Boron enolates of a hydantoin chiral auxiliary derived from l-phenylalanine: A versatile tool for asymmetric aldol reactions

Article abstract of DOI:10.1016/j.tetasy.2011.12.013

The aldol reactions of boron enolates derived from a hydantoin chiral auxiliary derived from l-phenylalanine occur in good yields with high syn diastereoselectivity. Aldol adduct 4a is readily cleaved by hydrolysis to afford (2S,3S)-3-hydroxy-2-methyl-3-p

Full text of DOI:10.1016/j.tetasy.2011.12.013

Tetrahedron: Asymmetry 23 (2012) 72–75
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Tetrahedron: Asymmetry
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Boron enolates of a hydantoin chiral auxiliary derived from L-phenylalanine:
a versatile tool for asymmetric aldol reactions
⇑
Ji-Shu Zhang, Cui-Fen Lu, Zu-Xing Chen, Yan Li, Gui-Chun Yang
Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules & School of Chemistry and Chemical Engineering, Hubei University,
Wuhan 430062, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The aldol reactions of boron enolates derived from a hydantoin chiral auxiliary derived from L-phenylalanine
occur in good yields with high syn diastereoselectivity. Aldol adduct 4a is readily cleaved by hydrolysis to afford
(2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid 5a in good yield and in almost enantiomerically pure
form.
Received 1 December 2011
Accepted 26 December 2011
Available online 31 January 2012
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
refluxed in 2 M HCl to give the desired chiral hydantoin 2 in a
70% yield. Then, 2 was treated with propionyl chloride in the pres-
Asymmetric synthesis is one of the most extensively used
methods for the synthesis of complex chiral compounds, especially
those with biological activities that render them useful as pharma-
ceuticals or agrochemicals. To generate the stereogenic centers for
such compounds, the use of chiral auxiliaries has proven to be a
powerful tool.1 In fact, asymmetric aldol reactions in the presence
of chiral auxiliaries is one of the most general methods employed
in these syntheses since one C–C bond and two stereogenic centers
can be formed in a single step.2
Yamaguchi et al. previously investigated the preparation of an
optically active hydantoin and its application as a chiral auxiliary
to induce diastereomeric conjugate additions.3 This reported chiral
auxiliary has some unique properties in comparison with conven-
tional chiral auxiliaries. However, other asymmetric reactions such
as aldol, alkylation or Diels–Alder have not been reported. Herein
ence of triethylamine and 4-(N,N-dimethylamino)pyridine (DMAP)
in CH2Cl2 to produce the N-acyl compound 3 in a 92% yield.
2.2. Diastereocontrolled aldol reactions
In order to examine the reactivity of the chiral auxiliary 2 in
asymmetric aldol reactions, N-propionylamide 3 enolate generated
by a different Lewis acid with benzaldehyde as a model reaction
was studied. The enolate of 3 was generated by reaction with
1.2 equiv of Lewis acid in CH2Cl2 at 0 °C for 15 min followed by
the addition of 1.2 equiv of N-diisopropylethylamine at the same
temperature and then stirring the resulting brown solution for
15 min. The enolate thus generated was then trapped with benzal-
dehyde at 0 °C for 6 h (Scheme 2).
With TiCl4, the reaction afforded the syn aldol product in mod-
erate yield with 81:19 stereoselectivity (the ratio of the major iso-
mer 4a versus the sum of all other isomers) (Table 1, entry 1). The
stereoselectivity was remarkably improved by the use of the tin
enolate generated by the reaction of 3 and the Lewis acid Sn(OTf)2
yielding the aldol product 4a with the stereoselectivity of 99:1, but
the chemical yield was only 23% (Table 1, entry 2). A satisfactory
result was obtained when the reaction was carried out using the
Lewis acid n-Bu2BOTf (Table 1, entry 3), the stereoselectivity was
99:1, and the chemical yield was 92%. The aldol reactions with
other aldehydes also exhibited excellent stereoselectivity using
the Lewis acid n-Bu2BOTf and produced aldol 4b–g with high
chemical yields as shown in Table 1. The syn/anti relative stereo-
chemistry of aldol adducts may be assigned on the basis of 1H
NMR vicinal coupling constants.4 For the compounds 4a–g, the
measured value for the aldol fragment’s vicinal protons was found
to be ꢀ3 Hz, consistent with the syn stereochemistry.
the utility of a chiral hydantoin derived from L-phenylalanine as
a chiral auxiliary in highly diastereoselective aldol reactions is
reported.
