Stereoselective synthesis of 3,4-diaryl β-lactams

Article abstract of DOI:10.1016/j.tetasy.2009.01.012

Novel 3,4-diaryl β-lactams were prepared with high stereoselectivity in an efficient manner by a palladium-catalyzed [2+2] carbonylative cycloaddition of benzyl halides with heteroarylidene amines. The type of alkyl group linked to the nitrogen atom influences the reaction's stereoselectivity. Moreover, using chiral imines, separable diastereomeric mixtures of chiral 3,4-diaryl-β-lactams were isolated with good yields and high trans diastereoselections.

Full text of DOI:10.1016/j.tetasy.2009.01.012

Tetrahedron: Asymmetry 20 (2009) 368–374
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of 3,4-diaryl b-lactams
*
Luigino Troisi , Emanuela Pindinelli, Valentina Strusi, Piera Trinchera
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, via Prov.le Lecce-Monteroni, 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 3,4-diaryl b-lactams were prepared with high stereoselectivity in an efficient manner by a palla-
dium-catalyzed [2+2] carbonylative cycloaddition of benzyl halides with heteroarylidene amines. The
type of alkyl group linked to the nitrogen atom influences the reaction’s stereoselectivity. Moreover,
using chiral imines, separable diastereomeric mixtures of chiral 3,4-diaryl-b-lactams were isolated with
good yields and high trans diastereoselections.
Received 15 December 2008
Accepted 20 January 2009
Available online 13 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
ner.33 According to the mechanism proposed,31,33 (Scheme 1) the
reaction starts with the complexation of the allyl halide by Pd(0)
The structure of 2-azetidinone is found in many compounds
with pharmacological application such as antibacterial,1,2 hypo-
cholesterolemic,3–5 antitumour,6–9 enzyme inhibitor10,11 and anti-
viral12 agents. In numerous articles reported in the literature it
has often been shown that the nature of the groups linked to the
N, C-3 and C-4 of the b-lactam influences strictly biological activity
and efficacy. These latter properties, together with possible toxic-
ity, may increase or decrease also with small variations of substit-
uents. Moreover, the ever increasing resistance of b-lactamases to
the inhibitors causes a decrease in the b-lactam activity, keeping
still live the interest of researchers towards new synthetic strate-
gies for b-lactams having substituents of different structure.
Staudinger0s strategy,13 consisting of a [2+2] cycloaddition of
ketene to imine, is still widely used; the trans/cis ratio of b-lactam
changes depending on the substituents present in the reagents and
on the reaction conditions.14 The imines also generate 2-azetidi-
and the insertion of CO with formation of an acyl-palladium-halide.
X
X
Pd(0)
CO
Pd+X-
O
Pd+X-
O
Pd+X-
Et3N
nones by [2+2] cycloaddition reactions with acids,15
a,b-unsatu-
Pd+X-
PdX
rated acids chlorides9,16,17 and enolates of esters.18,19 Other
methods are sometimes reported for preparing the b-lactam nu-
cleus, including the isocyanate–ketone cycloaddition,20 the chro-
mium carbene–imine reaction,21 the hydroxamate cyclization22
and the radical photocyclizations.23,24
O
O
-
PdX
-
Alper et al. reported the stereoselective synthesis of b-lactams by
therhodium-orcobalt-catalyzedexpansionofthe aziridinicring.25–29
The palladium-catalyzed cyclocarbonylation of allyl phosphates
in the presence of imines under strong CO pressure leads to the ster-
eoselective synthesis of b-lactams.30–32 We have simplified this
reaction and made it more accessible in conditions and reactants.
For instance, it has been possible to react also simple allyl halides
to give 2-azetidinones in good yields and in stereoselective man-
R
N
Ar
R
R
O
O
N
N
Ar
Ar
* Corresponding author. Tel.: +39 0832 298701; fax: +39 0832 298732.
E-mail address: luigino.troisi@unile.it (L. Troisi).
Scheme 1.
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.01.012

L. Troisi et al. / Tetrahedron: Asymmetry 20 (2009) 368–374
369
Subsequent action by base affords a carbanion
a to the carbonyl that
2. Results and discussion
causes the [2+2] cycloaddition with the imine (Scheme 1).
As an allyl halide is electronically very similar to a benzyl ha-
lide, we have considered the possibility that under the same reac-
tion conditions a benzyl halide might also afford the benzyl-
palladium-halide and, under basic conditions, could react with imi-
nes to afford 3-aryl-substituted b-lactams (Scheme 1). The results
of this investigation are reported herein.
The imine (1.0 mmol), benzyl halide (1.5 mmol), (Table 1)
Pd(OAc)2 (0.02 mmol), Ph3P (0.08 mmol) and Et3N (2.0 mmol) were
dissolved in THF (20 ml) and the mixture was placed in an auto-
clave with a small magnet and subsequently filled with CO
(400 psi). Heating to 100 °C under magnetic stirring was applied
for 60–90 h.
