4).
2.2. Asymmetric aldol-type reaction using a chiral
quaternary ammonium salt as a PTC
After succeeding with the one-pot synthesis of a-diazo-b-
hydroxyesters, we next investigated catalytic asymmetric
synthesis. Only one example of a catalytic asymmetric
With a stronger base such as aqueous KOH, the reaction
proceeded to give 4a at lower temperature (Table 4, entries
Table 3. Catalytic asymmetric aldol-type reaction of 2a with 3a using various PTCs
Entry
PTC
R1
R2
X
Time (h)
Yield (%)
ee (%)a
1
2
3
4
A
B
C
D
Ph
9-Anthracenyl
9-Anthracenyl
H
H
Allyl
Br
Cl
Br
2.5
2
3
51
84
96
76
6 (S)
14 (R)
0
3
24 (S)
a Determined by chiral HPLC analysis using DAICEL CHIRALCEL OD.

1392
K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
Table 4. Catalytic asymmetric aldol-type reaction of 2a with 3a using PTC D
Entry
Solvent
Base
3a (equiv)
Conditions
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
Et2O
Et2O
Et2O
Et2O
Et2O
PhMe
PhMe
PhMe
25% KOH
50% KOH
50% KOH
50% KOH
50% RbOH
50% KOH
50% RbOH
50% CsOH
5
5
5
1.5
1.5
1.5
1.5
1.5
K208C, 8 h
K408C, 2 h
K608C, 16 h
K408C, 14 h
K408C, 10 h
K408C, 38 h
K408C, 10 h
K408C, 20 h
70
74
65
96
72
83
96
76
25
39
20
48
51
45
56
56
1–3). Under biphase conditions of 50% KOH and Et2O at
K40 8C, 1.5 equiv of 3a was enough for the reaction to
proceed in 96% yield with moderate enantioselectivity
(entry 4). The best result (96% yield, 56% ee)8 was obtained
using 50% aqueous RbOH in toluene at K40 8C (entry 7).
The absolute stereochemistry of 4a was determined to be S
by comparison with the reported optical rotation10 after
diazo decomposition to b-hydroxyester 7 (Scheme 1 and
Section 3).
Table 5. Enantioselective synthesis of 4 with various aldehydes using
PTC D
Scheme 1. Determination of the absolute stereochemistry of 4a.
Entry
1
Aldehyde 3
Time (h)
120
Yield (%) ee (%)
3b: RZ4-
MeO–C6H4
4b: 56
0
Next, various aldehydes were used in this reaction under the
optimized conditions. The electron density on the aromatic
rings was found to strongly influence the enantioselectivity
(Table 5). For example, 3b, which has a 4-MeO group, gave
a racemate, while 3c which has an electron-withdrawing
group 4-CF3, gave 4c in 81% yield with 73% ee (entries 1
and 2). 4-Alkylated substrates were also converted with
lower ee (entries 4 and 5). 1- and 2-Naphthaldehydes were
converted to 4d and 4l in respective yields of 86% (79% ee)
and 94% (56% ee) (entries 3 and 6). In the case of aliphatic
substrates, primary and secondary aldehydes such as 3e–h
gave 22–42% ee (entries 7–10), but pivalaldehyde 3i was
transformed to 4i in 83% yield with 81% ee (entry 11).
2
3
4
5
6
7
8
9
3c: RZ4-CF3–C6H4 140
4c: 81
4d: 86
4j: 66
4k: 63
4l: 94
4e: 32
4f: 85
4g: 53
4h: 88
4i: 84
73
79
39
32
56
33
22
42
33
81
3d: RZ1-Napthyl
3j: RZ4-Me–C6H4
3k: RZ4-Bu–C6H4
3l: RZ2-Naphthyl
3e: RZPh(Ch2)2
3f: RZi-Bu
94
18
120
110
72
72
20
3g: RZi-Pr
10
11
3h: RZc-Hex
3i: RZt-Bu
10
72
aldehydes in the C–C bond-forming step or the reversal
retro-aldol step by kinetic resolution.
To test the latter possibility, (G)-4a was subjected to retro-
aldol conditions with 50% RbOH in toluene (10 h) in the
presence of PTC D, and the formation of 2a and 3a was
observed. However, the ee of the recovered 4a (72%) was
very low (Scheme 2). This result suggests that the
asymmetric induction of 4a occurs mainly not via kinetic
resolution in the retro-aldol step but rather through the
carbon–carbon bond-forming step. In the case of 4i, an
alcoholic proton might be less acidic than benzyl alcoholic
proton in 4a and the retro-aldol reaction seems to be
disfavored. As outlined in Scheme 3, k’S and k’R are
considered to be equal but the rate of C–C bond formation
(kS) is greater than kR in the reaction of 3a with 2a.
The aldol-type reaction of a-diazoesters under basic media
has been reported to include an equilibrium process,4f so the
time course of the chemical yield and ee of 4a and 4i during
asymmetric reactions were investigated. As shown in
Figure 1, in the case of aromatic aldehyde 3a both the
chemical yield and ee of 4a gradually increased. The
chemical yield reached equilibrium after 5 h and the ee
remained at about 60% ee after 3 h. In the reaction of
aliphatic aldehyde 3i, the initial ee of 4i was 70%, and this
gradually increased to 80% ee after 5 h. The former result
suggests the possibility of a retro-aldol reaction.11 With
regard to this reversible mechanism, enantioselection might
occur in the differentiation of the carbonyl plane of

K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
1393
O
O
O-t-Bu
O-t-Bu
OH
N2
OH
O
N2
O
2a
2a
t-Bu
O-t-Bu
PhCHO
t-BuCHO
Ph
O-t-Bu
50% RbOH
50% RbOH
N2
3a
N2
4a
3i
PhMe, -40˚C
PTC D (10 mol%)
PhMe, -40˚C
PTC D (10 mol%)
4i
100
80
100
80
4i
4a
60
60
(%)
(% )
40
20
0
40
20
Yield
Ee
Yield
Ee
0 0.5
1
3
5
10
20
0
1
3
5
1
0
Time (h)
Time (h)
Figure 1. Time course of yield and ee in the reaction of 2a with 3a and 3i.
OH
OH
PTC D (10 mol%)
CO t-Bu
CO t-Bu
2
2
Ph
Ph
50% RbOH
PhMe, -40˚C, 10h
N
N
2
2
(±)-4a
72% (3% ee)
Scheme 2. Retro aldol-type reaction of (G)-4a with PTC D.
PhMe, 50% RbOH,
CO t-Bu
2
PTC D (10 mol%), -40 ˚C
OH
N
2
2a
O H
k
S
k
R
R
CO t-Bu
2
CO t-Bu
2
Ph
+
Ph
N
N
2
2
k '
S
(R)-4a
k'
PhCHO
(S)-4a
3a
minor
major
kR< kS k'S
kR
Scheme 3. Postulated reaction pathway for the catalytic asymmetric aldol-type reaction.
The presence of this retro-aldol process for racemic 4a
explains the increase in ee in the initial step of the reaction
using 3a. In the same way, a large excess of 3a resulted in a
lower ee (Table 4, entry 2 vs 4).
high reactivity with late transition metals. However, only
limited examples of transformation using a-diazo-b-
hydroxyesters have been reported,13 since they are unstable
under basic (retro-aldol reaction) and acidic (diazo
decomposition) media. Furthermore, they gave simple 1,3-
dicarbonyl compounds via a 1,2-hydride shift by reacting
with transition metals (Scheme 4). To establish a new
synthetic transformation of a-diazo-b-hydroxyesters with-
out any loss of chiral centers, we attempted the reduction of
a diazo group to hydrazone or hydrazine as an amine
2.3. Transformation of optically active a-diazo-b-
hydroxyesters to a-amino-b-hydroxyester derivatives
Many organic transformations using a diazo-functionality
via diazo-decomposition have been reported12 due to its
OH
*
O
O
O
O
OH
O
O
strong base
Rh, Cu
or acid
1
2
+
2
1
2
R
OR
R
2
OR
R
OR
1
OR
R
H
1
H
N
N
2
2
1,2-hydride-shiht
Scheme 4. Decomposition of a-diazo-b-hydroxyesters.

1394
K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
LiHBEt3 proceeded smoothly but the stability of the product
was problematic and subsequent reduction with SmI2 and
protection with Boc2O gave amino alcohols in low yields.
Next, the initial protection of (G)-4a with TBSCl followed
by reduction of the diazo group by LiHBEt3 gave hydrazone
10 as a single isomer in 96% yield. Its configuration was
confirmed by X-ray crystallographic analysis to be E
(Fig. 2). Subsequent N-benzoylation (BzCl with pyridine
in CH2Cl2 at 0 8C) gave (E)-11 without significant
isomerization18 (Scheme 5).
The further diastereoselective reduction of C]N bond was
investigated (Table 6). The treatment of (E)-11 with NaBH4
at 0 8C in EtOH gave a-hydrazinoester anti-12 in 92% yield,
exclusively (entry 1). In the case of LiBH4, a mixture of 12
and 13 was obtained with respective yields of 55 and 12%.
However, no diastereoselectivities were observed in either
product (entry 2). The reaction of Red-Al with 11 in toluene
gave 13 as a separable diastereomixture in moderate yield,
while no selectivity was observed (entry 3).
