Preparation of β-lactams by mannich-type addition of ethyl(trimethylsilyl) acetate (ETSA) to N-(2-Hydroxyphenyl)aldimine sodium salts

Article abstract of DOI:10.1055/s-0029-1217729

The synthesis of highly substituted -lactams was achieved by addition of air-stable ethyl(trimethylsilyl)acetate derivatives to N-(2-hydroxyphenyl) aldimine sodium salts in a THF-EtCN mixture. This reaction proceeds with moderate to good yields and diaste

Full text of DOI:10.1055/s-0029-1217729

LETTER
2437
Preparation of b-Lactams by Mannich-Type Addition of Ethyl(trimethyl-
silyl)acetate (ETSA) to N-(2-Hydroxyphenyl)aldimine Sodium Salts
Preparation of
H
ig
i
hly Sub
n
stituted
b
-L
c
a
ctams ent Gembus, Thomas Poisson, Sylvain Oudeyer,* Francis Marsais, Vincent Levacher*
COBRA (UMR6014) IRCOF, CNRS, Université et INSA de Rouen, BP08, 76131 Mont-Saint-Aignan Cedex, France
Fax +33(235)522962; E-mail: sylvain.oudeyer@insa-rouen.fr
Received 12 June 2009
lactams 4 via the cyclization of ETSA addition products
intermediately formed (Scheme 1).
Abstract: The synthesis of highly substituted b-lactams was
achieved by addition of air-stable ethyl(trimethylsilyl)acetate deriv-
atives to N-(2-hydroxyphenyl)aldimine sodium salts in a THF–
EtCN mixture. This reaction proceeds with moderate to good yields
and diastereomeric ratio of up to 78:22. The reactivity of the N-(2-
hydroxyphenyl)aldimine can be modified by simply changing the
co-solvent from EtCN to MeCN to afford the cyanomethylated ad-
dition product.
4-MeOC6H4ONa
MeCN
HN
CN
X = H
R
3
see ref. 5
Key words: imines, lactams, silicon, phenols, tandem reactions
N
Na+
X
R
1
N
b-Lactams (azetidin-2-ones) are important compounds in
organic chemistry due to their biological activity1 and
their easy transformation into more complex molecules.2
Accordingly, much attention and effort have been devoted
in the past to the preparation of b-lactams. Among all the
existing methods3 [i.e. reaction of imines with ketenes,
[2+2]-cycloaddition of isocyanates to alkenes, reaction of
nitrones with terminal alkynes catalyzed by Cu(I), cycli-
zation reactions], the enolate–imine condensation is one
the most attractive because of its easiness to implement
and its efficiency, affording products in good yields under
rather mild conditions. In the last past years, various cata-
lytic Mannich-type additions of silyl enolates to aldimines
have been successfully reported.4 However, the poor sta-
bility of these silyl enolates along with their limited acces-
sibility may limit seriously such strategies in synthetic
applications. Herein, we report our investigation on the
use of more stable and readily accessible ethyl(trimethyl-
silyl)acetate (ETSA) derivatives in Mannich-type addi-
tions to provide an easy access to b-lactams.
OH
O–
+
R
TMSCH2CO2Et
O
SiMe3
2a
N
EtO2C
Favorable proximity effect ?
X = ONa
R
4
Scheme 1 Mannich-type addition of ETSA to N-(2-hydroxyphe-
nyl)aldimine sodium salts: working hypothesis
In a first attempt, the sodium salt of N-(2-hydroxyphe-
nyl)benzaldimine (1a) was generated by addition of a so-
lution of 1a in THF to a solution of NaH in THF followed
by addition of ETSA (2a; 1 equiv) and a large excess of
acetonitrile (MeCN).7 Under these conditions, the pres-
ence of the phenoxide sodium salt within the aldimine
substrate 1a did not change the outcome of the reaction,
affording MeCN addition product 3a in 57% yield as pre-
viously observed under autocatalytic conditions.5
Surprisingly, switching the solvent system from THF–
MeCN to THF–EtCN had a dramatic effect on the course
of the reaction. Thus, by conducting the reaction at room
temperature for two hours, we were pleased to observe
formation of the b-lactam 4aa in 85% conversion as the
sole product of the reaction. A complete conversion could
be reached by using ETSA in slight excess (Scheme 2).
