Carbonylation of silylated hydroxymethyl aziridines to β-lactams

Article abstract of DOI:10.1021/jo981568h

Functionalized β-lactams are synthesized by carbonylative ring expansion of silylated hydroxymethyl aziridines catalyzed by dicobalt octacarbonyl, a process that proceeds with inversion of configuration. Ring opening and elimination occurs on attempted carbonylation of aziridine carboxylates.

Full text of DOI:10.1021/jo981568h

5
18
J . Org. Chem. 1999, 64, 518-521
Ca r bon yla tion of Silyla ted Hyd r oxym eth yl Azir id in es to â-La cta m s
†
‡
‡
,†
Paolo Davoli, Irene Moretti, Fabio Prati, and Howard Alper*
Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada, and
Dipartimento di Chimica, Universit a` di Modena, Via Campi 183, 41100 Modena, Italy
Received August 4, 1998
Functionalized â-lactams are synthesized by carbonylative ring expansion of silylated hydroxymethyl
aziridines catalyzed by dicobalt octacarbonyl, a process that proceeds with inversion of configuration.
Ring opening and elimination occurs on attempted carbonylation of aziridine carboxylates.
In tr od u ction
Carbonylative ring expansion using carbon monoxide
Sch em e 1
in the presence of a transition-metal catalyst is a useful
reaction for the synthesis of a variety of heterocyclic
1
compounds. In this process, carbon monoxide is inserted
into a ring carbon-heteroatom bond, thus affording a
carbonyl-containing ring-expanded product. For instance,
â-lactams can be obtained by this methodology from
aziridines.
N-alkyl phenylaziridines give â-lactams in quantitative
2 2
yields using [Rh(CO) Cl] and CO pressure by regiospe-
tionalized aziridines. In particular, silylated hydroxym-
ethyl aziridines can be successfully carbonylated to
â-lactams in excellent yields.
cific insertion into the most substituted ring carbon-
nitrogen bond.2 This reaction is limited to aziridines
bearing an activating group at the 2-position, such as a
phenyl or vinyl. Carbonylation of alkylaziridines has been
also performed, in moderate yields, using excess quanti-
Resu lts a n d Discu ssion
4
ties of the highly toxic Ni(CO) , with CO insertion
Syn th esis a n d Attem p ted Ca r bon yla tion of Azir i-
d in eca r boxyla tes 3a ,b. Addition of bromine to com-
mercial ethyl crotonate (1) in carbon tetrachloride readily
afforded ethyl 2,3-dibromobutanoate (2) (98% yield)
occurring into the less substituted ring C-N bond with
3
net retention of configuration. A significant advance in
the carbonylation of simple N-alkylaziridines resulted
2 8
when catalytic amounts of Co (CO)
were used:4 the
(Scheme 1). Cyclization of 2 with benzylamine in absolute
reaction proceeded in excellent yields and CO insertion
ethanol gave a mixture of cis- and trans-1-benzyl-2-
occured into the less substituted carbon-nitrogen bond
ethoxycarbonyl-3-methylaziridines, 3a and 3b, respec-
by a S
N
2 like mechanism (inversion of configuration).
6,7a
tively, in a 73:27 ratio and in 86% total yield.
On the
The application of the Co
2
(CO)
8
-catalyzed reaction to
basis of H NMR spectral analysis ( J H-Hcis > 3J H-Htrans),
the cis stereochemistry was assigned to aziridine 3a ( J 2,3
.8 Hz) and trans stereochemistry to 3b ( J 2,3 2.6-2.9
1
3
the synthesis of more functionalized â-lactams by the
carbonylative ring expansion of aziridines was a desirable
goal: our attention was focused on cis- and trans-2-
alkoxycarbonyl- and silylated 2-hydroxymethyl-3-alky-
laziridines as possible substrates for carbonylation. In
fact, the presence of a carboxylic ester group may be of
use in a subsequent step of an extended synthesis, since
it can be easily transformed into different functionalities.
An alternative ring substituent can be a hydroxymethyl
group, acting as a “masked” ester function. Therefore,
aziridinecarboxylates and hydroxy-methylated aziridines
represent interesting substrates for carbonylation, taking
into account the fact that they can be obtained in optically
active form by several methods.5
3
3
6
Hz).