2. Results and discussion
2.1. Preparation of the chiral hydantoin 2 and the N-propionyl
derivative 3
Our synthetic strategy involves two steps as shown in Scheme 1.
In contrast to Yamaguchi’s reported method, our chiral hydantoin
2 was prepared in a one-pot reaction starting from L-phenylalanine
methyl ester 1. Compound 1 was reacted with phenyl isocyanate in
pyridine, and then after evaporation of pyridine, the residue was
The absolute configuration of the aldol adduct was determined
by evaluation of the hydrolyzed product. Adduct 4a was subjected
⇑
Corresponding author. Tel.: +86 27 50865322; fax: +86 27 88663043.
E-mail address: yangguichun@hubu.edu.cn (G.-C. Yang).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.12.013

J.-S. Zhang et al. / Tetrahedron: Asymmetry 23 (2012) 72–75
73
O
N
O
1) PhNCO
CH3CH2COCl
DMAP, Et3N
pyridine, r.t.
N
COOC2H5
NH2HCl
N
HN
2) 2 M HCl, reflux
CH2Cl2, 0ºC
O
O
O
1
2
3
Scheme 1.
O
O
N
1) Lewis acid, DIPEA
0ºC, CH2Cl2
N
N
N
Ar
º
2) ArCHO, 0 C
O
O
O
OH
O
3
4
Scheme 2.
Table 1
Entry
Product
Lewis acid
Ar
Stereoselectivitya
Yieldb (%)
1
2
3
4
5
6
7
8
9
4a
4a
4a
4b
4c
4d
4e
4f
TiCl4
Sn(OTf)2
C6H4
C6H4
C6H4
2,3-(OCH3)2C6H3
4-BrC6H4
2,4-Cl2C6H3
2-NO2C6H4
3-NO2C6H4
4-CNC6H4
81:19
99:1
99:1
99:1
99:1
99:1
91:9
90:10
92:8
87
23
92
93
94
88
83
85
92
n-Bu2BOTf
n-Bu2BOTf
n-Bu2BOTf
n-Bu2BOTf
n-Bu2BOTf
n-Bu2BOTf
n-Bu2BOTf
4g
a
The ratio of the major isomer 4 versus the sum of all other isomers, which was determined by HPLC.
Isolated adduct yield of the pure major product after silica gel chromatography.
b
to LiOH/H2O2 at 0 °C in THF/H2O to afford the corresponding carbox-
a very high diastereoselectivity. The formation of the major
(Syn,S,S)-4 product can be rationalized by a chelated transition
state involving the attack of the Z boron enolate on the Si face of
the aldehyde (Scheme 4).
ylic acid 5a in a 94% yield as well as the recovered auxiliary 2 in
nearly quantitative yield (Scheme 3). The b-hydroxyacid (S,S)-5a is
a known compound in the literature.5,6 Comparing the specific rota-
tions of the newly prepared b-hydroxyacid 5a {½a D20
¼ ꢂ29:8 (c 0.85,
ꢁ
CH2Cl2) versus lit.6 ½a D24
¼ ꢂ29:5 (c 1.02, CH2Cl2)} revealed that the
ꢁ
3. Conclusion
newly prepared b-hydroxyacid 5a was the (S,S)-enantiomer which
should be extended to the aldols 4a–g.
In conclusion, we have efficiently synthesized a chiral hydan-
Chiral auxiliary-based aldol reactions with boron enolates have
been extensively studied.7 The formation of the boron enolates is
generally performed with dialkylboron triflates in the presence of
N-diisopropylethylamine and the syn products are obtained with
toin in one-pot reaction starting from L-phenylalanine methyl ester
and utilized it as a highly effective chiral auxiliary in asymmetric
syn-aldol reactions, which is proven to be efficient for boron eno-
lates. Moreover, the efficient workup after the hydrolysis reaction
O
O
LiOH, H2O2
N
N
N
+
OH
HN
º
THF/H2O, 0 C
O
O
O
OH
O
OH
2
5a
4a
Scheme 3.

