Asymmetric synthesis of β-amino acid and amide derivatives by catalytic conjugate addition of aromatic amines to N-alkenoylcarbamates

Article abstract of DOI:10.1002/ejoc.200300740

We report a highly active palladium catalyst for the enantioselective conjugate addition of primary aromatic amines to N-alkenoylcarbamates, furnishing β-amino N-Boc-amides in extremely high yields (>99%) and unprecedented optical purity (>99% ee) with just 2 mol % catalyst loading. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300740

SHORT COMMUNICATION
Asymmetric Synthesis of β-Amino Acid and Amide Derivatives by Catalytic
Conjugate Addition of Aromatic Amines to N-Alkenoylcarbamates
Kelin Li,[a] Xiaohui Cheng,[b] and King Kuok (Mimi) Hii*[c]
Keywords: Asymmetric catalysis / Αmino acids / Enantioselectivity / Hydroamination / Palladium
We report a highly active palladium catalyst for the enantio-
selective conjugate addition of primary aromatic amines to
N-alkenoylcarbamates, furnishing β-amino N-Boc-amides in
extremely high yields (Ͼ99 %) and unprecedented optical
purity (Ͼ99 % ee) with just 2 mol % catalyst loading.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
ceeded to examine other activated α,β-unsaturated com-
pounds as potential substrates. In this paper, we report that
Very few catalysts can facilitate the addition of NϪH to the conjugate addition of primary aromatic amines to N-
double bonds (known as hydroamination, or the aza- alkenoylcarbamates 2, catalysed by 2Ϫ5 mol % of complex
Michael addition reaction) with high enantioselectivity.[1] 1, furnishes β-amino N-Boc-amides 3, precursors to
To date, only three late transition metal catalysts are known β-amino acid and amide derivatives, with some enantio-
to result in ee values of greater than 90 %. The first example meric excesses greater than 99 % (Scheme 1, Table 1) Ϫ the
(described by Togni) was a (diphosphane)iridium/fluoride highest recorded so far in conjugate additions of this kind.
system, which promoted the addition of aniline to norbor-
nene (24 % yield, 91 % ee).[2] More recently, the palladium-
catalysed addition of primary aromatic amines to 1,3-di-
enes[3] (up to 95 % ee) and the nickel-catalysed addition of
secondary aromatic amines to N-alkenoyloxazolidinones[4]
(up to 90 % ee) have been reported by Hartwig and
Jørgensen, respectively. In these cases, catalyst loadings of
5 mol % were employed at room temperature, but reaction
times between 40 h and 5 days were required to achieve sig-
nificant yields.
Results and Discussion
Recently, we reported the enantioselective addition of
primary and secondary aromatic amines to N-alkenoylox-
Scheme 1. Conjugate addition of anilines to tert-butyl N-alkenoyl-
carbamates
azolidinones, catalysed by the cationic palladium complex
[(R-BINAP)Pd(solvent)2]2ϩ[TfO]Ϫ 1, with enantiomeric
2
excesses up to 93 %.[5] Encouraged by these results, we pro-
Initially, the addition of aniline to tert-butyl N-butenoyl-
carbamate 2a was examined. Using 5 mol % of complex 1
as the catalyst, reactions proceeded cleanly to furnish prod-
uct 3a quantitatively and with high enantiomeric excess (97
% ee, Entry 1) after 18 h at room temperature in toluene.
The rate of the reaction was retarded (and a slight loss of
ee observed) when dichloromethane was employed as the
solvent (Entry 2), presumably due to competitive coordi-
nation of the solvent to the cationic metal centre. More sig-
[a]
Department of Chemistry, King’s College London,
Strand, London WC2R 2LS, United Kingdom
[b]
Institute of Polymer Chemistry, Nankai University,
Tianjin, 300071, P. R. China
[c]
Department of Chemistry, Imperial College London,
South Kensington, London SW7 2AZ, United Kingdom
Fax: (internat.) ϩ 44-20-7594-5804
E-mail: mimi.hii@imperial.ac.uk
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2004, 959Ϫ964
DOI: 10.1002/ejoc.200300740
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
959

K. Li, X. Cheng, K. K. M. Hii
SHORT COMMUNICATION
Table 1. Addition of arylamines to N-alkenoylcarbamates; unless
otherwise indicated, reactions were performed using 1 equiv. of am-
ine and 1.5 equiv. of carbamate ester in toluene at 25 °C
Entry
R
Y
Product [Pd]/mol % T/h Yield/%[a] ee/%[b]
1
2
3
4
5
6
7
8
Me
Me
Me
Me Cl
Me Cl
Me Me
Me OMe
Et
Et Cl
Et Me
Et OMe
H
H
H
3a
3a
3a
3b
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
5
5
2
5
2
5
5
5
5
5
5
5
5
5
5
18 Ͼ99
40 94
40 Ͼ99
18 Ͼ99
18 Ͼ99
97
94[c]
92
Ͼ99
Ͼ99
92
73
90
18
40
72
72
120
93
99
98
92
94
H
9
85
10
11
12
13
14
15
Ϫ[d]
72 Ͼ99
16
89
89
80
17
nPr
nPr Cl
nPr Me
nPr OMe
H
120
98
90
83
82
120
120
120
Figure 1. Rate of catalysed addition of p-chloroaniline (diamonds),
aniline (squares) and p-anisidine (triangles) to 2a (monitored using
1H NMR spectroscopy)
[a]
Isolated yield following column chromatography. [b] Determined
[c]
[d]
by chiral HPLC.
tically active).
In CH2Cl2.
Unresolved (but sample is op-
nificantly, quantitative conversions could be obtained
within 40 h when the catalytic loading was reduced to 2
mol %, with only a slight erosion in the stereoselectivity
(Entry 3).
sition metalcatalysed system. Concurrently, the enantiom-
eric excess of the product was monitored by chiral HPLC,
which showed that enantioselectivity was established at the
onset and remained constant throughout the course of the
reaction.
Homologation of the β-substituent to N-pentenoyl- and
hexenoylcarbamates (2b and 2c) reduced the rate of the
conjugate addition (Entries 8Ϫ15). The unusually long time
required for the reaction of p-toluidine to 2b (Entry 10),
compared with other amines (Entries 8, 9 and 11), is also
an interesting feature, and suggests the possibility of com-
petitive rate-determining steps. Nevertheless, good to excel-
lent conversions and yields were obtained, and the enanti-
oselectivity was high in most cases, except for the reactions
of p-anisidine, which proceeded with low selectivity (Entries
11 and 15).
