Asymmetric cyclopropanation using amino acid as chiral auxiliary

Article abstract of DOI:10.1016/j.tetasy.2008.11.009

The asymmetric cyclopropanation of cinnamoyl amides derived from amino acids with CH₂N₂ in the presence of catalytic Pd(OAc)₂ has been studied. The reaction proceeded with moderate to excellent diastereoselection. However,

Full text of DOI:10.1016/j.tetasy.2008.11.009

Tetrahedron: Asymmetry 19 (2008) 2678–2681
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Tetrahedron: Asymmetry
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Asymmetric cyclopropanation using amino acid as chiral auxiliary
*
Debarati Mitra, Arjun Sengupta, Kumar Biradha, Amit Basak
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The asymmetric cyclopropanation of cinnamoyl amides derived from amino acids with CH2N2 in the pres-
ence of catalytic Pd(OAc)2 has been studied. The reaction proceeded with moderate to excellent diaste-
reoselection. However, the selectivity depends upon the amino acid side chain as well as the electronic
nature of the cinnamoyl moiety.
Received 14 October 2008
Accepted 12 November 2008
Available online 17 January 2009
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
R2
CH2N2
R2
OAc
OAc
R1
R1
Small rings have played crucial roles in imparting or controlling
the biological activity of many important natural products.1
Amongst them, cyclopropanes have played a prominent role. They
are interesting due to their unusual bonding properties along with
an inherent strain, many natural products are endowed with the
cyclopropane moieties.2 2-Phenyl-1-cyclopropane carboxylates3
are very useful intermediates in the synthesis of these chiral com-
pounds. Compounds containing cyclopropanes have been exten-
sively used as a probe to solve mechanistic problems.4 These
have also provided synthetic analogues with improved biological
profiles. The natural and many synthetic analogues are chiral and
hence asymmetric cyclopropanation5 is an area which has drawn
the attention of synthetic organic chemists for a long time. Several
methods based on chiral auxiliaries as well as chiral catalysis have
been reported.6 Herein we report a simple chiral auxiliary based
approach to a cyclopropane carboxamide which proceeds with a
moderate to excellent degree of diastereoselectivity.
R1
R2
Pd
Pd(OAc)2
Scheme 1. Possible mechanism of Pd(OAc)2 catalyzed cyclopropanation.
low (Scheme 2), the metallo cyclobutane should then collapse to
the cyclopropane predominantly via the intermediate shown in or-
der to avoid the steric hindrance between the amino acid alkyl
group and the acyl group.
R
H
HN
OR1
O
R
O
O
R1
R1
N
COOR1
H
Pd
OAc
2. Results and discussion
Scheme 2. Possible stereoselective collapse of the metallocycle.
Since the discovery of the palladium(II)-catalyzed cyclopropa-
nation of olefins by Suda (Scheme 1),7 various reports have ap-
peared involving chiral palladium(II)-catalysis as well as auxiliary
based approaches to induce enantioselectivity/diastereoselectivity
in the reaction. The commonly accepted8 mechanism of cycloprop-
anation involving Pd(II) is shown below:
The addition of the carbene is stereospecific in the sense that
the geometry around the double bond is retained in the product.
In order to introduce enantio/diastereoselectivity, an additional
chiral ligand has to complex with the Pd(II). It occurred to us that
With this in mind, we proceeded to prepare the starting syn-
thons. Thus the various cinnamic acids were coupled with the
appropriate amino acid benzyl ester in the presence of EDCI9 and
diisopropyl ethylamine. The various amides were then treated
with excess diazomethane in presence of Pd(OAc)2 in dry ether
and the solution was stirred at rt for 6–7 h. It was then evaporated
and the residue was purified by chromatography over Si-gel. The
two cyclopropane diastereomers were checked for 1H NMR spec-
troscopy. The benzylic hydrogens showed up as separate signals
in the region of ꢀd 5.1 for the two diastereomers (Fig. 1). The com-
bined yields and the diastereomeric ratios are shown in Table 1.