Figure 2. X-ray structure of (E)-10.
equivalent,14,15 which are known to be useful building
blocks for the synthesis of polypeptides and biologically
important molecules.16,17
Further transformations of 12 and 13 are outlined in
Scheme 6. N–N bond cleavage of anti-12 with SmI2
followed by protection with Boc2O gave 14 (65% yield) as a
mixture of syn- and anti-isomers (1:2.6) due to epimeriza-
tion at the a-position.19 In the case of syn-13 and anti-13,
similar transformation gave the corresponding alcohols 15
First, we attempted to convert (G)-4a to hydrazonoester
without protection of its hydroxy group. Reduction with
LiHBEt
3
1) Sm I , M eOH
0 ˚ C, 5 m in
2
OH
o
OH
0
C, 10 m in
CO t-Bu
CO t- Bu
2
2
Ph
H N
Ph
2) B oc O, aq. NaO H,
2
THF, rt, 24 h
N
NHBoc
2
Anti : 24%
Sy n : 12%
O H
CO t-Bu
2
single isomer
Ph
N
2
(±)-4a
1) TBSCl, imi.
C to rt,7 h
BzCl, Py.
C, 21h
OTBS
CO t-Bu
OTBS
0˚
0
˚
CO t-Bu
2
2
Ph
Ph
H N
2) LiHBEt
3
N
N
BzHN
2
0˚C, 30 min
(E)-10 (96%, 2 steps)
(E)-11 (quant.)
single isomer
Scheme 5. Preparation of hydrazones.
Table 6. Diastereoselective reduction of (E)-11
OTBS
O TBS
OTBS
CO t-Bu
2
Reagents
Conditions
CO t-Bu
2
Ph
Ph
Ph
OH
+
N
HN
BzHN
HN
Solvent (0.2 M)
NHBz
NHBz
(E)-11
12
13
Entry
Reagents (equiv)
Solvent
Conditions
Yield (%)
12 (syn:anti)a
13 (syn:anti)a
1
2
3
NaBH4 (5)
LiBH4 (5)
Red-Al (5)
EtOH
THF
PhMe
08C, 2 h
08C to rt, 19 h
08C, 2 h
92 (anti only)
55 (1:1)
0
0
12 (1:1)
60 (1:1)
a Determined by 1H MNR analysis.

K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
1395
1) SmI ,MeOH
in respective yields of 81 and 71%. The stereochemistry
of anti-14 was determined by conversion to anti-16
(Scheme 7), the stereochemistry of which was confirmed
by comparison to the literature via anti-15.20 The relative
stereochemistry of anti-12 was also confirmed by conver-
sion to anti-13.
OTBS
OTBS
HN
2
0˚C, 2h
CO t-Bu
CO t-Bu
2
2
Ph
Ph
2) Boc O
NHBoc
2
10% aq. NaOH
NHBz
rt, 24 h
anti-12 (single isomer)
14 (anti: syn=2.6:1)
(65%, 2 steps)
To enhance the utility of this synthetic protocol, we next
investigated the diastereoselective one-pot transformation
of hydrazones to amino groups (Table 7). For example, the
1) SmI , MeOH
2
O TBS
OTBS
0˚C, 30min
Ph
OH
Ph
OH
NHBoc
19
2) Boc O
2
HN
reaction of (E)-10 with SmI2 in MeOH followed by
10% aq. NaOH
rt, 24 h
NHBz
protection with Boc2O gave the desired product 14 in
quantitative yield (syn/antiZ2:1). Higher diastereoselec-
tivity was observed when the reduction was carried out in
isopropanol (entries 1 and 2). The reduction of N-benzoyl-
hydrazone (E)-11 in isopropanol gave 14 in quantitative
yield with better selectivity (syn/antiZ6.7:1, entry 4).
15
anti-13
syn-13
71%, 2 steps from anti-13
81%, 2 steps from syn-13
Scheme 6. N–N bond cleavage of 12 and 13 by SmI2.
OTBS
After successfully developing an efficient transformation
to aminoesters, we next investigated the synthesis of
optically active aminoesters from (S)-4a (57% ee). Initial
transformation gave siloxyhydrazone (E)-10, the ee of
which was increased to 83% ee by recrystallization.
Subsequent reduction of (S)-(E)-11 with SmI2 followed
by BzCl (condition A) gave (2R,3S)-17 and (2S,3S)-17 in
respective yields of 88 and 12% without racemization.
The reduction of (S)-(E)-11 with NaBH4 (condition B)
gave (2S,3S)-12 in 91% yield, exclusively, without any
loss of optical purity. Treatment of these products with
TBAF gave the corresponding hydroxyesters 18 and 19
(Scheme 8).
O TBS
Red-Al, PhMe
CO t-Bu
Ph
OH
2
Ph
0˚
C,12h
HN
HN
NHBz
20%
NHBz
anti-12
anti-13
LiBH ,THF
OH
4
O TBS
OTBS
TBAF, THF
rt, 2 h
0˚
C to reflux
CO t-Bu
2
Ph
OH
NHBoc
Ph
OH
NHBoc
anti-15
Ph
7h, 51%
92%
NHBoc
anti-14
anti-16
Scheme 7. Determination of relative configuration.
Table 7. Diastereoselective reduction of hydrazones
In summary, we have developed the one-pot synthesis of
a-diazo-b-hydroxyesters with a single catalyst without any
isolation of explosive intermediates. A PTC-catalyzed
asymmetric aldol-type reaction using a-diazoester (up to
81% ee) with unique enantio enrichment and the trans-
formations of a-diazo-b-hydroxyesters to a-amino-b-
hydroxyesters in diastereoselective fashion were also
established. This synthetic protocol provides a practical
synthesis of optically active a-amino-b-hydroxyester
derivatives, which have been recognized as useful building
blocks for biologically important compounds or pharma-
ceuticals. Further studies of the application of this method
are currently underway.
1) SmI (6eq)
2
Solvent (0.1M)
OTBS
OTBS
CO t-Bu
0˚
C, 30min
CO t-Bu
2
2
Ph
Ph
2) Boc O,10%NaOH,
2
rt, 24 h
N
NHBoc
RHN
14
10 : R = H
11 : R = Bz
Entry
Substrate
Solvent
Yield (%)
syn:anti
1
2
3
4
10
10
11
11
MeOH
i-PrOH
MeOH
i-PrOH
100
100
77
2:1
3.3:1
5.4:1
6.7:1
100
Scheme 8. Transformation of optically active 4a.

1396
K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
3. Experimental
3.1.5. Ethyl 2-diazo-3-hydroxy-(1-naphthyl)propionate
(5d). Yellow oil; IR (neat) n: 3430, 3059, 2981, 2091,
1683 cmK1; 1H NMR (CDCl3, 400 MHz) d: 1.37 (t, 3H, JZ
7.2 Hz), 3.09 (br s, 1H), 4.29–4.39 (m, 2H), 6.67 (d, 1H, JZ
4.0 Hz), 7.55–7.66 (m, 3H), 7.87–8.02 (m, 4H); 13C NMR d:
(CDCl3, 100 MHz) 166.3, 134.0, 133.5, 129.4, 128.86,
128.81, 126.3, 125.8, 125.2, 123.2, 122.4, 66.0, 61.2, 14.3;
LRMS (FAB) m/z: 309 (MCK); HRMS (FAB) calcd for
C15H14O3N2K 309.0642, found: 309.0672.
3.1. A general procedure for the one-pot synthesis of
a-diazo-b-hydroxyester, synthesis of ethyl 2-diazo-3-
hydroxy-3-phenylpropionate (5a) (Table 1, entry 3)
To a solution of TsCl (200 mg, 1.05 mmol) and THAB
(45.5 mg, 0.1 mmol, 10 mol%) in diethylether (5.2 mL) was
added NaN3 (68.4 mg, 1.05 mmol) and water (0.3 mL) at rt.
The mixture was stirred for 1 h and 1b (0.14 mL,
1.05 mmol) and 3 N NaOH (1.17 g, 3.15 mmol)
were added with stirring for an additional 1.5 h. After
a-diazoacetoacetate had diappeared, benzaldehyde 3a
(0.53 mL, 5.25 mmol) was added at 0 8C and the mixture
was stirred for 3 h at 0 8C. The mixture was extracted with
AcOEt (10 mL!3) and the combined organic layers were
washed with brine, dried over Na2SO4 and concentrated in
vacuo. Subsequent flash column chromatography (hexane/
AcOEtZ10:1) gave the desired product 5a as a yellow oil
3.1.6. Ethyl 2-diazo-3-hydroxy-5-phenylpentanoate (5e).
Yellow oil; IR (neat) n: 3447, 3026, 2934, 2094, 1689 cmK1
;
1H NMR (CDCl3, 400 MHz) d: 1.30 (t, 3H, JZ7.2 Hz),
1.89–2.12 (m, 2H), 2.59 (br s, 1H), 2.70–2.88 (m, 2H), 4.26
(q, 2H, JZ7.2 Hz), 4.66–4.70 (m, 1H), 7.19–7.31 (m, 5H);
13C NMR (CDCl3, 100 MHz) d: 166.4, 140.8, 128.3, 128.2,
125.9, 65.7, 60.9, 35.6, 31.7, 14.3; LRMS (FAB) m/z: 287
(MCK); HRMS (FAB) calcd for C13H16N2O3K 287.0798,
found: 287.0779.