Treatment of 3a with carbon monoxide and Co
in 1,2-dimethoxyethane (DME) for 18 h at 110 °C and
2
(CO)
8
5
3
00 psi of CO gave only the elimination product, ethyl
-benzylamino-2-butenoate (3e), in 73% yield (Scheme 2).
1
The H NMR spectrum shows two singlets, one for the
methyl group and the other for the proton attached to
the double bond, and C NMR spectroscopy confirms the
13
presence of two unsaturated carbons. This result indi-
cates that the aziridine 3a undergoes nucleophilic ring
opening by the in situ-generated tetracarbonylcobaltate
-
anion [Co(CO)
4
] with attack at the C
2
ring carbon atom.
We now wish to report that the cobalt-catalyzed
carbonylation is applicable to different carbon-ring func-
Formation of the four-membered â-lactam ring requires
CO insertion into the C-Co bond and subsequent ring
closure by nucleophilic attack on the new carbonyl by the
†
University of Ottawa.
Universit a` di Modena.
‡
(
(
(
(
(
1) Khumtaveeporn K.; Alper H. Acc. Chem. Res. 1995, 28, 414.
2) Calet S.; Urso F.; Alper H. J . Am. Chem. Soc. 1989, 111, 931.
3) Chamchaang W.; Pinhas A. R. J . Org. Chem. 1990, 55, 2943.
4) Piotti M. E.; Alper H. J . Am. Chem. Soc. 1996, 118, 111.
5) Tanner D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599 and
(6) (a) Stolberg M. A.; O’Neill J . J .; Wagner-J auregg T. J . Am. Chem.
Soc. 1953, 75, 5045. (b) v. Capeller R.; Griot R.; H a¨ ring M.; Wagner-
J auregg T. Helv. Chim. Acta 1957, 40, 1652.
(7) (a) Andersson P. H.; Guijarro D.; Tanner D. J . Org. Chem. 1997,
62, 7364. (b) Deyrup J . A.; Moyer C. L. J . Org. Chem. 1970, 35, 3424.
A slightly modified procedure was adopted, using THF instead of ether
as solvent.
references therein. Bucciarelli M.; Forni A.; Moretti I.; Prati F.; Torre
G. J . Chem Soc., Perkin Trans. 1 1993, 3041.
1
0.1021/jo981568h CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/05/1999

Carbonylation of Silylated Hydroxymethyl Aziridines
J . Org. Chem., Vol. 64, No. 2, 1999 519
Sch em e 2
Sch em e 4
Sch em e 5
Sch em e 3
from the ring proton coupling constants (3J 3,4 1.9-2.1 Hz),
whereas the ring substitution pattern was determined
according to the MS fragmentation. From a vertical cross-
cleavage of the azetidinone ring, a base fragment at m/z
206 was observed for 6a but not for 7a , and therefore,
negative charged nitrogen: in this case, however, elimi-
nation to 3e is favored possibly because of the formation
of a conjugated system. Therefore, the presence of an
ester group on the aziridine ring is detrimental for the
carbonylation reaction. The synthetic strategy was then
to reduce the ester function and to perform the carbony-
lation on the corresponding aziridino alcohol, after pro-
tection as a tert-butyldimethylsilyl ether.
the TBDMSOCH - side chain was assigned at position
2
4 for 6a and at position 3 for 7a .
