Stereoselective synthesis and functionalization of N-alkyl-β-lactams

Article abstract of DOI:10.1016/j.tet.2008.10.027

Novel polyfunctionalized N-alkyl-β-lactams were prepared with high stereoselectivity in an efficient manner by a palladium-catalyzed [2+2] carbonylative cycloaddition of allyl bromide with heteroarylidene N-alkyl-amines The type of alkyl group linked to t

Full text of DOI:10.1016/j.tet.2008.10.027

Tetrahedron 64 (2008) 11632–11640
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective synthesis and functionalization of N-alkyl-b-lactams
*
Luigino Troisi , Catia Granito, Emanuela Pindinelli
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Via Prov.le Lecce-Monteroni, I-73100 Lecce, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel polyfunctionalized N-alkyl-b-lactams were prepared with high stereoselectivity in an efficient
Received 25 July 2008
Received in revised form
26 September 2008
Accepted 9 October 2008
Available online 15 October 2008
manner by a palladium-catalyzed [2þ2] carbonylative cycloaddition of allyl bromide with hetero-
arylidene N-alkyl-amines The type of alkyl group linked to the nitrogen atom influences the reaction
stereoselectivity. Moreover, the C-3 and the C-4 positions of the azetidinone ring can be further ster-
eoselectively functionalized inserting various groups through the generation of a stable azetidinyl
carbanion and then captured by various electrophiles.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
b-Lactams
Carbanions
Diastereoselectivity
Functionalization
1. Introduction
preparing b-lactam compounds, some protocols proceed with high
stereoselectivity, which depends either on the synthetic procedures
or on the type of starting materials employed. For instance, com-
plete trans-stereoselectivity has been observed in the carbonylative
ring expansion of aziridines trimethylsilylsubstituted, using
The
b-Lactam nucleus is the key to the biological activity of
a large class of compounds characterized by the presence of this
four-membered ring and differentiated by side chains, unsatura-
tions, heteroatoms, and, in many cases, by the presence of five- or
Co2(CO)8 as catalyst, to give
alkynes with nitrones catalyzed by Cu(I)/bis(aza-ferrocene) has
been reported to produce -lactams with excellent cis-diaster-
b
-lactams,11 while the coupling of
six-membered rings. The successful application of
b-lactam anti-
biotics in the treatment of infectious diseases has been well docu-
b
mented for many years.1 The potential use of some
b
-lactams as
eoselectivity.12 The stereoselectivity is very often linked to the
starting materials used for building the four-membered ring. As an
example, the Staudinger reaction performed starting from prochiral
imine chromium complexes showed complete cis-diaster-
eoselection,13 while high trans-diastereoselection was observed
starting from N-phenylsulfenylimines.14 Recently, modifiing
slightly Torii’s procedure,15 our research group has reported the
palladium-catalyzed [2þ2] carbonylative cycloaddition of N-aryl
therapeutic agents for lowering plasma cholesterol levels,2,3 as in-
hibitors of enzymes such as thrombin,4 HLE (human leukocyte
5
elastase) and the protease, responsible for capsid assembly and
viral maturation of HCMV (human cytomegalovirus),6 has been
documented as well. The b-lactam structure is also the essential
scaffold of several antagonists directed to the vasopressin V1 re-
ceptor,7 and 2-azetidinones have been reported to show apoptosis-
inducing properties against human solid tumor cell lines.8 Due to
imines of different structures to allyl halides to give a-vinyl b-lac-
the large pharmacological potential and use of the
b
-lactam sys-
tams with good stereoselectivity for trans-isomers.16 In this paper,
we report the different results obtained performing the cyclo-
carbonylation of N-alkyl imines with allyl bromide demonstrating
how the N-alkyl group can influence the stereoselection and in-
vestigating the mechanism.
tems, intensive research has generated numerous methods for
synthetizing this skeleton, and the topic has been deeply docu-
mented and reviewed several times.9,10 Moreover, it is known that
the biological activity performed by the
b-lactam molecules
depends not only on the type of substituents linked to the nitrogen
N-1, the C-3 and the C-4 carbon atoms of the four-membered ring,
but also on the stereochemistry of the b-lactam core. Among the
2. Results and discussion
numerous synthetic methodologies reported in the literature for
Novel cis and/or trans N-alkyl-4-aryl-3-vinyl-2-azetidinones
were stereoselectively synthetized following a palladium-catalyzed
[2þ2] carbonylative cycloaddition procedure. Previously known
(E)-arylidenalkyl amines 1–4,17 5–7,18 8,19 10,20 11,21 and unknown 9
underwent a [2þ2] cycloaddition with allyl bromide under CO
* Corresponding author. Tel.: þ39 0832 298701; fax: þ39 0832 298732.
E-mail address: luigino.troisi@unile.it (L. Troisi).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.027

L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
11633
pressure (300–400 psi), in THF and Pd(OAc)2/PPh3 as the catalyst
system, in the presence of triethylamine (Scheme 1), to afford the
with respect to the aryl and the vinyl substituents. NOESY NMR
experiments performed on compounds 1b–4b confirmed a high
configurational stability of the nitrogen atom bearing the tert-butyl
substituent. For instance, a strong NOESY interaction was noticed
b
-lactams 1a, 5a–11a, 1b–4b, 7b, 9b, and 10b.
between the tert-butyl protons, bearing the b-lactam nitrogen, and
R
Et3N, Pd(OAc2),
PPh3, CO
THF, 100 °C
R
R
the ones linked to the C-3 and the C-4 carbon atoms; while no
interactions were observed between the tert-butyl and the aryl or
the vinyl groups. Viceversa, in the remaining 2-azetidinones,
a strong NOESY interaction was observed for the protons of the R
group (n-Bu, i-Pr, and Et) either with the protons directly linked to
the C-3 and the C-4 or with the protons of the aryl and the vinyl
groups, indicating a fast interconversion at the nitrogen atom.
A strong energy difference also appears to persist in the carb-
anion generated by deprotonation of the C-3 carbon atom in the
N-tert-butyl derivatives with respect to the remaining N-alkyl
compounds. When 1b was treated with n-BuLi at ꢀ78 ꢁC in THF and
quenched with an electrophile such as methyl iodide or allyl bro-
mide, only cis-diastereomers 12b and 13b were isolated in high
yields (Scheme 2 and Table 2, entries 1 and 3). The cis-configuration
was unequivocally assigned by comparing the 1H NMR chemical
shift values of the vinyl moiety with those of similar structures.22
O
O
N
N
N
Br
+
+
Ar
1-11
Ar
1b-4b, 7b, 9b, 10b
Ar
1a, 5a-11a
Scheme 1.
The results herein reported show an interesting novelty as they
highlight the strategic role played by the alkyl group, linked to the
iminic nitrogen, in the -lactam formation. For instance, the het-
eroarylidene tert-butylamines 2–4 afforded, by the Pd catalyzed
[2þ2] cycloaddition, the cis -lactams 2b–4b in good yields (Table 1,
b
b
entries 2–4). The benzylidene tert-butylamine 1 produced both the
diastereoisomers 1a and 1b but a good cis-diastereoselection was
observed (cis/trans¼90:10; Table 1, entry 1). Using the arylidene
amines 5–11, having at the iminic nitrogen sterically less hindered
alkyl groups such as n-butyl (Table 1, entries 5–9), isopropyl (Table
1, entry 10), and ethyl substituents (Table 1, entry 11), a complete
inversion of diastereoselectivity was noticed. For instance, the
trans-isomer was the major product, while the cis-isomer was not
observed or was isolated in traces. The steric hindrance of the R
substituent at the lactamic nitrogen atom influences the ring for-
mation, as showed by the results collected in Table 1. During the
cyclization process, the bulky tert-butyl moiety drives the aryl and
R
O
E
N
R
O
H
Ar
N
Ar
1a, 5a, 8a, 10a
14b,16b, 18b, 20b,
1) n-BuLi
THF, -78 °C
2) E+
22b, 24b, 26b, 28b
+
the vinyl groups to the same side with respect to the b-lactam ring,
affording cis-structures. In the meantime, the tert-butyl moiety
assumes a stable and fixed configuration lying in the opposite side
R
R
O
O
N
N
E
H
Ar
1b-4b,10b
Ar
12b-28b
Table 1
Synthesis of N-alkyl-
Scheme 2.
b-lactams
Entry Imine
R
Ar
Ph
Total yielda
%
Product distributionb
Analogous behaviour was showed by the functionalized prod-
ucts obtained from 2b, 3b, and 4b after deprotonation and
quenching with methyl iodide (Table 2, entries 6, 8, and 10), while in
trans
cis
1
2
1
2
t-Bu
t-Bu
85
78
1a (10)
1b (90)
d
d
2b (100)
3b (100)
Table 2
Functionalization of N-alkyl-b-lactams
3
4
3
4
t-Bu
t-Bu
75
75
Entry
b-Lactam
R
E
Total
Product distributionb
yielda
%
trans
cis
1
2
3
4
5
6
7
8
1b
1a
1b
1a
1b
2b
2b
3b
3b
4b
4b
5a
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
i-Pr
CH3I
CH3I
CH2]CHCH2Br
D2O
D2O
CH3I
CH3OD
CH3I
CH3OD
CH3I
CH3OD
CH3I
CH3OD
CH3I
CH3OD
CH3I
CH3OD
CH3I
CH3OD
CH3I
>99
97
95
>99
>99
90
>99
>99
92
88
95
>99
>99c
88
97
93
>99
>99
>99
93
d
12b (100)
12b (100)
13b (100)
14b (78)
14b (78)
15b (100)
16b (86)
17b (100)
18b (98)
19b (100)
20b (85)
21b (100)
22b (55)
23b (100)
24b (45)
25b (100)
26b (54)
27b (100)
28b (70)
27b (100)
28b (70)
d
4b (100)
d
d
14a (22)
14a (22)
d
5
6
5
6
n-Bu
n-Bu
81
79
5a (98)
6a (98)
5b (Traces)
6b (Traces)
16a (14)
d
9
18a (2)
d
10
11
12
13
14
15
16
17
18
19
20
21
20a (15)
d
7
8
7
8
n-Bu
n-Bu
81
90
7a (90)
7b (10)
5a
8a
8a
9a
22a (45)
d
Ph
8a (100)
d
24a (55)
d
9a
26a (46)
d
9
9
n-Bu
i-Pr
Et
78
95
90
9a (83)
9b (17)
10b (10)
d
10a
10a
10b
10b
i-Pr
i-Pr
i-Pr
28a (30)
d
10
11
10
11
Ph
Ph
10a (90)
11a (100)
CH3OD
>99
28a (30)
a
Isolated yields.
b
c
Diastereomeric ratios measured by GC and 1H NMR spectroscopy.
