A novel synthesis of 1-nosyl 3,3-dichloro-β-lactams and derivatives

Article abstract of DOI:10.1021/jo8014193

(Chemical Equation Presented) We report herein an efficient and simple route to synthesize 1-nosyl 3,3-dichloro-β-lactams using a Staudinger reaction between N-nosyl imines and dichloroketene. The resulting dichloroazetidines were opened to afford highly functionalized building blocks.

Full text of DOI:10.1021/jo8014193

SCHEME 1. Synthesis of Lactams 4
A Novel Synthesis of 1-Nosyl
3,3-Dichloro-ꢀ-Lactams and Derivatives
Francisco Tato,* Vincent Reboul,* and Patrick Metzner
Laboratoire de Chimie Mole´culaire et Thio-organique,
ENSICAEN, UniVersite´ de Caen Basse-Normandie, CNRS, 6,
BouleVard du Mare´chal Juin, 14050, Caen, France
tionalization5 and their biological activities, especially as
antibacterial agents.6
Vincent.reboul@ensicaen.fr
ReceiVed June 30, 2008
Generally, the Staudinger reaction uses ketenes bearing alkyl
or aryl groups. Surprisingly, the use of dichloroketene7 as the
starting material has received much less attention, and its
reactivity has been studied only for N-alkyl8 or N-aryl imines.9
The latter method provided 3,3-dichloroazetidin-2-one, which
creates room for additional functionalization at the site bearing
the halogen substituents.10 Harmoniously with our continuing
interest in the reactivity of dichloroketene,11 this finding has
led us to examine the Staudinger reaction with imines possessing
an electron-withdrawing group, which thereafter could be easily
removed.
The preparation of dichloroketene, which is unstable and
polymerizes readily,12 has been performed by a dehydrohalo-
genation reaction of dichloroacetyl chloride (2 equiv) in the
presence of a Lewis base (2 equiv). Initially, various ben-
zylidenimines with different electron-withdrawing groups at-
tached to the nitrogen atom were investigated (Scheme 1 and
Table 1).
We report herein an efficient and simple route to synthesize
1-nosyl 3,3-dichloro-ꢀ-lactams using a Staudinger reaction
between N-nosyl imines and dichloroketene. The resulting
dichloroazetidines were opened to afford highly functional-
ized building blocks.
Although phosphinoylimines 1 and tosylimines 2 did not react
as expected (Table 1, entries 1 and 2),13 we found that the use
(5) For leading references on the chemistry of ꢀ-lactams, see: (a) Palomo,
C.; Aizpurua, J. M.; Ganboa, I.; Oiarbide, M. Synlett 2001, 1813. (b) Deshmukh,
A. R. A. S.; Bhawal, B. M.; Krishnaswamy, D.; Govande, V. V.; Shinkre, B. A.;
Jayanthi, A. Curr. Med. Chem. 2004, 11, 1889. (c) Alcaide, B.; Almendros, P.
Curr. Med. Chem. 2004, 11, 1921. (d) Alcaide, B.; Almendros, P.; Aragoncillo,
C. Chem. ReV. 2007, 4437.
(6) For leading references on the biological activity of ꢀ-lactams, see: (a)
Chemistry and Biology of ꢀ-Lactam Antibiotics; Morin, R. B.; Gorman, M., Eds.;
Academic Press: New York, 1982; Vols. 1-3. (b) Burnett, D. A. Curr. Med.
Chem. 2004, 11, 1873. (c) Buynak, J. D. Curr. Med. Chem. 2004, 11, 1951. (d)
Niccolai, D.; Tarsi, L.; Thomas, R. J. Chem. Commun. 1997, 2333.
(7) Recent uses of dichloroketene: (a) Brocksom, T. J.; Coelho, F.; Depres,
J.-P.; Greene, A. E.; Freire de Lima, M. E.; Hamelin, O.; Hartmann, B.;
Kanazawa, A. M.; Wang, Y. J. Am. Chem. Soc. 2002, 124, 15313. (b) Roche,
C.; Kadlecikova, K.; Veyron, A.; Delair, P.; Philouze, C.; Greene, A. E.; Flot,
D.; Burghammer, M. J. Org. Chem. 2005, 70, 8352. (c) Padwa, A.; Nara, S.;
Wang, Q. J. Org. Chem. 2005, 70, 8538. (d) Wang, Q.; Nara, S.; Padwa, A.