1
(189.4 mg, 0.86 mmol, 82%) (reg.# 27262-59-5), H NMR
3.1.7. Ethyl 2-diazo-3-hydroxy-5-methylhexanoate (5f).
d: (CDCl3, 400 MHz) 1.28 (t, 3H, JZ6.8 Hz), 3.03 (br s,
1H), 4.29 (q, 2H, JZ6.8 Hz), 5.92 (d, 1H, JZ2.8 Hz),
7.31–7.49 (m, 5H).
1
Yellow oil; IR (neat) n: 3433, 2959, 2094, 1685 cmK1; H
NMR (CDCl3, 400 MHz) d: 0.95 (d, 6H, JZ6.8 Hz), 1.28 (t,
3H, JZ7.2 Hz), 1.36–1.43 (m, 1H), 1.59–1.68 (m, 1H),
1.72–1.82 (m, 1H), 2.42 (br s, 1H), 4.23 (q, 2H, JZ7.2 Hz),
4.75–4.79 (m, 1H); 13C NMR (CDCl3, 100 MHz) d: 166.6,
64.8, 60.9, 42.6, 24.5, 22.8, 22.0, 14.4; LRMS (FAB) m/z:
239 (MCK); HRMS (FAB) calcd for C9H16N2O3K
239.0798, found: 239.0780.
3.1.1. tert-Butyl 2-diazo-3-hydroxy-3-phenylpropionate
(4a). Yellow oil; IR (neat) n: 3442, 2979, 2095, 1665 cmK1
;
1H NMR (CDCl3, 400 MHz) d: 1.46 (s, 9H), 2.99 (br s, 1H),
5.87 (d, 1H, JZ2.8 Hz), 7.30–7.46 (m, 5H); 13C NMR
(CDCl3, 100 MHz) d: 165.7, 139.0, 128.5, 128.0, 125.6,
82.0, 68.5, 28.2; LRMS (FAB) m/z: 287 (MCK); HRMS
(FAB) calcd for C13H16N2O3K 287.0798, found: 287.0807.
3.1.8. Ethyl 2-diazo-3-hydroxy-4-methylpentanoate (5g)
(reg.# 38491-54-2). Yellow oil; 1H NMR (CDCl3,
400 MHz) d: 0.95 (d, 3H, JZ6.8 Hz), 1.07 (d, 3H, JZ
6.8 Hz), 1.29 (t, 3H, JZ8.0 Hz), 1.85–1.94 (m, 1H), 2.48 (br
s, 1H), 4.22–4.29 (m, 3H).
3.1.2. Benzyl 2-diazo-3-hydroxy-3-phenyl-propionate
(6). Yellow oil; IR (neat) n: 3425, 3032, 2101, 1682 cmK1
;
1H NMR (CDCl3, 400 MHz) d: 2.90 (br s, 1H), 5.20 (s, 2H),
5.92 (d, 1H, JZ3.2 Hz), 7.29–7.43 (m, 10H); 13C NMR
(CDCl3, 100 MHz) d: 166.1, 138.7, 135.6, 128.7, 128.5,
128.34, 128.32, 128.1, 125.6, 68.6, 66.6; LRMS (FAB) m/z:
321 (MCK); HRMS (FAB) calcd for C16H14N2O3K
321.0642, found: 321.0630.
3.1.9. Ethyl 2-diazo-3-hydroxy-3-cyclohexylpropionate
(5h) (reg.# 39910-21-9). Yellow oil; 1H NMR (CDCl3,
400 MHz) d: 0.97–1.30 (m, 8H), 1.52–1.79 (m, 5H), 2.03 (d,
1H, JZ12.4 Hz), 2.38 (br s, 1H), 4.24 (q, 2H, JZ7.2 Hz),
4.30 (dd, 1H, JZ5.2, 8.4 Hz).
3.1.10. Ethyl 2-diazo-3-hydroxy-4,4-dimethyl-valerate
(5i) (reg.# 39910-22-0). Yellow oil; 1H NMR (CDCl3,
400 MHz) d: 0.98 (s, 9H), 1.28 (t, 3H, JZ6.8 Hz), 2.54 (br s,
1H), 4.19–4.27 (m, 3H).
3.1.3. Ethyl 2-diazo-3-hydroxy-3-(4-methoxyphenyl)-
propionate (5b) (reg.#39910-24-2). Yellow crystal; 1H
NMR (CDCl3, 400 MHz) d: 1.33 (t, 3H, JZ7.2 Hz), 2.95 (br
s, 1H), 3.84 (s, 3H), 4.32 (q, 2H, JZ7.2 Hz), 5.90 (d, 1H,
JZ2.0 Hz), 6.94 (d, 2H, JZ8.4 Hz), 7.38 (d, 2H, JZ
8.4 Hz).
3.2. Typical procedure for asymmetric synthesis of tert-
butyl 2-diazo-3-hydroxy-3-phenylpropionate (4a) using
PTC D (Table 4, entry 7)
3.1.4. Ethyl 2-diazo-3-hydroxy-3-(4-trifluoromethyl-
phenyl)propionate (5c). Yellow crystal; mp 55–59 8C
(hexane–CHCl3); IR (thin film) n: 3423, 3019, 2101,
To a solution of benzaldehyde 3a (56 mL, 0.53 mmol), tert-
butyl diazoacetate (50.0 mg, 0.35 mmol) and PTC D
(18.2 mg, 0.035 mmol, 10 mol%) in toluene (1.8 mL) was
added 50% RbOH (82.0 mL, 0.7 mmol) at K40 8C. The
mixture was stirred for 10 h and partitioned between AcOEt
and water. The aqueous layer was extracted with AcOEt
(5 mL!3) and the organic layers were washed with brine,
dried over Na2SO4 and concentrated in vacuo. Subsequent
flash column chromatography (hexane/AcOEtZ15:1) gave
the desired product 4a as a yellow oil (83.3 mg, 0.33 mmol,
96%). [a]2D3 K20.8 (c 1.06, CHCl3, 56% ee); HPLC:
DAICEL CHIRALCEL OD, 254 nm, flow rate 1.0 mL/min,
1
1677 cmK1; H NMR (CDCl3, 400 MHz) d: 1.30 (t, 3H,
JZ7.2 Hz), 3.14 (br s, 1H), 4.28 (q, 2H, JZ7.2 Hz), 5.97 (d,
1H, JZ4.0 Hz), 7.57 (d, 2H, JZ8.4 Hz), 7.65 (d, 2H, JZ
8.4 Hz); 13C NMR (CDCl3, 100 MHz) d: 166.2, 142.9,
130.3 (q, JZ32.0 Hz), 126.0, 125.6 (q, JZ3.3 Hz), 123.9
(q, JZ270.7 Hz), 68.0, 61.4, 14.4; LRMS (FAB) m/z: 327
(MCK); HRMS (FAB) calcd for C12H11N2O3F3K
327.0359, found: 327.0350. Anal. Calcd for
C12H11F3N2O3: C, 50.01; H, 3.85; N, 9.72. Found: C,
49.89; H, 3.80; N, 9.83.

K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
1397
hexane/i-PrOHZ99:1, retention time: 20.7 min (major, S)
and 23.1 min (minor, R).
28.3, 24.5, 22.8, 21.9; LRMS (FAB) 267 (MCK); HRMS
(FAB) calcd for C11H20N2O3K 267.1111, found: 267.1097;
[a]2D3 K12.0 (c 1.0, CHCl3, 22% ee); HPLC: DAICEL
CHIRALPAK AD-H, 254 nm, flow rate 0.5 mL/min,
hexane/i-PrOHZ99:1, retention time: 22.3 min (minor)
and 23.9 min (major).
3.2.1. tert-Butyl 2-diazo-3-hydroxy-3-(4-methoxy-
phenyl)propionate (4b). Yellow oil; IR (neat) n: 3449,
2978, 2095, 1729, 1667 cmK1; 1H NMR (CDCl3, 400 MHz)
d: 1.50 (s, 9H), 2.97 (br s, 1H), 3.81 (s, 3H), 5.82 (d, 1H, JZ
2.0 Hz), 6.89–7.36 (m, 4H); 13C NMR (CDCl3, 100 MHz) d:
165.8, 159.4, 130.9, 127.0, 114.0, 82.0, 68.4, 55.2, 28.3;
LRMS (FAB) m/z: 317 (MCK); HRMS (FAB) calcd
for C14H18N2O4K 317.0904, found: 317.0875; HPLC:
DAICEL CHIRALCEL OD, 254 nm, flow rate 0.5 mL/
min, hexane/i-PrOHZ95:5, retention time: 20.8 and
24.2 min.
3.2.6. tert-Butyl 2-diazo-3-hydroxy-4-methylpentanoate
(4g). Yellow oil; IR (neat) n: 3448, 2966, 2090, 1669 cmK1
;
1H NMR (CDCl3, 400 MHz) d: 0.94 (d, 3H, JZ6.8 Hz),
1.06 (d, 3H, JZ6.8 Hz), 1.49 (s, 9H), 1.82–1.94 (m, 1H),
2.58 (br s, 1H), 4.23 (dd, 1H, JZ4.4, 8.0 Hz); 13C NMR
(CDCl3, 100 MHz) d: 166.1, 81.7, 72.3, 32.8, 28.3, 18.7,
18.6; LRMS (FAB) 253 (MCK); HRMS (FAB) calcd for
C10H18N2O3K 253.0955, found: 253.0935; [a]2D2 K10.3 (c
0.6, CHCl3, 42% ee); HPLC: DAICEL CHIRALPAK
AD-H, 254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ
99:1, retention time: 32.2 min (minor) and 38.3 min (major).