Total yield evaluated by GC.
a
Isolated yields.
b
Diastereomeric ratios measured by GC and 1H NMR spectroscopy.

11634
L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
the quenching with Dþ (D2O or CH3OD) also a small amount of the
trans-isomers was formed (2–22%; Table 2, entries 5, 7, 9, and 11).
By deprotonation of the trans-isomer 1a and quenching with
CH3I, the cis-diastereomer 12b was still isolated as the only reaction
product (Table 2, entry 2). Moreover, the same carbanion quenched
with Dþ led to a cis/trans diastereomeric mixture (78:22; Table 2,
entry 4). These results may be explained assuming that the alkyl
halide binds the C-3 carbon from the face of the planar carbanion
not hindered by the close aryl group linked at C-4 (Scheme 3),
a carbanion of tetrahedral structure where a more free in-
terconversion at the -lactamic nitrogen atom lead to a small dif-
b
ference of thermal stability between the structures A and B
(Scheme 4). Moreover, the presence of two moieties linked at the
close C-3 carbon atom could contribute to weaken the energy dif-
ferences between the two structures. Then, smaller electrophiles
were attacked indifferently by structures A and B having similar
stability and leading to the two isomers with no diastereoselection.
Bulky electrophiles, instead, even if attacked by the two carbanions
A and B indifferently, preferred the less hindered cis-configuration
for the final products, allowing a cis-diastereoselectivity.
generating the cis-configurated b-lactam exclusively, even starting
from the trans-isomer. A small group, instead, such as Dþ binds the
C-3 indifferently from both sides of the planar carbanion leading to
a cis/trans diastereomeric mixture (Scheme 3).
R
R
O
O
N
N
Ar
CH3
Ar
CH3
R
O
E
A
N
N
R
O
29a-32a
H
R'
E+
R
R
n-BuLi
3 THF, -78 °C
O
O
N
R'X
+
CH
B
Ar
N
N
H
H
R
O
Ar
R
O
+
R
R
N
O
O
Ar
Ar
D
N
E
CH3
15b, 21b
N
CH3
+
H
D
H
Ar
29b-32b
Ar
Ar
Ar
D
B
Scheme 3.
Scheme 4.
The treatment of trans N-n-butyl-b-lactams 5a, 8a, and 9a with
n-BuLi at ꢀ78 ꢁC in THF led to the formation of a carbanion at C-3,
which quenching with CH3I still produced the functionalized cis
3. Conclusion
b
-lactams 21b, 23b, and 25b, respectively (Table 2, entries 12, 14,
and 16). Using, instead, the small electrophile Dþ, 1:1 di-
We prepared in
a diastereoselective way novel poly-
astereomeric mixtures of cis/trans were observed (Table 2, entries
13, 15, and 17). The N-isopropyl-b-lactams trans-10a and cis-10b
functionalized N-alkyl-
b
-lactams by palladium-catalyzed [2þ2]
carbonylative cycloaddition of N-alkyl imines to allyl bromide. The
variety of these compounds can be further widened by function-
alization reactions performed diastereoselectively. The steric
hindrance of the N-alkyl group influences the ring formation and
deprotonated with the same procedure described above, and
quenched with Dþ produced both the same diastereomeric mixture
showing cis/trans ratios of 70:30. The quenching, instead, of the
same carbanions with CH3I afforded the cis-diastereomer only.
Once more, a bulky electrophile such as R0X prefers to bind the C-3
from the less hindered face of the carbanion generating cis-
structures, exclusively. Viceversa, a small electrophile such as Dþ is
not influenced by the steric hindrance of the aryl group atC-4 affording
cis/trans diastereomeric mixtures in the proportion depending on the
bulkiness of the alkyl group linked at the nitrogen atom. For instance,
t-Bu, which is the more bulky, led preferentially to the cis-structure,
i-Pr allowed an increasing amount of the trans-products, while n-Bu
gave almost unitary diastereomeric ratios (Table 2).
Finally, the behavior of the carbanion generated by deprotona-
tion of the C-4 carbon atom was investigated. When 15b and 21b
were treated with n-BuLi at ꢀ78 ꢁC in THF, and quenched with Dþ,
always mixtures of both diastereomers 29a, 29b and 31a, 31b were,
respectively, isolated in almost 1:1 ratios (Table 3, entries 1 and 3).
Viceversa, a fairly good diastereoselectivity was observed in the
quenching with CH3I leading to trans/cis ratios of 30:70 for 30a, 30b
and 20:80 for 32a, 32b, respectively (Table 3, entries 2 and 4). These
different results could be explained by the generation of
the subsequent functionalization affording cis- or trans-b-lactam
depending on the C-3 and the C-4 carbon atom substituents. The
stereoselection mechanism is also investigated and discussed. The
continuous need to modify the structures of this class of pharma-
cologically relevant compounds, together with the ever-increasing
requirement of obtaining molecules of fixed configuration, give
a good relevance to this contribution. For instance, through the
described methodology, it is possible to obtain compounds of
desired configuration and variously substituted as the stereo-
selectivity can be controlled by the kind of the substituents and the
nature of the reactants.
4. Experimental
4.1. General
n-Butyllithium (n-BuLi) was a commercial solution in hexanes
(Aldrich) and was titrated with N-pivaloyl-o-toluidine prior to
use.23 THF, triethylamine, 4-formylmorpholine, 2-pyridinecarbox-
aldehyde, 3-pyridinecarboxaldehyde, 4-pyridinecarboxaldehyde,
4-methylthiazole, 2-aminothiazole, methanesulfonyl chloride,
2-aminopyridine, 3-aminopyridine, 2-aminothiophenol, glycolic
acid, n- and tert-butylamine, ethylamine, isopropylamine, palla-
dium(II) acetate, triphenylphosphine, and allyl bromide were of
commercial grade (Aldrich) and used without further purification.
Benzaldehyde of commercial grade (Aldrich) was purified by dis-
tillation prior to use. Petroleum ether refers to the 40–60 ꢁC boiling
fraction. The 1H and the 13C NMR spectra were recorded on a Bruker
Avance 400 apparatus (400.13 and 100.62 MHz, for 1H and 13C,
respectively) with CDCl3 as solvent and TMS as internal standard
Table 3
Functionalization of N-alkyl-3-methyl-b-lactams
Entry
b-Lactam
E
Total yielda
%
Product distributionb
trans
cis
1
2
3
4
15b
15b
21b
21b
D2O
CH3I
D2O
CH3I
92c
94
29a (50)
30a (31)
31a (45)
32a (20)
29b (50)
30b (69)
31b (55)
32b (80)
90c
95
a
Isolated yields.
(
d
¼7.24 for 1H spectra;
d
¼77.0 for 13C spectra). The IR spectra were
b
c
Diastereomeric ratios evaluated by GC and 1H NMR spectroscopy.
Total yield evaluated by GC.
recorded with an FT-IR spectrophotometer Digilab Scimitar Series

L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
11635
FTS 2000. GC–MS analyses were performed with an Agilent Tech-
nologies 6850 series II gas chromatograph (5% phenyl-poly-
methylsiloxane capillary column, 30 m, 0.25 mm i.d.), equipped
with a 5973 Network massselective detector operating at 70 eV.
The electrospray ionization (HR-ESI-MS) experiments were carried
out in a hybrid QqTOF mass spectrometer (PE SCIEX-QSTAR)
equipped with an ion spray ionization source. MS (þ) spectra were
2932, 1747, 1457, 1367, 1226 cmꢀ1; GC–MS (70 eV) m/z 229 (<1)
[M]þ, 146 (2), 130 (100), 129 (55), 115 (21), 84 (5), 79 (4), 57 (4);
HRMS-ESI: calcd for C15H20NO: 230.1546 [MþH]þ; found: 230.1546.
Compound 1b. Yield 175 mg (76.5%), yellow oil; 1H NMR
(400.13 MHz, CDCl3)
1H, CHCH]CH2), 4.84 (d, J¼5.7 Hz, 1H, CHAr), 5.00–5.04 (m, 1H,
CH]CH2), 5.26–5.29 (m, 2H, CH]CH2), 7.27–7.35 (m, 5H, ArH); 13
NMR (100.62 MHz, CDCl3): 28.1, 54.4, 57.2, 58.3,119.8,127.2, 128.0,
d
1.30 (s, 9H, (CH3)3), 3.96 (dd, J¼5.7, 5.8 Hz,
C
acquired by direct infusion (5
appropriate sample (10 pmol/
mL/min) of a solution containing the
d
mL), dissolved in a solution 0.1% acetic
128.3, 130.0, 137.9, 168.2; FTIR (CHCl3): 3065, 3009, 2976, 2931,
2873, 1734, 1367, 1265 cmꢀ1; GC–MS (70 eV) m/z 229 (<1) [M]þ,
146 (6), 130 (100), 129 (67), 115 (26), 77 (9), 84 (6), 57 (22); HRMS-
ESI: calcd for C15H20NO: 230.1546 [MþH]þ; found: 230.1546.
acid, methanol/water 50:50 at the optimum ion voltage of 4800 V.