Table 1
R
O
R
N
CO(400psi), Pd(OAc)2
Et3N, PPh3, THF, 100°C
N
+
Ar'CH2X
Ar
Ar'
Ar
1-12
Entry
Imine
Ar
Halide
Time t (min)
Total yielda (%)
b-Lactam 1–12
Product distributionb (%)
R
Ar0
X
cis
trans
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Br
Cl
70
90
82
84
1
1
4
8
96
92
3
4
5
Ph
Ph
Ph
Ph
Br
Br
Br
60
90
90
58
85
78
2
3
4
12
—
5
88
nBu
nBu
Ph
100
95
6
7
8
nBu
nBu
nBu
Ph
Ph
Ph
Br
Br
Cl
90
70
70
97
70
71
5
6
6
13
87
99
99
Traces
Traces
9
10
tBu
tBu
Ph
Ph
Ph
Ph
Br
Cl
70
70
93
91
7
7
53
52
47
48
11
12
13
14
15
16
17
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
Ph
Ph
Ph
Ph
Br
Cl
Cl
Br
Br
Br
Cl
Br
70
70
70
60
60
60
60
60
88
85
88
95
97
70
60
58
8
84
16
8
85
15
9
99
Traces
Traces
9
9
99
Ph
10
11
11
12
91
100
100
87
—
—
18
13
a
Isolated yields.
b
Diastereomeric ratios measured by GC and 1H NMR spectroscopy.

370
L. Troisi et al. / Tetrahedron: Asymmetry 20 (2009) 368–374
Even with longer reaction times than the allyl halides, the ben-
opposite sign. The absolute configuration has been assigned by
comparison with analogous compounds of which X-ray measure-
ments were performed.37
zyl halides afforded the 2-azetidinones 1–12; their yields and iso-
meric distribution are reported in Table 1. The longer reaction
times may be explained by the greater difficulty in the formation
of the p-benzyl-Pd-halide complex as it needs partial interruption
3. Conclusion
of the aromatic system. The yields and the diastereoselectivities
are almost always fair or good. In particular, analysis of the results
shows that a phenyl or a linear alkyl group (such as nbutyl group)
on the iminic nitrogen addresses the cyclization towards the for-
mation of the trans isomer, (Table 1, entries 1–8).
The Torii0s methodology,31 consisting of a [2+2] cycloaddition of
imines to allyl phosphates, that we have previously modified and
used with allyl halides, has successfully been used with benzyl ha-
lides in this work. Moreover, the high stereoselectivity found has
allowed the synthesis of b-lactams in enantiomerically pure form.
The benzyl halide type (chloride or bromide) seems not to have
any influence on yield or on diastereoselectivity (Table 1, entries 1,
2 and 7, 8). Conversely, a bulky group (such as tert-butyl group) on
the iminic nitrogen addresses the cyclization towards the forma-
tion of the cis isomer, (Table 1, entries 11–18). An equimolar mix-
ture of cis/trans structures has only been isolated once (Table 1,
entries 9 and 10). When there was the tert-butyl group on the imi-
nic nitrogen, the type of halogen and the Ar group do not signifi-
cantly influence the yields or the products distribution (Table 1,
entries 9, 10; 11, 12; 13, 14; 16, 17). The trans- and cis-structures
were assigned on the basis of the value of coupling constants J in
the 1H NMR spectra between the protons at the C-3 and C-4, as of-
ten reported in the literature: a small J value (1.8–2.5 Hz) for a
trans structure, a greater J value (5.8–6.5 Hz) for a cis-structure.
In the reactions with more modest yields (Table 1, entries 3, 17
and 18), the amides have been isolated: compound 1334 in the en-
try 3 and compound 1435 in the entries 17, 18, respectively. A par-
tial hydrolysis of the imine would afford an amine that, reacting
with the acyl-palladium-halide, would lead to the amide formation
(Scheme 2).
4. Experimental
4.1. General
n-Butyllithium (n-BuLi) was a commercial solution inhexanes (Al-
drich) and was titrated with N-pivaloyl-o-toluidine prior to use.38
THF, triethylamine, 4-formylmorpholine, 2-pyridinecarboxaldehyde,
3-pyridinecarboxaldehyde, 4-pyridinecarboxaldehyde, 4-methylthi-
azole, 2-aminothiophenol, glycolic acid, n- and t-butylamine, palla-
dium(II) acetate, triphenylphosphine, 4-methoxybenzyl chloride
and bromide, 4-metylbenzylchloride, (R)-(+)-1-phenylethylamine
were of commercial grade (Aldrich) and used without further purifi-
cation. Benzaldehyde, aniline, benzyl chloride and bromide, of
commercial grade (Aldrich) were purified by distillation 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 appa-
ratus (400.13 and 100.62 MHz, for 1H and 13C, respectively) with
CDCl3 assolvent and TMS as internalstandard (d = 7.26 for 1H spectra;
d = 77.0 for 13C spectra). The IR spectra were recorded with an FT-IR
spectrophotometer Digilab Scimitar Series FTS 2000. GC–MS analyses
were performed with an Agilent Technologies 6850 series II gas chro-
matograph (5% phenyl-polymethylsiloxane capillary column, 30 m,
0.25 mm i.d.) equipped with a 5973 Network mass-selective detector
operating at 70 eV. The electrospray ionization (HR-ESI-MS) experi-
ments were carried out in a hybrid QqTOF mass spectrometer (PE
SCIEX-QSTAR) equipped with an ion spray ionization source. MS (+)
O
O
Ar'
Ar'
R
+
H2NR
Pd+X-
N
H
13,14
13
: R, Ar' = C6H5
14: R = t-Bu, Ar' = p-OCH3C6H4
Scheme 2.