3.2.2. tert-Butyl 2-diazo-3-hydroxy-3-(4-trifluoromethyl-
phenyl)propionate (4c). Yellow oil; IR (neat) n: 3448,
2981, 2095, 1734, 1693 cmK1;1HNMR(CDCl3, 400 MHz)d:
1.50 (s, 9H), 3.04 (br s, 1H), 5.91 (d, 1H, JZ3.4 Hz), 7.55 (d,
2H, JZ8.4 Hz), 7.65 (d, 2H, JZ8.4 Hz); 13C NMR (CDCl3,
100 MHz)d: 165.5, 143.0, 130.3 (q, JZ32.1 Hz), 126.2,125.7
(q, JZ4.1 Hz), 124.0 (q, JZ271 Hz), 82.5, 68.3, 28.3; LRMS
(FAB) m/z: 355 (MCK); HRMS (FAB) calcd for
C14H15F3N2O3K 355.0672, found: 355.0657; [a]2D6 K21.7 (c
1.1, CHCl3, 73% ee); HPLC: DAICEL CHIRALCEL OD,
254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ97:3,
retention time: 14.2 min (major) and 16.1 min (minor).
3.2.7. tert-Butyl 2-diazo-3-hydroxy-3-cyclohexylpropio-
nate (4h). Yellow oil; IR (neat) n: 3440, 2927, 2088,
1
1666 cmK1; H NMR (CDCl3, 400 MHz) d: 0.97–1.30 (m,
5H), 1.48 (s, 9H), 1.52–1.79 (m, 5H), 2.02 (d, 1H, JZ
12.8 Hz), 2.38 (br s, 1H), 4.25 (dd, 1H, JZ5.2, 8.4 Hz); 13C
NMR (CDCl3, 100 MHz) d: 166.1, 81.6, 71.2, 42.0, 29.1,
29.0, 28.3, 26.1, 25.8, 25.6; LRMS (FAB) m/z: 293 (MCK);
HRMS (FAB) calcd for C13H22N2O3K 293.1268, found
293.1284; [a]1D9 K3.4 (c 0.9, CHCl3, 33% ee) HPLC:
DAICEL CHIRALCEL OJ, 254 nm, flow rate 0.5 mL/min,
hexane/i-PrOHZ99:1, retention time: 22.1 min (major) and
35.8 min (minor).
3.2.3. tert-Butyl 2-diazo-3-hydroxy-3-(1-naphthyl)-
propionate (4d). Yellow solid (racemate); mp: 94 8C
1
(hexane); IR (neat) n: 3435, 2979, 2094, 1685 cmK1; H
NMR (CDCl3, 400 MHz) d: 1.54 (s, 9H), 3.00 (br s, 1H),
6.59 (d, 1H JZ2.4 Hz), 7.49–7.56 (m, 3H), 7.82–7.96 (m,
4H); 13C NMR (CDCl3, 100 MHz) d: 165.7, 134.1, 133.5,
129.5, 128.8, 128.7, 126.5, 125.7, 125.2, 123.2, 122.5, 82.1,
66.1, 28.5; LRMS (FAB) m/z: 337 (MCK); HRMS (FAB)
calcd for C17H18N2O3K 337.0955, found: 337.0941. Anal.
Calcd for C17H18N2O3: C, 68.44; H, 6.08; N, 9.39. Found:
C, 68.30; H, 5.92; N, 9.51; optically active form
(yellow oil), [a]2D5 K68.0 (c 0.7, CHCl3, 79% ee); HPLC:
DAICEL CHIRALCEL OD, 254 nm, flow rate 0.5 mL/min,
hexane/i-PrOHZ97:3, retention time: 24.3 min (minor) and
37.4 min (major).
3.2.8. tert-Butyl 2-diazo-3-hydroxy-4,4-dimethylvalerate
(4i). Yellow solid; mp 58–61 8C; IR (KBr) n: 3469, 2960,
1
2103, 1647 cmK1; H NMR (CDCl3, 400 MHz) d: 0.97 (s,
9H), 1.47 (s, 9H), 2.75 (br s, 1H), 4.20 (s, 1H); 13C NMR
(CDCl3, 100 MHz) d: 166.4, 81.6, 73.7, 38.3, 28.3, 25.6;
LRMS (FAB) m/z 267 (MCK); HRMS (FAB) calcd for
C11H20N2O3K 267.1111, found: 267.1104. Anal. Calcd for
C11H20N2O3: C, 57.87; H, 8.83; N, 12.27. Found: C, 57.92;
H, 8.83; N, 12.51; [a]D24 K20.4 (c 1.1, CHCl3, 81% ee);
HPLC: DAICEL CHIRALPAK AD-H, 254 nm, flow rate
0.5 mL/min, hexane/i-PrOHZ99:1, retention time:
25.7 min (minor) and 27.4 min (major).
3.2.4. tert-Butyl 2-diazo-3-hydroxy-5-phenylpentanoate
(4e). Yellow oil; IR (neat) n: 3422, 3026, 2930, 2091,
3.2.9. tert-Butyl 2-diazo-3-hydroxy-3-(4-tert butyl-
phenyl)propionate (4k). Yellow oil; IR (neat) n: 3467,
2965, 2093, 1732, 1687 cmK1; 1H NMR (CDCl3, 400 MHz)
d: 1.31 (s, 9H), 1.50 (s, 9H), 2.86 (br s, 1H), 5.83 (d, 1H, JZ
3.6 Hz), 7.34 (d, 2H, JZ8.0 Hz), 7.40 (d, 2H, JZ8.0 Hz);
13C NMR (CDCl3, 100 MHz) d: 165.8, 151.1, 136.0, 125.5,
125.4, 81.9, 68.5, 34.5, 31.2, 28.3; LRMS (FAB) m/z: 343
(MCK); HRMS (FAB) calcd for C17H24N2O3K 343.1424,
found: 343.1432; [a]2D6 K6.6 (c 0.9, CHCl3, 32% ee);
HPLC: DAICEL CHIRALCEL OD, 254 nm, flow rate
0.5 mL/min, hexane/i-PrOHZ97:3, retention time:
13.3 min (major) and 17.3 min (minor).
1
1685 cmK1; H NMR (CDCl3, 400 MHz) d: 1.48 (s, 9H),
1.84–1.93 (m, 1H), 1.99–2.08 (m, 1H), 2.57 (br s, 1H),
2.67–2.75 (m, 1H), 2.79–2.86 (m, 1H), 4.61–4.65 (m, 1H),
7.19–7.31 (m, 5H); 13C NMR (CDCl3, 100 MHz) d: 165.9,
140.9, 128.4, 128.3, 125.9, 81.8, 65.7, 35.6, 31.8, 28.2;
LRMS (FAB) m/z: 315 (MCK); HRMS (FAB) calcd for
C15H20N2O3K 315.1111, found: 315.1100; [a]2D3 K5.68 (c
0.3, CHCl3, 33% ee); HPLC: DAICEL CHIRALCEL OD-
H, 254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ95:5,
retention time: 16.7 min (major) and 19.0 min (minor).
3.2.5. tert-Butyl 2-diazo-3-hydroxy-5-methylhexanoate
(4f). Yellow oil; IR (neat) n: 3443, 2958, 2871, 2089,
3.2.10. tert-Butyl 2-diazo-3-hydroxy-3-(2-naphthyl)pro-
pionate (4l). Yellow oil; IR (neat) n: 3432, 2978, 2095,
1
1693 cmK1; H NMR (CDCl3, 400 MHz) d: 0.95 (d, 6H,
1
JZ6.4 Hz), 1.33–1.41 (m, 1H), 1.49 (s, 9H), 1.57–1.67 (m,
1H), 1.73–1.83 (m, 1H), 2.47 (br s, 1H), 4.70–4.75 (m, 1H);
13C NMR (CDCl3, 100 MHz) d: 166.0, 81.7, 64.7, 42.6,
1667 cmK1; H NMR (CDCl3, 400 MHz) d: 1.51 (s, 9H),
3.21 (br s, 1H), 6.03 (d, 1H, JZ2.4 Hz), 7.45–7.54 (m, 3H),
7.82–7.86 (m, 3H), 7.94 (s, 1H); 13C NMR (CDCl3,

1398
K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
100 MHz) d: 165.7, 136.2, 133.2, 133.1, 128.6, 128.1,
127.6, 126.3, 126.2, 124.7, 123.6, 82.2, 68.9, 28.3; LRMS
(FAB) m/z: 337 (MCK); HRMS (FAB) calcd for
C17H18N2O3K 337.0955, found: 337.0924; [a]2D5 K28.2 (c
1.0, CHCl3, 56% ee); HPLC: DAICEL CHIRALCEL OD,
254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ97:3,
retention time: 26.7 min (major) and 28.4 min (minor).
HRMS (FAB) calcd for C19H33N2O3Si 365.2260, found:
365.2262. Anal. Calcd for C19H32N2O3Si: C, 62.60; H, 8.85;
N, 7.68. Found: C, 62.63; H, 8.82; N, 7.77; [a]2D3 K85.3 (c
1.0, CHCl3, 83% ee); HPLC DAICEL CHIRALPAK AD-H,
254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ97:3,
retention time: 16.3 min (major, S) and 18.5 min (minor, R).
