Diastereoselective atom transfer radical cyclization reactions of unsaturated α-bromo oxazolidinone imides catalyzed by Lewis acids

Article abstract of DOI:10.1016/j.tetasy.2003.06.001

A new Lewis acid-catalyzed atom transfer radical cyclization reaction of unsaturated α-bromo oxazolidinone imides is reported. In the presence of Lewis acids such as Mg(ClO₄)₂ and Yb(OTf)₃, a series of trans cyclic product

Full text of DOI:10.1016/j.tetasy.2003.06.001

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2927–2937
Diastereoselective atom transfer radical cyclization reactions
of unsaturated a-bromo oxazolidinone imides catalyzed by
Lewis acids
Dan Yang,* Bao-Fu Zheng, Shen Gu, Philip W. H. Chan and Nian-Yong Zhu
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China
Received 8 May 2003; accepted 24 June 2003
Abstract—A new Lewis acid-catalyzed atom transfer radical cyclization reaction of unsaturated a-bromo oxazolidinone imides is
reported. In the presence of Lewis acids such as Mg(ClO4)2 and Yb(OTf)3, a series of trans cyclic products was obtained in high
yield (up to 87%) between 0°C and room temperature. The loading of strong Lewis acids, such as Yb(OTf)3, can be reduced to
0.1 equiv. without significantly compromising the yield. Excellent diastereoselectivity could be achieved by using 1,2-stereocontrol
or a chiral oxazolidinone auxiliary. For substrates 1e and 1f bearing a b-methyl substituent and the chiral auxiliary,
(S)-(−)-4-benzyl-5,5-dimethyl-2-oxazolidinone, respectively, the diastereomeric ratio of the products was greater than 50:1.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
In recent years, significant progress has been made in
controlling the stereoselectivity of radical reactions
through Lewis acid chelation,5 especially the combina-
tion of Lewis acids with chiral oxazolidinone auxil-
iaries.5,6 Excellent levels of diastereoselectivity have
been achieved in Lewis acid-catalyzed radical allyla-
tion,7 conjugated radical addition8 and atom transfer
radical addition reactions9 using chiral oxazolidinone
auxiliaries. Sibi et al. reported extraordinarily high
levels of diastereoselectivity in radical allylation reac-
tions with an oxazolidinone chiral auxiliary derived
from diphenylalaninol (Scheme 2).10 Through the chela-
tion control of Lewis acids MgBr2 and Sc(OTf)3, the
diastereomeric ratios of the allylation products were
improved from 36:64 to greater than 99:1. Porter et al.
Radical cyclization is a powerful method for the syn-
thesis of cyclic compounds.1 The advantage of func-
tional group tolerance and the potential for tandem
cyclization make the radical cyclization an appealing
approach for the synthesis of highly functionalized
polycyclic natural products.2,3 Atom transfer radical
cyclization reactions, which involve the transfer of a
halogen atom (X=I, Br, or Cl) or an aryl chalcogen
group (X=SePh, or TePh) from one carbon center to
another with concomitant ring formation, is particu-
larly useful since the halogen atom or chalcogen group
retained in the product allows for further functionaliza-
tion (Scheme 1).4
Scheme 1.
* Corresponding author. E-mail: yangdan@hku.hk
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.06.001

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D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
2. Results and discussion
2.1. Preparation of substrates 1a–f
The synthesis of substrates 1a–f is shown in Scheme 4.
Carboxylic acids 2a–f were converted to the corre-
sponding mixed anhydride intermediates with
isobutylchloroformate. Subsequent treatment with the
anion of the oxazolidinone auxiliaries12 gave com-
pounds 3a–f in yields up to 87%. Finally, bromination
of 3a–f following Evans’ procedure13 gave substrates
1a–f in good to excellent yields (up to 90%).
Scheme 2.
2.2. Optimization of reaction conditions for atom trans-
fer radical cyclization
also obtained excellent diastereoselectivities in Lewis
acid-promoted atom transfer radical addition reactions
of secondary bromides to terminal alkenes by employ-
ing chiral benzyl and isopropyl oxazolidinone auxil-
iaries (Scheme 3).9a Using 1 equiv. of Sc(OTf)3 and 5
equiv. of 1-hexene, product yields up to 90% and
diastereomeric ratios greater than 95:5 were obtained.
We have been developing Lewis acid-catalyzed atom or
group transfer radical cyclization reactions for the
stereospecific construction of cyclic compounds.11 Here
we report the Lewis acid-catalyzed diastereoselective
atom transfer radical cyclization reactions of a series of
unsaturated a-bromo oxazolidinone imides.
With Et3B/O2 as the radical initiator, a series of Lewis
acids were surveyed with substrate 1a to determine their
efficiency in promoting atom transfer radical cyclization
(Table 1). In the absence of a Lewis acid, almost no
cyclization reaction was observed (entry 1). Several
common Lewis acids, MgI2, Zn(OTf)2, Sc(OTf)3 and
Mg(OTf)2, which were effective promoters of radical
allylation and addition reactions,7,8 failed to improve
the conversion significantly (entries 2–5). Lewis acids
such as Cu(OTf)2 and Cu(SbF6)2, commonly used to
catalyze the Diels–Alder, ene and aldol reactions for
oxazolidinone imides,14 also proved ineffective (entries
6 and 7). In contrast, the MgBr2-catalyzed reaction
Scheme 3.
Scheme 4. Reagents and conditions: (a) N-methyl morpholine, isobutylchloroformate, THF, −15°C, 5 min, then oxazolidinone,
NaH, THF, 0°C to rt, 6.5 h, 65–87%; (b) Et3N, Bu2BOTf, CH2Cl2, −78°C, 15 min, then 0°C, 1 h; NBS, CH2Cl2, −78°C, 3 h,
62–90%.

D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
2929
Table 1. Effect of Lewis acids on atom transfer radical cyclization reactions of 1aa
Entry
Lewis acid (equiv.)