The results indicated that there is considerable degree of asym-
metric induction in all the cyclopropanation reactions. The extent
of diastereoselectivity was found to be dependent upon the amino
acid side chain and the electronic nature of the cinnamoyl moiety
attaching an amino acid into an
a,b-unsaturated acid through an
amide linkage might bring in the extra conjugation as shown be-
* Corresponding author. Fax: +91 3222 55303.
E-mail address: absk@chem.iitkgp.emet.in (A. Basak).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.11.009

D. Mitra et al. / Tetrahedron: Asymmetry 19 (2008) 2678–2681
R
2679
H
OR2
HN
O
R
O
O
R1
R1
N
COOR2
H
Pd
OAc
α-face
Major
R
H
OR1
O
R
HN
O
R1
O
N
H
COOR2
R1
Pd
β-face
OAc
Minor
Figure 3. Explanation of the observed diastereoselectivity.
Figure 1. 1H NMR of the benzylic region as used for determination of diastereomeric
excess (A for 2d, B for 2a, C for 2b).
tent of distereoselectivity could be increased to >90%. Future work
regarding the generality of the reaction for aliphatic unsaturated
acid derivatives is currently underway.
Table 1
Results of cyclopropanation
4. Experimental
Entry
Compounds
Combined yield (%)
Diastereomeric ratio
1
2
3
4
5
6
7
8
9
2a (R = CH(CH3)2)
95
90
94
88
92
90
85
82
92
84
4:1
4:1
6:1
>19:1
7:3
2:1
3:2
6:1
4:1
4:1
4.1. Synthesis of cinnamic acid–amino acid conjugates
2b (R = CH2CH(CH3)2)
2c (R = CH(CH3)CH2CH3)
2d (R = CH2OH)
2e (R = CH3)
4a (R = CH(CH3)2)
4b (R = CH2CH(CH3)2)
4c (R = CH(CH3)CH2CH3)
6a (R = CH(CH3)2)
To cinnamic acid or its substituted analogue (dimethoxy/nitro)
in CH2Cl2 (30 ml) at 0 °C, 1.2 equiv of HOBT and 1.2 equiv of
EDCÁHCl were added and was allowed to stir for 1 hr. Then, the free
amine triflate (1.0 equiv) in CH2Cl2 (15 ml) was added followed by
the addition of 5.0 equiv of DIPEA at 0 °C. The reaction was stirred
for 12 h. Then it was partitioned between 2 Â 45 ml of 1 (N) HCl
and CH2Cl2 each. The CH2Cl2 layer was then washed with saturated
solution of NaHCO3, brine and then finally dried over anhydrous
Na2SO4. The corresponding target compounds were obtained by
column chromatography using suitable solvent systems depending
upon the polarity of the compounds.
10
6b (R = CH2CH(CH3)2)
(Scheme 3). The selectivity generally increased with an increase in
steric bulk of the side chain. However, the highest selectivity was
obtained when R = CH2OH (serine). Greater electron donation of
the phenyl moiety decreased the diastereoselectivity (entries 6–
8). Electron withdrawal however did not have any effect on the de-
gree of diastereoselectivity.
4.1.1. For compound 1a
State: oily liquid; Yield: 65%; m
max (KBr, cmÀ1): 1632, 1217, 772;
dH (400 MHz, CDCl3): 7.65 (1H, d, J = 15.5 Hz), 7.53-7.51 (2H, m),
7.37-7.34 (8H, m), 6.47 (1H, d, J = 15.5 Hz), 6.12 (1H, d, J = 8.5
Hz), 5.20 (2H, dd, J = 12.0, 8.0 Hz), 4.79 (1H, dd, J = 5.0, 4.0 Hz),
2.28-2.23 (1H, m), 0.97 (3H, d, J = 7.0 Hz,), 0.91 (3H, d, J = 7.0
Hz); dC (100 MHz, CDCl3): 172.0, 165.6, 141.8, 134.6, 129.7,
128.8, 128.6, 128.5, 128.4, 127.8, 120.1, 67.1, 57.0, 31.6, 18.9,
17.7; Mass (ESI) 338 (MH+).