3.3.2. tert-Butyl 2-(N-benzoylhydrazono)-3-(tert-butyl-
dimethylsilyloxy)-3-phenylpropionate (11) (Scheme 5).
To a solution of (E)-10 (298.5 mg, 0.82 mmol) in CH2Cl2
(8.2 mL) was added pyridine (0.40 mL, 4.9 mmol) and BzCl
(0.19 mL, 1.6 mmol) at 0 8C and the reaction mixture was
stirred for 21 h at 0 8C. After being diluted with water
(10 mL), the mixture was extracted with CH2Cl2 (5 mL!
3). The resulting organic layers were washed with brine,
dried over MgSO4 and concentrated in vacuo. Flash column
chromatography (hexane/Et2OZ10:1, hexane/AcOEtZ
5:1) gave (E)-11 as a pale yellow oil (383.7 mg,
0.82 mmol, quant.). IR (neat) n: 3288, 2930, 1740, 1698,
1680, 1253, 1155, 836 cmK1; 1H NMR (CDCl3, 400 MHz)
d: 0.14 (s, 3H), 0.18 (s, 3H), 0.95 (s, 9H), 1.58 (s, 9H), 6.31
(s, 1H), 7.23–7.54 (m, 9H), 7.83 (br s, 1H), 11.4 (br s, 1H);
13C NMR (CDCl3, 100 MHz) d: 162.9, 138.2, 132.1, 128.6,
128.4, 127.9, 127.0, 125.1, 82.7, 72.0, 27.7, 25.4, 17.9,
K5.3, K5.4; LRMS (FAB) m/z: 469 (MCH); HRMS
(FAB) calcd for C26H37N2O4Si 469.2523, found 469.2482;
HPLC: DAICEL CHIRALCEL OD-H, 254 nm, flow rate
0.5 mL/min, hexane/i-PrOHZ99:1, retention time:
18.8 min (major) and 23.7 min (minor); [a]2D4 C4.60 (c
1.0, CHCl3, 84% ee). All carbon signals were observed in
DMSO at 120 8C, however, isomerization to (Z)-11 was
observed.
3.3. Determination of the absolute configuration of 4a
(Scheme 1)
Using a procedure similar to that of Wang et al.,7 4a was
converted into the corresponding b-hydroxyester 7 by
hydrogenation. To a solution of optically active 4a (57%
ee, 188.5 mg, 0.76 mmol) in MeOH (10.8 mL) was added
5% of palladium charcoal (54.0 mg) and the resulting
suspension was stirred for 1 h under a hydrogen atmosphere.
After being filtered through a Celite pad, the mixture was
concentrated in vacuo. Purification of the crude mixture by
flash column chromatography gave 7 as a colorless oil
(104.3 mg, 0.47 mmol, 62%, 12% ee); [a]2D4 C5.3 (c 2.3,
CHCl3). Optical purity was determined by a chiral HPLC
column using DAICEL CHIRALPAK AS, 254 nm, flow
rate 0.5 mL/min, hexane/i-PrOHZ97:3, retention time:
15.9 min (major, R) and 17.3 min (minor, S).10
3.3.1. tert-Butyl 2-hydrazono-3-(tert-butyldimethyl-
silyloxy)-3-phenylpropionate (E)-10 (Schemes 5 and 8).
To a solution of 4a (1.80 g, 7.25 mmol) in DMF (24 mL)
was added imidazole (2.16 g, 31.7 mmol) and TBSCl
(1.62 g, 10.8 mmol) at 0 8C and the mixture was stirred
for 1 h under the same conditions. After being stirred for 6 h
at rt, the reaction mixture was diluted with H2O (10 mL) and
extracted with AcOEt (20 mL!3). The combined organic
layers were washed with brine, dried over MgSO4 and
concentrated in vacuo. Subsequent flash column chroma-
tography (hexane/AcOEtZ50:1) gave TBS ether as a
yellow oil (2.52 g, 6.96 mmol, 96%). IR (neat) n: 2929,
Compound (Z)-11 was obtained by acidic treatment of (E)-
11 as a colorless oil; IR (neat) n: 3255, 2954, 2930, 2857,
1
1704, 1676, 1132 cmK1; H NMR (CDCl3, 400 MHz) d:
0.10 (s, 3H), 0.12 (s, 3H), 0.97 (s, 9H), 1.29 (s, 9H), 5.75 (s,
1H), 7.21–7.59 (m, 8H), 7.95 (d, 2H, JZ7.2 Hz), 13.4 (br s,
1H); 13C NMR (CDCl3, 100 MHz) d: 163.7, 161.6, 142.5,
141.1, 132.4, 132.3, 128.6, 127.5, 126.7, 125.4, 84.0, 76.0,
27.5, 25.6, 18.0, K4.5, K5.2; LRMS (FAB) m/z: 469 (MC
H); HRMS (FAB) calcd for C26H37N2O4Si 469.2523,
found: 469.2494.
1
2857, 2094, 1685 cmK1; H NMR (CDCl3, 400 MHz) d:
0.05 (s, 3H), 0.10 (s, 3H), 0.88 (s, 9H), 1.47 (s, 9H), 5.72 (s,
1H), 7.26–7.38 (m, 5H); 13C NMR (CDCl3, 100 MHz) d:
164.8, 141.6, 128.3, 127.5, 125.3, 81.4, 68.7, 28.3, 25.6,
18.1, K5.0, K5.3; LRMS (FAB) m/z: 401 (MCK); HRMS
(FAB) calcd for C19H30N2O3SiK 401.1663, found:
401.1659; [a]2D4 K15.1 (c 1.1, CHCl3, 56% ee, for S
isomer).
3.3.3. Reduction of (E)-11, tert-butyl 2-(N-benzoyl-
hydrazino)-3-tert-butyldimethylsilyloxy-3-phenylpro-
pionate (12) (Table 6, entry 1). To a solution of (E)-11
(210.6 mg, 0.45 mmol) in EtOH (2.2 mL) was added
NaBH4 (83.6 mg, 2.2 mmol) at 0 8C and the solution was
stirred for 2 h under the same conditions. The reaction was
quenched with water (10 mL) and the mixture was
concentrated in vacuo. The resulting mixture was extracted
with AcOEt (5 mL!3) and the combined organic layers
were washed with brine, dried over MgSO4 and concen-
trated in vacuo. Flash column chromatography (hexane/
AcOEtZ5:1) gave anti-12 as a white amorphous solid
(193.6 mg, 0.41 mmol, 92%). syn-12 was synthesized under
the conditions described in Table 6.
To a solution of the TBS ether (1.05 g, 2.9 mmol) in dry
THF (41 mL) was added LiHBEt3 (1 M solution of THF,
8.7 mL, 8.7 mmol) at 0 8C under an argon atmosphere, and
the reaction mixture was stirred for 30 min. The reaction
was quenched with cold water (10 mL) and the resulting
organic layers were extracted with AcOEt (20 mL!3). The
combined organic extracts were washed with brine, dried
over MgSO4 and concentrated in vacuo. Flash column
chromatography (hexane/AcOEtZ5:1) gave (E)-10 as a
white solid (1.06 g, 2.9 mmol, quant.); mp: 55–56 8C (n-
hexane, 83% ee); IR (neat) n: 3411, 3286, 2926, 1689,
1
1052 cmK1; H NMR (CDCl3, 400 MHz) d: 0.12 (s, 3H),
0.14 (s, 3H), 0.94 (s, 9H), 1.56 (s, 9H), 6.19 (s, 1H), 7.02 (br
s, 2H), 7.23–7.40 (m, 5H); 13C NMR (CDCl3, 100 MHz) d:
164.0, 139.6, 136.6, 128.2, 127.2, 125.3, 81.2, 70.5, 28.1,
25.7, 18.2, K5.2, K5.3; LRMS (FAB) m/z: 365 (MCH);
Compound anti-12. White amorphous solid; IR (KBr) n:
3262, 2930, 2857, 1700, 1676, 1138 cmK1 1H NMR
;
(CDCl3, 400 MHz) d: K0.14 (s, 3H), 0.07 (s, 3H), 0.91 (s,
9H), 1.39 (s, 9H), 3.98 (t, JZ4.4 Hz, 1H), 5.11 (d, JZ

K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
1399
4.4 Hz, 1H), 5.36–5.39 (m, 1H), 7.26–7.68 (m, 11H); 13C
NMR (CDCl3, 100 MHz) d: 169.4, 166.3, 140.3 132.9,
131.6, 128.5, 127.94, 127.90, 127.3, 126.7, 81.9, 74.9, 70.0,
27.9, 25.7, 18.1, K4.8, K5.1; LRMS (FAB) m/z: 471 (MC
H); HRMS (FAB) calcd for C26H39N2O4Si 471.2679,
found: 471.2671; HPLC DAICEL CHIRAPAK AS,
254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ95:5,
retention time: 15.3 (minor: 2R,3R) and 23.9 (major:
2S,3S); [a]2D4 C10.1 (c 1.32, CHCl3, 83% ee, (2S,3S)).
0.42 mmol) at 0 8C under an argon atmosphere, and the
solution was stirred for 2 h at 0 8C. The reaction mixture
was quenched with water (1 mL) and concentrated in vacuo.