The trans ring substitution of both 6a and 7a suggests
N
an S 2-like mechanism with inversion of configuration
4
as previously reported, with nucleophilic ring opening
of the aziridine by the in situ-generated tetracarbonyl-
cobaltate anion (Scheme 5). Moreover, the isomeric ratio
-
Syn th esis a n d Ca r bon yla tion of Silyla ted Hy-
d r oxym eth yl Azir id in es 5a ,b. Reduction of isomeric
indicates preferential nucleophilic attack by [Co(CO)
at the alkyl-bearing ring carbon atom (C
at the O-protected hydroxymethyl-bearing carbon atom
(C ) of the aziridinic ring in 5a . After initial nucleophilic
attack by tetracarbonylcobaltate at C with inversion of
4
]
3
) rather than
4
aziridine carboxylic esters 3a ,b with LiAlH in tetrahy-
drofuran (THF) at room temperature 6 gave the corre-
sponding hydroxymethyl aziridines, cis- and trans-1-
benzyl-2-hydroxymethyl-3-methylaziridine (4a and 4b)
b,7
2
3
configuration, giving 8, subsequent CO insertion into the
C-Co bond should proceed with retention of configura-
(
5
(
Scheme 3). The latter were protected as TBDMS-ethers
a ,b by treatment with tert-butyldimethylsilyl chloride
TBDMSCl) and 4-(dimethylamino)pyridine (DMAP) in
4
tion to form 9. Finally, ring closure by intramolecular
nucleophilic attack provides the â-lactam 6a and regen-
erates the catalyst. Therefore, the cobalt carbonyl cata-
lyzed carbonylation of the protected hydroxymethyl
aziridine cis-5a is quantitative and highly regioselective.
Under the same reaction conditions, trans-5b gave a
mixture of cis-â-lactams 1-benzyl-3-methyl-4-((tert-bu-
tyldimethylsilyloxy)methyl)-azetidin-2-one (6b) and 1-ben-
zyl-4-methyl-3-((tert-butyldimethylsilyloxy)methyl)-aze-
tidin-2-one (7b) in a 88:12 ratio and 63% overall isolated
yield (Scheme 6).
dichloromethane at room temperature, in 83% and 48%
overall yields, respectively.
Treatment of cis-aziridine 5a with carbon monoxide
2 8
and Co (CO) in DME for 16 h at 100 °C and 500 psi of
CO using a 12:1 ratio of aziridine/catalyst gave a 92:8
mixture of trans-â-lactams 1-benzyl-3-methyl-4-((tert-
butyldimethylsilyloxy)methyl)azetidin-2-one (6a ) and
1
-benzyl-4-methyl-3-((tert-butyldimethylsilyloxy)methyl)-
azetidin-2-one (7a ) in a total 99.8% isolated yield
(
Scheme 4).
The relative cis stereochemistry of regioisomers 6b and
Carbonyl insertion was confirmed by 13C NMR spec-
7b was determined by H NMR spectroscopy ( J 3,4 5.4
Hz), and the ring substitution pattern was assigned
according to the MS fragmentation analogous to 6a and
7a . For the trans-aziridine 5b, the carbonylation reaction
1
3
troscopy, with the carbonyl carbon occurring at 170.8
ppm for 6a . The relative trans stereochemistry of the
â-lactam ring of regioisomers 6a and 7a was assigned

5
20 J . Org. Chem., Vol. 64, No. 2, 1999
Davoli et al.
Sch em e 6
dq, J ) 6.8, 5.6 Hz, CH
3
CH-), 2.22 (1H, d, J ) 6.8 Hz,
-
J
2
CHCOOEt), 3.56 (1H, d, J ) 13.9 Hz, -CH Ph), 3.65 (1H, d,
) 13.9 Hz, -CH
2
Ph), 4.21 (2H, dq, J ) 1.4, 7.1 Hz,
-
COOCH CH ), 7.24-7.34 (5H, m, aromatic); MS m/z 219
2
3
+
(
M ).
tr a n s-3b: major invertomer, 1H NMR (400 MHz) δ 1.22
3H, t, J ) 7.1 Hz, -COOCH CH ), 1.26 (3H, d, J ) 5.4 Hz,
CH-), 2.34 (1H, dq, J ) 2.9, 5.4 Hz, CH CH-), 2.46 (1H,
d, J ) 2.9 Hz, -CHCOOEt), 3.89 (1H, d, J ) 13.8 Hz, -CH
Ph), 4.06 (1H, d, J ) 13.8 Hz, -CH Ph), 4.13 (2H, q, J ) 7.1
Hz, -COOCH CH ), 7.20-7.40 (5H, m, aromatic); minor
invertomer, 1H NMR (400 MHz) δ 1.27 (3H, t, J ) 7.6 Hz,
COOCH CH ), 1.39 (3H, d, J ) 5.9 Hz, CH CH-), 2.02 (1H,
d, J ) 2.6 Hz, -CHCOOEt), 2.62 (1H, dq, J ) 2.6, 5.9 Hz,
CH CH-),3.69 (1H, d, J ) 14.3 Hz, -CH Ph), 3.86 (1H, d, J
14.3, -CH Ph), 4.18 (2H, q, J ) 7.6 Hz, -COOCH CH ),
.20-7.40 (5H, m, aromatic); MS m/z 219 (M ).
cis-1-Ben zyl-2-h ydr oxym eth yl-3-m eth ylazir idin e (4a).