Examining other para-substituted anilines, we observed
that the rate and enantioselectivity of the reactions are sen-
sitive to the electronic characteristics of the aromatic amine.
Remarkably, the reaction of p-chloroaniline with 2a pro-
ceeded with perfect enantioselectivity (Ͼ99 % ee, Entry 4);
it also showed the highest turnover. In this case, the catalyst
loading could be reduced to 2 mol % without affecting
either the yield or selectivity (Entry 5). Conversely, electron-
donating substituents on the aromatic ring suppressed the
enantioselectivity of the process. Whilst the reaction of p-
toluidine proceeded with a yield and ee value similar to that
of aniline (Entry 6), the reaction of electron-rich p-anisidine
displayed the same number of turnovers, but only after
40 h, with a moderate ee of 73 % (Entry 7).
Previously, the addition of nitrogen nucleophiles to acti-
vated olefins, such as N-alkenoyloxazolidinones, was
thought to proceed by a Lewis acidpromoted process,[4,5]
in which attack of the weak nucleophile is facilitated by
chelation of the oxazolidinone functionality to a cationic
metal centre. Therefore, we were rather astonished to find
that the relative rates of addition of amines to the N-alk-
enoylcarbamate 2a increased in the order p-anisidine Ͻ ani-
line Ͻ p-chloroaniline (Figure 1), i.e. the least nucleophilic
amine is, in fact, the most reactive. What we have observed
in the present system clearly contradicts the earlier hypo-
thesis, thus indicating the operation of either a competitive
rate-determining step, or an entirely different reaction
mechanism.
The bulky NHBoc group appeared to play no part in the
outcome of the reaction, as shown by the addition of ani-
line to the methyl carbamate 4 (Scheme 2), which also pro-
ceeded in high yield (95 %) and enantioselectivity (92 % ee).
Scheme 2. Conjugate addition of aniline to to N-butenoyl-methyl-
carbamate
With a 5 mol % catalyst loading, the reaction of p-chlo-
The NHBoc functionality may be easily transformed un-
roaniline was essentially complete within five hours. Corre- der mild basic or acidic conditions to afford valuable op-
sponding to a turnover rate of 4 hϪ1, this is not only the tically active β-amino acid or amide derivatives. Hence, 3a
most selective, but also, by far, the most active late tran- was converted quantitatively into the corresponding β-am-
960
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 959Ϫ964

Asymmetric Synthesis of β-Amino Acid and Amide Derivatives
SHORT COMMUNICATION
in THF (20 mL) at Ϫ78 °C in the following quantities: (nBuLi, 2-
butenoyl chloride) (5.34, 0.41), (2.67, 0.21), (1.34, 0.10), (0.67, 0.05)
and (0.34, 0.03) mL. Stirring was continued for 30 min, the reaction
mixture poured into an ice-cooled solution of saturated aq.
NaHCO3 (50 mL) and extracted with EtOAc. The combined or-
ganic layers were washed with brine, dried over MgSO4, and the
solvents evaporated. The crude product was purified by flash chro-
matography (Et2O/pet. ether, 1:3).
Scheme 3. Conversions to β-amino acid and amide
tert-Butyl (E)-But-2-enoylcarbamate (2a): White solid (1.28 g, 81
1
%). Rf ϭ 0.4 (Et2O/pet. ether, 1:3). M.p. 138Ϫ139 °C. H NMR:
ino acid 6 and the β-amino amide 7 (Scheme 3). N-Aryl-β-
amino acids have been prepared previously by Pd/Cu-cata-
lysed aryl amination of β-amino acids with aryl halides.[6,7]
The absolute stereochemistry of 6 (and therefore 7) was
thus established to be (S), by comparison of its optical ro-
tation with the literature value.[8]
δ ϭ 1.49 (s, 9 H, tBu), 1.92 (dd, 1 H, CH3CH, 2JH,H ϭ 6.8, 3JH,H ϭ
2
3
1.5 Hz), 6.82 (dd, 1 H, COCH, JH,H ϭ 15.2, JH,H ϭ 1.5 Hz),
7.05Ϫ7.15 (m, 1 H, CH3CH), 7.31 (br. s, 1 H, NH) ppm. 13C NMR:
δ ϭ 15.9 (CH3CH), 27.9 [C(CH3)3], 82.3 [C(CH3)3], 121.2 (COCH),
145.5 (CH3CH), 150.5 (CO2), 166.3 (COCH) ppm. m/z (HR-
ESMS): calcd. 185.1052 [Mϩ]; found 185.1046. C9H15NO3: calcd.
C 58.36, H 8.16, N 7.56; found C 58.08, H 8.05, N 7.63.
Conclusion
tert-Butyl (E)-Pent-2-enoylcarbamate (2b): White solid (1.19 g, 70
%). Rf ϭ 0.4 (Et2O/pet. ether, 1:3). M.p. 78Ϫ79 °C. 1H NMR: δ ϭ
In summary, we have demonstrated that the cationic pal-
ladium() complex 1 catalyses the addition of primary aro-
matic amines to N-alkenoylcarbamates under mild con-
ditions with unprecedentedly high turnovers and enantiose-
lectivities. The products can easily be converted into op-
tically active β-amino acid or amide derivatives, providing
a novel and facile way to synthesise these valuable com-
pounds.[9,10] The reactivity of the present system precludes
an outright Lewis acid mechanism. This will be examined
in our future work.