To the crude residue was added THF (1.9 mL), Boc2O
(207 mg, 0.95 mmol) and 10% aqueous NaOH (380 mg,
0.95 mmol) and the resulting solution was stirred for 24 h at
rt. The reaction mixture was then diluted with water (3 mL)
and extracted with AcOEt (5 mL!3). The combined
organic layers were washed with brine, dried over MgSO4
and concentrated in vacuo. Flash column chromatography
(hexane/AcOEtZ100:1–20:1) gave anti-14 (less polar) as a
colorless oil (40.9 mg, 0.09 mmol 47%) and syn-14 (more
polar) as a colorless oil (15.6 mg, 0.03 mmol, 18%),
respectively.
Compound syn-12. White amorphous solid; IR (neat) n:
3306, 2923, 2853, 1717, 1669, 1097 cmK1 1H NMR
;
(CDCl3, 400 MHz) d: K0.23 (s, 3H), 0.07 (s, 3H), 0.90 (s,
9H), 1.20 (s, 9H), 3.92 (d, JZ7.2 Hz, 1H), 4.88 (d, JZ
7.2 Hz, 1H), 5.66 (br s, 1H), 7.26–7.81 (m, 11H); 13C NMR
(CDCl3, 100 MHz) d: 169.8, 166.5, 140.7, 132.8, 131.7,
128.6, 128.12, 128.10, 127.5, 126.8, 81.6, 75.6, 70.9, 27.7,
25.7, 18.1, K4.5, K5.0; LRMS (FAB) m/z: 471 (MCH);
HRMS (FAB) calcd for C26H39N2O4Si 471.2679, found:
471.2639.
Compound anti-14. Colorless oil; IR (neat) n: 3444, 2930,
1
2857, 1714 cmK1; H NMR (CDCl3, 400 MHz) d: K0.08
(s, 3H), 0.08 (s, 3H), 0.93 (s, 9H), 1.25 (s, 8/9H), 1.29 (br s,
1/9H) 1.46 (s, 9H), 4.25 (br s, 1/10H), 4.42 (dd, JZ2.8,
7.6 Hz, 0.2/1H), 5.04 (br s, 0.8/1H), 5.15 (s, 8/9H), 5.42 (d,
JZ7.6 Hz, 1H); 7.20–7.41 (m, 5H); 13C NMR (CDCl3,
100 MHz) d: 168.1, 154.9, 141.0, 127.6, 127.0, 126.1, 81.7,
79.5, 75.5, 61.4, 28.3, 27.7, 25.7, 18.2, K4.8, K5.2; LRMS
(FAB) m/z: 452 (MCH); HRMS (FAB) calcd for
C24H42NO5Si 452.2832, found: 452.2859.
3.3.4. Reduction of (E)-11, synthesis of 2-(N-benzoyl-
hydrazino)-1-tert-butyldimethylsilyloxy-1-phenylpropa-
nol (13) (Table 6, entry 3). To a solution of (E)-11
(56.0 mg, 0.12 mmol) in toluene was added Red-Al (65%
solution in toluene, 0.14 mL, 0.48 mmol) at 0 8C under an
argon atmosphere and the solution was stirred for an
additional 2 h. The reaction mixture was quenched with
saturated Rochelle salt solution (2 mL) and MeOH (three
portions). The resulting residue was extracted with CHCl3
(5 mL!3) and the combined organic layers were dried over
MgSO4 and concentrated in vacuo. Flash column chroma-
tography (hexane/AcOEtZ3:1) gave a mixture of syn-13
and anti-13 isomers as a white amorphous solid (28.8 mg,
0.07 mmol, 60%). These isomers were separated by
additional column chromatography (hexane:AcOEt).
Compound syn-14. Colorless oil; IR (neat) n: 3452, 2931,
1
2857, 1727, 1706 cmK1; H NMR (CDCl3, 400 MHz) d:
K0.20 (s, 3H), 0.03 (s, 3H), 0.88 (s, 9H), 1.21 (br s, 2/9H),
1.35 (s, 7/9H) 1.45 (s, 7/9H), 1.49 (s, 2/9H), 4.07 (d, JZ
9.6 Hz, 7/9H), 4.25 (dd, JZ2.8, 9.6 Hz, 0.8/1H), 5.01 (d,
JZ9.6 Hz, 0.2/1H), 5.15 (d, JZ2.8 Hz, 1H), 5.19 (d, JZ
2.8 Hz, 0.8/1H), 7.22–7.30 (m, 5H); 13C NMR (CDCl3,
100 MHz) d: 169.8, 155.4, 141.0, 127.9, 127.6 126.5, 81.8,
79.3, 74.8, 61.0, 28.2 28.0, 25.7, 18.0, K4.4, K5.2; LRMS
(FAB) m/z: 452 (MCH); HRMS (FAB) calcd for
C24H42NO5Si 452.2832, found: 452.2815.
Compound anti-13. White amorphous solid; IR (KBr) n:
1
3256, 2927, 1635, 1251, 1065 cmK1; H NMR (CDCl3,
3.3.6.
2-tert-Buthoxycarbonylamino-1-tert-butyl-
400 MHz) d: K0.21 (s, 3H), 0.06 (s, 3H), 0.86 (s, 9H), 3.08–
3.13 (m, 1H), 3.71 (dd, 1H, JZ6.4 Hz, 11.2 Hz), 3.89 (dd,
1H, JZ2.8 Hz, 11.2 Hz), 4.66 (d, 1H, JZ7.6 Hz), 7.29–
7.41 (m, 8H), 7.47–7.52 (m, 3H); 13C NMR (CDCl3,
100 MHz) d: 167.7, 142.5, 132.2, 131.8, 128.5, 128.3,
127.8, 127.0, 126.7, 75.0, 68.6, 59.8, 25.6, 18.0, K4.6,
K5.6; LRMS (FAB) m/z: 401 (MCH); HRMS (FAB) calcd
for C22H33O3N2Si 401.2260, found: 401.2227.
dimethylsilyloxy-1-phenylpropanol anti-15 (Scheme 6).
To a solution of anti-13 (55.0 mg, 0.14 mmol) in MeOH
(1.4 mL) was added SmI2 (0.1 M solution in THF, 3.0 mL,
0.3 mmol) at 0 8C under an argon atmosphere and the
reaction mixture was stirred for 30 min. After being
quenched with water (1 mL), the resulting mixture was
concentrated in vacuo. To the crude residue was added THF
(1.4 mL), Boc2O (90 mg, 0.41 mmol) and aqueous 10%
NaOH (165 mg, 0.41 mmol), and the mixture was stirred for
24 h at rt. After the mixture was diluted with water
(3.0 mL), it was extracted with AcOEt (5 mL!3). The
combined organic layers were washed with brine, dried over
MgSO4 and concentrated in vacuo. Flash column chroma-
tography (hexane/AcOEtZ5:1) gave anti-15 as a white
solid (36.6 mg, 0.10 mmol, 71%). As described above,
syn-15 was synthesized from syn-13 in 81% yield (two
steps).
Compound syn-13. White amorphous solid; IR (KBr) n:
3301, 2929, 1635, 1061, 836, 701 cmK1; 1H NMR (CDCl3,
400 MHz) d: K0.18 (s, 3H), 0.04 (s, 3H), 0.87 (s, 9H), 3.07–
3.11 (m, 1H), 3.44 (dd, 1H, JZ6.8, 11.6 Hz), 3.60 (dd, 1H,
JZ2.8, 11.6 Hz), 3.83 (br s, 1H), 4.82 (d, 1H, JZ6.0 Hz),
5.09 (br s, 1H), 7.27–7.70 (m, 11H); 13C NMR (CDCl3,
100 MHz) d: 167.7, 141.8, 132.5, 131.8, 128.5, 128.3,
127.8, 126.9, 126.7, 75.1, 68.5, 59.7, 25.7, 18.0, K4.5,
K5.1; LRMS (FAB) m/z: 401 (MCH); HRMS (FAB) calcd
for C22H33N2O3Si 401.2260, found: 401.2289.
Compound anti-15. White solid; mp 136 8C (hexane); IR
1
(neat) n: 3341, 3232, 2926, 1671, 1056 cmK1; H NMR
3.3.5. tert-Butyl 2-(tert-buthoxycarbonylamino)-3-(tert-
butyldimethylsilyloxy)-3-phenylpropionate (14) (Scheme 6).
To a solution of anti-12 (89.3 mg, 0.19 mmol) in MeOH
(1.9 mL) was added SmI2 (0.1 M solution in THF, 4.2 mL,
(CDCl3, 400 MHz) d: K0.09 (s, 3H), 0.08 (s, 3H), 0.93 (s,
9H), 1.47 (s, 9H), 2.97 (d, JZ10.8 Hz, 1H), 3.39–3.46 (m,
1H), 3.60 (br s, 1H), 3.84 (d, JZ10.8 Hz, 1H), 5.19 (s, 1H),
5.48 (d, 1H, JZ8.0 Hz) 7.20–7.40 (m, 5H); 13C NMR

1400
K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
(CDCl3, 100 MHz) d: 155.6, 141.0, 128.2, 127.4, 125.8,
79.5, 77.6, 61.2, 56.5, 28.4, 25.8, 18.0, K4.9, K5.3; LRMS
(FAB) m/z: 382 (MCH); HRMS (FAB) calcd for
C20H36NO4Si 382.2414, found: 382.2408. Anal. Calcd for
C20H35NO4Si: C, 62.95; H, 9.25; N, 3.67. Found: C, 62.74;
H, 9.49; N, 3.59.