spectra were acquired by direct infusion (5
taining the appropriate sample (10 pmol/
l
L/min) of a solution con-
For instance, when the tert-butylamine, instead of the imine,
was reacted with the p-methoxy-benzylchloride under the same
reaction conditions, amide 14 was produced in good yields. This
may be a good and new methodology to synthesize a peptidic
bond.
Considering the good stereoselectivity of the reaction, we
decided to realize a new version of it with the aim of obtaining
b-lactams in enantiomerically pure form. To this purpose, the
(R)-benzylidene-N-phenylethylamine was reacted with the ben-
zylbromide for a time of 60 h and under the same previously de-
scribed conditions. From the reaction mixture, it was possible to
isolate and characterize the two trans-diastereomers (3R,4S,10R)
and (3S,4R,10R) in enantiomerically pure form and in a ratio of
5:3, (Table 2, entry 1).
lL) dissolved in a solution,
0.1% acetic 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 skim-
mer 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 F-254 indicator; viewing was by UV light
(254 nm). Polarimetric measurements were performed by a Jasco
P-1020 polarimeter. 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 performed under nitrogen in oven-dried glassware using syr-
inge/septum cap techniques.
The presence of the cis-isomers could only be seen by GC–MS
and 1H NMR of the crude reaction mixture. The low amount ob-
served in each reaction (1–3%) did not allow their complete char-
4.2. General procedure for the preparation of the compounds
1–12, 15–21
acterization. Analogously to previous reactions,
a variable
quantity of the amide 2236 was isolated; its possible formation
has been described above. The reactions performed with other
(R)-arylidene-N-phenylethylamines have given almost equal re-
sults (Table 2, entries 2–8). Furthermore, when the (S)-benzyli-
dene-N-phenylethylamine was reacted with the benzylbromide
under the same reaction conditions, the diastereomers
(3R,4S,10S)-15 and (3S,4R,10S)-15 were isolated in an inverted ratio
of 3:5. The 1H and 13C NMR spectra were similar to those of the two
previous compounds 15, while the specific rotation values were of
A mixture of 1.0 mmol of imine, 1.5 mmol of benzyl halide,
0.08 mmol of PPh3, 0.02 mmol of Pd(AcO)2 and 2.0 mmol of Et3N
was 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 60–90 h. The crude mixture was
chromatographed (silica gel, petroleum ether/Et2O 1:1 for com-
pounds 4–6, 10 and 18, petroleum ether/Et2O 2:8 for 9, 11 and
12 petroleum ether/Et2O 4:6 for 16, 17 and 21, petroleum

L. Troisi et al. / Tetrahedron: Asymmetry 20 (2009) 368–374
371
Table 2
(R)
Ph
O
N
(S)
(R)
(R)
O
PH
Ar'
Ar
Ph
(R)
Ar'
CO(400psi), Pd(OAc)2
Et3N, PPh3, THF, 100°C
N
+
+
NH
22
Ar'CH2X
15-21
Ar
(R)
O
Ph
N
(R)
(S)
Ar'
Ar
Entry
Imine
Ar
Halide
Total yielda (%)
b-Lactam
15–21
Product distributionb (%)
Ar0
X
(3R,4S,10R)
(3S,4R,10R)
Amide 22
1
2
Ph
Ph
Br
56
90
15
16
50
30
20
Ph
Br
Cl
Br
Br
Br
Br
Br
56
51
35
54
56
50
65
37
34
25
34
39
44
35
7
3
4
5
6
7
Ph
Ph
Ph
Ph
Ph
81
61
78
67
52
89
16
17
18
19
20
21
15
40
12
5
4
8
—
a
Isolated yields.
b
Diastereomeric ratios measured by GC and 1H NMR spectroscopy.
ether/Et2O 8:2 for 8, 19 and 20) to afford the already known pure
b-lactams 1,39 2,40 3,41 7,29 1542 and the unknown b-lactams 4–6,
8–12 and 16–21, yields: 50–97%.