2
1.09 (t, 3 H, CH3CH2, JH,H ϭ 7.4 Hz), 1.47 (s, 9 H, tBu),
2
2.23Ϫ2.31 (m, 2 H, CH3CH2), 6.79 (d, 1 H, COCH, JH,H
ϭ
15.6 Hz), 7.11Ϫ7.19 (m, 1 H, CH2CH), 7.31 (br. s, 1 H, NH) ppm.
13C NMR: δ ϭ 12.1 (CH3CH2), 25.7 (CH3CH2), 28.0 [C(CH3)3],
82.4 [C(CH3)3], 120.7 (COCH), 150.5 (CH3CH), 152.1 (CO2), 166.3
(COCH) ppm. m/z (HR-ESMS): calcd. 199.1208 [Mϩ]; found
199.1203. C10H17NO3: calcd. C 60.28, H 8.60, N 7.03; found C
60.42, H 8.75, N 6.85.
tert-Butyl (E)-Hex-2-enoylcarbamate (2c): White solid (1.46 g, 80
%). Rf ϭ 0.4 (Et2O/pet. ether, 1:3). M.p. 71Ϫ72 °C. 1H NMR: δ ϭ
2
0.93 (t, 3 H, CH3CH2, JH,H ϭ 7.3 Hz), 1.45Ϫ1.55 (m, 2 H,
CH3CH2), 1.49 (s, 9 H, tBu), 2.20Ϫ2.26 (m, 2 H, CH3CH2CH2),
6.79 (d, 1 H, COCH, JH,H ϭ 15.4 Hz), 7.06Ϫ7.14 (m, 1 H,
2
Experimental Section
CH2CH), 7.36 (br. s, 1 H, NH) ppm. 13C NMR: δ ϭ 13.7
(CH3CH2), 21.3 (CH3CH2), 28.0 [C(CH3)3], 34.6 (CH2CH), 82.4
121.6 (COCH), 150.5 (CH3CH), 150.7 (CO2), 166.2 (COCH) ppm.
m/z (HR-ESMS): calcd. 213.1365 [Mϩ]; found 213.1359.
C11H19NO3: calcd. C 61.95, H 8.98, N 6.57; found C 62.24, H 8.93,
N 6.37.
General Remarks: Manipulations were performed using standard
Schlenk techniques under inert atmosphere (N2 or Ar). Dichloro-
methane, toluene and acetonitrile were dried over CaH2, distilled,
and stored under a nitrogen atmosphere prior to use. Column chro-
matography was performed on silica gel (Kieselgel 60, 63Ϫ200µm).
NMR spectra were recorded on Bruker Avance 360 (1H and 13C at
360 and 90.6 MHz, respectively) or 400 (1H and 13C at 400 and
100.6 MHz, respectively) instruments. Chemical shifts are refer-
enced to residual chloroform (for 1H) and [D]chloroform (for 13C).
Optical rotation values were measured on a Perkin-Elmer polari-
meter 343 using a 10 cm solution cell and the concentration of the
samples is given in g/mL. Melting points (uncorrected) were deter-
mined on an Electrothermal Gallenhamp apparatus. The elemental
analyses were carried out at London Metropolitan University.
Mass spectra (MS) were recorded using Electron Impact (EI, low
and high resolution) or Electrospray (ES, high resolution) tech-
niques. HPLC analyses were performed on a Gilson HPLC system
using Daicel Chiralpak AD or AS columns (equipped with an au-
toinjector with a 20 µL loop); detection was effected by UV absorp-
tion at 215 nm. Acid chlorides were prepared from the appropriate
acid by chlorination (thionyl chloride). Unless otherwise indicated,
all chemicals were obtained commercially and used as received. The
preparation of complex 1 has been previously reported.[11] Pal-
ladium salts were obtained from Johnson Matthey plc. through a
precious metals loan agreement.
Typical Catalytic Procedure: Complex 1 (0.022 g, 0.020 mmol) and
the appropriate tert-butyl alkenoylcarbamate (0.60 mmol) were
placed in a thick-walled Young’s tube. A solution of the corre-
sponding amine (0.40 mmol) in toluene (2.0 mL) was then added
by syringe. The Young’s tube was sealed (PTFE tap), and the reac-
tion mixture was stirred at 25 °C. After an appropriate period of
time, the resultant homogeneous red solution was absorbed onto
silica gel and subjected to column chromatography to furnish the
product.
tert-Butyl 3-Anilinobutanoylcarbamate (3a): White solid (111 mg,
Ͼ99 %). Rf ϭ 0.37 (Et2O/pentane, 1:3). M.p. 117Ϫ118 °C. HPLC
(Chiralpak AD, iPrOH/hexane, 2:98, 1.5 mL/min): tR ϭ 18.4 min
(major) and 23.6 min (minor). [α]2D0 ϭ Ϫ10.4 (c ϭ 0.041, CHCl3),
2
97 % ee. 1H NMR: δ ϭ 1.30 (d, 3 H, CHCH3, JH,H ϭ 6.4 Hz),
1
2
1.50 (s, 9 H, tBu), 2.88 (dd, 1 H, COCH2, JH,H ϭ 6.2, JH,H
ϭ
1
2
15.9 Hz), 3.08 (dd, 1 H, COCH2, JH,H ϭ 5.8, JH,H ϭ 15.9 Hz),
3.85 (br. s, 1 H, PhNH), 4.03Ϫ4.07 (m, 1 H, NHCH), 6.62 (d, 2
H, Ph, JH,H ϭ 8.6 Hz), 6.70 (t, 1 H, Ph, JH,H ϭ 7.4 Hz), 7.17 (t,
2 H, Ph, 2JH,H ϭ 7.4 Hz), 7.51 (br. s, 1 H, CONH) ppm. 13C NMR:
δ ϭ 20.8 (CH3CH), 27.9 [C(CH3)3], 42.1 (COCH2), 45.9 (NHCH),
2
2
Typical Procedure for the Synthesis of tert-Butyl Alkenoylcarbam-
ates 3a؊l and 5: n-Butyllithium and 2-butenoyl chloride were added 82.7 [C(CH3)3], 113.7 (Ph), 117.7 (Ph), 129.3 (Ph), 146.8 (Ph), 150.5
successively to a solution of tert-butyl carbamate (1.0 g, 8.54 mmol) (CO2), 172.8 (COCH2) ppm. m/z (HR-ESMS): calcd. 278.1630
Eur. J. Org. Chem. 2004, 959Ϫ964
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
961

K. Li, X. Cheng, K. K. M. Hii
[Mϩ]; found 278.1625. C15H22N2O3: calcd. C 64.73, H 7.97, N tert-Butyl 3-[(4-Chlorophenyl)amino]pentanoylcarbamate (3f): White
SHORT COMMUNICATION
10.06; found C 64.80, H 7.77, N 9.93.
solid (120 mg, 92 %). Rf ϭ 0.6 (Et2O/pentane, 1:2). M.p. 93Ϫ94
°C. HPLC (Chiralpak AD, iPrOH/hexane, 2:98, 1.0 mL/min): tR ϭ
32.1 min (major) and 37.3 min (minor). [α]2D0 ϭ Ϫ34.4 (c ϭ 0.052,
tert-Butyl 3-[(4-Chlorophenyl)amino]butanoylcarbamate (3b): White
solid (125 mg, Ͼ99 % ). Rf ϭ 0.26 (Et2O/pentane, 1:3). M.p.