The absolute configuration of the one of the cyclopropane deriv-
atives (R = CH3) was confirmed by single crystal X-ray analysis
(Fig. 2).10 It was found to be (2R,3R). The stereochemistry matched
with what has been predicted based on the following TS model
(Fig. 3).
4.1.2. For compound 1b
White solid; Yield: 78%; mmax (KBr, cmÀ1): 1638, 1218, 772; dH
(400 MHz, CDCl3): 7.65 (H, d, J = 15.6 Hz), 7.50 (3H, d, J = 5.6 Hz),
7.36 (7H, m), 6.43 (H, d, J = 15.6 Hz), 6.00 (H, d. J = 8.4 Hz), 5.19
(2H, s), 4.84 (H, m), 1.73–1.68 (2H, m), 1.25 (H, m), 0.97–0.93 (6H,
m); dC (100 MHz, CDCl3): 171.6, 163.2, 141.8, 129.8, 128.8, 128.6,
128.4, 128.2, 67.1, 50.9, 41.9, 24.8, 22.8. 22.0; Mass (ESI) 352 (MH+).
Figure 2. ORTEP structure of compound (2R,3R)-2-(2-phenyl carbonyl amino)
propionic acid benzyl ester 2e.
4.1.3. For compound 1c
White solid; Yield:75%; mmax (KBr, cmÀ1): 1637, 1350, 1212,
1189, 751; dH (400 MHz, CDCl3): 7.64 (H, d, J = 15.6 Hz), 7.52–
7.49 (10H, m), 6.45 (H, d, J = 15.6 Hz), 6.14 (H, d, J = 8.4 Hz), 5.20
(2H, dd, J = 12.0 Hz, J = 11.0 Hz), 4.83–4.80 (H, m), 1.98–1.96 (H,
m), 1.44–1.42 (H, m), 1.25–1.18 (H, m), 0.93–0.89 (6H, m); dC
(100 MHz, CDCl3): 172.0, 165.5, 141.7, 135.2, 134.6, 129.8, 128.8,
128.6, 128.4, 128.3, 127.8, 121.0, 67.1, 56.5, 38.3, 25.1, 15.4, 11.5.
3. Conclusion
In conclusion, we have developed a simple asymmetric cyclo-
propanation using a cinnamoyl (or its derivative) amide with a
protected amino acid. By varying the amino acid side chain, the ex-

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D. Mitra et al. / Tetrahedron: Asymmetry 19 (2008) 2678–2681
R
O
R
O
1. CH2N2 / ether
2.
CO2CH2Ph
CO2CH2Ph
Pd(OAc)2
3. 0o C- r.t.
N
H
N
H
1a-1e
2a-2e
R
O
R
O
1. CH2N2 / ether
CO2CH2Ph
CO2CH2Ph
2. Pd(OAc)2
N
H
N
H
3. 0oC- r.t.
MeO
MeO
OMe
OMe
3a-3c
4a, 4b, 4c
1. CH2N2 / ether
2. Pd(OAc)2
3. 0oC- r.t.
R
R
O
O
CO2CH2Ph
CO2CH2Ph
N
N
H
H
NO2
NO2
6a-6b
5a-5b
a
b
For compounds of series: R = -CH(CH3)2; For compounds of series R = -CH2CH(CH3)2
For compounds of c series: R = -CH(CH3)CH2CH3; For compounds of d series: R= --CH2OH
For compounds of e series: R = -CH3
Scheme 3. Cyclopropanation reactions.