Org. Lett. 2005, 7, 839. (e) Marino, J. P.; Zou, N. Org. Lett. 2005, 7, 1915. (f)
Ceccon, J.; Greene, A. E.; Poisson, J.-F. Org. Lett. 2006, 8, 4739. (g) Ussing,
B. R.; Hang, C.; Singleton, D. A. J. Am. Chem. Soc. 2006, 128, 7594. (h) Tidwell,
T. T. Sci. Synth. 2006, 23, 101.
(8) (a) Van Brabant, W.; Dejaegher, Y.; De Kimpe, N. Pure Appl. Chem.
2005, 77, 2061. (b) Dejaegher, Y.; Mangelinckx, S.; De Kimpe, N. J. Org. Chem.
2002, 67, 2075.
(9) Khajavi, M. S.; Sefidkon, F.; Hosseini, S. S. S. J. Chem. Res., Synop.
1998, 11, 724.
(10) Dejaegher, Y.; Denolf, B.; Stevens, C. V.; De Kimpe, N. Synthesis 2005,
193.
(11) Blot, V.; Reboul, V.; Metzner, P. Eur. J. Org. Chem. 2006, 1934.
(12) (a) Brady, W. T.; Liddell, H. G.; Vaughn, W. L. J. Org. Chem. 1966,
31, 626. (b) Brady, W. T.; Waters, O. H. J. Org. Chem. 1967, 32, 3703.
(13) The dehalogenation reaction of trichloroacetyl chloride in the presence
of the Zn-Cu amalgam did not afford satisfactory results due to the decomposi-
tion of starting imines 1-3.
The reaction between imines and ketenes to form the
corresponding ꢀ-lactams1 through a formal [2 + 2]-cycloaddi-
tion was discovered by Staudinger2 over a century ago. This
method represents one of the most effective routes for preparing
these compounds,3 and recently, catalytic asymmetric versions
have been developed.4 In addition, the chemistry of ꢀ-lactams
has received significant attention due to their selective func-
(1) (a) Ternansky, R. J.; Jr. In The Organic Chemistry of ꢀ-Lactams; Georg,
G. I., Ed.; Verlag Chemie: New York, 1993; p 257. (b) Singh, G. S. Tetrahedron
2003, 59, 7631.
(2) Staudinger, H. Justus Liebigs. Ann. Chem. 1907, 356, 51.
(3) (a) Palomo, C.; Aizpurua, J. M.; Ganboa, I.; Oiarbide, M. Curr. Med.
Chem. 2004, 11, 1837. (b) Palomo, C.; Aizpurua, J. M.; Ganboa, I.; Oiarbide,
M. Eur. J. Org. Chem. 1999, 3223. (c) Jiao, L.; Liang, Y.; Xu, J. J. Am. Chem.
Soc. 2006, 128, 6060.
(4) (a) Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Drury, W. J., III.;
Lectka, T. J. Am. Chem. Soc. 2000, 122, 7831. (b) Taggi, A. E.; Hafez, A. M.;
Wack, H.; Young, B.; Ferraris, D.; Lectka, T. J. Am. Chem. Soc. 2002, 124,
6626. (c) Hodous, B. L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 1578. (d)
Hodous, B. L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 1578. (e) Fu, G. C. Acc.
Chem. Res. 2004, 37, 542. (f) France, S.; Weatherwax, A.; Taggi, A. E.; Lectka,
T. Acc. Chem. Res. 2004, 37, 592. (g) France, S.; Shah, M. H.; Weatherwax,
A.; Wack, H.; Roth, J. P.; Lectka, T. J. Am. Chem. Soc. 2005, 127, 1206. (h)
Lee, E. C.; Hodous, B. L.; Bergin, E.; Shih, C.; Fu, G. C. J. Am. Chem. Soc.
2005, 127, 11586. (i) Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org.