114Ϫ115 °C. HPLC (Chiralpak AD, iPrOH/hexane, 2:98, 1.2 mL/
min): tR ϭ 35.7 min (major) and 41.0 min (minor, located using
1
2
CHCl3), 85 % ee. H NMR: δ ϭ 0.96 (t, 3 H, CH2CH3, JH,H
ϭ
7.4 Hz), 1.48 (s, 9 H, tBu), 1.57Ϫ1.68 (m, 2 H, CH2CH3), 2.88 (dd,
1
2
1 H, COCH2, JH,H ϭ 5.4, JH,H ϭ 15.8 Hz), 3.03 (dd, 1 H,
1
racemic catalyst). [α]2D0 ϭ Ϫ18.2 (c ϭ 0.036, CHCl3), Ͼ99 % ee. H
1
2
COCH2, JH,H ϭ 6.2, JH,H ϭ 15.8 Hz), 3.73Ϫ3.85 (m, 1 H,
2
NMR: δ ϭ 1.28 (d, 3 H, CHCH3, JH,H ϭ 6.3 Hz), 1.48 (s, 9 H,
NHCH), 3.86 (br. s, 1 H, PhNH), 6.53 (d, 2 H, Ph, 2JH,H ϭ 8.9 Hz),
1
2
tBu), 2.86 (dd, 1 H, COCH2, JH,H ϭ 6.0, JH,H ϭ 16.0 Hz), 3.07
2
7.08 (d, 2 H, Ph, JH,H ϭ 8.9 Hz), 7.33 (br. s, 1 H, CONH) ppm.
1
2
(dd, 1 H, COCH2, JH,H ϭ 5.8, JH,H ϭ 16.0 Hz), 3.89 (br. s, 1 H,
13C NMR: δ ϭ 10.4 (CH3CH2), 27.9 (CH3CH2), 28.0 [C(CH3)3],
40.8 (COCH2), 51.9 (NHCH), 82.8 [C(CH3)3], 114.5 (Ph), 121.8
(Ph), 129.1 (Ph), 145.9 (Ph), 150.5 (CO2), 173.0 (COCH2) ppm.
m/z (HR-ESMS): calcd. 326.1397 [Mϩ]; found 326.1394.
C16H23ClN2O3: calcd. C 58.80, H 7.09, N 8.57; found C 59.12, H
7.04, N 8.29.
2
PhNH), 3.92Ϫ4.08 (m, 1 H, NHCH), 6.53 (d, 2 H, Ph, JH,H
ϭ
8.8 Hz), 7.10 (d, 2 H, Ph, 2JH,H ϭ 8.8 Hz), 7.33 (br. s, 1 H, CONH)
ppm. 13C NMR: δ ϭ 20.7 (CH3CH), 27.9 [C(CH3)3], 41.9
(COCH2), 46.0 (NHCH), 83.8 [C(CH3)3], 115.7 (Ph), 122.1 (Ph),
129.1 (Ph), 145.5 (Ph), 150.6 (CO2), 172.9 (COCH2) ppm. m/z (HR-
ESMS): calcd. 312.1241 [Mϩ]; found 312.1237. C15H21N2O3: calcd.
C 57.60, H 6.77, N 8.96; found C 57.58, H 6.66, N 8.67.
tert-Butyl 3-[(4-Methylphenyl)amino]pentanoylcarbamate (3g):
White solid (115 mg, 94 %). Rf ϭ 0.3 (Et2O/pentane, 1:3). M.p.
96Ϫ97 °C. The enantiomers could not be resolved by chiral HPLC.
[α]2D0 ϭ Ϫ20.0 (c ϭ 0.058, CHCl3). 1H NMR: δ ϭ 0.96 (t, 3 H,
tert-Butyl 3-[(4-Methylphenyl)amino]butanoylcarbamate (3c): White
solid (109 mg, 93 %). Rf ϭ 0.23 (Et2O/pentane, 1:3). M.p. 84Ϫ85
°C. HPLC (Chiralpak AD, iPrOH/hexane, 2:98, 1.5 mL/min): tR ϭ
21.4 min (major) and 25.2 min (minor). [α]2D0 ϭ Ϫ13.6 (c ϭ 0.050,
2
CH2CH3, JH,H ϭ 7.4 Hz), 1.47 (s, 9 H, tBu), 1.57Ϫ1.68 (m, 2 H,
1
CH2CH3), 2.23 (s, 3 H, PhCH3), 2.86 (dd, 1 H, COCH2, JH,H
ϭ
1
2
CHCl3), 92 % ee. H NMR: δ ϭ 1.28 (d, 3 H, CHCH3, JH,H
ϭ
5.3, 2JH,H ϭ 15.5 Hz), 2.97 (dd, 1 H, COCH2, 1JH,H ϭ 6.4, 2JH,H ϭ
15.5 Hz), 3.69 (br. s, 1 H, PhNH), 3.77Ϫ3.83 (m, 1 H, NHCH),
6.55 (d, 2 H, Ph, 2JH,H ϭ 8.4 Hz), 6.97 (d, 2 H, Ph, 2JH,H ϭ 8.4 Hz),
7.61 (br. s, 1 H, CONH) ppm. 13C NMR: δ ϭ 10.4 (CH3CH2),
20.3 (PhCH3), 27.8 (CH3CH2), 27.9 [C(CH3)3], 40.0 (COCH2), 52.1
(NHCH), 82.5 [C(CH3)3], 113.9 (Ph), 126.8 (Ph), 129.8 (Ph), 144.9
(Ph), 150.4 (CO2), 173.0 (COCH2) ppm. m/z (HR-ESMS): calcd.
306.1943 [Mϩ]; found 306.1938. C17H26N2O3: calcd. C 66.64, H
8.55, N 9.14; found C 66.83, H 8.68, N 9.27.