Temp. (°C)
Time (h)
Conversion (%)b
Yield (%)c
1
2
3
4
5
6
7
8
None
25
25
25
25
25
25
25
25
0
24
24
24
24
24
24
24
24
3
<10
<10
<10
<10
40
<20
<15
70
>95
70
>95
>95
ND
ND
ND
ND
20
ND
ND
48
76
40
78
67
Zn(OTf)2 (1.0)
Sc(OTf)3 (1.0)
Mg(OTf)2 (1.0)
MgI2 (1.0)
Cu(OTf)2 (1.0)
Cu(SbF6)2 (1.0)
MgBr2 (1.0)
Mg(ClO4)2 (1.0)
Mg(ClO4)2 (0.3)
Yb(OTf)3 (1.0)
Yb(OTf)3 (0.3)
9
10
11d
12d
0
0
0
9
4
5
a Unless otherwise indicated, all reactions were carried out with indicated Lewis acid, 2.0 equiv. of Et3B/O2 at 0.025 M in CH2Cl2.
b Conversion determined by crude 1HNMR analysis.
c Isolated yield.
d Et2O as the solvent.
gave 4a in 48% yield (entry 8) whilst the Mg(ClO4)2 and
Yb(OTf)3-catalyzed reactions were found to give the
best results (entries 9–11). It is interesting to note that
the use of 0.3 equiv. of Yb(OTf)3 gave 67% yield,
comparable to that obtained for the reaction using a
stoichiometric amount of the same catalyst (entries 11
Figure 1. The electrophilicity of a-radicals.
and 12).
The effect of temperature on the cyclization reaction
was examined. Cyclization did not proceed efficiently at
lower temperature, such as −40 and −20°C, even with a
stoichiometric amount of Yb(OTf)3 (Table 2). Pre-
sumably, since a-radicals of oxazolidinone imides are
less electronically deficient and thereby less reactive
than those of b-keto esters11a,b (Fig. 1), higher tempera-
ture (0°C to room temperature) are required to pro-
mote the cyclization of unsaturated a-bromo
oxazolidinone imides.
2.3. Lewis acid-catalyzed radical cyclization of achiral
substrates 1b–d
Unsaturated a-bromo oxazolidinone imides 1b–d were
then examined under the above optimized radical
cyclization conditions (Table 3). Cyclization of 1b in
the presence of 1 equiv. of Yb(OTf)3 gave 5-exo cycliza-
tion product 4b in 45% yield and 6-endo cyclization 4b%
in 25% yield (entry 1). Switching to Mg(ClO4)2 led to
similar results (46% of 4b and 28% of 4b%; entry 2). For
the Mg(ClO4)2-catalyzed cyclization of substrate 1c, the
a-radical intermediate attacked the less substituted side
of the alkene to give the 6-endo cyclization product 4c
exclusively in 85% yield (entry 3). In the presence of 0.1
equiv. of Yb(OTf)3, 4c was obtained in 80% yield (entry
4). Substrate 1d gave a 6-exo cyclization product
Table 2. Effect of temperature on atom transfer radical
cyclization of substrate 1aa
Entry
Temp. (°C) Time (h)
Conversion
(%)b
Yield (%)c
1
cleanly as indicated from the H NMR analysis of the
crude reaction mixture. However, this product was
unstable on the silica gel column. Thus upon work-up,
Bu3SnH-mediated reduction was carried out to give
product 4d. The overall yield of these two steps was
more than 65% (entries 5 and 6). Note that in the
cyclization products 4a and 4d the 2-acyloxazolidinone
group was trans to the 3-alkyl group as determined by
NOESY analysis. These results demonstrate that excel-
lent regio- and diastereoselectivity can be achieved for
1
2
3
4
−40
−20
0
12
12
4
<10
<15
>95
>95
ND
ND
78
25
3
76
a All reactions were carried out with 1.0 equiv. of Yb(OTf)3 and 2.0
equiv. of Et3B/O2 in Et2O.
b Conversion determined by crude 1HNMR analysis.
c Isolated yield.

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D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
Table 3. Lewis acid-promoted bromo atom transfer cyclization reactions of 1b–da
aUnless otherwise indicated, all reactions were carried out at 0°C with indicated Lewis acid, 2.0 equiv. of Et3B/O2 at 0.025 M in CH2Cl2 for
Mg(ClO4)2 and Et2O for Yb(OTf)3.
bIsolation yield.
cReaction carried out at room temperature.
dOverall yield for the radical cyclization and subsequent reduction with Bu3SnH.
Table 4. Diastereoselective atom transfer radical cycliza-
tion reactions of chiral substrate 1ea
the Lewis acid-catalyzed radical cyclization reactions
of a-bromo 2-oxazolidinone imides.
2.4. Lewis acid-catalyzed asymmetric atom transfer
radical cyclization reactions of achiral substrates 1e–f
We then investigated the Lewis acid-catalyzed asym-
metric atom transfer cyclization reactions of substrates
1e and 1f bearing a b-methyl substituent and a chiral
‘Superquat’ oxazolidinone auxiliary,15 respectively.
Entry
Lewis acid (equiv.) Solvent
Reaction
time (h)
Yield
(%)b
Chiral substrate 1e was synthesized from commercially
available (R)-(+)-citronellic acid. Treatment of 1e with
1.0 equiv. of Mg(ClO4)2 under radical conditions gave a
single diastereomer 4e in 87% yield (Table 4, entry 1).
Slightly lower yields (77–78%) were obtained when
Yb(OTf)3 (0.3–1 equiv.) was used as the catalyst (Table
4, entries 2 and 3). In the 400 MHz 1H NMR spectra of
the crude reaction mixture, only one diastereomer was
found, suggesting the diastereomeric ratio to be greater
than 50:1. As indicated in the NOESY results of com-
pound 4e (Fig. 2), Hb only had NOE with the methyl
protons Hd and He, which suggested the absolute
configuration of compound 4e to be (1S,2S,5R).
1
2
3
Yb(OTf)3 (1.0)
Yb(OTf)3 (0.3)
Mg(ClO4)2 (1.0)
Et2O
Et2O
CH2Cl2
4
9
3
78
77
87
a Only one diastereomer was found from the 1H NMR (400 MHz)
spectra of the crude reaction mixture.
b Isolated yield.
The following transition state model is proposed to
account for the observed stereoselectivity (Fig. 3). The
two carbonyl groups are fixed in a syn orientation
through the bidentate chelation with the Lewis acid.
Figure 2. Summary of NOESY results of compound 4e.

D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
2931
Figure 3. Transition state model for the cyclization of substrate 1e.
Table 5. Diastereoselective atom transfer radical cycliza-
tion of substrate 1f with a chiral oxazolidinone auxiliarya
transition state D suffers from unfavorable steric inter-
action between substituents on the CꢀC bond and the
two carbonyl groups. As a result, transition state B is
the most favorable pathway, which led to the exclusive
formation of cyclization product 4e.