74
J.-S. Zhang et al. / Tetrahedron: Asymmetry 23 (2012) 72–75
CDCl3): d 1.25 (t, J = 7.2 Hz, 3H), 2.95 (q, J = 7.8 Hz, 2H), 3.36 (dd,
J = 1.8, 13.8 Hz, 1H), 3.67 (dd, J = 5.4, 13.8 Hz, 1H), 4.98 (dd,
J = 2.4, 4.8 Hz, 1H), 6.90–7.40 (m, 10H); 13C NMR (150 MHz, CDCl3):
d 8.40, 30.77, 34.71, 59.51, 126.44, 127.79, 128.67, 128.99, 129.19,
129.67, 130.25, 133.38, 152.38, 169.75, 173.33. Anal. Calcd for
O
N
O
N
O
N
C19H18N2O3: C, 70.79; H, 5.63; N, 8.69. Found: C, 70.82; H, 5.50;
H
N, 8.75.
N
Ar
Ar
n-Bu2B
O
H
O
O
4.4. General procedure for aldol reactions
OH
O
Me
Lewis acid (1.2 mmol) was added dropwise to a solution of N-
propionyl derivative 3 (0.32 g, 1.0 mmol) in anhydrous CH2Cl2
(10 mL) at 0 °C, and the solution was allowed to stir for 15 min.
Diisopropylethylamine (0.21 mL, 1.2 mmol) was added dropwise
to the mixture and the solution was allowed to stir for 15 min.
The appropriate aldehyde (1.2 mmol) was then added directly to
the enolate. The reaction was allowed to stir for 6 h at 0 °C fol-
lowed by the addition of saturated aqueous NH4Cl. The organic
layer was separated, and the aqueous layer was extracted with
CH2Cl2 (3 ꢃ 30 mL). The combined organic layers were dried over
MgSO4, filtered, and concentrated. The crude product was purified
by silica gel column chromatography (n-hexane/EtOAc, 4:1, v/v) to
give the desired aldol 4a–g.
Scheme 4.
allowed a quantitative recovery of the chiral auxiliary, and afforded
(2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid 5a in good
yield and in almost enantiomerically pure form.
4. Experimental
4.1. General
All solvents were obtained from commercial sources and dried
or purified by standard procedures before use. Separations by flash
chromatography were performed on 300–400 mesh silica gel.
Melting points were measured on a WRS-1A digital melting point
apparatus and are uncorrected. Optical rotations were measured
using a sodium D line on WZZ-2B Automatic Polarimeter. HPLC
analyses were carried out on a Dionex chromatograph (Ulti-
mate3000 pump, C8 reversed-phase chromatographic column)
equipped with a diode-array UV detector. NMR spectra were re-
corded on Varian Unity Inova 600 spectrometer in CDCl3 (1H at
600 MHz and 13C at 150 MHz) using TMS as the internal standard.
Elemental analyses were done on a VarioEL III (Germany) analyzer.
4.4.1. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
phenyl)propionylhydantoin 4a
Obtained in 92% yield from compound 3, using the general aldol
reaction procedure. Mp 85.5–86.0 °C;
½
a 2D5
ꢁ
¼ þ172:5 (c 1.00,
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.17 (d, J = 7.2 Hz, 3H),
2.72 (s, 1H), 3.32 (dd, J = 2.4, 13.8 Hz, 1H), 3.54 (dd, J = 5.4,
14.4 Hz, 1H), 4.02 (dq, J = 2.4, 7.2 Hz, 1H), 5.02 (dd, J = 3.0, 4.8 Hz,
1H), 5.24 (d, J = 2.4 Hz, 1H), 6.88–7.47 (m, 14H); 13C NMR
(150 MHz, CDCl3): d 10.31, 34.89, 46.76, 59.66, 73.25, 126.22,
126.50, 127.672, 127.79, 128.35, 128.63, 129.15, 129.25, 129.80,
130.11, 133.19, 141.74, 152.28, 169.54, 174.86. Anal. Calcd for
C26H24N2O4: C, 72.88; H, 5.65; N, 6.54. Found: C, 72.65; H, 5.59;
4.2. Preparation of chiral hydantoin 2
N, 6.42.