We recently reported the direct addition of alkyl nitriles to
unactivated imines using a catalytic ETSA–phenoxide so-
dium salt combination as source of ethyl acetate enolate.5
Under these conditions, the alkyl nitrile is initially depro-
tonated by ethyl acetate enolate prior to reaction with the
aldimine. The resulting catalytic amide salt intermediate,
basic enough to deprotonate the alkyl nitrile, is then in-
volved in an autocatalytic process (Scheme 1). According
to this mechanism, we postulated that N-(2-hydroxyphe-
nyl)aldimine sodium salts might display a favorable prox-
imity effect6 between the putative activated ETSA (2a)
and the imine double bond to promote the formation of b-
OH
1) NaH (1 equiv)
THF (0.8 mL)
O
N
N
2) TMSCH2CO2Et
OH
(2a, 1 equiv)
Ph
85% conversion
Ph
4aa
EtCN (1.2 mL)
1a
(0.5 mmol)
Scheme 2 Effect of the solvent on the course of Mannich-type
addition of ETSA
SYNLETT 2009, No. 15, pp 2437–2440
Advanced online publication: 27.08.2009
x
x
.x
x
.2
0
0
9
DOI: 10.1055/s-0029-1217729; Art ID: G18909ST
© Georg Thieme Verlag Stuttgart · New York

2438
V. Gembus et al.
LETTER
Table 2 ETSA Addition to Various Unactivated Imines
It is worth noting that conducting the reaction with N-(3-
hydroxyphenyl)benzaldimine (1b), no b-lactam could be
detected. The only product of the reaction was the prop-
ionitrile addition product 3b obtained as a 1:1 mixture of
diastereomers in 52% isolated yield.8 These findings point
out the importance of the position of the Lewis base (i.e.
sodium phenoxide) to set properly the activated ETSA
with respect to imine function, while strongly arguing in
favor of an intramolecular activation process (Scheme 3).
R
R
N
1) NaH (1 equiv),
THF (1.5 mL)
O
N
2) TMSCH2CO2Et
(2a, 1.5 equiv)
EtCN (0.5 mL)
Ar
Ar
1a,c–m
(0.5 mmol)
4aa,ca–ma
Entry
1
1
Ar
R
4: yield (%)a
4aa: 69
4ca: 63b
4da: 58b
4ea: 62b
4fa: 25c
4ga: 60b
4ha: 58
4ia: 68b
4ja: 40
1a
1c
1d
1e
1f
Ph
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
H
1) NaH (1 equiv)
THF (0.8 mL)
2
2-naphthyl
3,4-OCH2OC6H3
4-MeOC6H4
4-(Me)2NC6H4
4-PhC6H4
4-EtC6H4
4-ClC6H4
4-CNC6H4
4-CF3C6H4
2-FC6H4
NH
OH
3
N
OH 2) TMSCH2CO2Et
(2a, 1 equiv)
CN
Ph
1b
(0.5 mmol)
EtCN (1.2 mL)
4
Ph
3b
isolated yield: 52%
5
Scheme 3 Effect of the substrate on the course of the Mannich-type
reaction
6
1g
1h
1i
7
Then, different reaction conditions were screened to en-
sure a complete conversion of 1a to 4aa (Table 1).
8
9
1j
Table 1 Optimization of the Reaction Conditions
10
11
12
1k
1l
4ka: 59
4la: 51b
4ma: 0
HO
OH
1) NaH, THF
O
2) TMSCH2CO2Et (2a)
EtCN
N
N
1m
2-HOC6H4
a Isolated yield; complete conversions were observed unless other-
wise indicated.
1a
Ph
Ph
4aa
(0.5 mmol)
b The use of 1:1 ratio of THF–EtCN was necessary to ensure complete
conversion.
Entry NaH
ETSA
Solvent A
Solvent B
(mL)
Conversion
(%)a
(equiv) (equiv) (mL)
c The use of 0.6:1.4 ratio of THF–EtCN was necessary to ensure max-
imum (42%) conversion.
1
2
3
4
5
6
7
1
1.0
1.5
1.5
1.5
1.5
1.5
1.5
EtCN (1.2) THF (0.8) 85
EtCN (1.2) THF (0.8) 100
EtCN (0.5) THF (1.5) 100
EtCN (0.1) THF (1.9) 87
1
The various substituted N-(2-hydroxyphenyl)aldimines
1a and 1c–l afforded the b-lactams 4aa, 4ca–la in modest
to good yields (Table 2, entries 1–11). Although in all cas-
es NMR analysis revealed that the reaction proceeded to
completion, aldimines 1f and 1j (Table 2, entries 5 and 9)
provided rather modest isolated yields mainly due to dif-
ficulties encountered in the purification step. Aniline
imine of 2-hydroxybenzaldehyde 1m treated with one
equivalent of sodium hydride failed to promote the reac-
tion providing further evidence for the importance of the
2-hydroxyl group on aniline moiety (Table 2, entry 12).