Lewis acid-catalyzed radical cyclization reactions of
chiral substrate 1f, which was synthesized following
Scheme 4 with chiral auxiliary (S)-(−)-4-benzyl-5,5-
dimethyl-2-oxazolidinone, also gave 4f as a single
diastereomer (Table 5). Reduction of 4f was followed
by hydrolysis and conversion to the amide 7 (Scheme
5). The absolute configuration of amide 7 was deter-
mined to be (1R,2R) by X-ray analysis (Fig. 4), thus the
absolute stereochemistry of 4f was determined to be
(1R,2R).
Entry
Lewis acid
(equiv.)
Solvent
Time
(h)
Yield
(%)b
1
2
3
Yb(OTf)3 (1.0)
Yb(OTf)3 (0.3)
Mg(ClO4)2 (1.0)
Et2O
Et2O
CH2Cl2
4
9
4
80
72
78
a Only one diastereomer was found in the crude 1H NMR (400 MHz).
b Isolated yield.
As shown in Figure 5 for the cyclization of substrate 1f,
transition states G and H in which the alkenyl group
approaches the a-radical from the front face are disfa-
vored because the sterically hindered benzyl group
blocks the front face of the oxazolidinone imide. In
transition state E, substituents on the olefin have steric
interactions with the two carbonyl groups. Therefore,
the Lewis acid-catalyzed radical cyclization of 1f should
proceed via the most favorable transition state F to
yield product 4f.
The s-cis conformation of the a-amide radical is pre-
ferred due to the A1,3 strain.5b,16 When the b-methyl
group is in the pseudo-axial position, it would clash
with the amide carbonyl group (transition states A and
C). Therefore, radical cyclization should be more favor-
able via transition states B and D with the pseudo-
equatorial orientation of the b-methyl group. However,
Scheme 5. Reagents and conditions: (a) Bu3SnH, Et3B/O2, benzene, rt, 12 h, 84%; (b) LiOH, H2O2, THF/H2O, rt, 12 h, 70%; (c)
HOAt, EDCI, (S)-(−)-a-(1-naphthyl)ethylamine, CH2Cl2, rt, 12 h, 82%.

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D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
Figure 4. X-Ray structure of amide 7.
Figure 5. Transition state model for the cyclization of substrate 1f.
3. Conclusion
and moisture-sensitive compounds were introduced via
syringe through a rubber septum. THF and Et2O were
distilled over sodium/benzophenone before use.
Dichloromethane and toluene were distilled over cal-
cium hydride. Flash column chromatography was per-
formed on E. Merck silica gel 60 (230–400 mesh
ASTM) using ethyl acetate/n-hexane as eluting
solvents.
In summary, we have developed a new Lewis acid-cata-
lyzed, highly diastereoselective atom transfer radical
cyclization method for the formation of cyclic com-
pounds.
A variety of cyclization products were
obtained in good to excellent yields and in a regio- and
stereoselective manner. In instances where the sub-
strates employed contained a defined stereogenic centre
or chiral oxazolidinone auxiliary, the corresponding
cyclization products were obtained in good yields (up
to 87%) and excellent diastereoselectivity (greater than
50:1 dr). The application of this method in asymmetric
synthesis of natural products is in progress.
Nuclear magnetic resonance spectra were recorded in
deuteriochloroform (CDCl3) unless otherwise indicated,
with tetramethylsilane (TMS) as internal standard at
ambient temperature on a Bruker Avance DPX 400
1
Transform Spectrometer operating at 400 MHz for H
NMR and 100 MHz for 13C NMR a Bruker Avance
DPX 300 Transform Spectrometer operating at 300
MHz for 1H NMR and 75 MHz for 13C NMR.
Infrared absorption spectra were recorded as a solution
in CH2Cl2 with a Bio-Rad FTS 165 Fourier Tranform
Spectrophotometer. Mass spectra were recorded with a
4. Experimental
4.1. General
All reactions were performed in oven-dried flasks. Air-

D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
2933
Finnigan MAT 95 mass spectrometer for both low-
resolution and high-resolution mass spectra. Melting
points were determined by Axiolab ZEISS microscope
apparatus and were uncorrected.
Hz, 2H), 2.04 (d, J=7.6 Hz, 2H), 1.66 (s, 3H), 1.67–
1.60 (m, 2H), 1.52–1.47 (m, 2H); 13C NMR (75 MHz,
CDCl3) l 173.6, 152.6, 145.7, 110.3, 62.3, 42.7, 37.5,
35.1, 27.2, 24.0, 22.5; IR (CH2Cl2) 2965, 1765, 1690
cm−1; LRMS (EI, 20 eV): m/z 211 (M+, 9), 142 (26), 129
(100); HRMS (EI) calcd for C11H17O3N (M+):
211.1208, found 211.1214.
Compounds 2b and 2e are commercially available from
Aldrich. Compounds 2a, 2c and 2d were prepared
following literature procedures.17,18
4.2.4. 3-(8-Methyl-non-7-enoyl)-oxazolidin-2-one 3d.
80% yield; colorless liquid; analytical TLC (silica gel
60), 25% EtOAc in n-hexane, Rf=0.20; H NMR (300
4.2. Typical procedure for the preparation of compounds
3a–f
1
MHz, CDCl3) l 5.12–5.07 (m, 1H), 4.41 (t, J=7.8 Hz,
2H), 4.03 (t, J=7.9 Hz, 2H), 2.92 (t, J=7.6 Hz, 2H),
1.98–1.96 (m, 2H), 1.71–1.60 (m, 2H), 1.68 (s, 3H), 1.60
(s, 3H), 1.41–1.33 (m, 4H); 13C NMR (75 MHz, CDCl3)
l 173.8, 153.8, 132.0, 124.7, 62.5, 42.8, 35.6, 29.6, 28.2,
26.3, 25.4, 24.4, 18.0; IR (CH2Cl2) 2945, 1790, 1697
cm−1; LRMS (EI, 20 eV): m/z 239 (M+, 45), 152 (100),
108 (80); HRMS (EI) calcd for C13H21O3N (M+):
239.1521, found 239.1518.