J = 2.0 Hz, 1H), 4.88 (d, J = 2.0 Hz, 1H), 6.95 (s, 1H), 7,27–7.38 (m,
5H); 13C NMR (100.62 MHz, CDCl3) d 13.5, 17.0, 20.1, 29.7, 40.8,
60.5, 64.3, 114.3, 127.4, 127.8, 128.9, 134.2, 153.7, 167.3, 167.7;
GC–MS (70 eV) m/z 300 [M+] (3), 201 (95), 200 (100), 183 (5), 139
(3), 118 (11), 90 (9), 71(14); HRMS-ESI calcd for C17H20N2OS
300.13763; found 300.13771.
4.2.1. 1-Butyl-4-(4-methylthiazol-2-yl)-3-phenylazetidin-2-one 4
Total yield 78%. cis-4: Yield 11.7 mg, 3.9%, yellow oil; FT-IR
(CHCl3) 3065, 3030, 3008, 2964, 2933, 2875, 1749, 1629, 1454,
1401, 1315 cmꢀ1; 1H NMR (400.13 MHz, CDCl3) d 0.93 (t, J = 7.3 Hz,
3H), 1.38 (sextet, J = 7.3 Hz, 2H), 1.59 (quintet, J = 7.3 Hz, 2H), 2.31
(s, 3H), 3.08–3.15 (m, 1H), 3.58–3.66 (m, 1H), 4.93 (d, J = 5.6 Hz,
1H), 5.37 (d, J = 5.6 Hz, 1H), 6.65 (s, 3H), 7.11 7.31 (m, 5H); 13C
NMR (100.62 MHz, CDCl3) d 13.6, 16.8, 20.2, 29.6, 41.1, 58.3, 60.8,
114.4, 126.6, 127.4, 128.7, 132.0, 152.7, 165.9, 168.0; GC–MS
(70 eV) m/z 300 [M+] (23), 201 (43), 200 (100), 183 (51), 139 (11),
118 (60), 90 (21), 71 (12); HRMS-ESI calcd for C17H20N2OS
300.13763; found 300.13769. trans-4: Yield 222 mg, 74%, yellow so-
lid; mp = 42–44 °C, n-hexane; FT-IR (CHCl3) 3066, 3030, 3011, 2962,
2931, 2874, 1748, 1401 cmꢀ1; 1H NMR (400.13 MHz, CDCl3) d 0.91 (t,
J = 7.2 Hz, 3H), 1.35 (sextet, J = 7.2 Hz, 2H), 1.56 (quintet, J = 7.2 Hz,
2H), 2.47 (s, 3H), 3.01–3.08 (m, 1H), 3.57–3.64 (m, 1H), 4.41 (d,
4.2.2. 4-Benzothiazol-2-yl-1-butyl-3-phenylazetidin-2-one 5
Total yield: 97%. cis-5: Yield 42 mg, 12.6%, yellow oil; FT-IR
(CHCl3) 3066, 3032, 3011, 2962, 2932, 2875, 1754, 1456, 1398,
1315 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 0.93 (t, J = 7.3 Hz,
;
3H), 1.38 (sextet, J = 7.3 Hz, 2H), 1.62 (quintet, J = 7.3 Hz, 2H),
3.18 (dt, J = 7.3, 14.8 Hz, 1H), 3.70 (dt, J = 7.3, 14.8 Hz, 1H), 5.03
(d, J = 5.7 Hz, 1H), 5.47 (d, J = 5.7 Hz, 1H), 7.02–7.11 (m, 3H), 7.20
(d, J = 7.4 Hz, 2H), 7.30 (t, J = 7.8 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H),
7.70 (d, J = 7.8 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H); 13C NMR
(100.62 MHz, CDCl3) d 13.6, 20.3, 29.6, 41.4, 58.8, 60.9, 121.6,
123.0, 125.2, 126.0, 127.6, 128.3, 128.6, 131.6, 135.0, 152.8,
167.5, 168.1; GC–MS (70 eV) m/z 336 [M+] (22), 237 (33), 236
(100), 219 (20), 204 (3), 118 (38), 90 (11); HRMS-ESI calcd for

372
L. Troisi et al. / Tetrahedron: Asymmetry 20 (2009) 368–374
C20H20N2OS 336.13763; found 336.13768. trans-5: Yield 282 mg,
oxybenzylbromide): total yield 95%. cis-9: Yield 290 mg, 94%.
trans-9: traces.
84%, yellow oil; FT-IR (film) 3062, 3030, 2958, 2931, 2871, 1762,
1436, 1394, 1313 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 0.91 (t,
;
J = 7.3, 3H), 1.38 (sextet, J = 7.3 Hz, 2H), 1.61 (quintet, J = 7.3 Hz,
2H), 3.12 (dt, J = 7.7, 14.8 Hz, 1H), 3.68 (dt, J = 7.7, 14.8 Hz, 1H),
4.51 (d, J = 2.1 Hz, 1H), 5.01 (d, J = 2.1 Hz, 1H), 7.29–7.40 (m, 5H),
7.44 (t, J = 8.2 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.93 (d, J = 8.1 Hz,
1H), 8.00 (d, J = 8.2 Hz, 1H); 13C NMR (100.62 MHz, CDCl3) d 13.5,
20.1, 29.7, 41.1, 61.0, 64.3, 121.9, 123.4, 125.7, 126.5, 127.3,
127.9, 128.9, 133.9, 134.8, 153.2, 167.4, 169.0; GC–MS (70 eV) m/
z 336 [M+] (2), 237 (48), 236 (100), 219 (1), 204 (3), 118 (7), 90
(3); HRMS-ESI calcd for C20H20N2OS 336.13763; found 336.13770.