1
1
1
DMF (0.5)
THF (2)
THF (1.5) 55
1
–
0
0
0.2
EtCN (0.5) THF (1.5)
a Determined by 1H NMR after 2 h of reaction.
We first tried to optimize the quantity of ETSA (2a) and
we found that the use of 1.5 equivalents furnished a com-
plete conversion (Table 1, entries 1 and 2). A brief survey
of solvents revealed that THF failed to promote the reac-
tion in the absence of propionitrile, while addition of
DMF as co-solvent provided b-lactam 4aa in 55% conver-
sion (Table 1, entry 5). These findings highlight the need
to carry out the reaction in a solvent able to promote the
activation of ETSA through coordination to silicon.
We next envisaged using various substituted ETSA deriv-
atives to have access to highly substituted b-lactams.
Compounds 2b–c were easily prepared by deprotonation–
alkylation sequences in good overall yields10 (Scheme 4)
and were reacted with an assortment of aldimines 1a–k
(Table 3).
Isolated yields ranged from 38% to 70%, while as previ-
ously noticed, the reaction was completed within two
hours in almost all cases. When ETSA derivative 2c react-
ed with aldimines 1a, 1i and 1k (Table 3, entries 2, 4 and
5) some diastereoselectivity could be obtained in favor of
the trans isomer,11 while no diastereoselection was re-
Next, we investigated the scope and limitation of b-lactam
formation under the best conditions selected (i.e. THF–
EtCN;9 Table 2).
Synlett 2009, No. 15, 2437–2440 © Thieme Stuttgart · New York

LETTER
Preparation of Highly Substituted b-Lactams
2439
Bn
The first step would involve the coordination of the sili-
con atom of ETSA to the Lewis base 1-Na to form a hy-
pervalent silicon species A.13 A rapid screening of the
solvents gave some evidences that an additional coordina-
tion to silicon is crucial and suggests the formation of a
hexavalent silicon complex as the most likely reactive
species. The second step would take advantage of a favor-
able proximity effect to promote an intramolecular addi-
tion of the activated ETSA to the double bond imine; the
resulting sodium amide salt B affording the desired b-lac-
tams 4 after subsequent cyclization and hydrolysis of the
silyloxy group.
LDA (1.1 equiv)
BnBr (1.1 equiv)
90% yield
TMS
CO2Et
TMS
CO2Et
THF
2b
LDA (1.1 equiv)
MeI (2 equiv)
THF
Bn
Me
88% yield
TMS
CO2Et
2c
Scheme 4 ETSA functionalization
Table 3 Substituted ETSA Addition to Unactivated Imines
In conclusion, we have reported a straightforward ap-
proach for the preparation of b-lactams in moderate to
good yields by making use of stable ETSA or substituted
derivatives and N-(2-hydroxyphenyl)aldimines 1. The im-
portance of the solvent system in the outcome of the reac-
tion was evidenced by changing the co-solvent of the
reaction from MeCN to EtCN. Whereas the use of MeCN
lead to MeCN addition products,5 b-lactams 4 were exclu-
sively formed in the presence of propionitrile. On the ba-
sis of experimental data, an intramolecular activation of
ETSA by the sodium phenoxide salt has been suggested as
a key mechanistic element in the formation of ETSA ad-
dition products. Furthermore, N-(2-hydroxyphenyl)ald-
imines 1 may offer the advantage of easy removal of the
N-aryl group in b-lactams 4 by an O-methylation–CAN
[or PhI(OAc)2] deprotection sequence6b,d or by a direct
CAN deprotection.14
OH
HO
N
O
1) NaH (1 equiv),
THF (0.6 mL)
N
H
R2
R2 R3
2)
R3
(1.5 equiv)
CO2Et
2b,c
EtCN (1.4 mL)
1
TMS
4
(0.5 mmol)
R1
R1
Entry
1
R1
H
2
R2 R3 4: Yield (%)a cis/transb
1
2
3
4
5
1a
1a
2b Bn
H
4ab: 58
54:46
30:70
46:54
22:78
24:76
H
2c Bn Me 4ac: 56
1e OMe 2c Bn Me 4ec: 38c
1i
Cl
2c Bn Me 4ic: 70
1k CF3
2c Bn Me 4kc: 43
References and Notes
a Isolated yield; complete conversions were observed unless other-
wise indicated.