(
2
3
CH
3
3
2
-
2
2
3
-
2
3
3
proceeds with slightly lower regioselectivity and lower
yield than for 5a .
Con clu sion s. The well-established dicobalt octacar-
bonyl-catalyzed carbonylation described for alkylaziri-
dines has been applied to 2-ethoxycarbonyl- and silylated
3
2
)
7
2
2
3
+
6b,7
In a 250-mL two-necked round-bottom flask equipped with a
condenser and a drierite drying tube was dissolved aziridine
2
-hydroxymethyl-3-methylaziridines. N-Benzyl TBDMSO-
protected hydroxymethyl aziridines were successfully
carbonylated to â-lactams using Co (CO) as the cata-
3
a (1.25 g, 5.71 mmol) in freshly distilled anhydrous tetrahy-
drofuran (36 mL). At rt under magnetic stirring, 11.4 mL of a
.0 M LiAlH solution in THF was slowly added dropwise
syringe) through a rubber septum. After 30 min, TLC (ethyl
2
8
1
(
4
lyst: trans-â-lactams are obtained from a cis-aziridine
in quantitative yields, whereas cis-â-lactams were iso-
lated using a trans-aziridine. The reaction proceeds
through nucleophilic ring opening of the aziridine by the
in situ-generated tetracarbonylcobaltate anion and shows
high regioselectivity, with preferential CO insertion into
the alkyl-bearing ring carbon-nitrogen bond rather than
into the O-protected hydroxymethyl-bearing ring carbon-
nitrogen bond.
ether/petroleum ether 50:50) showed total disappearance of
the starting material: the reaction mixture was then cooled
to 0 °C, and 0.55 mL of water was carefully added, followed
by 0.55 mL of a 0.15 N KOH solution. The white precipitate
was filtered off and washed with abundant ether, the filtrate
4
was dried (MgSO ), and the solvent was evaporated in vacuo.
After flash chromatography on silica gel (ethyl ether/petroleum
ether 80:20 and finally pure ethyl ether), 4a was obtained as
a colorless sticky oil (0.87 g, 86% yield): 1H NMR (200 MHz)
These results further expand the range of aziridines
as useful substrates for the cobalt carbonyl catalyzed
carbonylation, thus making easily available a variety of
functionalized â-lactams, some of which can be used as
suitable precursors for antibiotic drugs.
δ 1.24 (3H, d, J ) 5.6 Hz, CH CH-), 1.78 (1H, dq, J ) 6.6, 5.6
3
Hz, CH CH-) 1.85 (1H, m, -CHCH OH), 2.31 (1H, br, -OH),
3
2
3.56 (2H, s, -CH
2
2
Ph), 3.57 (1H, dd, J ) 11.4, 6.2 Hz, -CH -
OH), 3.75 (1H, dd, J ) 11.4, 5.0 Hz, -CH
2
OH), 7.24-7.40 (5H,
+
m, aromatic); MS m/z 177 (M ).
tr a n s-1-Ben zyl-2-h yd r oxym et h yl-3-m et h yla zir id in e
b,7
(
4b).6 Following the above procedure for 4a , 6.5 mL of a 1.0
Exp er im en ta l Section
4
M LiAlH solution in THF was slowly added, at room temper-
ature, to a stirred solution of aziridine 3b (0.713 g, 3.25 mmol)
in THF (21 mL). After 1 h 30 min, water (0.4 mL) was added
dropwise at 0 °C, followed by 0.4 mL of a 0.15 N KOH solution.