Lett. 2008, 10, 277. (j) Duguet, N.; Campbell, C. D.; Slawin, A. M. Z.; Smith,
A. D. Org. Biomol. Chem. 2008, 6, 1108.
10.1021/jo8014193 CCC: $40.75
Published on Web 09/09/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 7837–7840 7837

TABLE 1. Reaction Conditions for the Synthesis of Lactams 4
TABLE 2. Synthesis of 3,3-Dichloro-ꢀ-Lactams
entry
imine
base
solvent
% conv.a
conv.a
entry
Ar (imine)
Ph (3a)
Ph (3a)
compound time (h) temp (°C) (yield)b
1
2
3
4
5
6
7
8
9
1
2
3
3
3
3
3
3
3
3
i-Pr2NEt
CH2Cl2
CH2Cl2
CH2Cl2
toluene
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
0
i-Pr2NEt or Et3N
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
Et3N
1
2
3
4
4a
4a
4a
4b
4b
4b
4b
4b
4c
4c
4c
4d
4e
4f
24
3
1
24
10
4
10
15
24
4
15
15
15
16
2
-78
0
rt
-78
0
rt
96
100 (80)
100
84
44
39
67
100 (82)
86
28
100 (77)
0
0
99
100 (85)
100
100 (79)
96
60
62
95
97
93
47
89
Ph (3a)
2-naphthyl (3b)
2-naphthyl (3b)
2-naphthyl (3b)
2-naphthyl (3b)
2-naphthyl (3b)
4-i-Pr-C6H4 (3c)
4-i-Pr-C6H4 (3c)
5c
6c
7d
8d,e
9d
10c
Me2NEt
Cy2NMe
pempidineb
BEMPc
0
-40
-78
rt
-40
-40
-40
-78
0
10
a Estimated by 1H NMR. b 1,2,2,6,6-Pentamethylpiperidine. c 2-tert-Butyli-
mino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine.
11d,e 4-i-Pr-C6H4 (3c)
12
13
14
15
16
17
4-Me2N-C6H4 (3d)
2-MeO-C6H4 (3e)
3-CN-C6H4 (3f)
3-CN-C6H4 (3f)
3-CN-C6H4 (3f)
2-F-C6H4 (3g)
SCHEME 2. Synthesis of ꢀ-Lactams 4a-g
4f
4f
0.3
rt
0
4g
2
a Estimated by 1H NMR. b Isolated yield (%) after crystallization.
c No further conversion was observed at longer reaction times. d Slow
addition of dichloroacetyl chloride for 3 h. e Three equivalents of base
and dichloroacetyl chloride were used.
SCHEME 3. Asymmetric Synthesis of ꢀ-Lactam 4a
of a nosyl group14 (3) substituted on the nitrogen atom afforded
the corresponding ꢀ-lactams in very high conversion degrees
(entry 3) when the reaction was performed in CH2Cl2.15
The use of both more polar solvent and less polar solvents
gave a significant decrease in conversion (entries 4 and 5). We
studied the effect of several amine bases, modulating both the
steric bulk and basicity of each. It was found that the bases
Et3N, Me2NEt, and Cy2NMe led to the formation of ꢀ-lactam
4 in similarly high conversion (entries 6-8). However, a
decrease in the reaction conversion was observed for the
pempidine base (entry 9), probably due to a lower efficiency in
the ketene formation. Moreover, the bulkiest amine BEMP
(entry 10) unexpectedly gave the ꢀ-lactam 4 also in high
conversion.
The scope of the reaction was then explored with several
substituted aromatic N-nosyl imines (Scheme 2 and Table 2),16
using the previously optimized conditions: Hu¨nig’s base (2
equiv) and dichloroacetyl chloride (2 equiv) in CH2Cl2 at
different temperatures.
The conversion was very high for the ꢀ-lactam 4a at -78
°C (Table 2, entry 1). Other imines provided the corresponding
ꢀ-lactams in only moderate conversion.17 Nevertheless, this
could be improved by performing the reaction at 0 °C or room
temperature, leading to very high conversion in both cases, and
the reaction times of 3 and 1 h, respectively (Table 2, entries 2
and 3). For the imine 3b, the conversion was higher at lower
temperature (-78 °C) than at 0 °C or room temperature (Table
2, entries 4-6), probably due to the decomposition of the ketene.
Decomposition can be partially avoided by a slow addition of
TABLE 3. Reaction in the Presence of Chiral Lewis Bases
entry
catalyst
conv. (%)a
ee (%)b
1
2
3
4
sparteine
benzoylquinidine
quinidine
79
75
80
77
0
0
8
TMS-quinidine
20
a Estimated by 1H NMR. b Enantiomeric excess was determined by
HPLC analysis (Daicel IC).
dichloroacetyl chloride over 3 h (Table 2, entry 7). The best
results were obtained when the reaction was carried out at -40
°C using 3 equiv of base and dichloroacetyl chloride (Table 2,
entry 8). A similar result was obtained with imine 3c (Table 2,
entry 11). However, all the attempts to synthesize ꢀ-lactam 4d
or 4e were unsuccessful due to the insolubility of the imines
3d and 3e, which were recovered. On the other hand, the
presence of an electron-withdrawing group (3-CN and 2-F)
enhanced the reactivity. Thus, the imines 3f and 3g gave the
corresponding ꢀ-lactams 4f and 4g with complete conversion
(Table 2, entries 14-17).