(1) Von Nussbaum, F.; Brands, M.; Hinzen, B.; Weigand, S.;
Häbich, D. Angew. Chem. Int. Ed. 2006, 45, 5072.
(2) Alcaide, B.; Almendros, P.; Aragoncillo, C. Chem. Rev.
2007, 107, 4437.
(3) Brandi, A.; Cicchi, S.; Cordero, F. M. Chem. Rev. 2008, 108,
3988.
(4) (a) Takahashi, E.; Fujisawa, H.; Yanai, T.; Mukaiyama, T.
Chem. Lett. 2005, 34, 216. (b) Takahashi, E.; Fujisawa, H.;
Yanai, T.; Mukaiyama, T. Chem. Lett. 2005, 34, 994.
(c) Matsukawa, S.; Obu, K. Chem. Lett. 2004, 33, 1626.
(d) Fujieda, H.; Kanai, M.; Kambara, T.; Iida, A.; Tomioka,
K. J. Am. Chem. Soc. 1997, 119, 2060.
b Ratio determined by 1H NMR of the crude product.
c Conversion: 80%.
corded in the other experiments (Table 3, entries 112 and
3).
Although not clearly elucidated, a plausible mechanism is
proposed in Scheme 5.
–
Na+
(5) Poisson, T.; Gembus, V.; Oudeyer, S.; Marsais, F.;
Levacher, V. J. Org. Chem. 2009, 74, 3516.
ETSA
EtCN
O
N
(6) For examples of the beneficial effect of the 2-aminophenol-
derived imines in nucleophilic addition reactions, see:
(a) Kobayashi, S.; Komiyama, S.; Ishitani, H. Angew. Chem.
Int. Ed. 1998, 37, 979. (b) Ishitani, H.; Komiyama, S.;
Hasegawa, Y.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122,
762. (c) Xue, S.; Yu, S.; Deng, Y.; Wulff, W. D. Angew.
Chem. Int. Ed. 2001, 40, 2271. (d) Sugiura, M.; Robvieux,
F.; Kobayashi, S. Synlett 2003, 1749. (e) Akiyama, T.; Itoh,
J.; Yokota, K.; Fuchibe, K. Angew. Chem. Int. Ed. 2004, 43,
1566. (f) Rabbat, P. M. A.; Corey Valdez, S.; Leighton, J. L.
Org. Lett. 2006, 8, 6119. (g) Jagtap, S. B.; Tsogoeva, S. B.
Chem. Commun. 2006, 4747.
N
Si
EtCN
ONa
1-Na
Ar
Ar
EtO2C
A
intramolecular addition
Na+
OTMS
N–
OH
O
1) cyclization
2) hydrolysis
O
N
Ar
OEt
Ar
(7) Typical Procedure for the Preparation of 3a: To a
suspension of NaH (0.5 mmol, 0.013 g) in THF (0.4 mL) was
added imine (0.5 mmol) as a solution in THF (0.4 mL). Then
MeCN (1.2 mL) was added. After 5 min, TMSCH2CO2Et
4
B
Scheme 5 Proposed mechanism for the formation of b-lactams
Synlett 2009, No. 15, 2437–2440 © Thieme Stuttgart · New York

2440
V. Gembus et al.
LETTER
(0.092 mL, 0.5 mmol) was added and the resulting mixture
was stirred until complete disappearance of the starting
materials. The solution was poured into brine and extracted
with Et2O (2 × 10 mL). The combined organic layers were
dried over MgSO4, and concentrated. The residue was
purified by flash chromatography to afford the
7.04–7.07 (m, 4 H), 7.30–7.42 (m, 5 H), 7.54 (d, J = 8.8 Hz,
2 H), 9.79 (s, 1 H). 13C NMR (75 MHz, CDCl3): d = 16.8,
41.8, 57.0, 62.2, 117.9, 119.3, 119.9, 124.8, 125.7, 125.8,
125.9, 125.95, 126.0, 127.0, 127.1, 127.6, 128.9, 130.2,
130.3, 130.7, 135.8, 138.5, 147.8, 171.9.