4.2.6. 4-Benzothiazol-2-yl-1-tert-butyl-3-phenylazetidin-2-one
10
Total yield 97%. cis-10: Yield 296 mg, 88%, yellow solid;
mp = 200–202 °C, n-hexane; FT-IR (CHCl3) 3066, 2978, 2930,
1748, 1370, 1350, 1229 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d
;
1.42 (s, 9H), 4.90 (d, J = 6.0 Hz, 1H), 5.53 (d, J = 6.0 Hz, 1H), 7.02–
7.09 (m, 3H), 7.20 (d, J = 7.4 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 7.39
(t, J = 7.8 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.91(d, J = 8.1 Hz, 1H);
13C NMR (100.62 MHz, CDCl3) d 28.0, 55.2, 57.6, 59.0, 121.5,
122.9, 125.1, 125.9, 127.4, 128.2, 128.5, 132.0, 135.0, 152.4,
167.5, 170.7; GC–MS (70 eV) m/z 336 [M+] (6), 280 (5), 236 (100),
219 (7), 163 (7), 135 (5), 118 (28), 90 (10), 57 (8); HRMS-ESI calcd
for C20H20N2OS 336.13763; found 336.13772. trans-10: Yield
29 mg, 8.7%, yellow solid; mp 97–99 °C; FT-IR (CHCl3) 3068,
4.2.3. 1-Butyl-3-phenyl-4-pyridin-2-ylazetidin-2-one 6
(From reaction with benzylbromide): total yield 70%. cis-6:
Traces; GC–MS (70 eV) m/z 280 [M+] (15), 180 (100), 152 (3), 90
(8), 77 (3). trans-6: Yield 194 mg, 69.3%, yellow oil; FT-IR (film)
3061, 3029, 2956, 2930, 2872, 1752, 1590, 1439, 1402 cmꢀ1
;
1H
2978, 2932, 1749, 1370, 1354, 1229 cmꢀ1 1H NMR (400.13 MHz,
;
NMR (400.13 MHz, CDCl3) d 0.88 (t, J = 7.3 Hz, 3H), 1.34 (sextet,
J = 7.3 Hz, 2H), 1.50 (quintet, J = 7.3 Hz, 2H), 2.90–2.97 (m, 1H),
3.62 (dt, J = 7.3, 14.4 Hz, 1H), 4.34 (d, J = 2.0 Hz, 1H), 4.67 (d,
J = 2.0 Hz, 1H), 7.25–7.37 (m, 7H), 7.75 (dd, J = 1.7, 7.6 Hz, 1H),
8.65 (d, J = 4.5 Hz, 1H); 13C NMR (100.62 MHz, CDCl3) d 13.5, 20.1,
29.7, 40.6, 63.1, 64.1, 121.1, 123.2, 127.3, 128.7, 129.3, 135.0,
136.9, 150.0, 157.3, 168.1; GC–MS (70 eV) m/z 280 [M+] (6), 180
(100), 152 (4), 90 (3), 77 (1); HRMS-ESI calcd for C18H20N2O
280.16553; found 280.16559. (From reaction with benzylchloride):
total yield 71%. cis-6: traces. trans-6: Yield 197 mg, 70.3%.
CDCl3) d 1.43 (s, 9H), 4.30 (d, J = 2.2 Hz, 1H), 5.04 (d, J = 2.2 Hz,
1H), 7.27–7.40 (m, 5H), 7.44 (t, J = 8.1 Hz, 1H), 7.51 (t, J = 8.1 Hz,
1H), 7.92 (d, J = 7.9 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H); 13C NMR
(100.62 MHz, CDCl3) d 28.1, 55.4, 60.4, 63.3, 122.0, 123.4, 125.7,
126.4, 127.4, 127.9, 129.0, 134.2, 134.8, 152.9, 167.8, 172.1; GC–
MS (70 eV) m/z 336 [M+] (1), 280 (1), 236 (100), 118 (5), 90 (3),
57 (4); HRMS-ESI calcd for C20H20N2OS 336.13763; found
336.13775.