L-Phenylalanine methyl ester 1 (5.0 g, 23.2 mmol) and phenyl
4.4.2. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
(200,300-dimethoxylphenyl)) propionylhydantoin 4b
isocyanate (2.51 mL, 23.2 mmol) were vigorously stirred for 2 h
at room temperature in pyridine (50 mL). The resulting mixture
was evaporated to dryness under reduced pressure. Aqueous HCl
(50 mL, 2 N) was added to the residue and the mixture refluxed
for 6 h. A precipitate appeared upon cooling and was recrystallized
from hot water to give a white solid (S)-2 (4.3 g, 70%). Mp 165–
Obtained in 93% yield from compound 3, using the general aldol
reaction procedure. Mp 77.2–77.7 °C;
½
a 2D5
ꢁ
¼ þ193:2 (c 1.01,
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.08 (d, J = 6.6 Hz, 3H),
3.05 (s, 1H), 3.43 (dd, J = 2.4, 13.8 Hz, 1H), 3.64 (dd, J = 3.0,
13.8 Hz, 1H), 3.67 (s, 6H), 3.96 (dq, J = 2.4, 6.6 Hz, 1H), 5.01 (dd,
J = 2.4, 5.4 Hz, 1H), 5.48 (d, J = 1.8 Hz, 1H), 6.80–8.07 (m, 13H);
13C NMR (150 MHz, CDCl3): d 10.21, 34.61, 42.85, 59.38, 69.18,
126.25, 126.38, 127.94, 128.61, 128.63, 129.04, 129.11, 129.15,
129.61, 129.73, 130.03, 131.85, 132.93, 133.65, 136.57, 151.61,
169.35, 177.10. Anal. Calcd for C28H28N2O6: C, 68.84; H, 5.78; N,
5.73. Found: C, 68.96; H, 5.63; N, 5.78.
166 °C, lit.8 mp 167–168 °C; ½a 2D5
ꢁ
¼ ꢂ159:8 (c 1.05, MeOH), lit.8
½
a 2D5
ꢁ
¼ þ161:1 (MeOH) for (R)-2; 1H NMR (600 MHz, CDCl3): d
3.04 (dd, J = 12.6, 20.4 Hz, 1H), 3.32 (dd, J = 5.4, 19.8 Hz, 1H), 4.40
(dd, J = 5.4, 12.6 Hz, 1H), 5.89 (br s, 1H), 7.20–7.45 (m, 10H); 13C
NMR (150 MHz, CDCl3): d 38.03, 58.11, 126.19, 127.61, 128.37,
128.92, 129.11, 129.41, 131.20, 134.76, 155.98, 171.91.
4.3. Preparation of N-propionyl derivative 3
4.4.3. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
(400-bromophenyl))propion-ylhydantoin 4c
To a solution of chiral hydantoin 2 (4.0 g, 15.0 mmol) in CH2Cl2
(50 mL) was added DMAP (0.37 g, 3.0 mmol), Et3N (2.67 mL,
18.04 mmol), and then propionyl chloride (1.68 mL, 19.03 mmol)
in CH2Cl2 (10 mL) was added dropwise to the reaction mixture at
0 °C. After stirring at 0 °C for 40 min, the reaction was quenched
with saturated aqueous NH4Cl, and the organic layer was sepa-
rated. The aqueous layer was extracted with CH2Cl2 (3 ꢃ 30 mL).
The organic layers were combined, washed with saturated aqueous
NaHCO3 and brine, dried with MgSO4, filtered, and concentrated.
Purification of the crude product by silica gel column chromatogra-
phy (n-hexane/EtOAc, 10:1, v/v) gave a white solid 3 (4.45 g, 92%).