To a solution of 2a–f (10 mmol) in THF (10 mL) at 0°C
were successively added N-methyl morpholine (1.11
mL, 10 mmol) and isobutyl chloroformate (0.8 mL, 10
mmol). After 1 min, the precipitated N-methyl morpho-
line hydrochloride was removed by filtration and
washed with THF. The washings were combined in a
large flask and stored in an ice-salt bath for use in the
next step. Meanwhile, to a solution of 2-oxazolidinone
(0.87 g, 10 mmol) in THF (20 mL) under an argon
atmosphere at 0°C was added NaH (60%, 0.48 g, 12
mmol) in one portion. After stirring at 0°C for 0.5 h,
the washing solution was transferred into this reaction
mixture slowly. The reaction was then stirred at room
temperature for about 10 h, quenched with 1 mL of
saturated NH4Cl solution and extracted with EtOAc.
The extracts were dried over MgSO4, filtered and con-
centrated. The crude residue was purified by flash
column chromatography to afford 3a–f.
4.2.5. (R)-(+)-3-(3,7-Dimethyl-oct-6-enoyl)-oxazolidin-2-
one 3e. 82% yield; slight yellow liquid; Analytical TLC
(silica gel 60), 40% EtOAc in n-hexane, Rf=0.28;
[h]2D0=+0.75 (c 1.20, CH2Cl2); 1H NMR (300 MHz,
CDCl3) l 5.12–5.07 (m, 1H), 4.41 (t, J=7.8 Hz, 2H),
4.02 (t, J=7.9 Hz, 2H), 2.92 (dd, J=5.8, 16.2 Hz, 1H),
2.78 (dd, J=8.0, 16.2 Hz, 1H), 2.12–1.95 (m, 3H), 1.68
(s, 3H), 1.60 (s, 3H), 1.47–1.35 (m, 1H), 1.31–1.19 (m,
1H), 0.97 (d, J=6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3) l 172.9, 153.5, 131.4, 124.3, 61.9, 42.5, 42.0,
36.8, 29.3, 25.7, 25.4, 19.6, 17.6; IR (CH2Cl2) 2968,
2926, 1779, 1701 cm−1; LRMS (EI, 20 eV): m/z 239
(M+, 19), 152 (100), 109 (49), 88 (90); HRMS (EI) calcd
for C13H21O3N (M+): 239.1521, found 239.1519.
4.2.1. 3-(7-Methyl-oct-6-enoyl)-oxazolidin-2-one 3a. 65%
yield; colorless liquid; analytical TLC (silica gel 60),
25% EtOAc in n-hexane, Rf=0.20; 1H NMR (400
MHz, CDCl3) l 5.08 (tt, J=1.4, 6.8 Hz, 1H), 4.41 (t,
J=7.8 Hz, 2H), 4.02 (t, J=7.9 Hz, 2H), 2.92 (t, J=7.5
Hz, 2H), 2.02 (q, J=7.2 Hz, 2H), 1.71–1.60 (m, 2H),
1.69 (s, 3H), 1.60 (s, 3H), 1.41–1.30 (m, 2H); 13C NMR
(100 MHz, CDCl3) l 173.9, 153.9, 132.1, 124.6, 62.3,
42.9, 35.4, 29.6, 28.1, 26.1, 24.3, 18.0; IR (CH2Cl2)
2930, 1782, 1701 cm−1; LRMS (EI, 20 eV): m/z 225
(M+, 21) 138 (100), 129 (36); HRMS (EI) calcd for
C12H19O3N (M+): 225.1365, found 225.1367.
4.2.6. (S)-(−)-4-Benzyl-5,5-dimethyl-3-(7-methyl-oct-6-
enoyl)-oxazolidin-2-one 3f. 87% yield; slight yellow oil;
analytical TLC (silica gel 60), 25% EtOAc in n-hexane,
1
Rf=0.58; [h]2D0=−31.7 (c 1.0, CH2Cl2); H NMR (400
MHz, CDCl3) l 7.31–7.23 (m, 5H), 5.12–5.07 (tt, J=
1.3, 6.8 Hz, 1H), 4.52 (dd, J=4.0, 9.6 Hz, 1H), 3.16
(dd, J=4.0, 9.2 Hz, 1H), 2.92 (td, J=2.0, 7.5 Hz, 2H),
2.87 (dd, J=8.0, 14.0 Hz, 1H), 2.02 (q, J=8.0 Hz, 2H),
1.69 (s, 3H), 1.60 (s, 3H), 1.64–1.58 (m, 2H), 1.40–1.32
(m, 2H), 1.36 (s, 3H), 1.35 (s, 3H); 13C NMR (100
MHz, CDCl3) l 173.5, 152.6, 137.0, 131.6, 129.0, 128.6,
126.7, 124.2, 82.0, 63.5, 35.6, 35.4, 29.3, 28.5, 27.7, 25.7,
24.0, 22.2, 17.7; IR (CH2Cl2) 2934, 1774, 1699 cm−1;
LRMS (EI, 20 eV): m/z 343 (M+, 44), 300 (97), 206
(64), 145 (100); HRMS (EI) calcd for C21H29O3N (M+):
343.2147, found 343.2152.
4.2.2. 3-Hept-6-enoyl-oxazolidin-2-one 3b. 76% yield;
slight yellow liquid; analytical TLC (silica gel 60), 50%
EtOAc in n-hexane, Rf=0.39; 1H NMR (300 MHz,
CDCl3) l 5.87–5.74 (m, 1H), 5.04–4.93 (m, 2H), 4.42 (t,
J=8.0 Hz, 2H), 4.02 (t, J=8.1 Hz, 2H), 2.92 (t, J=7.1
Hz, 2H), 2.09 (q, J=7.1 Hz, 2H), 1.68 (quintet, J=7.4
Hz, 2H), 1.48 (quintet, J=7.6 Hz, 2H); 13C NMR (75
MHz, CDCl3) l 173.3, 153.5, 138.4, 114.6, 62.0, 42.5,
34.9, 33.4, 28.2, 23.6; IR (CH2Cl2) 2927, 1781, 1702
cm−1; 1043 LRMS (EI, 20 eV): m/z 197 (M+, 10), 142
(25), 129 (100), 88 (89); HRMS (EI) calcd for
C10H15O3N (M+): 197.1052, found 197.1043.
4.3. General procedure for the preparation of com-
pounds 1a–f
To a solution of 3a–f (1.0 mmol) in CH2Cl2 (10 mL) at
−78°C under an argon atmosphere was added triethyl-
amine (0.17 mL, 1.2 mmol) followed by dibutylboron
triflate (1 M in dichloromethane, 1.05 mL, 1.05 mmol).