The nitrogen gas flow was set at 30 psi (pounds per square inch)
and the potentials of the orifice, the focusing ring and the skimmer
were kept at 30, 50, and 25 V relative to ground, respectively.
Melting points were determined using an Electrothermal melting
point apparatus and are uncorrected. TLC was performed on Merck
silica gel plates with F254 indicator; viewing was by UV light
(254 nm). Column chromatographies were performed on silica gel
(63–200 mm) using petroleum ether/diethyl ether (Et2O) mixtures
as eluents. All reactions involving air-sensitive reagents were per-
formed under nitrogen, in oven-dried glassware using syringe/
septum cap techniques.
4.3.2. 1-tert-Butyl-4-pyridin-2-yl-3-vinylazetidin-2-one 2b
Yield 179 mg (78%), yellow solid; mp 83.7–85.5 ꢁC (petroleum
ether); 1H NMR (400.13 MHz, CDCl3)
d 1.31 (s, 9H, (CH3)3), 4.06 (t,
J¼6.0 Hz, 1H, CHCH]CH2), 4.98 (d, J¼6.0 Hz, 1H, CHPh), 4.99–5.03
(m, 1H, CH]CH2), 5.28–5.30 (m, 2H, CH]CH2), 7.20–7.23 (m, 1H,
ArH), 7.39 (d, J¼7.9 Hz, 1H, ArH), 7.70 (td, J¼1.6, 7.9 Hz, 1H, ArH),
8.56 (d, J¼4.6 Hz, 1H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 28.1,
54.4, 56.9, 59.4, 120.3, 122.2, 122.7, 129.1, 136.0, 149.3, 158.1, 168.1;
FTIR (CHCl3): 3089, 3011, 2977, 2934, 1739, 1593, 1438, 1367 cmꢀ1
;
4.2. General procedure for the preparation of the N-alkyl-
arylimines 1–8
GC–MS (70 eV) m/z 230 (2) [M]þ, 174 (5), 147 (3), 130 (100), 78 (5),
57 (6); HRMS-ESI: calcd for C14H19N2O: 231.1499 [MþH]þ; found:
231.1498.
The heteroarylimines 1–11 were prepared by dehydration re-
action of 1 mmol of the appropriate amine with the corresponding
aldehyde (1 mmol) in anhydrous Et2O, in the presence of 7 g of
molecular sieves (Aldrich, 4 Å, 1.6 mm pellets) for 7–16 h, following
Taguchi’s protocol.24
4.3.3. 1-tert-Butyl-4-(4-methylthiazol-2-yl)-3-vinylazetidin-
2-one 3b
Yield 187.5 mg (75%), yellow solid; mp 53.5–54.8 ꢁC (petroleum
ether); 1H NMR (400.13 MHz, CDCl3)
d 1.32 (s, 9H, (CH3)3), 2.40 (s,
3H, CH3Ar), 4.04 (dd, J¼6.2, 6.5 Hz, 1H, CHCH]CH2), 5.09 (d,
J¼10.1 Hz, 1H, CH]CH2), 5.16 (d, J¼6.2 Hz, 1H, CHAr), 5.31 (d,
J¼17.0 Hz, 1H, CH]CH2), 5.39–5.43 (m, 1H, CH]CH2), 6.85 (s, 1H,
4.2.1. (1E)-N-(Benzothiazol-2-ylmethylene)butylamine 9
Yield 207 mg (95%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
d
0.96 (t, J¼7.3 Hz, 3H, CH3CH2), 1.42 (m, 2H, CH3CH2), 1.74 (m, 2H,
ArH); 13C NMR (100.62 MHz, CDCl3)
d 16.9, 28.0, 54.8, 56.0, 57.5,
CH3CH2CH2), 3.73 (dt, J¼1.2, 7.0 Hz, 2H, CH2CH2–N), 7.44 (t,
J¼7.9 Hz, 1H, ArH), 7.50 (t, J¼7.9 Hz, 1H, ArH), 7.90 (d, J¼7.9 Hz, 1H,
ArH), 8.07 (d, J¼7.9 Hz, 1H, ArH), 8.53 (s, 1H, N]CH); 13C NMR
113.9,121.1, 128.4, 152.8, 167.7,168.7. FTIR (CHCl3): 3089, 2976, 2927,
1749, 1527, 1368, 1345 cmꢀ1; GC–MS (70 eV) m/z 250 (2) [M]þ, 194
(2), 167 (3), 150 (100), 127 (4), 99 (2), 71 (6), 57 (7); HRMS-ESI calcd
for C13H19N2OS: 251.1220 [MþH]þ; found: 251.1220.
(100.62 MHz, CDCl3)
d 13.8, 20.4, 32.5, 61.1, 122.0, 124.0, 126.3,
126.4, 135.0, 153.4, 155.5, 167.4; FTIR (film): 2958, 2931, 2872, 1640,
1501, 1458, 1316, 760 cmꢀ1; GC–MS (70 eV) m/z 218 (5) [Mþ], 189
(5), 175 (100), 162 (11), 148 (38), 135 (7), 108 (7); HRMS-ESI: calcd
for C12H15N2S: 219.0957 [MþH]þ; found: 219.0958.
4.3.4. 4-Benzothiazol-2-yl-1-tert-butyl-3-vinylazetidin-2-one 4b
Yield 214.5 mg (75%), yellow solid; mp 116.7–118.0 ꢁC (petro-
leum ether); 1H NMR (400.13 MHz, CDCl3)
d 1.40 (s, 9H, (CH3)3), 4.18
(dd, J¼6.0, 7.2 Hz, 1H, CHCH]CH2), 5.09 (dd, J¼0.9, 10.1 Hz, 1H,
CH]CH2), 5.31 (d, J¼6.0 Hz, 1H, CHAr), 5.37 (dd, J¼0.9, 17.1 Hz, 1H,
CH]CH2), 5.48–5.52 (m, 1H, CH]CH2), 7.40 (t, J¼8.0 Hz, 1H, ArH),
7.48 (t, J¼8.0 Hz, 1H, ArH), 7.89 (d, J¼8.0 Hz, 1H, ArH), 8.00 (d,
4.3. General procedure for the preparation of the compounds
1a–11a, 1b–11b
A mixture of 1.0 mmol of 1–11, 1.5 mmol of allyl bromide,
0.08 mmol of PPh3, 0.02 mmol of Pd(AcO)2, and 2 mmol of Et3N
were dissolved in 10 mL of solvent (THF) and placed in a 45 mL
autoclave. The autoclave was purged, pressurized (400 psi CO), and
then heated to 100 ꢁC for 30–35 h. The reaction mixture was then
cooled to room temperature and concentrated in vacuo. The crude
mixture was chromatographed (silica gel, petroleum ether/Et2O 1:1
for compounds 1a, 1b, 3b, 4b, 6a, 6b, 10a, 10b, 11a, 11b; petroleum
ether/Et2O 6:4 for 8a, 9a, 9b; petroleum ether/Et2O 2:8 for 2b, 5a,
5b; only Et2O for 7a, 7b) to afford pure products 1a–11a, 1b–11b
(75–95%).
J¼8.0 Hz, 1H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 27.9, 54.9, 56.4,
57.7, 121.6, 121.7, 123.1, 125.4, 126.2, 128.0, 134.7, 153.0, 167.6, 170.9;
FTIR (CHCl3): 3070, 2980, 2936, 1747, 1370, 1348, 1229 cmꢀ1; GC–
MS (70 eV) m/z 286 (2) [M]þ, 230 (3), 186 (100), 135 (4), 57 (8);
HRMS-ESI: calcd for C16H19N2OS: 287.1220 [MþH]þ; found:
287.1220.
4.3.5. 1-n-Butyl-4-pyridin-2-yl-3-vinylazetidin-2-ones 5a, 5b
Overall yield 81%. Compound 5a. Yield 182 mg (79%), brown oil;
1H NMR (400.13 MHz, CDCl3)
d
0.84 (t, J¼7.2 Hz, 3H, CH3CH2), 1.23–
1.33 (m, 2H, CH3CH2), 1.39–1.47 (m, 2H, CH3CH2CH2), 2.83–2.89 (m,
1H, CH2CH2–N), 3.45–3.52 (m, 1H, CH2CH2–N), 3.74 (dd, J¼2.1,
7.6 Hz, 1H, CHCH]CH2), 4.49 (d, J¼2.1 Hz, 1H, CHAr), 5.24 (d,
J¼10.3 Hz, 1H, CH]CH2), 5.31 (d, J¼17.1 Hz, 1H, CH]CH2), 5.94–
6.02 (m, 1H, CH]CH2), 7.24 (dd, J¼4.8, 7.7 Hz, 1H, ArH), 7.29 (d,
J¼7.7 Hz, 1H, ArH), 7.71 (t, J¼7.7 Hz, 1H, ArH), 8.60 (d, J¼4.8 Hz, 1H,
4.3.1. 1-tert-Butyl-4-phenyl-3-vinylazetidin-2-ones 1a, 1b
Overall yield 85%. Compound 1a. Yield 19.5 mg (8.5%), yellow
solid; mp 68.9–70.3 ꢁC (petroleum ether); 1H NMR (400.13 MHz,
CDCl3)
d
1.25 (s, 9H, (CH3)3), 3.45 (dd, J¼2.0, 7.8 Hz, 1H,
CHCH]CH2), 4.33 (d, J¼2.0 Hz, 1H, CHPh), 5.23 (dd, J¼17.2, 20.3 Hz,
ArH); 13C NMR (100.62 MHz, CDCl3)
d 13.5, 19.8, 29.5, 40.6, 62.0,
2H, CH]CH2), 5.87–5.96 (m, 1H, CH]CH2), 7.30–7.37 (m, 5H, ArH);
62.2, 119.1, 120.8, 123.2, 131.1, 137.0, 149.9, 157.4, 168.0; FTIR (CHCl3):
3009, 2964, 2930, 2875, 1748, 1577, 1431, 1400 cmꢀ1; GC–MS
(70 eV) m/z 230 (20) [M]þ, 159 (10), 131 (93), 130 (100), 92 (10), 78
13C NMR (100.62 MHz, CDCl3)
d
28.1, 54.5, 60.6, 62.6, 118.7, 126.3,
128.2, 128.8, 131.3, 140.3, 168.1; FTIR (CHCl3): 3065, 3031, 2974,

11636
L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
(13); HRMS-ESI: calcd for C14H19N2O: 231.1499 [MþH]þ; found:
231.1499. Compound 5b: traces; GC–MS (70 eV) m/z 230 (5) [M]þ,
159 (3), 131 (19), 130 (100), 92 (4), 78 (3).