Obtained in 94% yield from compound 3, using the general aldol
reaction procedure. Mp 66.3–67.0 °C;
½
a 2D5
ꢁ
¼ þ222:5 (c 1.05,
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.14 (d, J = 7.2 Hz, 3H),
2.44 (s, 1H), 3.36 (dd, J = 2.4, 13.8 Hz, 1H), 3.58 (dd, J = 5.4,
14.4 Hz, 1H), 3.95 (dq, J = 2.4, 6.6 Hz, 1H), 4.98 (dd, J = 1.8, 7.2 Hz,
1H), 5.15 (d, J = 2.4 Hz, 1H), 6.88–7.50 (m, 14H); 13C NMR
(150 MHz, CDCl3): d 10.62, 34.92, 46.49, 59.72, 72.60, 121.50,
126.41, 126.47, 127.92, 127.98, 128.67, 129.20, 129.33, 129.74,
130.05, 131.40, 133.16, 140.66, 152.35, 169.45, 176.07. Anal. Calcd
for C26H23BrN2O4: C, 61.55; H, 4.57; N, 5.52. Found: C, 61.68; H,
4.46; N, 5.49.
Mp 86.6–87.3 °C; ½a D25
ꢁ
¼ ꢂ6:5 (c 1.02, CH2Cl2); 1H NMR (600 MHz,

J.-S. Zhang et al. / Tetrahedron: Asymmetry 23 (2012) 72–75
75
4.4.4. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
(200,400-dichlorophenyl))pro- pionylhydantoin 4d
CDCl3): d 9.13, 34.88, 46.11, 59.69, 72.24, 111.18, 118.69, 126.41,
126.80, 127.99, 128.66, 129.23, 129.61, 129.96, 132.03, 133.16,
146.87, 152.45, 169.42, 174.47. Anal. Calcd for C27H23N3O4: C,
71.51; H, 5.11; N, 9.27. Found: C, 71.68; H, 5.02; N, 9.33.
Obtained in 88% yield from compound 3, using the general aldol
reaction procedure. Mp 85.6–86.3 °C;
½
a 2D5
ꢁ
¼ þ177:3 (c 1.02,
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.10 (d, J = 7.2 Hz, 3H),
2.62 (s, 1H), 3.43 (dd, J = 1.8, 13.8 Hz, 1H), 3.65 (dd, J = 6.0,
14.4 Hz, 1H), 3.96 (dq, J = 1.8, 7.2 Hz, 1H), 5.01 (dd, J = 2.4, 5.4 Hz,
1H), 5.48 (d, J = 1.2 Hz, 1H), 6.80–8.07 (m, 13H); 13C NMR
(150 MHz, CDCl3): d 10.21, 34.61, 42.85, 59.38, 69.18, 126.25,
126.38, 127.94, 128.61, 128.63, 129.04, 129.11, 129.15, 129.61,
129.73, 130.03, 131.85, 132.93, 133.65, 136.57, 151.61, 169.35,
177.10. Anal. Calcd for C26H22Cl2N2O4: C, 62.79; H, 4.46; N, 5.63.
Found: C, 62.90; H, 4.54; N, 5.72.
4.5. Preparation of (2S,3S)-3-hydroxy-2-methyl-3-
phenylpropionic acid 5a
The appropriate aldol adduct 4a (0.34 g, 0.80 mmol) was treated
at 0 °C with LiOH (0.02 g, 0.88 mmol) and H2O2 (0.25 mL,
2.4 mmol) in a 1:1 mixture of THF/H2O (10 mL). The reaction was
stirred overnight at room temperature and then concentrated un-
der reduced pressure. The organic layer was extracted with CH2Cl2
(3 ꢃ 30 mL) and concentrated to recover quantitatively the chiral
auxiliary 2. Acidification of the aqueous layer to pH 1 and extrac-
tion with EtOAc furnished the desired acid 5a (0.13 g, 94%).
4.4.5. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
(200-nitrophenyl))propionyl hydantoin 4e
Obtained in 83% yield from compound 3, using the general aldol
½
a 2D0
ꢁ
¼ ꢂ29:8 (c 0.82, CH2Cl2), lit.6
½
a 2D4
ꢁ
¼ ꢂ29:5 (c 1.02, CH2Cl2);
reaction procedure. Mp 81.3–81.9 °C;
½
a 2D5
ꢁ
¼ þ185:5 (c 1.00,
1H NMR (600 MHz, CDCl3): d 1.14 (d, J = 7.2 Hz, 3H), 2.84 (dq,
J = 6.6, 3.0 Hz, 1H), 5.17 (d, J = 3.0 Hz, 1H), 7.27–7.36 (m, 5H); 13C
NMR (150 MHz, CDCl3): d 10.19, 46.12, 73.34, 125.87, 127.56,
128.26, 140.95, 180.81.