4.1.4. For compound 1d
J = 16.4 Hz), 6.31 (H, d, J = 31.2 Hz), 6.07 (H, d, J = 17.2 Hz), 5.18
(2H, s), 4.90–4.79 (H, m), 3.90 (6H, s), 1.70–1.67 (3H, m), 0.97–
0.91 (6H, m); dC (100 MHz, CDCl3): 173.2, 165.8, 150.6, 149.0,
141.6, 135.3, 128.6, 128.4, 128.2, 127.6, 122.1, 117.8, 111.0,
109.5, 67.1, 55.9, 55.8, 50.9, 41.8, 29.6, 24.8, 22.8, 21.9.
White solid, Yield: 82%; m
max (KBr, cmÀ1), 1654, 1638, 1219, 553;
dH (400 MHz, CDCl3): 7.67 (H, d, J = 15.6 Hz), 7.53–7.51 (2H, m),
7.38–7.34 (8H, m), 6.58 (H, d, J = 6.4 Hz), 6.49 (H, d, J = 15.6 Hz),
5.26 (2H, s), 4.05 (2H, m), 2.46 (H, t, J = 6.0 Hz); dC (100 MHz, CDCl3):
170.3, 166.1, 142.3, 134.9, 134.4, 130.0, 128.8, 128.7, 128.6, 128.2,
127.9, 119.6, 67.6, 63.8, 55.1; Mass (ESI) 326 (MH+).
4.1.8. For compound 3c
Oily mass; mmax (KBr, cmÀ1): 1736, 1541, 1263, 1025, 754; dH
(400 MHz, CDCl3): 7.70 (H, d, J = 15.2 Hz), 7.35–7.32 (5H, m), 7.08–
7.02 (2H, m), 6.84 (H, d, J = 8.4 Hz), 6.34 (H, d, J = 15.6 Hz), 6.20 (H,
d, J = 8.8 Hz), 5.18 (2H, dd, J = 12.0, 11.6 Hz), 4.83–4.80 (H, m), 3.90
(6H, s), 1.96 (H, m), 1.76 (H, m), 1.46–1.40 (H, m), 1.27–1.14 (H,
m), 0.93–0.89 (5H, m); dC (100 MHz, CDCl3): 172.1, 165.8, 150.6,
149.0, 141.5, 135.2, 128.6, 128.4, 128.3, 127.6, 122.1, 118.0, 110.9,
109.4, 67.0, 56.5, 55.9, 55.8, 38.3, 25.1, 15.4, 11.6.
4.1.5. For compound 1e
Oily liquid, Yield: 80%; mmax (KBr, cmÀ1), 1638, 1220, 772; dH
(400 MHz, CDCl3): 7.64 (H, d, J = 15.6 Hz), 7.52–7.47 (3H, m),
7.42–7.32 (7H, m), 6.44 (H, d, J = 15.6 Hz), 6.32 (H, d, J = 14.8 Hz),
5.21 (2H, s), 4.80 (H, t, J = 14.4 Hz), 1.49 (3H, d, J = 14.4Hz); dC
(100 MHz, CDCl3): 173.1, 165.3, 141.7, 135.3, 134.7, 129.8, 128.8,
128.7, 128.5, 128.2, 127.9, 120.1, 67.3, 48.4, 18.7; Mass (ESI) 310
(MH+).
4.1.9. For compound 5a
4.1.6. For compound 3a
Oily mass; mmax (KBr, cmÀ1): 1656, 1530, 1352, 1192, 978, 771;
dH (400 MHz, CDCl3): 8.38 (H, s), 8.21 (H, m), 7.79 (H, d, J = 7.6 Hz),
7.69 (H, d, J = 15.6 Hz), 7.57 (H, t, J = 8.0 Hz), 7.38–7.34 (5H, m),
6.61 (H, d, J = 15.6 Hz), 6.24 (H, d, J = 8.8 Hz), 5.24–5.16 (2H, m),
4.80–4.77 (H, m), 2.29–2.24 (H, m), 0.97 (3H, d, J = 8.0 Hz) 0.92
(3H, d, J = 8.0Hz); dC (100 MHz, CDCl3): 171.8, 164.7, 148.6, 139.1,
136.4, 135.1, 133.8, 129.9, 128.6, 128.5, 128.4, 124.1, 123.2,
121.8, 67.2, 57.2, 31.6, 18.9, 17.6; Mass (ESI) 383 (MH+).