The asymmetric version of the Staudinger reaction is de-
scribed in the literature for alkyl and arylketenes, usually
employing catalytic amounts of a chiral Lewis base.4 With this
idea in mind, we have attempted the preparation of 3,3-dichloro-
ꢀ-lactam 4a in the presence of enantiopure tertiary amines such
as sparteine or quinidine derivatives in the presence of Hu¨nig’s
base (Scheme 3 and Table 3).18
(14) N-Nosyl imines were also used in the Staudinger reaction with
arylalkylketenes: Sereda, O.; Wilhelm, R. Synlett 2007, 19, 3032.
(15) The best conditions were obtained using 2 equiv of base and slowly
adding acetyl chloride (2 equiv) for 2 h, in order to avoid the decomposition
and polymerization of dichloroketene.
(16) Aromatic N-nosyl imines were prepared by reaction between 4-nitroben-
zenesulfonamide and aldehydes (see Supporting Information), catalyzed by
(EtO)4Si at high temperature (73-89% yield): (a) Hayashi, T.; Ishigedani, M.
J. Am. Chem. Soc. 2000, 122, 976. (b) Love, B. E.; Raje, P. S.; Williams, T. C.,
II. Synlett 1994, 493.
The use of sparteine or benzoylquinidine did not provide any
enantiomeric excess (Table 3, entries 1 and 2). However, in
(17) The purification on both silica gel and aluminum oxide was not effective
due to the decomposition of most products. Simple crystallization was more
efficient.
(18) This base should not attack the ketene because of its steric
hindrance: Tennyson, R.; Romo, D. J. Org. Chem. 2000, 65, 7248.
7838 J. Org. Chem. Vol. 73, No. 19, 2008

SCHEME 4. Derivatization of ꢀ-Lactam 4a
SCHEME 6. Synthesis of Thioester 8
SCHEME 7. Different Mechanistic Routes for the
Staudinger Reaction
SCHEME 5. Synthesis of ꢀ-Aminoamide 7
the presence of quinidine, some stereoselectivity was observed,
affording the product in 8% ee (Table 3, entry 3). An
improvement in stereoselectivity to 20% ee was accomplished
with the use of TMS-quinidine (Table 3, entry 4).19
Next, we studied the possibility of derivatizing these com-
pounds through simple reactions, such as opening the ꢀ-lactam
ring by esterification to obtain ꢀ-aminoester 5 and reduction to
prepare the 1,3-aminoalcohol 6 (Scheme 4).
SCHEME 8. Mechanistic Routes Using Dichloroketene
We previously observed the unstability of the ꢀ-lactams
during purification on silica gel. Therefore, we used this solid
support as an acid catalyst to perform the esterification. Thus,
when silica gel was added to a solution of compound 4a in
EtOH, ꢀ-aminoester 5 was obtained in 97% yield. Treatment
of ꢀ-lactam 4a with LiAlH4 provided its complete reduction to
afford the corresponding 1,3-aminoalcohol 6 in 78% yield.
Finally, the preparation of the ꢀ-aminoamide 7 was also
accomplished in the presence of benzylamine in 83% yield
without any purification of the intermediate (Scheme 5).
Other transformations such as the reduction of the 2-azeti-
dinone ring to the azetidine were attempted. Several reducing
agents such as AlH2Cl,20 BH3 ·SMe2,21 NaBH4/I2,22 or LiEt3BH/
We have made a step toward the understanding of the
mechanism of this reaction as well as the high levels of
conversion even with the bulkiest amines. Traditionally, the
Staudinger reaction consists in the attack of the imine nitrogen
lone electron pair to the central atom of the ketene (Scheme 7,
route A). However, this only occurs with N-alkyl or N-aryl
imines and stable ketenes such as diphenylketene. For the imines
with electron-withdrawing groups attached at the nitrogen atom,
this route is not favored due to the poor nucleophilic character
of the nitrogen atom. Another possibility is that the reaction
could also be promoted by the tertiary amine (used to prepare
the ketene in situ), to form a zwitterionic enolate, which reacts
with the electrophilic imine carbon, affording the corresponding
ꢀ-lactam (Scheme 7, route B). However, route B could not
explain the results obtained in this communication, as bulky
amines such as i-Pr2NEt should not be able to attack the ketene
due to steric hindrance.18
23
Et3SiH-Et2O·BF3 were assayed, but all the attempts were
unsuccessful, affording only the corresponding 1,3-aminoalcohol
6 in moderate yield.