JZ6.8 Hz), 7.24–7.85 (m, 10H); 13C NMR (CDCl3,
100 MHz) d: 168.2, 166.4, 141.1, 133.9, 131.7, 128.6,
127.7, 127.1 126.9, 126.1, 82.2, 75.3, 60.9, 27.8, 25.7, 18.2,
K4.7, K5.1; LRMS (FAB) m/z: 456 (MCH); HRMS
(FAB) calcd for C26H38NO4Si 456.2570, found: 456.2615;
HPLC: DAICEL CHIRALCEL OD-H, 245 nm, flow rate
0.5 mL/min, hexane/i-PrOHZ96:4, retention time: 8.0 min
(minor) and 14.8 min (major); [a]2D5 C40.6 (c 0.9, CHCl3,
84% ee).
Compound syn-15. Colorless oil; IR (neat) n: 3447, 2929
2857, 1697 1496 1167 cmK1; 1H NMR (CDCl3, 400 MHz)
d: K0.15 (s, 3H), 0.06 (s, 3H), 0.90 (s, 9H), 1.36 (s, 9H),
2.35 (br s, 1H), 3.60–3.77 (m, 3H), 4.90 (br s, 1H), 4.91 (d,
1H, JZ3.6 Hz), 7.22–7.33 (m, 5H); 13C NMR (CDCl3,
100 MHz) d: 156.1, 141.5, 128.1, 127.5, 126.3, 79.5 73.7,
63.0, 58.5, 28.3, 25.8, 18.1, K4.6, K5.2; LRMS (FAB) m/z:
382 (MCH); HRMS (FAB) calcd for C20H36NO4Si
382.2414, found: 382.2448.
Compound (2R,3S)-17. White solid; mp: 68 8C; IR (neat) n:
3448, 2954, 2929, 2856, 1728, 1668 cmK1 1H NMR
;
(CDCl3, 400 MHz) d: K0.15 (s, 3H), 0.09 (s, 3H), 0.94 (s,
9H), 1.47 (s, 9H), 4.76 (dd, 1H, JZ2.8, 8.8 Hz), 5.31 (d, 1H,
JZ2.8 Hz) 6.82 (d, 1H, JZ8.8 Hz), 7.23–7.74 (m, 10H);
13C NMR (CDCl3, 100 MHz) d: 169.3, 167.0, 140.8, 134.4,
131.4, 128.5, 128.0, 127.8, 126.8, 126.2, 82.2, 74.4, 60.2,
28.0, 25.7, 18.0, K4.4, K5.2; LRMS (FAB) m/z: 456 (MC
H); HRMS (FAB) calcd for C26H38NO4Si, 456.2570, found:
456.2572. Anal. Calcd for C26H37NO4Si: C, 68.53; H, 8.18;
N, 3.07. Found: C, 68.42; H, 8.39; N, 2.99; HPLC: DAICEL
CHIRALCEL OD-H, 254 nm, flow rate 0.5 mL/min,
hexane/i-PrOHZ96:4, retention time: 9.9 min (major) and
13.2 min (minor); [a]D25 C52.3 (c 1.0, CHCl3, 83% ee).
3.4. Direct synthesis of 14 via a one-pot procedure
(Table 7, entry 4)
To a solution of (E)-11 (75.0 mg, 0.16 mmol) in isopropanol
(1.6 mL) was added SmI2 (0.1 M solution in THF, 9.6 mL,
0.96 mmol) at 0 8C under an argon atmosphere and the
mixture was stirred for 30 min. After being quenched with
water (1.0 mL), the resulting mixture was concentrated in
vacuo. To the crude residue was added THF (1.6 mL),
Boc2O (104 mg, 0.48 mmol) and 10% aqueous NaOH
(192 mg, 0.48 mmol), and the mixture was stirred for 24 h at
rt. After dilution with water (3.0 mL), the mixture was
extracted with AcOEt (5 mL!3). The combined organic
layers were washed with brine, dried over MgSO4 and
concentrated in vacuo. Flash column chromatography
(hexane/AcOEtZ100:1–20:1) gave anti-14 (less polar) as
a colorless oil (9.3 mg, 0.02 mmol, 13%) and syn-14 (more
polar) as a colorless oil (62.7 mg, 0.14 mmol, 87%),
respectively.
3.4.3. tert-Butyl 2-(N-benzoylamino)-3-hydroxy-phenyl-
propionate (18) (Scheme 8). Compound (2R,3S)-18. To a
solution of (2R,3S)-17 (71.0 mg, 0.16 mmol) in THF
(0.75 mL) was added TBAF (1 M solution of THF,
0.23 mL, 0.23 mmol) at rt under an argon atmosphere and
the reaction mixture was stirred for 10 min. After being
quenched with water (1.0 mL), the reaction mixture was
extracted with AcOEt (5.0 mL!3). The combined organic
layers were washed with brine, dried over MgSO4 and
concentrated in vacuo. Flash column chromatography
(hexane/AcOEtZ2:1) gave (2R,3S)-18 (49.2 mg,
0.14 mmol, 92%) as a white solid; mp: 134–138 8C
(hexane–AcOEt); IR (neat) n: 3368, 2977, 1731, 1639,
3.4.1. Direct synthesis of 17 via a one-pot procedure
(Scheme 8, condition A). To a solution of (S)-(E)-11
(113.0 mg, 0.24 mmol) in isopropanol (2.4 mL) was added
SmI2 (0.1 M solution in THF, 14.4 mL, 1.44 mmol) at 0 8C
under an argon atmosphere and the mixture was stirred for
30 min. After being quenched with water (5.0 mL), the
resulting mixture was extracted with AcOEt (10 mL!3).
The combined organic layers were washed with brine dry
over MgSO4 and concentrated in vacuo. To the crude
residue was added CH2Cl2 (2.4 mL), BzCl (41 mL,
0.36 mmol) and pyridine (38 mL, 0.48 mmol), and the
mixture was stirred for 10 min at 0 8C. After being diluted
with water (1.0 mL), the mixture was extracted with AcOEt
(5 mL!3). The combined organic layers were washed with
brine, dried over MgSO4 and concentrated in vacuo. Flash
column chromatography (hexane/AcOEtZ100:1–15:1)
gave (2S,3S)-17 (less polar) as a colorless oil (13.7 mg,
0.030 mmol, 12%) and (2R,3S)-17 (more polar) as a white
solid (95.9 mg, 0.21 mmol, 88%), respectively.
1
1521, 1149 cmK1; H NMR (CDCl3, 400 MHz) d: 1.42 (s,
9H), 3.13 (br s, 1H), 4.96 (dd, 1H, JZ3.6, 7.6 Hz), 5.26 (br
s, 1H), 6.85 (d, 1H, JZ7.6 Hz), 7.27–7.72 (m, 10H); 13C
NMR (CDCl3, 100 MHz) d: 169.3, 167.7, 139.8, 133.8,
131.6, 128.4, 128.3, 128.0, 127.0, 126.1, 82.8, 74.5, 59.0,
27.8; LRMS (FAB) m/z: 342 (MCH); HRMS (FAB) calcd
for C20H24NO4 342.1705, found: 342.1689. Anal. Calcd for
C20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C, 70.34; H,
6.83; N, 4.10; HPLC: DAICEL CHIRALCEL OJ-H,
254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ93:7,
retention time: 19.7 min (minor) and 22.6 min (major);
[a]2D4 C36.1 (c 1.04, CHCl3, 98.1% ee).
Compound (2S,3S)-18. According to the procedure
described above, (2S,3S)-18 was synthesized as a white
solid from (2S,3S)-17. White solid; mp: 134–138 8C
(hexane–AcOEt); IR (neat) n: 3427, 3322, 2925, 1735,
1
1636, 1159 cmK1; H NMR (CDCl3, 400 MHz) d: 1.46 (s,
9H), 4.86 (br s, 1H), 5.15 (dd, 1H, JZ2.4, 6.0 Hz), 5.39 (s,
1H), 6.95 (d, 1H, JZ6.0 Hz), 7.24–7.63 (m, 10H); 13C
NMR (CDCl3, 100 MHz) d: 168.7, 168.2, 139.3, 133.1,
132.1, 128.6, 128.1, 127.8, 127.1, 126.0, 83.6, 75.5, 60.2,
27.9; LRMS (FAB) m/z: 342 (MCH); HRMS (FAB) calcd
for C20H24NO4 342.1705, found: 341.1676. Anal. Calcd for
C20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C, 70.06; H,
3.4.2. tert-Butyl 2-benzoylamino-3-(tert-butyldimethyl-
silyloxy)-3-phenylpropionate (17) (Scheme 8). Compound
(2S,3S)-17. Colorless oil; IR (neat) n: 3434, 2929, 2857,
1
1725, 1661 cmK1; H NMR (CDCl3, 400 MHz) d: K0.10
(s, 3H), K0.01 (s, 3H), 0.93 (s, 9H), 1.30 (s, 9H), 4.88 (dd,
1H, JZ2.4, 6.8 Hz), 5.33 (d, 1H, JZ2.4 Hz), 7.13 (d, 1H,

K. Hasegawa et al. / Tetrahedron 62 (2006) 1390–1401
1401
J. Am. Chem. Soc. 1972, 94, 8084–8090. (g) Burkoth, T. L.
Tetrahedron Lett. 1969, 10, 5049–5052. (h) Woolsey, N. F.;
Khalil, M. H. J. Org. Chem. 1972, 37, 2405–2408. For
catalytic aldol-type reaction of a-trimethylsilyldiazoesters
with aldehydes, see: (i) Kanemasa, S.; Araki, T.; Kanai, T.;
Wada, E. Tetrahedron Lett. 1999, 40, 5059–5062.