J¼2.2, 7.4 Hz, 1H, CHCH]CH2), 4.83 (d, J¼2.2 Hz, 1H, CHAr), 5.30 (d,
J¼10.2 Hz, 1H, CH]CH2), 5.38 (d, J¼17.1 Hz, 1H, CH]CH2), 5.94–
6.03 (m, 1H, CH]CH2), 7.40 (t, J¼8.1 Hz, 1H, ArH), 7.49 (t, J¼8.1 Hz,
1H, ArH), 7.88 (d, J¼8.1 Hz, 1H, ArH), 8.00 (d, J¼8.1 Hz, 1H, ArH); 13C
4.3.6. 1-n-Butyl-4-pyridin-3-yl-3-vinylazetidin-2-ones 6a, 6b
Overall yield 79%. Compound 6a. Yield 177 mg (77%), brown oil;
NMR (100.62 MHz, CDCl3) d 13.4, 20.0, 29.4, 41.0, 58.9, 63.1, 119.9,
121.9, 123.2, 125.6, 126.4, 130.0, 134.7, 153.1, 167.2, 169.1; FTIR (film):
3064, 2958, 2931, 2872, 1766, 1437, 1391, 1313, 926 cmꢀ1; GC–MS
(70 eV) m/z 286 (8) [M]þ, 259 (6), 219 (6), 186 (100), 175 (8), 148 (6);
HRMS-ESI: calcd for C16H19N2OS 287.1220 [MþH]þ; found:
287.1220. Compound 9b. Yield 37 mg (13%), yellow oil; 1H NMR
1H NMR (400.13 MHz, CDCl3)
d
0.87 (t, J¼7.3 Hz, 3H, CH3CH2), 1.24–
1.34 (m, 2H, CH3CH2), 1.41–1.48 (m, 2H, CH3CH2CH2), 2.80–2.86 (m,
1H, CH2CH2–N), 3.43–3.45 (m, 1H, CH2CH2–N), 3.61 (dd, J¼2.0,
7.7 Hz, 1H, CHCH]CH2), 4.36 (d, J¼2.0 Hz, 1H, CHAr), 5.27 (d,
J¼10.8 Hz, 1H, CH]CH2), 5.31 (d, J¼17.4 Hz, 1H, CH]CH2), 5.92–
6.00 (m, 1H, CH]CH2), 7.34 (dd, J¼4.8, 7.8 Hz, 1H, ArH), 7.64 (d,
J¼7.8 Hz, 1H, ArH), 8.57 (s, 1H, ArH), 8.61 (d, J¼4.8 Hz, 1H, ArH); 13C
(400.13 MHz, CDCl3)
d
0.90 (t, J¼7.3 Hz, 3H, CH3CH2), 1.35 (sextet,
J¼7.3 Hz, 2H, CH3CH2), 1.58 (quintet, J¼7.3 Hz, 2H, CH3CH2CH2),
3.11–3.18 (m, 1H, CH2CH2–N), 3.64 (dt, J¼7.8, 14.0 Hz, 1H, CH2CH2–
N), 4.32 (dd, J¼5.6, 7.0 Hz, 1H, CHCH]CH2), 5.10 (d, J¼10.2 Hz, 1H,
CH]CH2), 5.26 (d, J¼5.6 Hz, 1H, CHAr), 5.38 (d, J¼16.0 Hz, 1H,
CH]CH2), 5.47–5.56 (m, 1H, CH]CH2), 7.42 (t, J¼8.0 Hz, 1H, ArH),
7.50 (t, J¼8.0 Hz, 1H, ArH), 7.89 (d, J¼8.0 Hz, 1H, ArH), 8.00 (d,
NMR (100.62 MHz, CDCl3)
d 13.5, 20.0, 29.6, 40.5, 59.0, 63.4, 119.6,
124.0, 130.7, 133.3, 133.5, 148.4, 150.1, 167.6; FTIR (CHCl3): 3010,
2963, 2932, 2875, 1748, 1579, 1432, 1400 cmꢀ1; GC–MS (70 eV) m/z
230 (<1) [M]þ, 163 (3), 131 (95), 130 (100), 104 (8), 92 (5), 78 (3);
HRMS-ESI: calcd for C14H19N2O: 231.1499 [MþH]þ; found:
231.1499. Compound 6b: traces; GC–MS (70 eV) m/z 230 (<1) [M]þ,
163 (5), 131 (53), 130 (100), 104 (8), 92 (5), 78 (3).
J¼8.0 Hz, 1H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 13.5, 20.2, 29.5,
41.3, 57.4, 59.4, 121.8, 123.2, 125.5, 126.3, 127.7, 128.5, 134.8, 153.3,
167.5, 168.1; FTIR (CHCl3): 3066, 3011, 2963, 2934, 2875, 1753, 1514,
1437, 1314 cmꢀ1; GC–MS (70 eV) m/z 286 (5) [M]þ, 259 (3), 219 (3),
186 (100), 175 (5), 148 (3), 77 (2); HRMS-ESI: calcd for C16H19N2OS:
287.1220 [MþH]þ; found: 287.1220.
4.3.7. 1-n-Butyl-4-pyridin-4-yl-3-vinylazetidin-2-ones 7a, 7b
Overall yield 81%. Compound 7a. Yield 168 mg (73%), brown oil;
1H NMR (400.13 MHz, CDCl3)
d
0.87 (t, J¼7.3 Hz, 3H, CH3CH2), 1.25–
1.34 (m, 2H, CH3CH2), 1.40–1.49 (m, 2H, CH3CH2CH2), 2.81–2.88 (m,
1H, CH2CH2–N), 3.44–3.52 (m, 1H, CH2CH2–N), 3.55 (dd, J¼2.0,
7.8 Hz, 1H, CHCH]CH2), 4.31 (d, J¼2.0 Hz, 1H, CHAr), 5.27 (d,
J¼9.3 Hz, 1H, CH]CH2), 5.30 (d, J¼16.1 Hz, 1H, CH]CH2), 5.90–5.99
(m, 1H, CH]CH2), 7.21 (d, J¼5.4 Hz, 2H, ArH), 8.62 (d, J¼5.4 Hz, 2H,
4.3.10. 1-Isopropyl-4-phenyl-3-vinylazetidin-2-ones 10a, 10b
Overall yield 95%. Compound 10a. Yield 184 mg (85.5%), yellow
oil; 1H NMR (400.13 MHz, CDCl3)
d
1.03 (d, J¼6.7 Hz, 3H, (CH3)2CH),
1.28 (d, J¼6.7 Hz, 3H, (CH3)2CH), 3.56 (dd, J¼2.1, 7.7 Hz, 1H,
CHCH]CH2), 3.77 (heptet, J¼6.7 Hz, 1H, (CH3)2CH), 4.33 (d,
J¼2.1 Hz, 1H, CHAr), 5.23 (d, J¼10.4 Hz, 1H, CH]CH2), 5.28 (d,
J¼17.1 Hz, 1H, CH]CH2), 5.90–5.99 (m, 1H, CH]CH2), 7.32–7.40 (m,
ArH); 13C NMR (100.62 MHz, CDCl3)
d 13.5, 20.0, 29.6, 40.7, 60.1,
63.8, 119.7, 121.1, 130.5, 147.0, 150.5, 167.5; FTIR (CHCl3): 3022, 3011,
2933, 2872, 1750, 1604, 1417 cmꢀ1; GC–MS (70 eV) m/z 230 (<1)
[M]þ, 163 (1), 131 (68), 130 (100), 104 (9), 78 (5); HRMS-ESI: calcd
for C14H19N2O: 231.1499 [MþH]þ; found: 231.1499. Compound 7b.
5H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 20.3, 21.2, 45.0, 60.3, 63.1,
119.0, 126.5, 128.4, 128.8, 131.1, 139.0, 167.9; FTIR (film): 3063, 3030,
2975, 2931, 1747, 1457, 1380, 1370 cmꢀ1; GC–MS (70 eV) m/z 215
(<1) [M]þ, 148 (2), 130 (100), 129 (67), 115 (27), 77 (6); HRMS-ESI:
calcd for C14H18NO: 216.1389 [MþH]þ; found: 216.1390. Compound
10b. Yield 20 mg (9.5%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
Yield 18.4 mg (8%), oil; 1H NMR (400.13 MHz, CDCl3)
d 0.90 (t,
J¼7.3 Hz, 3H, CH3CH2), 1.28–1.37 (m, 2H, CH3CH2), 1.43–1.55 (m, 2H,
CH3CH2CH2), 2.90–2.97 (m, 1H, CH2CH2–N), 3.53–3.62 (m, 1H,
CH2CH2–N), 4.19 (dd, J¼5.6, 6.3 Hz, 1H, CHCH]CH2), 4.79 (d,
J¼5.6 Hz, 1H, CHAr), 5.07 (d, J¼9.6 Hz, 1H, CH]CH2), 5.15–5.23 (m,
1H, CH]CH2), 5.28–5.35 (m, 1H, CH]CH2), 7.15 (d, J¼5.4 Hz, 2H,
ArH), 8.62 (d, J¼5.4 Hz, 2H, ArH); 13C NMR (100.62 MHz, CDCl3)
d
1.12 (d, J¼6.7 Hz, 3H, (CH3)2CH), 1.32 (d, J¼6.7 Hz, 3H, (CH3)2CH),
3.79 (heptet, J¼6.7 Hz, 1H, (CH3)2CH), 4.03 (dd, J¼5.3, 5.5 Hz, 1H,
CHCH]CH2), 4.82 (d, J¼5.5 Hz, 1H, CHAr), 5.02–5.05 (m, 1H,
CH]CH2), 5.25–5.31 (m, 2H, CH]CH2), 7.26–7.39 (m, 5H, ArH); 13
C
d
13.5, 20.2, 29.6, 40.8, 58.0, 58.8, 121.1, 122.3, 128.4, 145.2, 150.0,
NMR (100.62 MHz, CDCl3) d 20.3, 21.3, 45.3, 58.0, 120.0, 127.6, 128.1,
167.6; FTIR (CHCl3): 3026, 3010, 2934, 2873, 1749, 1605, 1417 cmꢀ1
;
128.4, 129.5, 136.7, 168.2; FTIR (film): 3064, 3030, 2977, 2931, 1748,
1456, 1380, 1370 cmꢀ1; GC–MS (70 eV) m/z 215 (<1) [M]þ, 148 (2),
130 (100), 129 (67), 115 (27), 77 (6); HRMS-ESI: calcd for C14H18NO:
216.1389 [MþH]þ; found: 216.1389.