4.2.7. cis-1-tert-Butyl-3-(4-methoxyphenyl)-4-pyridin-2-ylaze-
tidin-2-one 11
4.2.4. 1-tert-Butyl-4-phenyl-3-p-tolylazetidin-2-one 8
(From reaction with 4-methoxybenzylbromide): total yield 70%.
cis-11: Yield 217 mg, 70%, yellow solid; mp = 81–84 °C, n-hexane;
FT-IR (CHCl3) 3024, 2976, 2938, 1735, 1602, 1514, 1367,
(From reaction with 4-metylbenzylbromide): total yield 88%.
cis-8: Yield 217 mg, 74%, yellow solid; mp = 102–103 °C, n-hexane;
FT-IR (CHCl3) 3030, 3010, 2976, 2926, 1732, 1517, 1456, 1368,
1250 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 1.35 (s, 9H), 3.65 (s,
;
1349 cmꢀ1
;
1H NMR (400.13 MHz, CDCl3) d 1.33 (s, 9H), 2.16 (s,
3H), 4.74 (d, J = 5.9 Hz, 1H), 5.17 (d, J = 5.9 Hz, 1H), 6.58 (d,
J = 8.6 Hz, 2H), 6.94 (d, J = 8.6 Hz, 2H), 6.98 (dd, J = 7.6, 5.0 Hz,
1H), 7.04 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 8.38 (d,
J = 5.0 Hz, 1H); 13C NMR (100.62 MHz, CDCl3) d 28.0, 54.5, 54.9,
57.9, 60.5, 113.3, 122.0, 122.3, 124.9, 129.6, 135.5, 148.7, 157.8,
158.2, 168.5; GC–MS (70 eV) m/z 310 [M+] (6), 210 (100), 196 (4),
167 (13), 148 (19), 120 (7), 91 (4), 77 (3); HRMS-ESI calcd for
C19H22N2O2 310.17609; found 310.17615. (From reaction with 4-
methoxybenzylchloride): total yield 60%. cis-11: Yield 186 mg,
60%.
3H), 4.66 (d, J = 5.8 Hz, 1H), 5.00 (d, J = 5.8 Hz, 1H), 6.84–6.89 (m,
4H), 7.06–7.12 (m, 5H); 13C NMR (100.62 MHz, CDCl3) d 20.9,
28.1, 54.4, 58.5, 59.4, 127.5, 127.7, 128.5, 130.0, 136.0, 137.5,
168.4; GC–MS (70 eV) m/z 293 [M+] (<1), 194 (100), 179 (36),
165 (3), 132 (26), 104 (10), 77 (4); HRMS-ESI calcd for C20H23NO
293.18592; found 293.18599. trans-8: Yield 41 mg, 14%, yellow
oil; FT-IR (CHCl3) 3030, 3011, 2976, 2927, 2873, 1736, 1515,
1456, 1367, 1347 cmꢀ1; .1H NMR (400.13 MHz, CDCl3) d 1.32 (s,
9H), 2.33 (s, 3H), 3.93 (d, J = 1.9 Hz, 1H), 4.43 (d, J = 1.9 Hz, 1H),
7.11–7.16 (m, 4H), 7.33–7.42 (m, 5H); 13C NMR (100.62 MHz,
CDCl3) d 21.1, 28.3, 54.7, 63.4, 63.5, 126.4, 127.2, 128.3, 128.9,
129.5, 132.6, 137.2, 140.5, 168.7; GC–MS (70 eV) m/z 293 [M+]
(<1), 194(100), 179 (34), 165 (3), 132 (4), 104 (4), 77 (3); HRMS-
ESI calcd for C20H23NO 293.18592; found 293.18602. (From reac-
tion with 4-metylbenzylchloride): total yield 85%. cis-8: Yield
211 mg, 72%. trans-8: Yield 37 mg, 12.7%.
4.2.8. 1-tert-Butyl-3-(4-methoxyphenyl)-4-pyridin-4-ylazetidin-
2-one 12
Total yield 58%. cis-12: Yield 155 mg, 50%, solid; mp = 102–
104 °C, n-hexane; FT-IR (CHCl3) 3028, 2973, 2930, 1738, 1604,
1514, 1369, 1251 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 1.35 (s,
;
9H), 3.67 (s, 3H), 4.71 (d, J = 5.9 Hz, 1H), 4.96 (d, J = 5.9 Hz, 1H),
6.60 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 7.03 (d, J = 6.0 Hz,
2H), 8.36 (d, J = 6.0 Hz, 2H); 13C NMR (100.62 MHz) d 28.2, 54.9,
55.1, 58.4, 58.5, 113.7, 122.5, 124.1, 129.7, 147.6, 149.1, 150.0,
158.7, 168.1; GC–MS (70 eV) m/z 310 [M+] (2), 211 (100), 167
(15), 148 (55); HRMS-ESI calcd for C19H22N2O2 310.17609; found
310.17617. trans-12: The trans isomer was isolated as unseparable
mixture of trans- and cis-diastereomers; yield 23 mg, 7.5%; 1H NMR
(400.13 MHz) d 1.33 (s, 9H), 3.79 (s, 3H), 3.87 (d, J = 1.8 Hz, 1H),
4.40 (d, J = 1.8 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.5 Hz,
2H), 7.35 (d, J = 5.2 Hz, 2H), 8.63 (d, J = 5.2 Hz, 2H); GC–MS
(70 eV) m/z 310 [M+] (<1), 211 (100), 167 (12), 148 (48); IR and
13C NMR data were measured on the mixture; FT-IR (CHCl3)
4.2.5. 1-tert-Butyl-3-(4-methoxyphenyl)-4-phenylazetidin-2-
one 9
(From reaction with 4-methoxybenzylchloride): total yield 88%.