Removal of the nosyl group was also examined with thiolate
anion, as reported in the literature.24 However, as could be
expect, the thiolate anion reacted with the amide group of the
ꢀ-lactam without deprotection of the sulfonyl group, giving the
corresponding thioester 8 (Scheme 6).25
(19) Different experimental conditions such as solvents (THF, toluene, Et2O),
bases (K2CO3, NaH, Bu3N, Cy2MeN, pempidine, BEMP, phosphazene-P2-t-Bu),
and catalysts (from 0.1 to 0.3 equiv) and addition modes of acyl chloride were
tested. Nevertheless, no improvement in the enantiomeric excess was observed,
leading to poorer results than the 20% ee achieved with TMS-quinidine. It is
important to note that, in all assays, the reaction provided the ꢀ-lactam 4a in
high conversion (>85%).
(20) (a) Van Driessche, B.; Van Brabandt, W.; D’hooghe, M.; Dejaegher,
Y.; De Kimpe, N. Tetrahedron 2006, 62, 6882. (b) Van Brabandt, W.; De Kimpe,
N. Synlett 2006, 2039.
(21) Hu, W.-P.; Tsai, P.-C.; Hsu, M.-K.; Wang, J.-J. J. Org. Chem. 2004,
69, 3983.
(22) Haldar, P.; Ray, J. K. Tetrahedron Lett. 2003, 44, 8229.
(23) Pedregal, C.; Ezquerra, J.; Escribano, A.; Carren˜o, M. C.; Ruano, L. C.
Tetrahedron Lett. 1994, 35, 2053.
Alternatively, we could consider the reaction between the
imine and the tertiary amine as described by Fu with N-triflyl
imine (Scheme 8, route C).4h
1
However, no evidence for the adduct 9 was found by H
NMR26 at low temperature or by in situ IR.27 Therefore, we
propose another route wherein dichloroketene behaves as a
nucleophilic species (Scheme 8, route D), able to attack the
imine (through a resonance hybrid more important in dichlo-
(24) (a) Kan, T.; Fukuyama, T. Chem. Commun. 2004, 353. (b) Kurosawa,
W.; Kan, T.; Fukuyama, T. Org. Synth. 2002, 79, 186. (c) Fukuyama, T.; Jow,
C.-K.; Cheung, M. Tetahedron Lett. 1995, 36, 6373.
(25) The deprotection of the N-nosyl group of 8 was never observed even
when an excess of thiolate was used.
J. Org. Chem. Vol. 73, No. 19, 2008 7839

44.90; H, 2.51; N, 6.98. Found: C, 44.97; H, 2.82; N, 6,74. HPLC
(Diacel IC column; CH2Cl2/heptane 1:1; flow: 1 mL/min): T ) 9.96
and 11.04.
roketene than in the case of alkylketenes), as reported with
electron-poor aldehydes.28 This route could also account for our
poor results on the asymmetric induction of this reaction.
In conclusion, a straightforward methodology preparing 3,3-
dichloro-ꢀ-lactams in high yields was developed following the
Staudinger reaction between dichloroketene and N-nosyl imines.
Additionally, the preparation of corresponding derivatives such
as ꢀ-aminoesters, 1,3-aminoalcohols, and ꢀ-aminoamides was
also performed in high yields by simple transformations.