The inorganic salts were removed by filtration and washed
with ether, the filtrate was dried (MgSO ) and rotary evapo-
4
rated, and the residue was flash chromatographed on silica
gel (ethyl ether/petroleum ether 90:10 and finally pure ethyl
Eth yl 2,3-Dibr om obu ta n oa te (2). Bromine (1.14 mL, 22.2
mmol) was slowly added dropwise at room temperature to a
stirred solution of commercial ethyl crotonate (1) (2.51 g, 22
mmol) in carbon tetrachloride (100 mL). After gentle reflux
for 2 h, the solution was cooled and rotary evaporated,
affording ethyl 2,3-dibromobutanoate (2) (5.90 g, 98% yield)
as an amber sweet-scented liquid that was used without
1
ether) to give 0.39 g of 4b as a pale light yellow oil (67%
further purification: H NMR (200 MHz) δ 1.36 (3H, t, J )
1
yield): H NMR (200 MHz) δ 1.36 (3H, d, J ) 6.1 Hz, CH
3
-
7
.1, -CH
2
CH
3
), 1.93 (3H, d, J ) 6.3 Hz, CH
CH
, 4.48 (1H, dq, J ) 11.0, 6.3 Hz, CH
3
CHBr-), 4.32 (2H,
CH-), 1.67 (1H, dt, J ) 3.4, 5.2 Hz, -CHCH
dq, J ) 3.4, 6.1 Hz, CH CH-), 2.51 (1H, t, J ) 5.8 Hz, -OH),
3.44 (1H, ddd, J ) 11.2, 5.7, 5.3 Hz, -CH OH), 3.60 (1H, d, J
13.8 Hz, -CH Ph), 3.77 (1H, m, -CH OH), 3.82 (1H, d, J )
3.8 Hz, -CH Ph), 7.24-7.42 (5H, m, aromatic); MS m/z 177
2
OH), 2.19 (1H,
q, J ) 7.1, -CH
)
2
3
), 4.36 (1H, d, J ) 11.0 Hz, -CHBrCOO-
CHBr-); MS m/z 248 -
3
3
+
2
2
46 - 244 ([M - 28] ).
cis-1-Ben zyl-2-eth oxyca r bon yl-3-m eth yla zir id in e (3a )
a n d tr a n s-1-Ben zyl-2-eth oxyca r bon yl-3-m eth yla zir id in e
)
2
2
1
2
+
(M ).
6
,7a
(
3b).
A solution of ethyl 2,3-dibromobutanoate (2) (5.299 g,
cis-1-Ben zyl-2-((ter t-bu tyld im eth ylsilyloxy)m eth yl)-3-
1
9.3 mmol) in 40 mL of absolute ethanol was slowly added
m eth yla zir id in e (5a ). DMAP (1.319 g, 10.8 mmol) and
TBDMSCl (0.781 g, 5.18 mmol) were added at room temper-
ature to a stirred solution of 4a (0.764 g, 4.32 mmol) in freshly
distilled dichloromethane (25 mL) (nitrogen atmosphere). After
dropwise at 0 °C, with magnetic stirring, to a solution of
benzylamine (7.40 mL, 67.7 mmol) in anhydrous ethanol (100
mL). The reaction mixture was then left to warm to room
temperature and stirred overnight. After evaporation of the
solvent under reduced pressure, the residue was dissolved in
ether (100 mL) and washed with water (200 mL), and the
aqueous phase was extracted twice with ether (30 mL). The
4
(
0 min, the reaction mixture was diluted with dichloromethane
30 mL), washed with water (2 × 50 mL) and with brine (50
mL), dried (MgSO ), and rotary evaporated. Flash chromatog-
raphy of the residue on silica gel (petroleum ether/ethyl ether
0:20) gave 1.12 g of 5a as a pale yellow liquid (96% yield):
4
combined organic phases were dried (MgSO
to give a crude dark yellow oil that was subjected to flash
chromatography on SiO (petroleum ether/ethyl ether 80:20
4
) and concentrated
8
1
H NMR (200 MHz) δ 0.096 (6H, s, -OSiMe
2
tBu), 0.94 (9H, s,
CH-), 1.73 [2H,
O-; decoupled from -CH O-: 1.69
CH-), 1.76 (1H, d, J ) 6.6 Hz,
Ph), 3.61 (1H, dd, J ) 10.9,
2
-
m, CH
OSiMe
2
tBu), 1.23 (3H, d, J ) 5.5 Hz, CH
3
and finally 60:40), affording cis-aziridine 3a (2.68 g) and trans-
aziridine 3b (0.97 g) as yellow oils in a 73:27 ratio and in 86%
3
CH- and -CHCH
2
2
1
(1H, dq, J ) 6.6, 5.5 Hz, CH
-
3
total yield. H NMR spectroscopy showed compound 3b as a
CHCH
2
O-)], 3.55 (2H, s, -CH
2
6
1:39 mixture of two invertomers at nitrogen, due to slow
7
a,8
nitrogen inversion on the NMR scale.