cis Isomer (trans/cis mixture = 63:36): pale yellow oil;
Rf 0.28 (30% Et2O in PE). 1H NMR (300 MHz, CDCl3): d =
1.50 (s, 3 H), 2.26 (d, J = 14.1 Hz, 1 H), 2.74 (d, J = 14.1 Hz,
1 H), 5.04 (s, 1 H), 6.43 (app. d, J = 7.6 Hz, 1 H), 6.60–6.67
(m, 1 H), 6.90–6.94 (m, 2 H), 7.03–7.08 (m, 3 H), 7.09–7.13
(m, 3 H), 7.30–7.41 (m, 1 H), 7.57 (app. d, J = 8.1 Hz, 2 H),
9.85 (s, 1 H). 13C NMR (75 MHz, CDCl3): d = 21.0, 38.6,
56.1, 66.3, 118.1, 119.6, 120.1, 125.2, 126.15, 126.2,
126.25, 126.3, 127.0, 127.2, 127.8, 129.2, 130.2, 130.4,
135.6, 138.4, 148.1, 172.0. FTIR (KBr): 748, 1068, 1125,
1168, 1326, 1498, 1714, 2929, 3067 cm–1. HRMS (EI): m/z
calcd for C24H20NO2F3: 411.1446; found: 411.1450.
(10) Typical Procedure for the Preparation of 2b and 2c: To a
solution of diisopropylamine (1.1 equiv) in anhyd THF was
added n-BuLi (2.5 M in hexane, 1.1 equiv) dropwise at –78
°C under nitrogen. The solution was warmed to r.t. for 10
min, then cooled to –78 °C prior to addition of ETSA (1
equiv) dropwise over 5 min. The solution was maintained at
–78 °C for further 1 h before addition of the electrophile (1.1
equiv for BnBr or 2 equiv for MeI). The resulting solution
was warmed to r.t. and stirred until complete disappearance
of the starting materials. Saturated aq NH4Cl solution was
added and the mixture was extracted with EtOAc (2 × 20
mL). The combined organic layers were washed with brine
and then dried over anhyd MgSO4. The residue was purified
by flash chromatography to afford the alkylated product.
Spectral data of 2b were in agreement with those described
in the literature: Kuwajima, I.; Matsumoto, K.; Inoue , T.
Chem. Lett. 1979, 8, 41.
corresponding cyanomethylated product.
3-Phenyl-3-(2-hydroxyphenylamino)propanenitrile (3a):
orange solid; mp 119–120 °C. Purification: SiO2; 30% Et2O
in PE. 1H NMR (300 MHz, CDCl3): d = 2.86 (d, J = 6.2 Hz,
2 H), 4.72 (t, J = 6.4 Hz, 1 H), 6.52 (d, J = 7.9 Hz, 1 H), 6.62–
6.68 (m, 1 H), 6.73–6.78 (m, 2 H), 7.31–7.43 (m, 5 H). 13
C
NMR (75 MHz, CDCl3): d = 26.4, 54.9, 113.8, 114.8, 117.5,
119.3, 121.4, 126.3, 128.5, 129.2, 134.5, 140.0, 144.3. FTIR
(KBr): 610, 703, 734, 1128, 1199, 1244, 1445, 1510, 1522,
1613, 2264, 3380 cm–1. HRMS (EI): m/z calcd for
C15H14N2O: 238.1106; found: 238.1111.
(8) Spectral Data for 2-Methyl-3-phenyl-3-(3-hydroxy-
phenylamino)propanenitrile (3b): pale yellow solid; mp
<50 °C (syn/anti = 1:1 mixture). Purification: SiO2; 30–50%
Et2O in PE. 1H NMR (300 MHz, CDCl3;
syn/anti = 1:1 mixture): d = 1.12 (d, J = 7.2 Hz, 3 H), 1.27
(d, J = 7.2 Hz, 3 H), 2.29–2.95 (m, 1 H), 3.11–3.17 (m, 1 H),
4.32–4.37 (m, 1 H + 1 H), 5.98–6.00 (m, 2 H), 6.07–6.12 (m,
4 H), 6.83–6.90 (m, 2 H), 7.16–7.23 (m, 10 H). 13C NMR (75
MHz, CDCl3; syn/anti = 1:1 mixture): d = 14.9, 16.0, 59.4,
59.9, 101.1, 105.8, 105.9, 106.8, 120.9, 126.0, 126.6, 127.3,
128.4, 128.6, 129.0, 130.3, 130.4, 130.5, 137.9, 139.6,
147.6, 147.9, 156.8, 156.9. FTIR (KBr): 772, 1161, 1219,
1338, 1599, 1732, 2921, 3378 cm–1. HRMS (EI): m/z calcd
for C16H16N2O: 252.1263; found: 252.1272.