Oily liquid; Yield: 82%; mmax (KBr, cm-1): 2345, 2079, 1639,
1262, 1141, 1025, 772, 689; dH 7.57 (1H, d, J = 15.5 Hz), 7.35-
7.32 (5H, m), 7.06 (1H, d, J = 8.5 Hz),7.01 (1H, s), 6.83 (1H, d, J =
8.5 Hz), 6.36 (1H, d, J = 15.5 Hz), 6.25 (1H, s), 5.12 (2H, dd, J =
12.0, 9.0 Hz), 4.79 (1H, dd, J = 5.0, 4.0 Hz), 3.89 (6H, s), 2.26-2.21
(1H, m), 0.96 (3H, d, J = 7.0 Hz), 0.90 (3H, d, J = 7.0 Hz); dC 172.2,
166.0, 150.6, 149.0, 141.5, 135.2, 128.5, 128.4, 128.3, 127.6,
122.1, 118.0, 110.9, 109.5, 67.1, 57.1, 55.9, 55.8, 31.5, 29.6, 19.0,
17.7; Mass (ESI) 398 (MH+).
4.2. Synthesis of cyclopropane derivatives of cinnamic acid–
amino acid conjugates
4.1.7. For compound 3b
Oily liquid; Yield: 78%; mmax (KBr, cmÀ1): 1736, 1654, 1624,
1263, 1147, 1025, 768; dH (400 MHz, CDCl3): 7.61 (H, d,
J = 15.6 Hz), 7.36–7.32 (5H, s), 7.09–7.01 (2H, m), 6.84 (H, d,
To the ether solution of cinnamic acid–amino acid conjugates,
0.1 mol percent of Pd(OAc)2 was added followed by the addition
of freshly generated CH2N2 in ether (ꢀ50-fold excess). The reaction

D. Mitra et al. / Tetrahedron: Asymmetry 19 (2008) 2678–2681
2681
was allowed to stir for 6–7 h. It was then filtered through a silica
column to get the pure product. The spectral and other physical
data are mentioned for the major isomer.
m), 5.18–5.14 (2H, m), 4.73–4.70 (H, m), 3.86 (6H, d, J = 5.6 Hz),
2.47–2.45 (H, m), 1.68–1.60 (4H, m), 1.43–1.28 (2H, m), 1.18–
1.16 (6H, m); dC 172.9, 171.7, 147.6, 135.3, 133.1, 128.5, 128.4,
128.2, 117.7, 117.6, 111.2, 110.0, 109.8, 67.0, 55.9, 55.8, 51.0,
41.9, 41.8, 31.9, 29.6, 29.3, 26.3, 26.1, 24.9, 24.8, 22.7, 22.6, 16.0,
15.7, 14.1; Mass (ESI) 426 (MH+).
4.2.1. For compound 2a
State: Oily liquid; Yield: 95%; [
a
]
D = À76 (c 0.34, CHCl3); mmax
(KBr, cmÀ1): 1654, 1638, 1262, 1220, 1145, 1027, 771; dH 7.40–
7.36 (5H, m), 7.35–7.29 (2H, m), 7.22–7.18 (H, m), 7.11–7.07 (2H,
m), 6.20 (H, d, J = 8.4 Hz), 5.22–5.11 (2H, m), 4.69–4.65 (1H, m),
2.54–2.49 (H, m), 2.21–2.16 (H, m), 1.74–1.69 (2H, m), 1.65–1.59
(H, m), 0.95–0.86 (6H, m); dC 172.0, 171.9, 140.7, 135.2, 128.6,
128.5, 128.4, 128.3, 126.2, 126.0, 125.9, 67.0, 57.1, 31.5, 31.4,
29.6, 26.6, 26.5, 25.3, 25.2, 18.9, 17.7, 17.6, 16.3, 16.1; Mass (ESI)
352 (MH+).