1
cis-3a : H NMR (200 MHz) δ 1.27 (3H, t, J ) 7.1 Hz,
(8) Pierre, J .-L.; Baret, P.; Arnaud, P. Bull. Soc. Chim. Fr. 1971,
-
COOCH
2
CH
3
), 1.30 (3H, d, J ) 5.6 Hz, CH CH-), 2.01 (1H,
3
3619.

Carbonylation of Silylated Hydroxymethyl Aziridines
J . Org. Chem., Vol. 64, No. 2, 1999 521
+
6
7
.2 Hz, -CH
.24-7.41 (5H, m, aromatic); MS m/z 291 (M ). Anal. Calcd
29NOSi: C, 70.05; H, 10.03; N, 4.80. Found: C, 69.84;
2
O-), 3.82 (1H, dd, J ) 10.9, 5.5 Hz, -CH
2
O-)
7.40 (5H, m, aromatic); MS m/z 319 (M ). Anal. Calcd for
+
18 2
C H29NO Si: C, 67.66; H, 9.15; N, 4.38. Found: C, 67.58; H,
for C17
H
9.25; N, 4.33.
H, 10.27; N, 4.82.
tr a n s-1-Ben zyl-2-((ter t-bu tyld im eth ylsilyloxy)m eth yl)-
cis-1-Ben zyl-3-m eth yl-4-((ter t-bu tyld im eth ylsilyloxy)-
m eth yl)a zetid in -2-on e (6b) a n d cis-1-Ben zyl-4-m eth yl-3-
((ter t-bu tyld im eth ylsilyloxy)m eth yl)a zetid in -2-on e (7b).
Following the same protocol as for 5a , trans-aziridine 5b (318.9
mg, 1.10 mmol) was dissolved in DME (10 mL), and the
catalyst was added (31.2 mg, 0.019 mmol). After being purged
with CO, the autoclave was filled with 500 psi of CO and kept
in an oil bath for 16 h at 100 °C. An identical workup as above
gave a crude dark brown-olive oil that was flash chromato-
graphed on a SiO2 column (petroleum ether/ethyl ether 60:
40), affording the two â-lactam isomers cis-6b (192.8 mg) and
cis-7b (26.3 mg) in a 88:12 ratio in 63% total isolated yield.
3
4
-m eth yla zir id in e (5b). As for the procedure for 5a , aziridine
b (0.326 g, 1.84 mmol) was dissolved in dichloromethane (15
mL): DMAP (0.563 g, 4.61 mmol) and finally TBDMSCl (0.335
g, 2.22 mmol) were added at room temperature under magnetic
stirring (nitrogen atmosphere). After 35 min, TLC analysis
showed disappearance of the starting material: the reaction
mixture was then diluted with dichloromethane (25 mL),
washed with water (2 × 30 mL) and brine (30 mL), dried
(
MgSO
SiO
a light yellow oil (0.39 g, 72% yield): H NMR (200 MHz) δ
.073 (6H, s, -OSiMe tBu), 0.92 (9H, s, -OSiMe tBu), 1.37
3H, d, J ) 6.0 Hz, CH CH-), 1.61 (1H, dt, J ) 3.2, 5.7 Hz,
CHCH O-), 2.05 (1H, dq, J ) 3.2, 6.0 Hz, CH CH-), 3.58
1H, dd, J ) 11.0, 5.7 Hz, -CHCH O-), 3.59 (1H, d, J ) 14.0
Hz, -CH Ph), 3.68 (1H, dd, J ) 11.0, 5.7 Hz, -CHCH O-),
.80 (1H, d, J ) 14.0 Hz, -CH Ph), 7.22-7.45 (5H, m,
aromatic); MS m/z 291 (M ). Anal. Calcd for C17 29NOSi: C,
0.05; H, 10.03; N, 4.80. Found: C, 69.80; H, 10.29; N, 4.74.