6.4 Hz), 1.48 (s, 9 H, tBu), 2.23 (s, 3 H, PhCH3), 2.84 (dd, 1 H,
1
2
COCH2, JH,H ϭ 6.1, JH,H ϭ 15.9 Hz), 3.02 (dd, 1 H, COCH2,
1JH,H ϭ 5.9, 2JH,H ϭ 15.9 Hz), 3.68 (br. s, 1 H, PhNH), 3.96Ϫ3.99
2
(m, 1 H, NHCH), 6.56 (d, 2 H, Ph, JH,H ϭ 8.3 Hz), 6.98 (d, 2 H,
Ph, 2JH,H ϭ 8.3 Hz), 7.63 (br. s, 1 H, CONH) ppm. 13C NMR: δ ϭ
20.3 (PhCH3), 20.7 (CH3CH), 27.9 [C(CH3)3], 42.1 (COCH2), 46.3
(NHCH), 82.4 [C(CH3)3], 114.1 (Ph), 127.0 (Ph), 129.7 (Ph), 144.5
(Ph), 150.5 (CO2), 173.0 (COCH2) ppm. m/z (HR-ESMS): calcd.
292.1787 [Mϩ]; found 292.1766. C16H24N2O3: calcd. C 65.73, H
8.27, N 9.58; found C 65.64, H 8.43, N 9.64.
tert-Butyl 3-[(4-Methoxyphenyl)amino]pentanoylcarbamate (3h):
White solid (128 mg, Ͼ99 %). Rf ϭ 0.6 (Et2O/pentane, 1:1). M.p.
65Ϫ66 °C. HPLC (Chiralpak AD, iPrOH/hexane, 2:98, 1.2 mL/
min): tR ϭ 43.9 min (major) and 52.7 min (minor). [α]2D0 ϭ Ϫ5.2
(c ϭ 0.067, CHCl3), 16 % ee. 1H NMR: δ ϭ 0.96 (t, 3 H, CH2CH3,
2JH,H ϭ 7.4 Hz), 1.47 (s, 9 H, tBu), 1.58Ϫ1.66 (m, 2 H, CH2CH3),
tert-Butyl 3-[(4-Methoxyphenyl)amino]butanoylcarbamate (3d):
White solid (122 mg, 99 %). Rf ϭ 0.4 (Et2O/pentane, 1:1). M.p.
70Ϫ71 °C. HPLC (Chiralpak AD, iPrOH/hexane, 3:97, 1.2 mL/
min): tR ϭ 30.1 min (major) and 37.8 min (minor). [α]2D0 ϭ Ϫ10.4
(c ϭ 0.078, CHCl3), 73 % ee. 1H NMR: δ ϭ 1.26 (d, 3 H, CHCH3,
2JH,H ϭ 6.4 Hz), 1.47 (s, 9 H, tBu), 2.80 (dd, 1 H, COCH2, 1JH,H ϭ
5.8, 2JH,H ϭ 15.9 Hz), 2.98 (dd, 1 H, COCH2, 1JH,H ϭ 5.8, 2JH,H ϭ
15.9 Hz), 3.50 (br. s, 1 H, PhNH), 3.74 (s, 3 H, OCH3), 3.88Ϫ3.93
1
2
2.88 (dd, 1 H, COCH2, JH,H ϭ 5.3, JH,H ϭ 15.8 Hz), 2.93 (dd, 1
H, COCH2, 1JH,H ϭ 6.4, 2JH,H ϭ 15.8 Hz), 3.52 (br. s, 1 H, PhNH),
3.69Ϫ3.76 (m, 1 H, NHCH), 3.73 (s, 3 H, OCH3), 6.60 (d, 2 H,
2
2
2
Ph, JH,H ϭ 8.6 Hz), 6.76 (d, 2 H, Ph, JH,H ϭ 8.6 Hz), 7.61 (br. s,
1 H, CONH) ppm. 13C NMR: δ ϭ 10.4 (CH3CH2), 27.7
(CH3CH2), 27.9 [C(CH3)3], 40.0 (COCH2), 53.0 (NHCH), 55.7
(OCH3), 82.5 [C(CH3)3], 114.9 (Ph), 115.4 (Ph), 141.2 (Ph), 150.5
(CO2), 152.4 (Ph), 172.9 (COCH2) ppm. m/z (HR-ESMS): calcd.
322.1893 [Mϩ]; found 322.1887. C17H26N2O4: calcd. C 63.33, H
8.13, N 8.69; found C 63.47, H 8.00, N 8.66.
(m, 1 H, NHCH), 6.61 (d, 2 H, Ph, JH,H ϭ 8.8 Hz), 6.77 (d, 2 H,
Ph, 2JH,H ϭ 8.8 Hz), 7.79 (br. s, 1 H, CONH) ppm. 13C NMR: δ ϭ
20.8 (CH3CH), 27.9 [C(CH3)3], 42.2 (COCH2), 47.3 (NHCH), 55.7
(OCH3), 82.5 [C(CH3)3], 114.9 (Ph), 115.8 (Ph), 140.8 (Ph), 150.4
(CO2), 152.6 (Ph), 172.8 (COCH2) ppm. m/z (HR-ESMS): calcd.
308.1736 [Mϩ]; found 308.1730. C16H24N2O4: calcd. C 62.32, H
7.84, N 9.08; found C 62.43, H 7.93, N 8.86.
tert-Butyl 3-Anilinopentanoylcarbamate (3e): White solid (115 mg,
tert-Butyl 3-Anilinohexanoylcarbamate (3i): White solid (120 mg, 98
98 %). Rf ϭ 0.4 (Et2O/pentane, 1:3). M.p. 105Ϫ106 °C. HPLC %). Rf ϭ 0.3 (Et2O/pentane, 1:4). M.p. 103Ϫ104 °C. HPLC (Chiral-
(Chiralpak AD, iPrOH/hexane, 2:98, 1.2 mL/min): tR ϭ 20.4 min
pak AD, EtOH/hexane, 3:97, 1.0 mL/min): tR ϭ 15.5 min (major)
(major) and 24.3 min (minor). [α]2D0 ϭ Ϫ29.0 (c ϭ 0.041, CHCl3),
and 17.5 min (minor). [α]2D0 ϭ Ϫ22.1 (c ϭ 0.056, CHCl3), 89 % ee.