4.2.8. For compound 4c
Oily liquid; Yield: 93%; mmax (KBr, cmÀ1): 1655, 1390, 1255,
1106, 772; dH 7.36 (5H, m), 6.80–6.78 (H, m), 6.64–6.62 (2H, m),
6.16 (H, d, J = 8.4 Hz), 5.23–5.12 (2H, m), 4.71–4.68 (H, m), 3.86
(6H, d, J = 6.0 Hz), 2.49–2.44 (H, m), 1.92–1.88 (H, m), 1.64–1.62
(H, m), 1.57–1.55 (H, m), 1.25–1.20 (2H, m), 0.89–0.86 (7H, m);
dC 172.2, 172.1, 149.2, 147.9, 135.5, 133.5, 128.8, 128.7, 128.6,
118.0, 117.9, 111.6, 111.5, 110.3, 110.1, 67.2, 56.8, 56.2, 56.1,
38.5, 38.4, 29.9, 26.7, 26.6, 25.4, 25.2, 16.3, 16.1, 15.7, 11.8.
4.2.2. For compound 2b
Oily liquid; Yield: 90%; [
a
]
D = À27 (c 0.34, CHCl3); mmax (KBr,
cmÀ1): 1639, 1220, 772, 689; dH: 7.38–7.36 (5H, m), 7.34–7.28
(3H, m), 7.21–7.19 (H, m), 7.10–7.06 (H, m), 6.09 (H, d,
J = 8.0 Hz), 5.18–5.15 (2H, m), 4.73–4.70 (H, m), 2.51–2.48 (H, m),
1.69–1.54 (4H, m), 1.28–1.23 (2H, m), 0.94–0.88 (6H, m); dC
173.0, 171.6, 140.7, 135.3, 128.5, 128.4, 128.3, 128.2, 126.2,
126.0, 125.9, 67.0, 50.9, 41.8, 29.6, 26.5, 26.4, 25.2, 25.1, 24.8,
22.7, 21.9, 16.3, 15.9; Mass (ESI) 366 (MH+).
4.2.9. For compound 6a
Oily liquid; Yield: 95%; mmax (KBr, cmÀ1): 3963, 3834, 3764,
2370, 2080; dH 8.06–8.04 (H, m), 7.90–7.87 (H, m), 7.57–7.45
(2H, m), 7.40–7.35 (5H, m), 6.22 (H, d, J = 8.0 Hz), 5.23–5.14 (2H,
m), 4.67–4.64 (2H, m), 2.65–2.60 (H, m), 2.22 (H, m), 1.83–1.78
(H, m), 1.71–1.66 (H, m), 1.34–1.31 (H, m), 0.98–0.87 (6H, m); Mass
(ESI) 397 (MH+).
4.2.3. For compound 2c
4.2.10. For compound 6b
Oily liquid; Yield: 90%; mmax (KBr, cmÀ1): 1639, 1220, 1190,
1144, 1079, 1028, 772; dH 7.36–7.34 (4H, m), 7.30–7.34 (3H, m),
7.22–7.20 (H, m), 7.10–7.08 (2H, m) 6.15 (H, d, J = 8.4 Hz), 5.18
(2H, dd, J = 12.4, 16.4 Hz), 4.72–4.68 (H, m), 2.52–2.48 (H, m),
1.90–1.89 (H, m), 1.70–1.67 (H, m), 1.66–1.58 (H, m), 1.39–1.37
(H, m), 1.28–1.23 (H, m), 1.16–1.14 (H, m) 0.89–0.86 (6H, m); dC
172.0, 171.7, 140.7, 135.2, 128.5, 128.4, 128.3, 126.3, 126.0,
125.9, 77.3, 77.2, 77.0, 76.6, 67.0, 56.5, 38.2, 26.6, 26.5, 25.2,
25.1, 16.3, 15.4, 11.5; Mass (ESI) 366 (MH+).