6.82; N, 4.04; HPLC: DAICEL CHIRALCEL OJ-H,
254 nm, flow rate 0.5 mL/min, hexane/i-PrOHZ95:5,
retention time: 24.4 min (minor) and 28.5 min (major);
[a]2D5 C69.8 (c 0.13, CHCl3, 96.5% ee).
3.4.4. (2S,3S) tert-Butyl 2-(N-benzoylhydrazino)-3-
hydroxy-phenylpropionate (19), (Scheme 8). According
to the procedure described above, (2S,3S)-19 was syn-
thesized as a white amorphous material from (2S,3S)-12.
White amorphous; IR (neat) n: 3296, 2977, 1721, 1641,
5. Jiang, N.; Wang, J. Tetrahedron Lett. 2002, 43, 1285–1287.
6. (a) Ledon, H. J. Org. Synth. 1979, 59, 66–71. (b) Kumar, S. M.
Synth. Commun. 1987, 17, 1015–1020.
7. Yao, W.; Wang J. Org. Lett. 2003, 5, 1527–1530.
8. For asymmetric induction, recrystallization of PTC D (mp:
169–1718C, [a]2D4 K438.0 (c 1.1, CHCl3)) is essential from
MeOH before use. The direct use of commercially available
material (from Aldrich) without recrystallization gave 42% ee
(69% yield).
1
1152 cmK1; H NMR (CDCl3, 400 MHz) d: 1.32 (s, 9H),
3.94 (d, 1H, JZ4.8 Hz), 5.11 (d, 1H, JZ4.8 Hz), 5.25 (br s,
1H), 7.27–7.69 (m, 10H), 7.94 (br s, 1H); 13C NMR (CDCl3,
100 MHz) d: 169.5, 167.6, 139.6, 132.2, 132.0, 128.6,
128.1, 127.7, 126.9, 126.4, 82.6, 72.6, 69.3, 27.8; LRMS
(FAB) m/z: 395 (MCK); HRMS (FAB) calcd for
C20H24N2O4K 395.1373, found: 395.1383; HPLC: DAICEL
CHIRALPAK AS-H, 254 nm, flow rate 1.0 mL/min,
hexane/i-PrOHZ80:20, retention time: 15.2 min (minor)
and 28.2 min (major); [a]2D3 C15.9 (c 0.65, CHCl3, 87% ee).
9. Examples of asymmetric synthesis using PTCs derived from
N-anthracenyl cinchona alkaloids, see: (a)
Lygo, B.;
Wainwright, P. G. Tetrahedron Lett. 1997, 38, 8595–8598.
(b) Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997,
119, 12414–12415. (c) Corey, E. J.; Noe, M. C.; Xu, F.
Tetrahedron Lett. 1998, 39, 5347–5350. (d) Perrard, T.;
´
Plaquevent, J. C.; Desmurs, J. R.; Hebraut, D. Org. Lett. 2000,
Acknowledgements
2, 2959–2962. (e) A-d-Sousa, J.; Prabhakar, S.; Lobo, A. M.;
Rosa, A. M.; Gomes, M. J. S.; Corvo, M. C.; Williams, D. J.;
White, A. J. P. Tetrahedron: Asymmetry 2001, 12, 3349–3365.
(f) Lygo, B.; Daniel, C. M. Tetrahedron Lett. 2002, 43,
2360–2361. (g) Bhunnoo, R. A.; Yulai, Hu.; Laine, D. I.;
Brown, C. D. Angew. Chem., Int. Ed. 2002, 41, 3479–3480.
(h) Zhang, Fu.-Y.; Corey, E. J. Org. Lett. 2004, 6, 3397–3399.
This work was supported by Grant-in-Aid for Young
Scientists B (16790007) and Scientific Research in Priority
Areas (17035014) from The Ministry of Education, Culture,
Sports, Science and Technology (MEXT).
´ ´ ´
10. Andres, J. M.; Martın, Y.; Pedrosa, R.; Perez-Encabo, A.
Tetrahedron 1997, 53, 3787–3794.
References and notes
11. For asymmetric induction via kinetic resolution and retro-aldol
reaction under PTC conditions, see: Arai, S.; Shirai, Y.;
Ishida, T.; Shioiri, T. Tetrahedron 1999, 55, 6375–6386.
12. For reviews of a-diazo carbonyl compounds, see: (a) Doyle,
M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds; Wiley Inter-
science: New York, 1998. (b) Ye, T.; McKervey, M. A.
Chem. Rev. 1994, 94, 1091–1160.
1. For general reviews of asymmetric PTC reactions see: (a)
O’Donnell, M. J. Acc. Chem. Res. 2004, 37, 506–517. (b)
Lygo, B.; Andrews, B. I. Acc. Chem. Res. 2004, 37, 518–525.
(c) Maruoka, K.; Ooi, T. Chem. Rev. 2003, 103, 3013–3028.
(d) Shioiri, T.; Arai, S. In Stimulating Concepts in Chemistry;
¨
Vogtle, F., Stoddart, J. F., Shibasaki, M., Eds.; Wiley: New
York, 2000; pp 123–143. Recent examples of new chiral
ammonium salts as PTCs, (e) Arai, S.; Tsuji, R.; Nishida, A.
Tetrahedron Lett. 2002, 43, 9535–9537. (f) Shibuguchi, T.;
Fukuta, Y.; Akachi, Y.; Sekine, A.; Ohshima, T.; Shibasaki, M.
Tetrahedron Lett. 2002, 43, 9539–9543. (g) Mase, N.; Ohno,
T.; Hoshikawa, N.; Ohishi, K.; Morimoto, H.; Yoda, H.;
Takabe, K. Tetrahedron Lett. 2003, 44, 4073–4075.
13. For transformation using b-amino-a-diazoesters, see: Shi, W.;
Jiang, N.; Zhang, S.; Wu, W.; Du, D.; Wang, J. Org. Lett.
2003, 5, 2243–2246.
´ ´ ´
14. Sarabia Garcıa, F.; Pedaraza Cebrian, G. M.; Heras Lopez, A.;
´
Lopez Herrera, F. J. Tetrahedron 1998, 54, 6867–6896.
15. (a) Khan, N. M.; Kidwai, A. R. J. Org. Chem. 1973, 38, 822–825.
(b) Denton, T. D.; Seib, T.; Bridges, R. J.; Thompson, C. M.
Bioorg. Med. Chem. Lett. 2002, 12, 3209–3213.
2. (a) Dolling, U.-H.; Davis, P.; Grabowski, E. J. J. J. Am. Chem.
Soc. 1984, 106, 446–447. (b) O’Donnell, W. J.; Bennett, W. D.;
Wu, S. J. Am. Chem. Soc. 1989, 111, 2353–2355.
16. Hannachi, J.-C.; Vidal, J.; Mulatier, J.-C.; Collet, A. J. Org.
Chem. 2004, 69, 2367–2373 and references cited therein.
17. Blaskovich, M. A.; Evindar, G.; Rose, N. G. W.; Wilkinson, S.;
Luo, Y.; Lajoie, G. A. J. Org. Chem. 1998, 63, 3631–3646 and
reference cited therein.
3. Arai, S.; Hasegawa, K.; Nishida, A. Tetrahedron Lett. 2004,
45, 1023–1026 and 2005, 46, 6171.
4. For an aldol-type reaction of diazoester promoted by strong
¨
bases, see: (a) Schollkopf, U.; Frasnelli, H.; Hoppe, D. Angew.
18. (E)-11 and (Z)-11 were easily separated by silica gel
chromatography. Acidic treatment of (E)-11 (1 equiv of
benzoic acid in CH2Cl2) gave a mixture of (E) and (Z)-11
(3:2).
´
¨
Chem., Int. Ed. 1970, 9, 300–302. (b) Schollkopf, U.; Banhidai, B.;
Frasnelli, H.; Meyer, R.; Beckhaus, H. Liebigs Ann. Chem.
1974, 1767–1783. (c) Pellicciari, R.; Natalini, B. J. Chem.
Soc., Perkin Trans. 1 1977, 1822–1824. (d) Pellicciari, R.;
Natalini, B.; Sadeghpour, B. M.; Marinozzi, M.; Snyder, J. P.;
Williamson, B. L.; Kuethe, J. T.; Padwa, A. J. Am. Chem. Soc.
1996, 118, 1–12. (e) Moody, C. J.; Taylor, R. J. Tetrahedron
Lett. 1987, 28, 5351–5352. (f) Wenkert, E.; McPherson, A. A.
19. Burk, M. J.; Feaster, J. E. J. Am. Chem. Soc. 1992, 114,
6266–6267.
´
20. Williams, L.; Zhang, Z.; Shao, F.; Carroll, P. J.; Joullie, M. M.
Tetrahedron 1996, 52, 11673–11694.