1
2
2
90 % ee. H NMR: δ ϭ 0.97 (t, 3 H, CH2CH3, JH,H ϭ 7.4 Hz), 1H NMR: δ ϭ 0.92 (t, 3 H, CH2CH3, JH,H ϭ 7.3 Hz), 1.36Ϫ1.50
1.48 (s, 9 H, tBu), 1.60Ϫ1.72 (m, 2 H, CH2CH3), 2.88 (dd, 1 H, (m, 2 H, CH2CH3), 1.47 (s, 9 H, tBu), 1.53Ϫ1.62 (m, 2 H,
1
2
1
2
COCH2, JH,H ϭ 5.0, JH,H ϭ 15.4 Hz), 3.01 (dd, 1 H, COCH2,
1JH,H ϭ 5.9, 2JH,H ϭ 15.4 Hz), 3.84 (br. s, 2 H, NHCH and PhNH),
CH2CH2CH3), 2.89 (dd, 1 H, COCH2, JH,H ϭ 5.5, JH,H ϭ
1
2
15.9 Hz), 3.00 (dd, 1 H, COCH2, JH,H ϭ 6.4, JH,H ϭ 15.9 Hz),
6.61 (d, 2 H, Ph, 2JH,H ϭ 7.3 Hz), 6.68 (t, 1 H, Ph, 2JH,H ϭ 7.3 Hz), 3.81 (br. s, 1 H, PhNH), 3.88Ϫ3.96 (m, 1 H, NHCH), 6.61 (d, 2
2
2
2
7.15 (t, 2 H, Ph, JH,H ϭ 7.3 Hz), 7.50 (br. s, 1 H, CONH) ppm.
H, Ph, JH,H ϭ 7.4 Hz), 6.68 (t, 1 H, Ph, JH,H ϭ 7.4 Hz), 7.15 (t,
13C NMR: δ ϭ 10.4 (CH3CH2), 27.9 [C(CH3)3], 28.0 (CH3CH2), 2 H, Ph, 2JH,H ϭ 7.4 Hz), 7.41 (br. s, 1 H, CONH) ppm. 13C NMR:
40.0 (COCH2), 51.7 (NHCH), 82.6 [C(CH3)3], 113.5 (Ph), 117.5
(Ph), 129.3 (Ph), 147.3 (Ph), 150.5 (CO2), 173.0 (COCH2) ppm. m/z
δ
ϭ
14.0 (CH3CH2), 19.3 (CH3CH2), 27.9 [C(CH3)3], 37.5
(CH2CH2CH3), 40.4 (COCH2), 50.0 (NHCH), 82.6 [C(CH3)3],
(HR-ESMS): calcd. 292.1787 [Mϩ]; found 292.1781. C16H24N2O3: 113.4 (Ph), 117.4 (Ph), 129.3 (Ph), 147.3 (Ph), 150.5 (CO2), 173.0
calcd. C 65.73, H 8.27, N 9.58; found C 65.95, H 8.12, N 9.49.
(COCH2) ppm. m/z (HR-ESMS): calcd. 306.1943 [Mϩ]; found
962
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 959Ϫ964

Asymmetric Synthesis of β-Amino Acid and Amide Derivatives
SHORT COMMUNICATION
2
306.1938. C17H26N2O3: calcd. C 66.64, H 8.55, N 9.14; found C
66.72, H 8.49, N 9.02.
1.94 (dd, 1 H, CH3CH, JH,H ϭ 6.8, 3JH,H ϭ 1.4 Hz), 3.78 (s, 3 H,
2
3
OCH3), 6.84 (dd, 1 H, COCH, JH,H ϭ 15.0, JH,H ϭ 1.3 Hz),
7.10Ϫ7.20 (m, 1 H, CH3CH), 7.89 (br. s, 1 H, NH) ppm. 13C NMR:
δ ϭ 18.4 (CH3CH), 53.0 (OCH3), 122.7 (COCH), 146.6 (CH3CH),
152.4 (CO2), 166.1 (COCH) ppm. m/z (HR-EIMS): calcd. 143.0582
[Mϩ]; found 143.0577. C9H9NO3: calcd. C 50.35, H 6.34, N 9.79;
found C 50.44, H 6.59, N 9.94.
tert-Butyl 3-[(4-Chlorophenyl)amino]hexanoylcarbamate (3j): White
solid (123 mg, 90 %). Rf ϭ 0.4 (Et2O/pentane, 1:4). M.p. 76Ϫ77
°C. HPLC (Chiralpak AS, iPrOH/hexane, 2:98, 1.0 mL/min): tR
ϭ
20.6 min (major) and 26.2 min (minor). [α]2D0 ϭ Ϫ28.6 (c ϭ 0.046,
1
2
CHCl3), 89 % ee. H NMR: δ ϭ 0.91 (t, 3 H, CH2CH3, JH,H
ϭ
Methyl 3-Anilinobutanoylcarbamate (5): Colourless oil (90 mg, 95
%). Rf ϭ 0.4 (Et2O/pentane, 1:1). HPLC (Chiralpak AD, iPrOH/
hexane, 5:95, 1.0 mL/min): tR ϭ 26.8 min (major) and 33.8 min
7.3 Hz), 1.33Ϫ1.45 (m, 2 H, CH2CH3), 1.48 (s, 9 H, tBu),
1.53Ϫ1.59 (m, 2 H, CH2CH2CH3), 2.88 (dd, 1 H, COCH2, 1JH,H ϭ
2.6, 2JH,H ϭ 15.4 Hz), 3.02 (dd, 1 H, COCH2, 1JH,H ϭ 4.8, 2JH,H ϭ
15.4 Hz), 3.85 (br. s, 2 H, PhNH, NHCH), 6.52 (d, 2 H, Ph,
(minor). [α]2D0 ϭ Ϫ6.5 (c ϭ 0.037, CHCl3), 92 % ee. H NMR: δ ϭ
1
2
2
2JH,H ϭ 8.8 Hz), 7.08 (d, 2 H, Ph, JH,H ϭ 8.8 Hz), 7.38 (br. s, 1
1.30 (d, 3 H, CHCH3, JH,H ϭ 6.8 Hz), 2.89 (dd, 1 H, COCH2,
2
1
1JH,H ϭ 5.9, JH,H ϭ 15.9 Hz), 3.05 (dd, 1 H, COCH2, JH,H
ϭ
H, CONH) ppm. 13C NMR: δ ϭ 13.9 (CH3CH2), 19.3 (CH3CH2),
27.9 [C(CH3)3], 37.4 (CH2CH2CH3), 40.3 (COCH2), 50.2 (NHCH),
82.7 [C(CH3)3], 114.4 (Ph), 121.8 (Ph), 129.1 (Ph), 146.0 (Ph), 150.5
(CO2), 173.1 (COCH2) ppm. m/z (HRMS): calcd. 340.1554 [Mϩ];
found 340.1550. C17H25ClN2O3: calcd. C 59.90, H 7.39, N 8.22;
found C 60.08, H 7.14, N 8.05.