GC–MS (70 eV) m/z 230 (<1) [M]þ, 163 (2), 131 (57), 130 (100), 104
(10), 78 (4); HRMS-ESI: calcd for C14H19N2O: 231.1499 [MþH]þ;
found: 231.1499.
4.3.8. 1-n-Butyl-4-phenyl-3-vinylazetidin-2-one 8a
4.3.11. 1-Ethyl-4-phenyl-3-vinylazetidin-2-one 11a
Yield 206 mg (90%), yellow oil; 1H NMR (400.13 MHz, CDCl3):
Yield 181 mg (90%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
d
0.88 (t, J¼7.3 Hz, 3H, CH3CH2), 1.25–1.35 (m, 2H, CH3CH2), 1.42–
d
1.09 (t, J¼7.3 Hz, 3H, CH3CH2), 2.93–2.99 (m,1H, CH3CH2–N), 3.48–
1.49 (m, 2H, CH3CH2CH2), 2.79–2.86 (m, 1H, CH2CH2–N), 3.46–3.53
(m, 1H, CH2CH2–N), 3.59 (dd, J¼1.5, 7.7 Hz, 1H, CHCH]CH2), 4.33 (d,
J¼1.5 Hz, 1H, CHAr), 5.24 (d, J¼10.3 Hz, 1H, CH]CH2), 5.30
(d, J¼17.1 Hz, 1H, CH]CH2), 5.93–6.02 (m, 1H, CH]CH2), 7.30
(d, J¼7.0 Hz, 2H, ArH), 7.33–7.41 (m, 3H, ArH); 13C NMR
3.57 (m, 1H, CH3CH2–N), 3.60 (dd, J¼2.1, 6.9 Hz, 1H, CHCH]CH2),
4.37 (d, J¼2.1 Hz, 1H, CHAr), 5.26 (d, J¼10.4 Hz, 1H, CH]CH2), 5.30
(d, J¼17.1 Hz, 1H, CH]CH2), 5.93–6.02 (m, 1H, CH]CH2), 7.31–7.42
(m, 5H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 12.8, 35.4, 60.9, 63.7,
119.1, 126.3, 128.5, 129.0, 131.1, 137.7, 167.9; FTIR (film): 3032, 2978,
2934, 1756, 1457, 1397, 1360 cmꢀ1; GC–MS (70 eV) m/z 201 (<1)
[M]þ, 130 (100), 129 (87), 115 (36), 91 (9), 77 (8); HRMS-ESI: calcd
for C13H16NO: 202.1233 [MþH]þ; found: 202.1233.
(100.62 MHz, CDCl3)
d 13.5, 20.1, 29.6, 40.2, 61.4, 63.8, 119.0, 126.3,
128.5, 129.0, 131.3, 137.6, 168.1; FTIR (film): 3032, 2958, 2931, 2873,
1757, 1457, 1397 cmꢀ1; GC–MS (70 eV) m/z 229 (<1) [M]þ, 162 (4),
130 (100), 129 (79), 115 (33), 104 (5), 91 (4), 77 (6); HRMS-ESI: calcd
for C15H20NO: 230.1546 [MþH]þ; found: 230.1546.
4.4. General procedure for the functionalization of
compounds 1a, 5a, 8a–10a, 1b–4b, 10b
4.3.9. 4-Benzothiazol-2-yl-1-n-butyl-3-vinylazetidin-2-ones 9a, 9b
Overall yield 78%. Compound 9a. Yield 186 mg (65%), yellow oil;
To a stirred solution of 1 mmol of 1a, 5a, 8a–10a, 1b–4b, 10b in
THF (30 mL) at ꢀ78 ꢁC, n-BuLi (2.5 M in hexanes, 0.5 mL, 1.2 mmol)
was added dropwise under nitrogen. The resulting mixture was
stirred at ꢀ78 ꢁC for 20 min, and then the electrophile was added
1H NMR (400.13 MHz, CDCl3)
d
0.87 (t, J¼7.3 Hz, 3H, CH3CH2), 1.26–
1.36 (m, 2H, CH3CH2), 1.49–1.56 (m, 2H, CH3CH2CH2), 3.02–3.08 (m,
1H, CH2CH2–N), 3.55 (dt, J¼7.7, 14.1 Hz, 1H, CH2CH2–N), 3.92 (dd,

L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
11637
(1.5 mmol). The reaction mixture was warmed up to room tem-
perature and quenched with saturated aq NH4Cl. The aqueous layer
was extracted with Et2O (3ꢂ20 mL) and the combined organic
layers were dried over anhydrous Na2SO4 and concentrated in
CHAr), 5.25 (d, J¼10.4 Hz, 1H, CH]CH2), 5.31 (d, J¼17.5 Hz, 1H,
CH]CH2), 5.91–6.00 (m, 1H, CH]CH2), 7.24 (dd, J¼4.6, 7.7 Hz, 1H,
ArH), 7.44 (d, J¼7.7 Hz, 1H, ArH), 7.73 (t, J¼7.7 Hz, 1H, ArH), 8.58 (d,
J¼4.6 Hz, 1H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 28.1, 54.5, 61.2,
vacuo to afford the pure functionalized
b
-lactams 14a, 16a, 18a, 20a,
61.3,119.0,120.9,123.1,131.1,136.9,149.5,159.8,168.0; FTIR (CHCl3):
3019, 2973, 2934, 1738, 1593, 1438, 1367 cmꢀ1; GC–MS (70 eV) m/z
231 (3) [M]þ, 174 (6), 158 (4), 131 (100), 78 (4); HRMS-ESI: calcd for
C14H18DN2O: 232.1561 [MþH]þ; found: 232.1562. Compound 16b.
Yield 196 mg (85%), yellow oil; the FTIR, 1H and 13C NMR data are
the same of those reported for 2b. In the 1H NMR spectrum the
double doublet at 4.06 ppm disappears, while the doublet at
4.98 ppm becomes a singlet; GC–MS (70 eV) m/z 231 (2) [M]þ, 174
(4), 147 (3), 131 (100), 78 (5), 57 (5); HRMS-ESI: calcd for
C14H18DN2O: 232.1561 [MþH]þ; found: 232.1562.
22a, 24a, 26a, 28a, 12b–28b; yields: 88–99%.
4.4.1. 1-tert-Butyl-3-methyl-4-phenyl-3-vinylazetidin-2-one 12b
From
49.3.5–50.1 ꢁC (petroleum ether); 1H NMR (400.13 MHz, CDCl3)
1.23 (s, 9H, (CH3)3), 1.36 (s, 3H, CH3CCH]CH2), 4.31 (s, 1H, CHAr),
b-lactam 1b. Yield 241.6 mg (>99%), yellow solid; mp
d
4.87 (dd, J¼1.6, 10.3 Hz, 1H, CH]CH2), 5.08–5.15 (m, 1H, CH]CH2),
5.24 (dd, J¼1.6, 17.2 Hz, 1H, CH]CH2), 7.18–7.28 (m, 5H, ArH); 13C
NMR (100.62 MHz, CDCl3)
d 20.9, 28.1, 54.1, 60.0, 66.8, 116.6, 127.5,
127.9, 128.2, 135.0, 138.2, 172.0; FTIR (CHCl3): 3030, 3018, 2977,
2931, 2857, 1746, 1370, 1344 cmꢀ1; GC–MS (70 eV) m/z 243 (<1)
[M]þ, 187 (5), 144 (70), 129 (100), 128 (28), 115 (7), 82 (5), 57 (9);
HRMS-ESI: calcd for C16H22NO: 244.1703 [MþH]þ; found: 244.1703.
4.4.6. 1-tert-Butyl-3-methyl-4-(4-methylthiazol-2-yl)-3-
vinylazetidin-2-one 17b
Yield 262 mg (>99%), yellow solid; mp 79.2–80.5 ꢁC (petroleum
From
b-lactam 1a. Yield 236 mg (97%).
ether); 1H NMR (400.13 MHz, CDCl3)
d 1.35 (s, 9H, (CH3)3), 1.51 (s,
3H, CH3CCH]CH2), 2.43 (s, 3H, CH3Ar), 4.77 (s, 1H, CHAr), 5.05 (dd,
J¼2.9, 8.9 Hz, 2H, CH]CH2), 5.36–5.39 (m, 1H, CH]CH2), 6.87 (s,
4.4.2. 3-Allyl-1-tert-butyl-4-phenyl-3-vinylazetidin-2-one 13b
Yield 255.5 mg (95%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
1H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 16.9, 20.6, 27.9, 54.5, 61.1,
d
1.20 (s, 9H, (CH3)3), 2.46 (d, J¼7.1 Hz, 2H, CCH2CH]CH2), 4.47 (s,
64.0, 114.0, 117.9, 133.7, 152.6, 169.5, 171.7; FTIR (CHCl3): 3025, 3015,
2983, 2934, 1735, 1461, 1369, 1343 cmꢀ1; GC–MS (70 eV) m/z 264
(4) [M]þ, 208 (8), 164 (100), 150 (11), 126 (7), 113 (11), 82 (23), 57
(16); HRMS-ESI: calcd for C14H21N2OS: 265.1376 [MþH]þ; found:
265.1377.