The resulting yellow solution was stirred at −78°C for
15 min and then at 0°C for 1 h. The reaction was
cooled down to −78°C again, and N-bromosuccinimide
4.2.3. 3-(6-Methyl-hept-6-enoyl)-oxazolidin-2-one 3c.
74% yield; slight yellow liquid; analytical TLC (silica
1
gel 60), 25% EtOAc in n-hexane, Rf=0.28; H NMR
(300 MHz, CDCl3) l 4.69 (s, 1H), 4.67 (s, 1H), 4.40 (t,
J=7.5 Hz, 2H), 4.05 (t, J=7.8 Hz, 2H), 2.92 (d, J=7.5

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D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
(198 mg, 1.1 mmol) was added in portions. The result-
ing purple slurry was stirred at −78°C for 2 h and
quenched by pouring into a saturated solution of
ammonium chloride. The solution was extracted with
ethyl acetate, and the combined organic layers were
washed with 1 M sodium thiosulfate followed by brine.
The extracts were dried over anhydrous sodium sul-
phate and concentrated in vacuum. The residue was
purified by flash column chromatography to afford
1a–f.
4.3.5. (R)-(+)-3-(2-Bromo-3,7-dimethyl-oct-6-enoyl)-oxa-
zolidin-2-one 1e. 82% yield; slight yellow liquid. Analyt-
ical TLC (silica gel 60), 50% EtOAc in n-hexane,
Rf=0.51; 1H NMR (300 MHz, CDCl3) l 5.62 (d,
J=7.4 Hz, 1H), 5.09–5.04 (m, 1H), 4.53–4.41 (m, 2H),
4.15–4.04 (m, 2H), 2.19–1.96 (m, 3H), 1.68 (s, 3H), 1.60
(s, 3H), 1.49–1.37 (m, 1H), 1.34–1.20 (m, 1H), 1.11 (d,
J=6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) l 169.0,
152.7, 132.1, 123.6, 62.2, 51.6, 43.0, 35.6, 34.4, 25.7,
25.4, 17.6, 16.6; IR (CH2Cl2) 2971, 1783, 1706 cm−1;
LRMS (EI, 20 eV): m/z 319 (M+, 3), 317 (M+, 3), 238
(33), 149 (51), 111 (45), 69 (100); HRMS (EI) calcd for
C13H20O3NBr (M+): 317.0627, found 317.0573.
4.3.1. 3-(2-Bromo-7-methyl-oct-6-enoyl)-oxazolidin-2-one
1a. 78% yield; slight yellow oil; analytical TLC (silica
1
gel 60), 25% EtOAc in n-hexane, Rf=0.23; H NMR
(400 MHz, CDCl3) l 5.61 (t, J=7.2 Hz, 1H), 5.09 (tt,
J=1.4, 6.8 Hz, 1H), 4.48–4.44 (m, 2H), 4.13–4.07 (m,
2H), 2.17–2.00 (m, 4H), 1.68 (s, 3H), 1.60 (s, 3H),
1.52–1.38 (m, 2H); 13C NMR (100 MHz, CDCl3) l
169.2, 152.7, 132.0, 123.9, 62.2, 52.0, 43.0, 35.5, 28.0,
26.2, 24.3, 18.0; IR (CH2Cl2) 2940, 1786, 1719 cm−1;
LRMS (EI, 20 eV): m/z 305 (M+, 3), 303 (M+, 3), 224
(M+−Br, 18), 142 (40), 136 (100); HRMS (EI) calcd for
C12H18O3NBr (M+): 303.0470, found 303.0454.
4.3.6.
(S)-(−)-4-Benzyl-3-(2-bromo-7-methyl-oct-6-
enoyl)-5,5-dimethyl-oxazolidin-2-one 1f. 90% yield; slight
yellow oil; analytical TLC (silica gel 60), 25% EtOAc in
n-hexane, Rf=0.60; 1H NMR (400 MHz, CDCl3) l
7.31–7.23 (m, 5H), 5.65 (t, J=7.2 Hz, 1H), 5.08 (tt,
J=1.3, 6.9 Hz, 1H), 4.52 (dd, J=3.3, 8.6 Hz, 1H), 3.20
(dd, J=3.3, 8.9 Hz, 1H), 2.88 (dd, J=10.0, 15.5 Hz,
1H), 2.09–1.95 (m, 4H), 1.70 (s, 3H), 1.60 (s, 3H),
1.55–1.40 (m, 2H), 1.38 (s, 3H), 1.34 (s, 3H); 13C NMR
(100 MHz, CDCl3) l 169.6, 151.6, 137.0, 132.8, 129.4,
129.1, 127.2, 123.9, 82.8, 64.3, 44.8, 34.2, 33.4, 28.6,
27.5, 26.9, 25.7, 22.4, 17.7; IR (CH2Cl2) 2940, 1774,
1701 cm−1; LRMS (EI, 20 eV): m/z 423 (M+, 3), 421
(M+, 3), 342 (M+−Br, 46), 260 (46), 136 (100); HRMS
(EI) calcd for C21H28O3NBr (M+): 421.1253, found
421.1253.
4.3.2. 3-(2-Bromo-hept-6-enoyl)-oxazolidin-2-one 1b.
62% yield; slight yellow liquid; analytical TLC (silica
1
gel 60), 50% EtOAc in n-hexane, Rf=0.52; H NMR
(300 MHz, CDCl3) l 5.85–5.71 (m, 1H), 5.61 (dd,
J=6.7, 7.9 Hz, 1H), 5.07–4.96 (m, 2H), 4.50–4.45 (m,
2H), 4.13–4.06 (m, 2H), 2.17–2.00 (m, 4H), 1.66–1.45
(m, 2H); 13C NMR (75 MHz, CDCl3) l 169.2, 152.5,
137.6, 115.3, 62.1, 43.3, 42.8, 33.2, 32.8, 26.3; IR
(CH2Cl2) 2971, 1783, 1706 cm−1; LRMS (EI, 20 eV):
m/z 196 (M+−Br, 39) 150 (7), 109 (100); HRMS (EI)
calcd for C10H14O3N (M+−Br): 196.0970, found
196.0974.
4.4. Typical procedures for atom transfer cyclization of
substrates 1a–f
To a solution of 1a–f (0.25 mmol) in a dry solvent (10
mL) at room temperature was added Lewis acid (0.3–1
equiv.) in one portion under an argon atmosphere.