tr a n s-1-Ben zyl-3-m eth yl-4-((ter t-bu tyldim eth ylsilyloxy)-
m eth yl)a zetid in -2-on e (6a ) a n d tr a n s-1-Ben zyl-4-m eth yl-
-((ter t-bu tyldim eth ylsilyloxy)m eth yl)azetidin -2-on e (7a).
4
), and concentrated. After flash chromatography on
(petroleum ether/ethyl ether 80:20), 5b was obtained as
2
1
cis-6b: 1H NMR (400 MHz) δ 0.024 (3H, s, -OSiMe tBu),
2
0
(
-
(
2
2
0.030 (3H, s, -OSiMe tBu), 0.87 (9H, s, -OSiMe tBu), 1.22
2
2
3
(3H, d, J ) 7.6 Hz, CH CH-), 3.26 (1H, dq, J ) 5.4, 7.6 Hz,
3
2
3
CH CH-), 3.59 (1H, q, J ) 5.6 Hz, -CHCH O-), 3.69 (1H,
3
2
2
dd, J ) 10.7, 5.8 Hz, -CHCH O-), 3.72 (1H, dd, J ) 10.7, 5.7
2
2
2
Hz, -CHCH O-), 4.16 (1H, d, J ) 15.0 Hz, -CH Ph), 4.65
2
2
3
2
(1H, d, J ) 15.0, -CH Ph), 7.24-7.36 (5H, m, aromatic); 13
C
2
+
H
NMR (200 MHz) δ -5.6, 8.7, 18.1, 25.8, 45.0, 46.1, 55.3, 62.3,
127.5, 128.2, 128.6, 136.4, 171.1; MS m/z 319 (M ). Anal. Calcd
for C H NO Si: C, 67.66; H, 9.15; N, 4.38. Found: C, 67.60;
7
+
1
8
29
2
H, 9.24; N, 4.31.
3
cis-7b: 1H NMR (400 MHz) δ 0.057 (3H, s, -OSiMe
2
tBu),
2
tBu), 1.22
In a 45-mL stainless steel autoclave equipped with a glass liner
and a stirring bar was dissolved cis-aziridine 5a (531.1 mg,
0
(
-
-
.063 (3H, s, -OSiMe
2
tBu), 0.88 (9H, s, -OSiMe
), 3.36 (1H, dq, J ) 5.4, 7.6 Hz,
), 3.70 (1H, m, -OCH CH-), 3.93 (2H, AB system,
CH-), 4.15 (1H, d, J ) 15.2 Hz, -CH Ph), 4.54 (1H,
Ph), 7.24-7.36 (5H, m, aromatic); MS
Si: C, 67.66; H, 9.15;
3H, d, J ) 7.6 Hz, -CHCH
3
1
.82 mmol) in freshly distilled anhydrous and O
2
-free DME
CHCH
OCH
3
2
(
10 mL), and Co (CO) (52 mg, 0.15 mmol) was added. The
2
8
2
2
autoclave was purged four times with 300 psi of CO, charged
with 500 psi of CO, and placed in an oil bath at 95 °C for 16
h. After release of CO, the autoclave was opened, and the
brown clear solution was left in contact with air for some
hours, adding ether to accelerate the decomposition of the
catalyst. The reaction mixture was then filtered through a
d, J ) 15.2 Hz, -CH
2
+
m/z 319 (M ). Anal. Calcd for C18H29NO
2
N, 4.38. Found: C, 67.55; H, 9.25; N, 4.32.