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.21 (d, J = 7.2 Hz, 3H),
3.35 (dd, J = 2.4, 13.8 Hz, 1H), 3.70 (dd, J = 3.0, 13.8 Hz, 1H), 3.91
(s, 1H), 4.13 (dq, J = 2.4, 7.2 Hz, 1H), 5.01 (dd, J = 2.4, 5.4 Hz, 1H),
5.48 (d, J = 1.8 Hz, 1H), 6.80–8.07 (m, 14H); 13C NMR (150 MHz,
CDCl3):
d
10.21, 34.61, 42.85, 59.80, 70.05, 124.92, 126.31,
Acknowledgments
126.49, 127.95, 128.42, 129.09, 129.15, 129.81, 129.92, 132.68,
133.27, 136.39, 147.37, 151.70, 169.13, 177.27. Anal. Calcd for
We gratefully acknowledge the National Natural Sciences Foun-
dation of China (Nos. 20772026 and 21042005), the Natural Sci-
ences Foundation of Hubei province in China (No. 2010CDA019)
and 2011 National Major Scientific Instrument and Equipment
Development Project (No. 2011YQ12003505) for financial support.
C26H23N3O6: C, 65.95; H, 4.90; N, 8.87. Found: C, 66.05; H, 4.96;
N, 8.92.
4.4.6. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
(300-nitrophenyl))propionyl hydantoin 4f
Obtained in 85% yield from compound 3, using the general aldol
References
reaction procedure. Mp 84.6–85.0 °C;
½
a 2D5
ꢁ
¼ þ180:7 (c 1.01,
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.07 (d, J = 7.2 Hz, 3H),
3.11 (s, 1H), 3.41 (dd, J = 2.4, 14.4 Hz, 1H), 3.64 (dd, J = 3.0,
13.8 Hz, 1H), 3.96 (dq, J = 3.0, 7.2 Hz, 1H), 5.01 (dd, J = 2.4, 5.4 Hz,
1H), 5.30 (d, J = 2.4 Hz, 1H), 6.92–8.33 (m, 14H); 13C NMR
(150 MHz, CDCl3): d 9.15, 34.86, 46.12, 59.66, 71.97, 121.03,
122.49, 126.37, 128.01, 128.66, 129.21, 129.25, 129.57, 129.93,
132.19, 133.14, 143.62, 148.27, 152.37, 169.39, 174.60. Anal. Calcd
for C26H23N3O6: C, 65.95; H, 4.90; N, 8.87. Found: C, 66.01; H, 4.98;
N, 8.86.
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4.4.7. (20S,30S,5S)-5-Benzyl-3-phenyl-1-(30-hydroxy-20-methyl-30-
(400-cyanophenyl))propionyl -hydantoin 4g
Obtained in 92% yield from compound 3, using the general aldol
a 2D5
ꢁ
¼ þ202:2 (c 1.00,
5. Bonner, M. P.; Thornton, E. R. J. Am. Chem. Soc. 1991, 113, 1299–1308.
6. Casper, D. M.; Burgeson, J. R.; Esken, J. M.; Ferrence, G. M.; Hitchcock, S. R. Org.
Lett. 2002, 4, 3739–3742.
7. For a very recent review see: Geary, L. M.; Hultin, P. G. Tetrahedron: Asymmetry
2009, 20, 131–173. and references cited therein.
reaction procedure. Mp 73.6–74.0 °C;
½
CH2Cl2); 1H NMR (600 MHz, CDCl3): d 1.07 (d, J = 6.6 Hz, 3H),
3.41 (dd, J = 1.8, 13.8 Hz, 1H), 3.64 (dd, J = 5.4, 14.4 Hz, 1H), 3.91
(s, 1H), 4.13 (dq, J = 2.4, 6.6 Hz, 1H), 5.02 (dd, J = 3.0, 4.8 Hz, 1H),
5.25 (d, J = 2.4 Hz, 1H), 6.92–8.33 (m, 14H); 13C NMR (150 MHz,
8. Zhai, Z.; Wang, H.; Chen, J.; Zhang, Q. Synth. Commun. 2003, 32, 1873–1883.