1H, CHAr), 4.91 (dd, J¼1.4, 10.8 Hz, 1H, CCH2CH]CH2), 5.00–5.18
(m, 3H, CH]CH2), 5.32 (dd, J¼1.4, 17.3 Hz, 1H, CH]CH2), 5.76–5.87
(m, 1H, CH]CH2), 7.15–7.32 (m, 5H, ArH); 13C NMR (100.62 MHz,
CDCl3)
d 28.2, 39.9, 54.2, 62.9, 63.0, 117.1, 118.7, 127.6, 127.7, 128.0,
133.2, 133.9, 137.9, 170.5; FTIR (CHCl3): 3024, 3004, 2983, 2930,
1738,1456, 1367,1341 cmꢀ1; GC–MS (70 eV) m/z 269 (<1) [M]þ, 213
(2), 170 (19), 155 (9), 141 (13), 129 (100), 91 (10), 79 (9); HRMS-ESI:
calcd for C18H24NO: 270.1859 [MþH]þ; found: 270.1860.
4.4.7. 1-tert-Butyl-3-deutero-4-(4-methylthiazol-2-yl)-3-
vinylazetidin-2-ones 18a, 18b
Overall yield 92%. Compound 18a: traces; GC–MS (70 eV) m/z
251 (1) [M]þ, 194 (3), 167 (4), 151 (100), 127 (3), 71 (3), 57 (3).
Compound 18b. Yield 226 mg (90%), yellow solid; mp 53.5–54.8 ꢁC
(petroleum ether); the FTIR, 1H and 13C NMR data are the same of
those reported for 3b. In the 1H NMR spectrum the double doublet
at 4.04 ppm disappears, while the doublet at 5.16 ppm becomes
a singlet; GC–MS (70 eV) m/z 251 (2) [M]þ, 194 (4), 167 (3), 151
(100), 127 (5), 71 (5), 57 (5); HRMS-ESI: calcd for C13H18DN2OS:
252.1282 [MþH]þ; found: 252.1283.
4.4.3. 1-tert-Butyl-3-deutero-4-phenyl-3-vinylazetidin-
2-ones 14a, 14b
Overall yield 99%. Compound 14a. Yield 50 mg (21.7%), yellow
oil; The FTIR, 1H and 13C NMR data are the same of those reported
for 1a. In the 1H NMR spectrum the signal at 3.45 ppm disappears,
while the doublet at 4.33 ppm becomes a singlet; GC–MS (70 eV)
m/z 230 (<1) [M]þ, 146 (1), 131 (100), 130 (45), 115 (18), 84 (3), 79
(3), 57 (5); HRMS-ESI: calcd for C15H19DNO: 231.1609 [MþH]þ;
found: 231.1609. Compound 14b. Yield 177 mg (77%), yellow oil; the
FTIR, 1H and 13C NMR data are the same of those reported for 1b. In
the 1H NMR spectrum the doublet at 3.96 ppm disappears, while
the signal at 4.84 ppm becomes a singlet; GC–MS (70 eV) m/z 230
(<1) [M]þ, 146 (4), 131 (100), 129 (54), 115 (22), 77 (8), 84 (5), 57
(20); HRMS-ESI: calcd for C15H19DNO: 231.1609 [MþH]þ; found:
231.1609.
4.4.8. 4-Benzothiazol-2-yl-1-tert-butyl-3-methyl-3-vinylazetidin-
2-one 19b
Yield 264 mg (88%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
d
1.39 (s, 9H, (CH3)3), 1.57 (s, 3H, CH3CCH]CH2), 4.88 (s, 1H, CHAr),
5.03 (dd, J¼2.1, 9.5 Hz, 1H, CH]CH2), 5.37–5.45 (m, 2H, CH]CH2),
7.41 (t, J¼7.9 Hz, 1H, ArH), 7.49 (t, J¼7.9 Hz, 1H, ArH), 7.88 (d,
J¼7.9 Hz, 1H, ArH), 8.00 (d, J¼7.9 Hz, 1H, ArH); 13C NMR
(100.62 MHz, CDCl3) d 20.8, 27.9, 54.7, 61.5, 64.4, 118.3, 121.8, 123.0,
4.4.4. 1-tert-Butyl-3-methyl-4-pyridin-2-yl-3-vinylazetidin-
2-one 15b
125.4, 126.2, 133.3, 134.8, 153.1, 171.4, 171.5; FTIR (CHCl3): 3029,
3018, 2977, 2931, 1745, 1371, 1343 cmꢀ1; GC–MS (70 eV) m/z 300 (4)
[M]þ, 244 (7), 200 (100), 186 (9), 135 (5), 82 (11); HRMS-ESI: calcd
for C17H21N2OS: 301.1376 [MþH]þ; found: 301.1377.
Yield 220 mg (90%), yellow solid; mp 74.2–75.5 ꢁC (petroleum
ether); 1H NMR (400.13 MHz, CDCl3)
d 1.31 (s, 9H, (CH3)3), 1.53 (s,
3H, CH3CCH]CH2), 4.59 (s, 1H, CHAr), 4.94 (dd, J¼1.7, 10.2 Hz, 1H,
CH]CH2), 5.16–5.23 (m, 1H, CH]CH2), 5.28 (dd, J¼1.7, 17.4 Hz, 1H,
CH]CH2), 7.20 (dd, J¼4.6, 7.7 Hz, 1H, ArH), 7.36 (d, J¼7.7 Hz, 1H,
ArH), 7.69 (t, J¼7.7 Hz, 1H, ArH), 8.54 (d, J¼4.6 Hz, 1H, ArH); 13C
4.4.9. 4-Benzothiazol-2-yl-1-tert-butyl-3-deutero-3-vinylazetidin-
2-ones 20a, 20b
Overall yield 95%. Compound 20a. Yield 40 mg (14%), yellow oil;
NMR (100.62 MHz, CDCl3)
d
20.9, 28.0, 54.1, 60.4, 67.6, 117.0, 122.1,
1H NMR (400.13 MHz, CDCl3)
d 1.35 (s, 9H, (CH3)3), 4.88 (s, 1H,
122.6, 134.4, 136.0, 149.1, 158.6, 171.9; FTIR (CHCl3): 3019, 2972,
2931, 1736, 1593,1437,1368 cmꢀ1; GC–MS (70 eV) m/z 244 (2) [M]þ,
188 (22), 173 (3), 144 (100), 130 (25), 78 (7); HRMS-ESI: calcd for
C15H21N2O: 245.1655 [MþH]þ; found: 245.1656.
CHAr), 5.31 (d, J¼10.1 Hz, 1H, CH]CH2), 5.37 (d, J¼17.1 Hz, 1H,
CH]CH2), 5.90–5.98 (m, 1H, CH]CH2), 7.42 (t, J¼7.8 Hz, 1H. ArH),
7.51 (t, J¼7.8 Hz, 1H, ArH), 7.90 (d, J¼7.8 Hz, 1H, ArH), 8.00 (d,
J¼7.8 Hz, 1H, ArH); 13C NMR (100.62 MHz, CDCl3)
d 28.0, 55.2, 58.2,
62.2, 119.8, 122.0, 123.3, 125.7, 126.4, 130.8, 134.8, 152.9, 167.5,
172.3; FTIR (CHCl3): 3018, 2980, 2932, 1747, 1224 cmꢀ1; GC–MS
(70 eV) m/z 287 (3) [M]þ, 230 (3), 187 (100), 135 (4), 57(8); HRMS-
ESI: calcd for C16H18DN2OS: 288.1282 [MþH]þ; found: 288.1283.
Compound 20b. The FTIR,1H and 13C NMR data are the same of those
4.4.5. 1-tert-Butyl-3-deutero-4-pyridin-2-yl-3-vinylazetidin-
2-ones 16a, 16b
Overall yield >99%. Compound 16a. Yield 32 mg (13.8%), yellow
oil; 1H NMR (400.13 MHz, CDCl3)
d 1.25 (s, 9H, (CH3)3), 4.52 (s, 1H,

11638
L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
reported for 4b. In the 1H NMR spectrum the double doublet at
4.18 ppm disappears, while the doublet at 5.31 ppm becomes a sin-
glet; GC–MS (70 eV) m/z 287 (2) [M]þ, 230 (3), 187 (100), 135 (4),
57(8); HRMS-ESI: calcd for C16H18DN2OS: 288.1282 [MþH]þ; found:
288.1283.
J¼7.2 Hz, 2H, ArH), 7.30–7.40 (m, 3H, ArH); 13C NMR (100.62 MHz,
CDCl3)
d 13.6, 20.2, 29.6, 40.4, 58.8, 59.0, 120.1, 127.4, 128.2, 128.6,
129.3, 135.6, 168.2; FTIR (film): 3032, 2958, 2931, 2873, 1757, 1457,
1397 cmꢀ1; GC–MS (70 eV) m/z 230 (<1) [M]þ, 163 (2), 132 (13), 131
(100), 139 (48), 104 (10), 78 (4); HRMS-ESI: calcd for C15H19DNO:
231.1609 [MþH]þ; found: 231.1609.