After the mixture was stirred for 0.5 h at room temper-
ature, it was cooled down to 0°C. After 15 min, Et3B (1
M in n-hexane, 0.50 mL, 0.50 mmol) was added fol-
lowed by oxygen gas (2.5 mL) via a syringe. The
reaction was monitored by TLC. On completion, the
mixture was diluted with diethyl ether, and washed with
water. The organic layer was dried over MgSO4, filtered
and concentrated. The crude residue was purified by
flash column chromatography (35% EtOAc in n-hex-
ane) to afford product 4a–f.
4.3.3. 3-(2-Bromo-6-methyl-hept-6-enoyl)-oxazolidin-2-
one 1c. 82% yield; yellow liquid; analytical TLC (silica
1
gel 60), 25% EtOAc in n-hexane, Rf=0.30; H NMR
(300 MHz, CDCl3) l 5.62 (dt, J=6.6 Hz, 1H), 4.73 (s,
1H), 4.68 (s, 1H), 4.45 (t, J=8.0 Hz, 2H), 4.07 (t,
J=7.5 Hz, 2H), 2.09–2.03 (m, 4H), 1.71 (s, 3H), 1.56–
1.49 (m, 2H); 13C NMR (75 MHz, CDCl3) l 169.6,
152.9, 145.0. 111.0, 62.4, 43.7, 43.2, 37.2, 33.7, 25.8,
22.5; IR (CH2Cl2) 2950, 1770, 1685 cm−1; LRMS (EI,
20 eV): m/z 209 (M+−Br, 28), 142 (76), 122 (80); HRMS
(EI) calcd for C11H16O3N (M+−Br): 210.1130, found
210.1114.
4.4.1.
3-[2-(1-Bromo-1-methyl-ethyl)-cyclopentanecar-
4.3.4.
3-(2-Bromo-8-methyl-non-7-enoyl)-oxazolidin-2-
bonyl]-oxazolidin-2-one 4a. 78% yield; slight yellow oil;
analytical TLC (silica gel 60), 25% EtOAc in n-hexane,
Rf=0.21; 1H NMR (400 MHz, CDCl3) l 4.41 (t, J=8.2
Hz, 2H), 4.17–4.11 (m, 1H), 4.03 (t, J=8.0 Hz, 2H),
2.88 (q, J=8.1 Hz, 1H), 2.22–2.15 (m, 1H), 2.00–1.93
(m, 1H), 1.80–1.70 (m, 1H), 1.74 (s, 3H), 1.69 (s, 3H),
1.69–1.62 (m, 3H); 13C NMR (100 MHz, CDCl3) l
177.1, 153.5, 72.4, 62.1, 55.5, 46.5, 43.4, 34.3, 33.6, 32.5,
30.9, 26.5; IR (CH2Cl2) 2966, 1765, 1696 cm−1; LRMS
(EI, 20 eV): m/z 223 (M+−Br, 19), 139 (57), 136 (100);
HRMS (EI) calcd for C12H18O3N (M+−Br): 223.1219,
found 223.1208.
one 1d. 86% yield; slight yellow oil; analytical TLC
1
(silica gel 60), 25% EtOAc in n-hexane, Rf=0.23; H
NMR (300 MHz, CDCl3) l 5.61 (t, J=7.2 Hz, 1H),
5.08 (tt, J=1.4, 6.8 Hz, 1H), 4.48–4.45 (m, 2H), 4.14–
4.08 (m, 2H), 2.06–1.97 (m, 4H), 1.68 (s, 3H), 1.60 (s,
3H), 1.49–1.33 (m, 4H); 13C NMR (75 MHz, CDCl3) l
169.2, 152.7, 132.0, 123.9, 62.3, 52.0, 43.0, 35.6, 28.2,
26.0, 25.4, 24.4, 18.1; IR (CH2Cl2) 2940, 1786, 1719
cm−1; LRMS (EI, 20 eV): m/z 238 (M+−Br, 26), 152
(100), 108 (76); HRMS (EI) calcd for C13H20O3N (M+−
Br): 238.1439, found 238.1436.

D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
2935
4.4.2. 3-(2-Bromomethyl-cyclopentanecarbonyl)-oxazo-
lidin-2-one 4b. 48% yield; slight yellow oil; analytical
TLC (silica gel 60), 50% EtOAc in n-hexane, Rf=0.39;
1H NMR (300 MHz, CDCl3) l 4.42 (t, J=8.3 Hz, 2H),
4.08–4.01 (m, 2H), 3.81 (q, J=7.9 Hz, 1H), 3.48–3.42
(m, 2H), 2.90–2.85 (m, 1H), 2.25–2.20 (m, 1H), 2.03–
28.5, 18.5; IR (CH2Cl2) 2963, 2929, 1780, 1693 cm−1;
LRMS (EI, 20 eV): m/z 319 (M+, 8), 317 (M+, 8), 238
(34), 109 (99), 69 (100); HRMS (EI) calcd for
C13H20O3NBr (M+): 317.0627, found 317.0578.
4.4.7. (4S)-Benzyl-(3R)-[(2R)-(1-bromo-1-methyl-ethyl)-
cyclopentanecarbonyl]-5,5-dimethyl-oxazolidin-2-one 4f.
80% yield; slight yellow oil; analytical TLC (silica gel
60), 25% EtOAc in n-hexane, Rf=0.58; [h]2D0=+86.8 (c
1.98 (m, 1H), 1.80–1.70 (m, 3H), 1.55–1.47 (m, 1H); 13
C
NMR (75 MHz, CDCl3) l 175.5, 153.3, 61.9, 47.8, 45.1,
42.9, 37.4, 31.7, 31.6, 24.8; IR (CH2Cl2) 2948, 1782,
1699 cm−1; LRMS (EI, 20 eV): m/z 277 (M+, 2), 275
(M+, 2), 196 (100), 195 (51), 109 (64); HRMS (EI) calcd
for C10H14O3NBr (M+): 275.0157, found 275.0155.