cis-9: Yield 269 mg, 87%, yellow oil; FT-IR (CHCl3) 3030, 3010,
2975, 2926, 1731, 1517, 1456, 1210 cmꢀ1 1H NMR (400.13 MHz,
;
CDCl3) d 1.33 (s, 9H), 3.79 (s, 3H), 4.63 (d, J = 5.7 Hz, 1H), 4.99 (d,
J = 5.7 Hz, 1H), 6.58 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H)
7.05–7.11 (m, 5H); 13C NMR (100.62 MHz, CDCl3) d 28.2, 54.5,
55.2, 58.2, 59.6, 113.9, 125.3, 127.5,127.8, 128.5, 137.5, 158.2,
159.1, 168.6; GC–MS (70 eV) m/z 309 [M+] (4), 210 (100), 195
(10), 165 (12), 148 (93), 120 (16), 91 (10), 77 (7); HRMS-ESI calcd
for C20H23NO2 309.18082; found 309.18090. trans-9: Traces; GC–
MS (70 eV) m/z 309 [M+] (<1), 210 (100), 195 (8), 165 (8), 148
(4), 120 (2), 91 (3), 77 (2). (From reaction with 4-meth-
3028, 2975, 2935, 1739, 1603, 1515, 1369, 1252 cmꢀ1 13C NMR
;
(100.62 MHz) d 28.1, 28.2, 54.7, 54.9, 55.1, 55.2, 58.4, 58.5, 62.1,
63.1, 113.7, 114.4, 121.0, 122.5, 124.1, 126.7, 128.3, 129.7, 147.6,

L. Troisi et al. / Tetrahedron: Asymmetry 20 (2009) 368–374
373
149.1, 149.8, 150.0, 158.7, 159.2, 168.1, 168.4; HRMS-ESI calcd for
C19H22N2O2 310.17609; found 310.17613.
140.4, 148.5, 149.8, 167.8; GC–MS (70 eV) m/z 328 [M+] (<1), 181
(84), 180 (100), 152 (7), 105 (14), 77 (7); HRMS-ESI calcd for
C22H20N2O 328.16553; found 328.16562. (+)-(3S,4R,10R)-18: Yield
4.2.9. 3-Phenyl-1-(1-phenylethyl)-4-pyridin-2-ylazetidin-2-one
16
85 mg, 26%, yellow oil; ½a D28:2
ꢁ
¼ þ51:5 (c 0.010, CHCl3); FT-IR
(CHCl3) 3032, 3008, 2928, 2855, 1745, 1378 cmꢀ1 1H NMR
;
(From reaction with benzylbromide): total yield 90%. (ꢀ)-
(400.13 MHz, CDCl3) d 1.42 (d, J = 7.2 Hz, 3H), 4.14 (d, J = 2.3 Hz,
1H), 4.22 (d, J = 2.3 Hz, 1H), 5.15 (q, J = 7.2 Hz, 1H), 7.07–7.09 (m,
2H), 7.18–7.36 (m, 9H), 7.67 (dd, J = 7.9, 1.8 Hz, 1H), 8.48 (d,
J = 1.8 Hz, 1H), 8.60 (dd, J = 1.3, 4.7 Hz, 1H); 13C NMR
(100.62 MHz, CDCl3) d 18.8, 52.7, 60.8, 64.3, 123.8, 127.3, 127.8,
128.1, 128.4, 128.8, 128.9, 134.0, 134.7, 139.5, 148.7, 149.4,
150.1, 168.3; GC–MS (70 eV) m/z 328 [M+] (2), 181 (84), 180
(100), 152 (8), 105 (13), 77 (7); HRMS-ESI calcd for C22H20N2O
328.16553; found 328.16560. 2-Phenyl-N-[(1R)-phenylethyl]acet-
amide 22:36 Yield 22 mg, 9.4%.