Oily liquid; Yield: 92%; m
max (KBr, cmÀ1): 3963, 3764, 2370, 2080;
dH 8.05–8.04 (H, m), 7.90 (H, s), 7.46–7.42(2H, m), 7.39–7.33 (5H, m),
6.11 (H, d, J = 8.0 Hz), 5.21–5.14 (2H, m), 4.74–4.69 (H, m), 2.65–2.60
(H, m), 1.79–1.74 (H, m), 1.71–1.62 (2H, m), 1.35–1.25 (3H, m), 0.94–
0.90 (6H, m); dC 172.8, 170.8, 170.7, 148.4, 142.9, 136.5, 135.2, 132.9,
132.7, 129.3, 129.2, 128.6, 128.4, 128.2, 121.3, 120.3, 116.1, 67.1,
51.1, 41.8, 31.9, 31.4, 30.1, 29.6, 29.3, 26.6, 24.8, 24.5, 24.4, 22.7,
22.6, 22.0, 19.7, 16.4, 14.1; Mass (ESI) 411 (MH+).
Acknowledgements
4.2.4. For compound 2d
White solid; Yield: 88%; [
a
]
D = À85 (c 0.34, CHCl3); mmax (KBr,
The author DM is grateful to CSIR, Government of India for a fel-
lowship. DST is thanked for providing funds for 400 MHz NMR
facility under the IRPHA program.
cmÀ1): 1638, 1193, 698; dH 7.40–7.35 (4H, m), 7.28 (3H, t,
J = 7.6 Hz), 7.20 (H, m), 7.09 (2H, d, J = 7.6 Hz), 6.63 (H, d,
J = 6.8 Hz), 5.23 (2H, s), 4.75 (H, m), 3.99–3.96 (2H, m), 2.53–2.44
(1H, m), 1.75–1.72 (H, m), 1.65–1.63 (H, m), 1.31–1.26 (H, m); dC
172.5, 170.3, 140.3, 135.0, 128.6, 128.5, 128.4, 128.2, 126.4, 126.0,
125.9, 116.1, 67.6, 63.7, 55.1, 26.4, 25.6, 16.5; Mass (ESI) 340 (MH+).
References
1. (a) Chemistry and Biology of b-Lactam Antibiotics;
Vols. 1–3 Morin, R. B.,
Gorman, M., Eds.; Academic Press, 1982; (b) Nicolaou, K. C.; Dai, W. M. Angew.
Chem., Int. Ed. Engl. 1991, 30, 1387; (c) Basak, A.; Mandal, S. M.; Bag, S. S. Chem.
Rev. 2003, 10, 4077; (d) Klein, M.; Walenzyk, T.; Konig, B. Collect. Czech. Chem.
Commun. 2004, 69, 945; (e) Kar, M.; Basak, A. Chem. Rev. 2007, 107, 2861; (f)
Grisom, J. W.; Gunawardena, G. U.; Klingberg, D.; Huang, D. Tetrahedron 1996,
52, 6453; (g) Guanti, G.; Banfi, L. Angew. Chem., Int. Ed. Engl. 1995, 34, 2393; (h)
Banfi, L.; Guanti, G. Eur. J. Org. Chem. 2002, 3745; (i) Basak, A.; Khamrai, U. K.;
Mallik, U. Chem. Commun. 1996, 749; (j) Basak, A.; Mandal, S. Tetrahedron Lett.