1
1.0, CH2Cl2); H NMR (400 MHz, CDCl3) l 7.30–7.23
(m, 4H), 7.22–7.18 (m, 1H), 4.52 (dd, J=3.3, 10.4 Hz,
1H), 4.24–4.18 (m, 1H), 3.17 (dd, J=3.2, 10.4 Hz, 1H),
2.88–2.82 (m, 2H), 2.22–2.16 (m, 1H), 2.02–1.95 (m,
1H), 1.82–1.76 (m, 1H), 1.74 (s, 3H), 1.67 (s, 3H),
1.70–1.61 (m, 3H), 1.35 (s, 3H), 1.34 (s, 3H); 13C NMR
(100 MHz, CDCl3) l 177.0, 152.3, 137.2, 129.0, 128.7,
126.8, 81.9, 72.0, 64.0, 55.2, 46.6, 35.1, 33.9, 33.5, 32.3,
30.7, 28.7, 26.3, 22.4; IR (CH2Cl2) 2972, 1773, 1696
cm−1; LRMS (EI, 20 eV): m/z 423 (M+, 1), 421 (M+, 1),
342 (15), 298 (10), 136 (100); HRMS (EI) calcd for
C21H28O3NBr (M+): 421.1253, found 421.1254.
4.4.3. 3-(3-Bromo-cyclohexanecarbonyl)-oxazolidin-2-one
4b%. 28% yield; slight yellow oil; analytical TLC (silica
1
gel 60), 50% EtOAc in n-hexane, Rf=0.43; H NMR
(300 MHz, CDCl3) l 4.42 (t, J=8.1 Hz, 2H), 4.16–3.97
(m, 3H), 3.32 (quintet, J=3.7 Hz, 1H), 2.16 (q, J=4.6
Hz, 2H), 2.07–1.81 (m, 4H), 1.70–1.63 (m, 1H), 1.54–
1.42 (m, 1H); 13C NMR (75 MHz, CDCl3) l 175.7,
152.9, 62.0, 51.9, 42.7, 37.7, 36.5, 34.6, 28.7, 20.8; IR
(CH2Cl2) 2965, 1780, 1698 cm−1; LRMS (EI, 20 eV):
m/z 277 (M+, 0.6), 275 (M+, 0.6), 196 (44), 195 (22), 109
(100); HRMS (EI) calcd for C10H14O3NBr (M+):
275.0157, found 275.0152.
4.5. (4S)-Benzyl-(3R)-[(2S)-isopropyl-cyclopentanecar-
bonyl]-5,5-dimethyl-oxazolidin-2-one 5
To a solution of compound 4f (40 mg, 0.095 mmol) in
dry benzene (6 ml) was added Bu3SnH (55 mg, 0.190
mmol) at room temperature. Et3B (1 M in n-hexane,
0.20 mL, 0.20 mmol) was then added followed by
oxygen gas (2.5 mL) via a syringe. The mixture was
stirred at room temperature overnight. After removal
of benzene, the residue was diluted with Et2O. Then
1,8-diazabicyclo[5,4,0]undec-7-ene (DBU, 40.7 mg) was
added, which resulted in the formation of a white
precipitate. A solution of iodine in ether was added
slowly to the stirred mixture until the yellow color of
iodine persisted. The mixture was then filtered through
a thin pad of silica gel and eluted with ether. After
concentration, the residue was purified by flash column
chromatography to give 5 (28 mg, 84% yield) as a
colorless oil; analytical TLC (silica gel 60), 25% EtOAc
4.4.4. 3-(3-Bromo-3-methyl-cyclohexanecarbonyl)-oxazo-
lidin-2-one 4c. 85% yield; slight yellow oil; analytical
TLC (silica gel 60), 25% EtOAc in n-hexane, Rf=0.23;
1H NMR (300 MHz, CDCl3) l 4.43 (t, J=8.1 Hz, 2H),
4.07–3.97 (m, 3H), 2.32–2.24 (m, 1H), 2.24–2.10 (m,
2H), 2.06–1.95 (m, 1H), 1.87 (s, 3H), 1.72–1.64 (m, 2H),
1.42–1.22 (m, 2H); 13C NMR (100 MHz, CDCl3) l
176.2, 153.2, 69.1, 62.2, 44.1, 43.1, 42.3, 39.9, 36.3, 28.9,
23.0; IR (CH2Cl2) 3032, 2939, 1768 cm−1; LRMS (EI,
20 eV): m/z 210 (M+−Br, 6), 122 (100); HRMS (EI)
calcd for C11H16O3N (M+−Br): 210.1130, found
210.1118.
4.4.5. 3-(2-Isopropyl-cyclohexanecarbonyl)-oxazolidin-2-
one 4d. 68% yield; slight yellow oil; analytical TLC
1
1
(silica gel 60), 25% EtOAc in n-hexane, Rf=0.25; H
in n-hexane, Rf=0.56; [h]2D0=+111 (c 0.8, CH2Cl2); H
NMR (300 MHz, CDCl3) l 4.43 (t, J=3.3 Hz, 2H),
4.05 (t, J=7.0 Hz, 2H), 3.78–3.70 (m, 1H), 1.98–1.93
(m, 1H), 1.87–1.68 (m, 3H), 1.63–1.52 (m, 1H), 1.49–
1.22 (m, 4H), 1.18–1.04 (m, 1H), 0.88 (d, J=6.9 Hz,
3H), 0.80 (d, J=6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) l 176.8, 151.7, 61.7, 44.6, 44.1, 42.7, 31.2, 29.6,
25.9, 25.3, 23.9, 21.3, 16.3; IR (CH2Cl2) 2972, 1773,
1696 cm−1; LRMS (EI, 20 eV): m/z 239 (M+, 47), 196
(76), 152 (100); HRMS (EI) calcd for C13H21O3N (M+):
239.1521, found 239.1518.
NMR (400 MHz, CDCl3) l 7.31–7.23 (m, 5H), 4.52
(dd, J=3.3, 10.0 Hz, 1H), 3.84–3.77 (m, 1H), 3.16 (dd,
J=3.4, 12.0 Hz, 1H), 2.85 (dd, J=10.0, 14.4 Hz, 1H),
2.28–2.24 (m, 1H), 2.15–2.10 (m, 1H), 1.92–1.88 (m,
1H), 1.70–1.58 (m, 3H), 1.53–1.48 (m, 1H), 1.35 (s, 3H),
1.33 (s, 3H), 1.35–1.29 (m, 1H), 0.89 (d, J=6.8 Hz,
3H), 0.83 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) l 177.7, 152.5, 137.2, 129.0, 128.6, 126.7, 81.7,
63.9, 50.1, 46.7, 35.2, 32.5, 32.3, 30.7, 28.6, 25.7, 22.3,
21.8, 20.7; IR (CH2Cl2) 3050, 2988, 1772, 1695 cm−1;
LRMS (EI, 20 eV): m/z 343 (M+, 14), 300 (19), 252
(32), 139 (100); HRMS (EI) calcd for C21H29O3N (M+):
343.2147, found 343.2148.