2
5.9, JH,H ϭ 15.9 Hz), 3.76 (s, 4 H, 1 H, PhNH, 3 H, OCH3),
3.99Ϫ4.08 (m, 1 H, NHCH), 6.64 (d, 2 H, Ph, JH,H ϭ 7.7 Hz),
2
6.72 (t, 1 H, Ph, 2JH,H ϭ 7.3 Hz), 7.18 (t, 2 H, Ph, 2JH,H ϭ 7.3 Hz),
7.72 (br. s, 1 H, CONH) ppm. 13C NMR: δ ϭ 20.8 (CH3CH), 42.2
(COCH2), 46.0 (NHCH), 53.0 (OCH3), 113.9 (Ph), 118.0 (Ph),
129.3 (Ph), 146.7 (Ph), 152.2 (CO2), 172.5 (COCH2) ppm. m/z (HR-
ESMS): calcd. 236.1161 [Mϩ]; found 236.1155. C12H16N2O3: calcd.
C 61.00, H 6.83, N 11.86; found C 59.95, H 6.60, N 11.47.
tert-Butyl
3-[(4-Methylphenyl)amino]hexanoylcarbamate
(3k):
White solid (107 mg, 83 %). Rf ϭ 0.3 (Et2O/pentane, 1:4). M.p.
63Ϫ64 °C. HPLC (Chiralpak AS, iPrOH/hexane, 1:99, 1.0 mL/
min): tR ϭ 30.2 min (major) and 27.2 min (minor). [α]2D0 ϭ Ϫ21.5
(c ϭ 0.052, CHCl3), 80 % ee. 1H NMR: δ ϭ 0.92 (t, 3 H, CH2CH3,
2JH,H ϭ 7.3 Hz), 1.37Ϫ1.50 (m, 2 H, CH2CH3), 1.48 (s, 9 H, tBu),
1.53Ϫ1.61 (m, 2 H, CH2CH2CH3), 2.23 (s, 3 H, PhCH3), 2.87 (dd,
Formation of β-Amino Acid 6 by Deprotection of Compound 3a:
Compound (Ϫ)-3a (0.10 g, 0.36 mmol, 90 % ee) was hydrolysed
with 1  KOH in MeOH (2.5 equiv.) at room temperature for 1 h,
after which the reaction solvents were evaporated. The residue was
then dissolved in water, and washed with portions of Et2O. The
aqueous phase was acidified with 1  HCl (pH 4), before extracting
with EtOAc (4 ϫ 10 mL). The combined organic layers were
washed with brine, dried over MgSO4 and the solvents evaporated
1
2
1 H, COCH2, JH,H ϭ 5.5, JH,H ϭ 15.8 Hz), 2.96 (dd, 1 H,
1
2
COCH2, JH,H ϭ 6.2, JH,H ϭ 15.8 Hz), 3.65 (br. s, 1 H, PhNH),
3.82Ϫ3.90 (m, 1 H, NHCH), 6.53 (d, 2 H, Ph, JH,H ϭ 8.4 Hz),
6.97 (d, 2 H, Ph, JH,H ϭ 8.4 Hz), 7.53 (br. s, 1 H, CONH) ppm.
2
2
to afford β-amino acid 6 (64 mg, quantitatively). [α]2D0 ϭ ϩ18.1 (c ϭ
13C NMR: δ ϭ 14.0 (CH3CH2), 19.3 (CH3CH2), 20.3 (PhCH3),
28.0 [C(CH3)3], 37.4 (CH2CH2CH3), 40.5 (COCH2), 50.5 (NHCH),
82.5 [C(CH3)3], 113.8 (Ph), 126.8 (Ph), 129.8 (Ph), 144.9 (Ph), 150.4
(CO2), 172.9 (COCH2) ppm. m/z (HR-ESMS): calcd. 320.2100
[Mϩ]; found 320.2095. C18H28N2O3: calcd. C 67.47, H 8.81, N 8.74;
found C 67.41, H 8.97, N 8.65.
2
0.032, CHCl3). 1H NMR: δ ϭ 1.29 (d, 3 H, CHCH3, JH,H
ϭ
1
2
6.4 Hz), 2.51 (dd, 1 H, COCH2, JH,H ϭ 6.4, JH,H ϭ 15.4 Hz),
2.66 (dd, 1 H, COCH2, JH,H ϭ 5.9, JH,H ϭ 15.4 Hz), 3.89Ϫ3.98
(m, 1 H, CH3CH), 6.30 (br. s, 2 H, CHNH and COOH), 6.68 (d,
1
2
2
2
2 H, Ph, JH,H ϭ 7.8 Hz), 6.78 (t, 1 H, Ph, JH,H ϭ 7.4 Hz), 7.21
(t, 2 H, Ph, JH,H ϭ 7.4 Hz) ppm. 13C NMR: δ ϭ 20.6 (CH3CH),
2
tert-Butyl 3-[(4-Methoxyphenyl)amino]hexanoylcarbamate (3l):
Colourless oil (110 mg, 82 %). Rf ϭ 0.6 (Et2O/pentane, 1:1). HPLC
40.6 (COCH2), 46.5 (NHCH), 114.5 (Ph), 118.7 (Ph), 129.4 (Ph),
146.1 (Ph), 176.6 (CO2H) ppm. m/z (HR-EIMS): calcd. 179.0946
[Mϩ]; found 179.0941.