2002, 43, 4241; (k) Basak, A.; Khamrai, U. K. Tetrahedron Lett. 1995, 36, 7913; (l)
Doroshow, J. H. J. Natl. Cancer Inst. 1992, 84, 1138.
4.2.5. For compound 2e
White solid; Yield: 95%; [
a]
D = À38 (c 0.34, CHCl3); mmax (KBr,
cmÀ1): 3916, 3866, 3834, 2370, 2079, 1471, 1220, 766, 694; dH
7.38–7.31 (4H, m), 7.28–7.19 (4H, m), 7.11–7.07 (2H, m), 6.22,
(H, d, J = 14.0 Hz), 5.18 (2H, s), 4.69 (H, t, J = 14.4 Hz), 2.53–2.45
(H, m), 1.68–1.66 (2H, m), 1.45–1.44 (3H, m), 1.32–1.21 (H, m);
dC 173.0, 171.4, 140.7, 135.3, 128.6, 128.5, 128.2, 126.3, 126.1,
126.0, 116.4, 100.0, 67.2, 48.3, 26.5, 26.4, 25.3, 18.7, 16.3, 16.0.
2. (a) Lebel, H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103,
971; (b) Li, Z. N.; Liu, G. S.; Zheng, Z.; Chen, H. Tetrahedron 2000, 56, 7187.
3. Huang, K.; Huang, Z.-Z. Synlett 2005, 10, 1621.
4. Baldwin, J. E.; Adlington, R. M.; Domayne-Hayman, B. P.; Knight, G.; Ting, H.-H.
J. Chem. Soc., Chem. Commun. 1987, 1661.
5. (a) Gnad, F.; Reiser, O. Chem. Rev. 2003, 103, 1603; (b) Larionov, O. V.; de
Meijere, A. Org. Lett. 2004, 6, 2153.
6. Uozumi, Y.; Kyota, H.; Kishi, E.; Kitayama, K.; Hayashi, T. Tetrahedron:
Asymmetry 1996, 7, 1603.
7. Soda, M. Synthesis 1981, 714.
8. Denmark, S. E.; Scavenger, R. A.; Faucet, A.-M.; Edwards, J. P. J. Org. Chem. 1997,
62, 3375.
9. Jiang, W.; Wanner, J.; Lee, R. J.; Bounaud, P.-Y.; Boger, D. L. J. Am. Chem. Soc.
2003, 125, 1877.
4.2.6. For compound 4a
Oily liquid; Yield: 95%; m
max (KBr, cmÀ1): 1640, 1220, 1144, 1027,
772; dH 7.35 (5H, d, J = 5.2 Hz), 6.80–6.77 (H, m), 6.64–6.23 (2H, m),
6.13 (H, d, J = 8.8 Hz), 5.23–5.12 (2H, m), 4.67–4.64 (H, m), 3.91–3.86
(6H, m), 2.50–2.45 (H, m), 2.21–2.16 (H, m), 1.67–1.64 (3H, m), 0.94–
0.87 (6H, m); dC 172.0, 171.9, 148.9, 147.6, 135.2, 133.2, 128.6, 128.4,
128.3, 117.7, 117.6, 111.2, 110.0, 109.7, 67.0, 57.2, 56.0, 55.8, 31.4,
26.4, 25.0, 24.9, 18.9, 17.7, 16.1; Mass (ESI) 412 (MH+).
10. The CCDC number is CCDC 706633. The absolute configuration has not been
established by anomalous dispersion effects in diffraction measurements on
the crystal as the molecule contains lighter atoms than Si. The enantiomer was
assigned by reference to an unchanging stereogenic centre originating from the
amino acid in the synthetic procedure.
4.2.7. For compound 4b
State: Oily liquid; Yield: 90%;
dH 7.40–7.34 (5H, m), 6.80 (H, m), 6.64–6.60 (2H, m), 6.04–6.01 (H,
m
max (KBr, cmÀ1): 1638, 1253, 698;