4.4.10. 1-n-Butyl-3-methyl-4-pyridin-2-yl-3-vinylazetidin-
2-one 21b
4.4.14. 4-Benzothiazol-2-yl-1-n-butyl-3-methyl-3-vinylazetidin-
Yield 242.6 mg (>99%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
2-one 25b
d
0.91 (t, J¼7.1 Hz, 3H, CH3CH2), 1.30–1.39 (m, 2H, CH3CH2), 1.47–
Yield 279 mg (93%); 1H NMR (400.13 MHz, CDCl3)
d 0.89 (t,
1.54 (m, 2H, CH3CH2CH2), 1.61 (s, 3H, CH3CCH]CH2), 2.92–2.99 (m,
1H, CH2CH2–N), 3.61–3.68 (m, 1H, CH2CH2–N), 4.60 (s, 1H, CHAr),
4.92–4.95 (m, 1H, CH]CH2), 5.23–5.27 (m, 2H, CH]CH2), 7.17 (d,
J¼7.8 Hz, 1H, ArH), 7.23 (dd, J¼4.6, 7.8 Hz, 1H, ArH), 7.70 (t, J¼7.8 Hz,
1H, ArH), 8.59 (d, J¼4.6 Hz, 1H, ArH); 13C NMR (100.62 MHz, CDCl3)
J¼7.3 Hz, 3H, CH3CH2), 1.34 (sextet, J¼7.3 Hz, 2H, CH3CH2), 1.55
(quintet, J¼7.3 Hz, 2H, CH3CH2CH2), 1.59 (s, 3H, CH3CCH]CH2),
3.09–3.15 (m,1H, CH2CH2–N), 3.61–3.66 (m, 1H, CH2CH2–N), 4.95 (s,
1H, CHAr), 5.12 (d, J¼9.9 Hz, 1H, CH]CH2), 5.40–5.55 (m, 2H,
CH]CH2), 7.39 (t, J¼7.9 Hz, 1H, ArH), 7.50 (t, J¼7.9 Hz, 1H, ArH), 7.90
(d, J¼7.9 Hz, 1H, ArH), 8.00 (d, J¼7.9 Hz, 1H, ArH); 13C NMR
d
13.5, 20.1, 20.7, 29.5, 40.2, 62.6, 68.0, 117.0, 121.5, 122.7, 134.2,
136.3, 149.6, 156.5, 171.4; FTIR (CHCl3): 3010, 2963, 2932, 2875,
1748,1579,1432,1400 cmꢀ1; GC–MS (70 eV) m/z 244 (22) [M]þ, 229
(5), 215 (4), 201 (3), 187 (5), 173 (15), 145 (68), 144 (100), 130 (43),
92 (19), 78 (14); HRMS-ESI: calcd for C15H21N2O 245.1655 [MþH]þ;
found: 245.1656.
(100.62 MHz, CDCl3) d 13.5, 20.2, 20.5, 29.0, 41.1, 56.0, 57.0, 121.8,
123.2, 126.0, 126.3, 127.5, 128.5, 134.8, 153.2, 167.5, 168.2; FTIR
(film): 3065, 2956, 2930, 2871, 1769, 1435, 1389, 1310 cmꢀ1; GC–MS
(70 eV) m/z 300 (8) [M]þ, 259 (6), 219 (6), 201 (100),175 (8),148 (6);
HRMS-ESI: calcd for C17H21N2OS: 301.1376 [MþH]þ; found:
301.1377.
4.4.11. 1-n-Butyl-3-deutero-4-pyridin-2-yl-3-vinylazetidin-
2-ones 22a, 22b
4.4.15. 4-Benzothiazol-2-yl-1-n-butyl-3-deutero-3-vinylazetidin-
2-ones 26a, 26b
Inseparable mixture of two trans- and cis-configurated di-
astereomers (dr¼1:1 by 1H NMR), the reaction was followed only
via GC and 1H NMR spectroscopy showing the formation of two
compounds. From the 1H NMR spectrum of the mixture we iden-
tified and assigned separate signals for 22a and 22b, respectively.
Compound 22a. The 1H NMR data are the same of those reported
for 5a except the double doublet at 3.74 ppm that disappears, while
the doublet at 4.49 ppm becomes a singlet. Compound 22b. 1H
Overall yield (>99%). Compound 26a. Yield 129 mg (45%), yellow
oil. The FTIR,1H and 13C NMR data are the same of those reported for
9a. In the 1H NMR spectrum the double doublet at 3.92 ppm dis-
appears, while the doublet at 4.83 ppm becomes a singlet; GC–MS
(70 eV) m/z 287 (8) [M]þ, 259 (6), 219 (6), 187 (100), 175 (8), 148 (6);
HRMS-ESI: calcd for C16H18DN2OS 288.1282 [MþH]þ; found:
288.1283. Compound 26b. Yield 129 mg (45%), yellow oil; the FTIR,
1H and 13C NMR data are the same of those reported for 9b. In the 1H
NMR spectrum the double doublet at 4.32 ppm disappears, while
the doublet at 5.26 ppm becomes a singlet; GC–MS (70 eV) m/z 287
(5) [M]þ, 259 (3), 219 (3), 187 (100), 175 (5), 148 (3), 77 (2); HRMS-
ESI: calcd for C16H18DN2OS: 288.1282 [MþH]þ; found 288.1283.
NMR (400.13 MHz, CDCl3)
d
0.85 (t, J¼7.2 Hz, 3H, CH3CH2),1.22–1.32
(m, 2H, CH3CH2), 1.38–1.46 (m, 2H, CH3CH2CH2), 2.90–2.98 (m, 1H,
CH2CH2–N), 3.53–3.59 (m, 1H, CH2CH2–N), 4.88 (s, 1H, CHAr), 4.92–
4.95 (m, 1H, CH]CH2), 5.26–5.29 (m, 2H, CH]CH2), 7.22–7.28 (m,
2H, ArH), 7.61 (t, J¼7.7 Hz, 1H, ArH), 8.60 (d, J¼4.8 Hz, 1H, ArH). GC–
MS performed on the mixture showed two peaks having the same
fragmentation and [M]þ¼231 (18).
4.4.16. 1-Isopropyl-3-methyl-4-phenyl-3-vinylazetidin-2-one 27b
From
(400.13 MHz, CDCl3)
b
-lactam 10a. Yield 228 mg (>99%), yellow oil; 1H NMR
4.4.12. 1-n-Butyl-3-methyl-4-phenyl-3-vinylazetidin-2-one 23b
d
1.13 (d, J¼6.8 Hz, 3H, (CH3)2CH), 1.33 (d,
Yield 214 mg (88%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
J¼6.8 Hz, 3H, (CH3)2CH), 1.49 (s, 3H, CH3CCH]CH2), 3.78 (heptet,
J¼6.8 Hz, 1H, (CH3)2CH), 4.39 (s, 1H, CHAr), 4.98 (d, J¼9.5 Hz, 1H,
d
0.90 (t, J¼7.3 Hz, 3H, CH3CH2), 1.27 (sextet, J¼7.3 Hz, 2H, CH3CH2),
1.51 (quintet, J¼7.3 Hz, 2H, CH3CH2CH2), 1.60 (s, 3H, CH3CCH]CH2),
2.90–2.95 (m, 1H, CH2CH2–N), 3.50–3.55 (m, 1H, CH2CH2–N), 4.75
(s, 1H, CHAr), 5.00–5.05 (m, 1H, CH]CH2), 5.27–5.29 (m, 2H,
CH]CH2), 7.21 (d, J¼7.2 Hz, 2H, ArH), 7.30–7.40 (m, 3H, ArH); 13C
CH]CH2), 5.20–5.30 (m, 2H, CH]CH2), 7.22–7.35 (m, 5H, ArH); 13
C
NMR (100.62 MHz, CDCl3)
d 20.4, 20.6, 21.2, 45.0, 61.3, 66.5, 116.7,
127.6, 128.1, 128.3, 130.3, 134.9, 171.7; FTIR (film): 3062, 3030, 2975,
2933, 1747, 1457, 1380, 1370 cmꢀ1; GC–MS (70 eV) m/z 229 (<1)
[M]þ, 214 (2), 186 (4), 144 (67), 129 (100), 104 (9), 82 (10); HRMS-
ESI: calcd for C15H20NO: 230.1546 [MþH]þ; found: 230.1546.
NMR (100.62 MHz, CDCl3)
d 13.6, 20.2, 21.0, 29.7, 40.4, 58.9, 59.1,
120.1, 127.3, 128.1, 128.6, 129.4, 135.7, 168.3; FTIR (film): 3032, 2957,
2930, 2875, 1758, 1455, 1396 cmꢀ1; GC–MS (70 eV) m/z 243 (20)
[M]þ, 228 (5), 144 (100), 91 (18), 77 (10); HRMS-ESI: calcd for
C16H22NO: 244.1703 [MþH]þ; found: 244.1703.
Compound 27b (from b-lactam 10b). Yield 213 mg (93%).
4.4.17. 3-Deutero-1-isopropyl-4-phenyl-3-vinylazetidin-2-ones
28a, 28b
4.4.13. 1-n-Butyl-3-deutero-4-phenyl-3-vinylazetidin-2-ones
24a, 24b
Overall yield >99%. Compound 28a (from b-lactam 10a). Yield
64 mg (29.7%). The FTIR, 1H and 13C NMR data are the same of those
reported for 10a. In the 1H NMR spectrum the double doublet at
3.56 ppm disappears, while the doublet at 4.33 ppm becomes
a singlet; GC–MS (70 eV) m/z 216 (<1) [M]þ, 148 (2), 131 (100), 129
(60), 115 (23), 77 (6); HRMS-ESI: calcd for C14H17DNO 217.0121
Overall yield (97%). Compound 24a. Yield 122 mg (53%), yellow
oil; the FTIR, 1H and 13C NMR data are the same of those reported
for 8a. In the 1H NMR spectrum the double doublet at 3.59 ppm
disappears, while the doublet at 4.33 ppm becomes a singlet; GC–
MS (70 eV) m/z 230 (<1) [M]þ, 162 (2), 131 (100), 130 (57), 104 (10),
78 (4); HRMS-ESI: calcd for C15H19DNO: 231.1609 [MþH]þ; found:
231.1609. Compound 24b. Yield 99 mg (43%), yellow oil; 1H NMR
[MþH]þ; found: 217.0121. Compound 28b (from
b-lactam 10a).