Typical Procedure for the Preparation of 3,3-Dichloro-ꢀ-
lactams 4b and 4c (Table 2, entry 8, ꢀ-lactam 4b as an example):
Diisopropylethylamine (0.6 mmol) was added to a solution of imine
3b (0.2 mmol) in CH2Cl2 (2 mL) at -40 °C and under N2
atmosphere. Dichloroacetyl chloride (0.6 mmol) in CH2Cl2 (1 mL)
was slowly added by syringe pump for 3 h. The reaction was stirred
at -40 °C for 15 h and hydrolyzed as previously indicated. After
crystallization from EtOAc/heptane, ꢀ-lactam 4b was obtained as
a white solid in 82% yield: mp 167.7-169.3 °C; IR ν 3106, 1817,
Experimental Section
1
1532, 1385, 1347, 1180, 1137, 739 cm-1; H NMR (400 MHz,
Typical Procedure for the Preparation of 3,3-Dichloro-ꢀ-
lactams 4a, 4f, and 4g (Table 2, entry 2, ꢀ-lactam 4a as an
example): Diisopropylethylamine (0.4 mmol) was added to a
solution of imine 3a (0.2 mmol) in CH2Cl2 (2 mL) at 0 °C and
under N2 atmosphere. Dichloroacetyl chloride (0.4 mmol) was then
added, and the reaction was stirred for 3 h. The reaction mixture
was hydrolyzed with a solution of 10% HCl (2 mL), and the organic
layer was washed with brine (2 mL), dried over MgSO4, and
evaporated under vacuum. The residue was purified by chroma-
tography on silica gel column (acetone/pentane 1:8) to provide the
desired ꢀ-lactam 4a as a white solid in 80% yield: mp 134.1-135.5
°C (EtOAc/heptane); IR ν 3106, 1820, 1528, 1385, 1352, 1180,
CDCl3) δ 8.35 and 8.07 (AA′BB′ system, 4H), 7.91-7.64 (m, 4H),
7.52-7.52 (m, 2H), 7.18 (dd, J ) 8.5 and 1.4 Hz, 1H), 5.67 (s,
1H) ppm; 13C NMR (100.6 MHz, CDCl3) δ 157.7, 151.4, 142.7,
134.1, 132.7, 129.5, 128.9, 128.7, 128.2, 128.0, 127.8, 127.7, 127.3,
124.8, 124.2, 83.9, 77.3 ppm; MS (EI+) m/z 454 (6), 452 (26),
and 450 (36) [M+], 415 (30) and 417 (12) [M+ - Cl], 340 (51),
222 (100) and 224 (65), 129 (43), 114 (99); HRMS calcd for
C19H12Cl2N2O5S [M+] 449.9844; found 449.9856.
Acknowledgment. We thank the “Crunch” Network (Centre
de Recherche Universitaire Normand de Chimie), the Re´gion
Basse-Normandie, the Ministe`re de la Recherche, CNRS (Centre
National de la Recherche Scientifique), the European Union
(FEDER funding) for financial support, and Margareth Lemarie´
for the enantioselective HPLC analysis.
1
1122, 740 cm-1; H NMR (400 MHz, CDCl3) δ 8.41 and 8.10
(AA′BB′ system, 4H), 7.50-7.35 (m, 3H), 7.22-7.15 (m, 2H), 5.49
(s, 1H) ppm; 13C NMR (100.6 MHz, CDCl3) δ 157.6, 151.4, 142.5,
130.6, 130.4, 129.3, 128.8, 127.9, 124.8, 83.7, 76.3 ppm; MS (EI+)
m/z 404 (0.3), 402 (2), and 400 (3) [M+], 365 (4) and 367 (1.6)
[M+ - Cl], 301 (6) and 303 (5.5), 186 (5.4) and 188 (2.5), 172
(100) and 174 (64); HRMS calcd for C15H10Cl2N2O5S [M+]
399.9687; found 399.9692. Anal. Calcd for C15H10Cl2N2O5S: C,
Supporting Information Available: Spectroscopic data (1H
and 13C NMR) of the imines 3a-g, ꢀ-lactams 4a-c, 4f-g, and
the derivatization products 5-8; HPLC for the ꢀ-lactam 4a and
in situ IR for ꢀ-lactam 4g. This material is available free of
charge via the Internet at http://pubs.acs.org.
(26) 1H NMR experiments were carried out in CD2Cl2 of an equimolecular
mixture of imine 3a and various bases such as Et3N, Me2NEt, and i-Pr2NEt, but
no variation was observed after the addition of the bases in comparison with the
starting imine.
JO8014193
(27) We were not able to detect any intermediate by in situ IR (see Supporting
Information). On the other hand, a direct and fast transformation to ꢀ-lactam 4g
was observed.
(28) (a) Brady, W. T.; Smith, L. Tetrahedron Lett. 1970, 2963. (b) Borrmann,
D.; Wegler, R. Chem. Ber. 1969, 102, 64. (c) Krabbenhoft, H. O. J. Org. Chem.
1978, 43, 1305.
7840 J. Org. Chem. Vol. 73, No. 19, 2008