(9) Typical Procedure for the Preparation of 4: To a
suspension of NaH (0.5 mmol, 0.013 g) in THF (0.5 mL) was
added imine (0.5 mmol) as a solution in THF (1 mL). Then
EtCN (0.5 mL) was added. After 5 min, TMSCH2CO2Et
(0.138 mL, 0.75 mmol) was added and the resulting mixture
was stirred until complete disappearance of the starting
materials. The solution was poured into brine and extracted
with Et2O (2 × 10 mL). The combined organic layers were
dried over MgSO4, and concentrated. The residue was
purified by flash chromatography to afford the
Ethyl 2-Methyl-3-phenyl-2-(trimethylsilyl)propanoate
(2c): colorless oil. Purification: SiO2; 0–2% EtOAc in PE; Rf
0.73 (10% EtOAc in PE). 1H NMR (300 MHz, CDCl3): d =
0.00 (s, 9 H), 0.91 (s, 3 H), 1.09 (t, J = 7.2 Hz, 3 H), 2.33 (d,
J = 13.4 Hz, 1 H), 3.40 (d, J = 13.4 Hz, 1 H), 3.96 (q, J = 7.0
Hz, 2 H), 6.97–7.10 (m, 5 H). 13C NMR (75 MHz, CDCl3):
d = –4.1, 14.2, 15.9, 20.6, 37.9, 38.9, 59.6, 125.9, 127.8,
129.5, 176.0. FTIR (KBr): 844, 1180, 1199, 1252, 1262,
1454, 1715, 2963, 3030 cm–1. HRMS: m/z [M + H]+ calcd for
C15H24O2Si: 265.1624; found: 265.1631..
corresponding b-lactam.
1-(2-Hydroxyphenyl)-4-(2-naphthyl)azetidin-2-one
(4ca): pale yellow solid; mp 136–138 °C. Purification: SiO2;
20–30% Et2O in PE; Rf 0.56 (33% EtOAc in PE). 1H NMR
(300 MHz, CDCl3): d = 2.99 (dd, J = 15.6, 2.4 Hz, 1 H), 3.58
(dd, J = 15.4, 5.4 Hz, 1 H), 5.22 (dd, J = 2.3, 1.8 Hz, 1 H),
6.54–6.62 (m, 2 H), 6.99–7.04 (m, 2 H), 7.43–7.55 (m, 3 H),
7.83–7.89 (m, 4 H), 9.92 (s, 1 H). 13C NMR (75 MHz,
CDCl3): d = 43.9, 54.3, 117.6, 119.0, 119.8, 122.7, 125.6,
125.9, 126.7, 126.9, 127.9, 128.0, 129.6, 133.3, 133.5,
134.4, 147.7, 166.2. FTIR (KBr): 742, 1377, 1495, 1707,
2967, 3016 cm–1. HRMS (EI): m/z calcd for C19H15NO2:
289.1103; found: 289.1106.
(11) A NOESY experiment was conducted on trans-4kc. Strong
NOE correlation was observed between CH2Ph and H(4)
indicating a cis relationship between these substituents. The
stereochemistry of the other b-lactams 4 was assigned by
extrapolation of these findings along with the fact that H(4)
of the major isomer always exhibit a higher chemical shift
than that observed in the minor isomer.
(12) cis- and trans-b-Lactam 4ab resulting from the reaction with
2b can be easily identified by comparison with literature
data: Jiao, L.; Liang, Y.; Xu, J. J. Am. Chem. Soc. 2006, 128,
6060.
3-Benzyl-1-(2-hydroxyphenyl)-3-methyl-4-[4-
(trifluoromethyl)phenyl]azetidin-2-one (4kc):
purification: SiO2; 10–15% Et2O in PE.
trans Isomer: white solid; mp 154–156 °C; Rf 0.47 (30%
Et2O in PE). 1H NMR (300 MHz, CDCl3): d = 0.93 (s, 3 H),
3.09 (d, J = 14.0 Hz, 1 H), 3.26 (d, J = 13.9 Hz, 1 H), 5.17
(s, 1 H), 6.32 (dd, J = 0.8, 7.7 Hz, 1 H), 6.61–6.67 (m, 1 H),
(13) For examples of such hexavalent silicon species, see:
(a) Fujisawa, H.; Nakagawa, T.; Mukaiyama, T. Adv. Synth.
Catal. 2004, 346, 1241. (b) Kawano, Y.; Fujisawa, H.;
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Synlett 2009, No. 15, 2437–2440 © Thieme Stuttgart · New York

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