Yield 149 mg (69%); the FTIR, 1H and 13C NMR data are the same of
those reported for 10b. In the 1H NMR spectrum the double doublet
at 4.03 ppm disappears, while the doublet at 4.82 ppm becomes
a singlet; GC–MS (70 eV) m/z 216 (<1) [M]þ, 148 (2), 131 (100), 130
(65), 115 (23), 77 (5); HRMS-ESI: calcd for C14H17DNO 217.0121
[MþH]þ; found: 217.0122.
(400.13 MHz, CDCl3)
d
0.89 (t, J¼7.3 Hz, 3H, CH3CH2), 1.27–1.36 (m,
2H, CH3CH2), 1.47–1.54 (m, 2H, CH3CH2CH2), 2.89–2.95 (m, 1H,
CH2CH2–N), 3.53–3.60 (m, 1H, CH2CH2–N), 4.82 (s, 1H, CHAr), 4.99–
5.03 (m, 1H, CH]CH2), 5.26–5.29 (m, 2H, CH]CH2), 7.21 (d,

L. Troisi et al. / Tetrahedron 64 (2008) 11632–11640
11639
4.5. General procedure for the preparation of compounds
29a–32a, 29b–32b
(d, J¼17.1 Hz, 1H, CH]CH2), 6.05–6.10 (m, 1H, CH]CH2), 7.17
(d, J¼7.7 Hz, 1H, ArH), 7.25 (dd, J¼4.7, 7.7 Hz, 1H, ArH), 7.65 (t,
J¼7.7 Hz, 1H, ArH), 8.60 (d, J¼4.7 Hz, 1H, ArH). Compound 31b. The
1H NMR data are the same of those reported for 21b except
the singlet at 4.60 ppm that disappears. GC–MS performed on the
mixture showed two peaks having the same fragmentation and
[M]þ¼245 (18).
To a stirred solution of 1 mmol of the 2-azetidinone 15b, or 21b
in THF (30 mL) at ꢀ78 ꢁC, n-BuLi (2.5 M in hexanes, 0.5 mL,
1.2 mmol) was added dropwise under nitrogen. The resulting
mixture was stirred at ꢀ78 ꢁC for 30 min, and then the electrophile
was added (1.5 mmol). The reaction was warmed up to room
temperature and quenched with saturated aq NH4Cl. The aqueous
layer was extracted with Et2O (3ꢂ20 mL) and the combined organic
layers were dried over anhydrous Na2SO4 and concentrated in
4.5.4. 1-n-Butyl-3,4-dimethyl-4-pyridin-2-yl-3-vinylazetidin-2-
ones (32aþ32b)
Overall yield 245 mg (95%), oil; inseparable mixture of two trans-
and cis-configurated diastereomers (dr¼1:4 by 1H NMR). Compound
32a. Yield 49 mg (19%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
vacuo to afford the pure functionalized
b-lactams 29a–32a and
29b–32b; yields: 90–95%.
d
0.79 (s, 3H, CH3CCH]CH2), 0.94 (t, J¼7.3 Hz, 3H, CH3CH2),1.22–1.30
4.5.1. 1-tert-Butyl-4-deutero-3-methyl-4-pyridin-2-yl-3-
vinylazetidin-2-ones 29a, 29b
(m, 2H, CH3CH2), 1.61–1.68 (m, 2H, CH3CH2CH2),1.71 (s, 3H, CH3CAr),
2.92–2.99 (m,1H, CH2CH2–N), 3.24–3.30 (m, 1H, CH2CH2–N), 5.26 (d,
J¼9.5 Hz, 1H, CH]CH2), 5.43 (d, J¼17.3 Hz, 1H, CH]CH2), 5.90–5.96
(m, 1H, CH]CH2), 7.15–7.27 (m, 2H, ArH), 7.70 (t, J¼8.0 Hz, 1H, ArH),
8.62 (d, J¼4.5 Hz, 1H, ArH). Compound 32b. Yield 196 mg (76%),
Inseparable mixture of two trans- and cis-configurated di-
astereomers (dr¼1:1 by 1H NMR), the reaction was followed
only via GC and 1H NMR spectroscopy showing the formation of
two compounds. From the 1H NMR spectrum of the mixture we
identified and assigned separate signals for 29a and 29b, re-
yellow oil; 1H NMR (400.13 MHz, CDCl3)
d
0.94 (t, J¼7.3 Hz, 3H,
CH3CH2), 1.20–1.28 (m, 2H, CH3CH2), 1.46 (s, 3H, CH3CCH]CH2,),
1.60–1.67 (m, 2H, CH3CH2CH2),1.80 (s, 3H, CH3CAr), 3.08–3.12 (m,1H,
CH2CH2–N), 3.44–3.49 (m,1H, CH2CH2–N), 4.77 (dd, J¼3.0, 8.8 Hz,1H,
CH]CH2), 5.08–5.14 (m, 2H, CH]CH2), 7.15–7.24 (m, 2H, ArH), 7.66
(t, J¼7.9 Hz, 1H, ArH), 8.59 (d, J¼4.0 Hz, 1H, ArH). Compounds
spectively. Compound 29a. 1H NMR (400.13 MHz, CDCl3)
d 0.90
(s, 3H, CH3CCH]CH2), 1.32 (s, 9H, (CH3)3), 5.20 (d, J¼10.1 Hz, 1H,
CH]CH2), 5.35 (d, J¼17.1 Hz, 1H, CH]CH2), 5.80–5.90 (m, 1H,
CH]CH2), 7.10–7.20 (m, 2H, ArH), 7.58 (t, J¼7.5 Hz, 1H, ArH),
8.55 (d, J¼4.5 Hz, 1H, ArH). Compound 29b. The 1H NMR data
are the same of those reported for 15b except the singlet at
4.59 ppm that disappears. GC–MS performed on the mixture
showed two peaks having the same fragmentation and
[M]þ¼245 (<1).
(32aþ32b): 13C NMR (100.62 MHz, CDCl3)
d 12.4, 13.7, 16.8, 17.9, 19.8,
20.0, 20.6, 21.3, 31.2, 31.6, 39.2, 39.4, 40.6, 45.5, 64.4, 69.4,115.5,116.6,
117.0, 120.6, 121.0, 121.5, 121.9, 122.7, 135.9, 136.1, 149.1, 149.4, 161.0,
161.1, 171.5, 171.8; FTIR (CHCl3): 3010, 2961, 2931, 2873, 1747, 1579,
1432, 1400 cmꢀ1; GC–MS (70 eV) m/z 258 (3) [M]þ, 243 (2), 215 (1),
187 (5),159 (33),158 (100),144 (21), 106 (9), 78 (7); HRMS-ESI: calcd
for C16H23N2O: 259.1812 [MþH]þ; found: 259.1812.
4.5.2. 1-tert-Butyl-3,4-dimethyl-4-pyridin-2-yl-3-vinylazetidin-2-
ones (30aþ30b)
Overall yield 243 mg (94%), oil; inseparable mixture of two
trans- and cis-configurated diastereomers (dr¼1:2 by 1H NMR).
Compound 30a. Yield 75 mg (29%), yellow oil; 1H NMR
Acknowledgements
We would like to thank the University of Salento and the
C.I.N.M.P.I.S. (Consorzio Interuniversitario Nazionale Metodologie e
Processi Innovativi di Sintesi) for the financial support.
(400.13 MHz, CDCl3)
d 0.73 (s, 3H, CH3CCH]CH2), 1.35 (s, 9H,
(CH3)3), 1.86 (s, 3H, CH3CAr), 5.25 (d, J¼10.8 Hz, 1H, CH]CH2), 5.39
(d, J¼16.4 Hz, 1H, CH]CH2), 5.83–5.89 (m, 1H, CH]CH2), 7.19 (dd,
J¼4.7, 7.7 Hz, 1H, ArH), 7.51 (d, J¼7.7 Hz, 1H, ArH), 7.67 (t, J¼7.7 Hz,
1H, ArH), 8.60 (d, J¼4.7 Hz, 1H, ArH); GC–MS (70 eV) m/z 258 (<1)
[M]þ, 202 (10), 158 (100), 144 (20), 79 (7). Compound 30b. Yield
References and notes
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168 mg (65%), yellow oil; 1H NMR (400.13 MHz, CDCl3)
d 1.39 (s, 9H,
(CH3)3), 1.45 (s, 3H, CH3CCH]CH2), 1.95 (s, 3H, CH3CAr), 4.77
(d, J¼10.6 Hz, 1H, CH]CH2), 4.99–5.06 (m, 1H, CH]CH2), 5.19
(d, J¼17.5 Hz, 1H, CH]CH2), 7.16 (dd, J¼4.6, 7.8 Hz, 1H, ArH), 7.44
(d, J¼7.8 Hz, 1H, ArH), 7.64 (t, J¼7.8 Hz, 1H, ArH), 8.56 (d, J¼4.6 Hz,
1H, ArH); GC–MS (70 eV) m/z 258 (<1) [M]þ, 202 (4), 158 (100), 144
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d
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115.5, 116.7, 121.6, 121.8, 122.5, 135.3, 135.5, 136.3, 148.5, 148.8,
162.2, 162.3, 171.5, 171.6; FTIR (CHCl3): 3015, 2970, 2930, 1735, 1594,
1438, 1368 cmꢀ1
; HRMS-ESI: calcd for C16H23N2O: 259.1812
[MþH]þ; found: 259.1812.
4.5.3. 1-n-Butyl-4-deutero-3-methyl-4-pyridin-2-yl-3-
vinylazetidin-2-ones 31a, 31b
Inseparable mixture of two trans- and cis-configurated di-
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Compound 31a. 1H NMR (400.13 MHz, CDCl3)
d
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