Attem p ted Ca r bon yla tion of Azir id in es 3a ,b. Reaction
of aziridinecarboxylate 3a (265.3 mg, 1.21 mmol) with Co
(
(
2
(CO)
34.8 mg, 0.10 mmol) in DME (10 mL) under similar conditions
110 °C, 500 psi of CO, 18 h) and identical workup gave a crude
(petroleum ether/
ethyl ether 60:40), affording 195 mg of ethyl 3-benzylamino-
8
2
small SiO column to remove the violet precipitate and then
washed with abundant ether. After rotary evaporation, the
crude yellow oil was flash chromatographed on a silica gel
column (petroleum ether/ethyl ether 60:40), thus affording, as
pale yellow oils, the two â-lactam regioisomers trans-6a (531.9
mg) and trans-7a (49.1 mg) in a 92:8 ratio in 99.8% total
oil that was flash chromatographed on SiO
2
9
1
2
(
-
-butenoate (3e) as a lemon yellow oil (73% yield): H NMR
CH ), 1.91 (3H, s,
-), 4.10 (2H, q, J ) 7.1 Hz, -OCH CH ), 4.41 (1H,
Ph), 4.44 (1H, s, -CH Ph), 4.53 (1H, s, -CHdCCH
200 MHz) δ 1.26 (3H, t, J ) 7.1 Hz, -OCH
2
3
CHdCCH
3
2
3
isolated yield.
s, -CH
)
2
2
3
-
1
tr a n s-6a : H NMR (200 MHz) δ 0.028 (6H, s, -OSiMe
2
3
-
-
13
2
, 7.24-7.34 (5H, m, aromatic), 8.95 (1H, br, -NHCH Ph); C
tBu), 0.88 (9H, s, -OSiMe
CH-), 2.93 (1H, dq, J ) 1.9, 7.3 Hz, CH
J ) 5.2, 4.2, 1.9 Hz, -CHCH O-), 3.63 (1H, dd, J ) 10.9, 5.2
O-), 3.71 (1H, dd, J ) 10.9, 4.2 Hz, -CHCH O-
Ph), 4.70 (1H, d, J ) 15.1
2
tBu), 1.27 (3H, d, J ) 7.3 Hz, CH
NMR (200 MHz) δ 14.6, 19.4, 46.8, 58.4, 83.1, 126.7, 127.3,
3
CH-), 3.18 (1H, ddd,
+
1
28.9, 138.7, 161.8, 170.6; MS m/z 219 (M ).
2
Reaction of 3a and 3b at lower temperature (50-55 °C) and
at higher CO pressure (1000 psi) gave only a complex mixture
of unidentified products.
Hz, -CHCH
2
2
)
, 4.10 (1H, d, J ) 15.1 Hz, -CH
2
1
3
Hz, -CH Ph), 7.25-7.35 (5H, m, aromatic); C NMR (200
2
MHz) δ -5.6, 12.7, 18.1, 22.6, 44.8, 46.6, 60.1, 63.1, 127.5,
+
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
for support of this research. We also profited from
helpful discussions with Marcelo Piotti and Fran c¸ ois
Maltais.
1
28.1, 128.6, 136.4, 170.8; MS m/z 319 (M ). Anal. Calcd for
Si: C, 67.66; H, 9.15; N, 4.38. Found: C, 67.62; H,
18 2
C H29NO
9
.23; N, 4.35.
tr a n s-7a : 1H NMR (200 MHz) δ 0.051 (6H, s, -OSiMe
-
2
tBu), 0.86 (9H, s, -OSiMe
CHCH ), 2.87 (1H, m, -OCH
.1 Hz, -CHCH ), 3.85 (1H, dd, J ) 10.9, 3.7 Hz, -OCH
, 3.92 (1H, dd, J ) 10.9, 5.2 Hz, -OCH CH-), 4.07 (1H, d, J
15.4 Hz, -CH Ph), 4.66 (1H, d, J ) 15.4 Hz, -CH Ph), 7.20-
2
tBu), 1.22 (3H, d, J ) 6.1 Hz,
CH-), 3.61 (1H, dq, J ) 2.1,
CH-
-
6
3
2
J O981568H
3
2
)
2
)
2
2
(9) Schad, H. P. Helv. Chim. Acta 1955, 38, 1117.