4.4.6. (3R)-[(2S)-(1-Bromo-1-methyl-ethyl)-(5R)-methyl-
cyclopentanecarbonyl]-oxazolidin-2-one 4e. 87% yield;
slight yellow oil; Analytical TLC (silica gel 60), 40%
EtOAc in n-hexane, Rf=0.37; [h]2D0=+10.2 (c 1.0,
4.6. (1R,2S)-2-Isopropyl-cyclopentanecarboxylic acid 6
1
CH2Cl2); H NMR (300 MHz, CDCl3) l 4.41 (t, J=7.6
Hz, 2H), 4.13–3.98 (m, 3H), 2.99–2.91 (m, 1H), 2.23–
2.13 (m, 1H), 2.03–1.83 (m, 2H), 1.74 (s, 3H), 1.71 (s,
3H), 1.79–1.64 (m, 1H), 1.50–1.37 (m, 1H), 1.09 (d,
J=16.8 Hz, 3H); 13C NMR (125 MHz, CDCl3) l 177.2,
153.3, 71.5, 61.7, 57.9, 51.8, 43.3, 43.2, 34.7, 33.6, 31.3,
In a 10 mL round-bottom flask, compound 5 (110 mg,
0.32 mmol) and 4:1 tetrahydrofuran/H2O 5 mL were
mixed and cooled to 0°C. To this solution was added
H2O2 (30%, 0.2 mL) and the mixture was stirred for 5
min, followed by addition of a solution of LiOH·H2O

2936
D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
(20 mg) in water (7.5 mL). The mixture was stirred for
30 min at 0°C and for 4 h at room temperature. The
excess amounts of peroxides were quenched with a
solution of sodium sulfite in water (1.1 g in 5 mL).
Hydrolyzed auxiliary was removed by bringing up the
solution in NaOH (25 mL, 0.25 M) and washing with
dichloromethane. The desired acid was isolated by acid-
ifying with 2N HCl and extracting with ethyl acetate. The
extracts were dried with anhydrous magnesium sulfate,
filtered, and concentrated. The residue was purified by
flash column chromatography to give compound 6 (32
mg, 70% yield). Analytical TLC (silica gel 60), 25%
EtOAc in n-hexane, Rf=0.23; [h]2D0=+3.3 (c 0.4,
CH2Cl2); 1H NMR (400 MHz, CDCl3) l 2.48 (q, J=8.4,
16.0 Hz, 1H), 2.09–2.01 (m, 1H), 1.95–1.80 (m, 3H),
1.69–1.56 (m, 3H), 1.35–1.28 (m, 1H), 0.93 (d, J=6.8 Hz,
3H), 0.87 (d, J=8.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) l 183.5, 50.9, 47.7, 32.1, 31.6, 30.0, 25.6, 21.3,
20.0; IR (CH2Cl2) 3458, 2970, 1700 cm−1; LRMS (EI, 20
eV): m/z 138 (M+−H2O, 19), 125 (17), 113 (100); HRMS
(EI) calcd for C9H14O (M+−H2O): 138.1044, found
138.1040.
References
1. (a) Curran, D. P. In Comprehensive Organic Synthesis;
Trost, B. M., Flemming, I., Eds.; Pergamon: Oxford,
1991; Vol. 4, Chapter 4.2; (b) Radicals in Organic Syn-
thesis, Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, 2001, Vol. 2.
2. For a review on free radical reactions in the synthesis
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4.7. (1R,2S)-2-Isopropyl-cyclopentanecarboxylic acid
[(1%S)-naphthalen-2%-yl-ethyl]-amide 7
To a solution of compound 6 (26 mg, 0.20 mmol) in
CH2Cl2 was added HOAt (1-hydroxy-7-azabenzotria-
zole) (41 mg, 0.30 mmol) and (S)-(−)-a-(1-naph-
thyl)ethylamine (39 mL, 0.24 mmol) at room temperature.
After the solution was clear, EDCI (1-[3-(dimethyl
amino)propyl]-3-ethylcarbodiimide methiodide) (119
mg, 0.40 mmol) was added and the solution was stirred
overnight. The solution mixture was diluted with
CH2Cl2, washed with 5% aqueous NaHCO3, followed
with brine. The organic layer was dried over anhydrous
magnesium sulfate and concentrated. The residue was
purified by flash column chromatography to give com-
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pound
7
(66 mg, 84%). Mp 197°C; [h]2D0=
−13.2 (c 0.5, CH2Cl2); analytical TLC (silica gel 60), 25%
EtOAc in n-hexane, Rf=0.40; 1H NMR (600 MHz,
CDCl3) l 8.08 (d, J=8.4 Hz, 1H), 7.87–7.70 (m, 2H),
7.54–7.44 (m, 4H), 5.93–5.89 (m, 1H), 5.62 (d, J=7.8 Hz,
1H), 2.16–2.09 (m, 2H), 1.87–1.82 (m, 1H), 1.78–1.74 (m,
2H), 1.73–1.68 (m, 1H), 1.66 (d, J=6.8 Hz, 3H), 1.54–
1.50 (m, 1H), 1.25–1.20 (m, 2H), 0.90 (d, J=7.4 Hz, 3H),
0.88 (d, J=7.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
l 175.6, 138.4, 134.0, 131.3, 128.7, 128.4, 126.5, 125.9,
125.1, 123.7, 122.6, 50.5, 50.4, 44.4, 32.3, 32.2, 30.1, 29.7,
25.5, 21.5, 20.3; IR (CH2Cl2) 3446, 2988, 1733 cm−1;
LRMS (EI, 20 eV): m/z 309 (M+, 100), 294 (15), 266 (11),
171 (16), 155 (66); HRMS (EI) calcd for C21H27ON (M+):
309.2092, found 309.2090.
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122, 8873–8879.
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Yang, D.; Gu, S.; Yan, Y.-L.; Zhao, H.-W.; Zhu, N.-
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Acknowledgements
This work was supported by The University of Hong
Kong and the Hong Kong Research Grants Council.
D.Y. acknowledges the Bristol-Myers Squibb Founda-
tion for an Unrestricted Grant in Synthetic Organic
Chemistry and the Croucher Foundation for a Croucher
Senior Research Fellowship.

D. Yang et al. / Tetrahedron: Asymmetry 14 (2003) 2927–2937
2937
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