(Chiralpak AD, iPrOH/hexane, 1.6:98.4, 1.2 mL/min): tR
ϭ
56.1 min (major) and 62.9 min (minor). [α]2D0 ϭ Ϫ4.2 (c ϭ 0.043,
Formation of β-Amino Amide 7 by Deprotection of Compound 3a:
Compound (Ϫ)-3a (0.10 g, 0.37 mmol, 94 % ee) was dissolved in
CH2Cl2/TFA (1:1, 2 mL). The mixture was stirred at room tem-
perature for 1 h and the solvents evaporated in vacuo. The residue
was purified by chromatography (EtOAc/Et3N, 50:1) to give the
1
2
CHCl3), 17 % ee. H NMR: δ ϭ 0.90 (t, 3 H, CH2CH3, JH,H
ϭ
7.2 Hz), 1.34Ϫ1.44 (m, 2 H, CH2CH3), 1.46 (s, 9 H, tBu),
1.49Ϫ1.59 (m, 2 H, CH2CH2CH3), 2.82 (dd, 1 H, COCH2, 1JH,H ϭ
5.4, 2JH,H ϭ 15.6 Hz), 2.92 (dd, 1 H, COCH2, 1JH,H ϭ 6.2, 2JH,H ϭ
15.6 Hz), 3.51 (br. s, 1 H, PhNH), 3.72 (s, 3 H, OCH3), 3.75Ϫ3.81
pure amide 7 (66 mg, quantitative). [α]2D0 ϭ ϩ37.4 (c ϭ 0.033,
2
(m, 1 H, NHCH), 6.60 (d, 2 H, Ph, JH,H ϭ 8.9 Hz), 6.75 (d, 2 H,
2
CHCl3). 1H NMR (CDCl3): δ ϭ 1.29 (d, 3 H, CHCH3, JH,H
ϭ
Ph, 2JH,H ϭ 8.9 Hz), 7.79 (br. s, 1 H, CONH) ppm. 13C NMR: δ ϭ
14.9 (CH3CH2), 19.3 (CH3CH2), 27.9 [C(CH3)3], 37.3
(CH2CH2CH3), 40.4 (COCH2), 51.4 (NHCH), 55.7 (OCH3), 82.4
[C(CH3)3], 114.9 (Ph), 115.3 (Ph), 141.2 (Ph), 150.4 (CO2), 152.3
(Ph), 173.0 (COCH2) ppm. m/z (HR-ESMS): calcd. 336.2049 [Mϩ];
found 336.2043. C18H28N2O4: calcd. C 64.26, H 8.39, N 8.33;
found C 64.13, H 8.07, N 8.15.
1
2
6.4 Hz), 2.39 (dd, 1 H, COCH2, JH,H ϭ 5.5, JH,H ϭ 15.0 Hz),
2.48 (dd, 1 H, COCH2, JH,H ϭ 6.4, JH,H ϭ 15.0 Hz), 3.73 (br. s,
1
2
1 H, PhNH), 3.88Ϫ3.96 (m, 1 H, CH3CH), 5.60 (br. s, 1 H,
2
CONH2), 6.03 (br. s, 1 H, CONH2), 6.66 (d, 2 H, Ph, JH,H
ϭ
7.8 Hz), 6.75 (t, 1 H, Ph, 2JH,H ϭ 7.3 Hz), 7.19 (t, 2 H, Ph, 2JH,H ϭ
7.3 Hz) ppm. 13C NMR (CDCl3): δ ϭ 20.8 (CH3CH), 42.1
(COCH2), 46.6 (NHCH), 114.1 (Ph), 118.3 (Ph), 129.4 (Ph), 146.7
(Ph), 173.5 (CONH2) ppm. m/z (HR-EIMS): calcd. 178.1106 [Mϩ];
found 178.1101. C10H14N2O: calcd. C 67.39, H 7.92, N 15.72;
found C 67.23, H 8.07, N 15.90.
Methyl (E)-But-2-enoylcarbamate (4): Styrene (30 mL) and CuCl
(0.1 g) were added successively to a mixture of methyl carbamate
(1.0 g, 8.54 mmol) and 2-butenoyl chloride (2.4 mL, 25.0 mmol).
The reaction mixture was stirred at 114 °C for 16 h. It was then
cooled to room temperature and the solvents evaporated to give a
white residue, which was dissolved in dichloromethane, washed
with water and brine and dried over MgSO4. The solution was
concentrated; the addition of pentane to the residue furnished 4 as
Acknowledgments
This work was supported by a ROPA grant from the EPSRC (grant
number: GR/R50332/01, PDRA support to K. L.). X. C. was sup-
a white precipitate (0.93 g, 76 %). M.p. 149Ϫ150 °C. 1H NMR: δ ϭ ported by the K. C. Wong Foundation, British Foreign and Com-
Eur. J. Org. Chem. 2004, 959Ϫ964
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
963

K. Li, X. Cheng, K. K. M. Hii
K. Li, K. K. Hii, Chem. Commun. 2003, 1132Ϫ1133.
SHORT COMMUNICATION
monwealth Office and the Ministry of Education, China. We thank
Johnson Matthey plc for the loan of palladium salts.
[5]
[6]
[7]
[8]
D. Ma, J. Jiang, Tetrahedron: Asymmetry 1998, 9, 1137Ϫ1142.
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Our observed [α]2D0 value for compound 6 is considerably higher
than that reported.[6,7] Racemisation of amino acids has been
known to occur in copper-catalysed N-arylation reactions: J. B.
Clement, J. F. Hayes, H. M. Sheldrake, P. W. Sheldrake, A. S.
Wells, Synlett 2001, 1423Ϫ1427.
[1]
Recent reviews: [1a] J. Brunet, D. Neibecker in Catalytic Hetero-
functionalization, A. Togni, H. Grützmacher (Eds.), Wiley-
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[9]
berger, C. G. Hartung, J. Seayad, O. R. Thiel, A. Tillack, H.
Review on the asymmetric synthesis of β-amino acid deriva-
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Previously, AlIII(salen) complex-catalysed conjugate addition
of hydrazoic acid to activated α,β-unsaturated imides had been
reported as a method for the synthesis of β-amino acid deriva-
tives: J. K. Myers, E. N. Jacobsen, J. Am. Chem. Soc. 1999,
121, 8959Ϫ8960.
[1c]
Trauthwein, Synlett 2002, 1579Ϫ1594.
M. Nobis, B.
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Drießen-Holscher, Angew. Chem. 2001, 113, 4105Ϫ4106, An-
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R. Dorta, P. Egli, F. Zurcher, A. Togni, J. Am. Chem. Soc.
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K. Li, P. N. Horton, M. B. Hursthouse, K. K. Hii, J. Or-
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W. Zhuang, R. G. Hazell, K. A. Jørgensen, Chem. Commun.
2001, 1240Ϫ1241.
Received November 21, 2003
964
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 959Ϫ964