(3R,4S,10R)-16: Yield 164 mg, 50%, yellow oil; ½a 3D0:6
¼ ꢀ99:25 (c
ꢁ
0.008, CHCl3); FT-IR (CHCl3) 3033, 3005, 2957, 2928, 2855,
1748 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 1.83 (d, J = 7.1 Hz,
;
3H), 4.34 (d, J = 2.2 Hz, 1H), 4.50 (d, J = 2.2 Hz, 1H), 4.58 (q,
J = 7.1 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 7.15–7.34 (m, 12 H), 7.53
(t, J = 7.6 Hz, 1H), 8.57 (d, J = 4.6 Hz, 1H); 13C NMR (100.62 MHz,
CDCl3) d 19.7, 54.3, 62.3, 63.2, 121.6, 122.9, 125.8, 126.9, 127.4,
128.4, 128.7, 129.0, 135.0, 136.5, 140.7, 149.8, 157.1, 168.1; GC–
MS (70 eV) m/z 328 [M+] (3), 180 (100), 167 (2), 152 (4), 105 (7),
77 (4); HRMS-ESI calcd for C22H20N2O 328.16553; found
328.16561. (+)-(3S,4R,10R)-16: Yield 108 mg, 33%, yellow solid;
4.2.12. 4-(4-Methylthiazol-2-yl)-3-phenyl-1-(1-phenylethyl)-
azetidin-2-one 19
mp = 114–117 °C, n-hexane; ½a D31:4
ꢁ
¼ þ113:9 (c 0.015, CHCl3); FT-
IR (CHCl3) 3032, 3006, 2960, 2928, 2856, 1749 cmꢀ1
;
1H NMR
Total yield 67%. (ꢀ)-(3R,4S,10R)-19: Yield 130 mg, 37,5%, yellow
(400.13 MHz, CDCl3) d 1.34 (d, J = 7.1 Hz, 3H), 4.40 (d, J = 2.3 Hz,
1H), 4.43 (d, J = 2.3 Hz, 1H), 5.13 (q, J = 7.1 Hz, 1H), 7.14–7.34 (m,
12H) 7.64 (dd, J = 1.5, 7.6 Hz, 1H), 8.63 (dd, J = 1.5, 4.6 Hz, 1H);
13C NMR (100.62 MHz, CDCl3) d 18.5, 52.4, 62.4, 63.4, 121.9,
123.3, 127.2, 127.5, 127.8, 128.0, 128.6, 128.8, 135.0, 136.7,
140.1, 149.9, 158.2, 168.4; GC–MS (70 eV) m/z 328 [M+] (3), 180
(100), 167 (2), 152 (4), 105 (7), 77 (4); HRMS-ESI calcd for
C22H20N2O 328.16553; found 328.16564. 2-Phenyl-N-[(1R)-phenyl-
ethyl]acetamide 22:36 Yield 15 mg, 6.3%. (From reaction with ben-
zylchloride): total yield 81%. (ꢀ)-(3R,4S,10R)-16: Yield 134 mg,
41%. (+)-(3S,4R,10R)-16: Yield 90 mg, 27.5%. 2-Phenyl-N-[(1R)-phen-
ylethyl]acetamide 22:36 Yield 28.6 mg, 12%.
oil; ½a 2D3:0
¼ ꢀ88:1 (c 0.010, CHCl3); FT-IR (CHCl3) 3033, 3009, 2928,
ꢁ
2855, 1745, 1379 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 1.86 (d,
;
J = 7.1 Hz, 3H), 2.40 (s, 3H), 4.40 (d, J = 2.2 Hz, 1H), 4.59 (q,
J = 7.1 Hz, 1H), 4.72 (d, J = 2.2 Hz, 1H), 6.83 (s, 1H), 7.21–7.33 (m,
10H); 13C NMR (100.62 MHz, CDCl3) d 16.9, 19.8, 54.8, 59.3, 63.5,
114.3, 126.8, 127.3, 127.6, 127.7, 128.5, 128.8, 134.2, 140.7,
153.3, 167.2, 167.7; GC–MS (70 eV) m/z 348 [M+] (<1), 201 (71),
200 (100), 168 (4), 105 (15), 77 (7); HRMS-ESI calcd for C21H20N2OS
348.13763; found 348.13770. (+)-(3S,4R,10R)-19: Yield 90 mg, 26%,
yellow solid; mp = 83–86 °C, n-hexane; ½a D23:0
¼ þ100:6 (c 0.012,
ꢁ
CHCl3); FT-IR (CHCl3) 3034, 3008, 2928, 2854, 1745, 1380 cmꢀ1
;
1H NMR (400.13 MHz, CDCl3) d 1.49 (d, J = 7.2 Hz, 3H), 2.44 (s,
3H), 4.42 (d, J = 2.3 Hz, 1H), 4.69 (d, J = 7.2 Hz, 1H), 5.10 (q,
J = 7.2 Hz, 1H), 6.89 (s, 1H), 7.11–7.13 (m, 2H), 7.23–7.34 (m,
8H); 13C NMR (100.62 MHz, CDCl3) d 16.9, 18.6, 53.0, 59.5, 63.7,
114.4, 127.2, 127.3, 127.7, 127.9, 128.7, 128.8, 134.1, 139.8,
153.3, 168.0, 168.1; GC–MS (70 eV) m/z 348 [M+] (<1), 201 (69),
200 (100), 168 (4), 105 (16), 77 (6); HRMS-ESI calcd for C21H20N2OS
348.13763; found 348.13771. 2-Phenyl-N-[(1R)-phenylethyl]acet-
amide 22:36 Yield 8 mg, 3.3%.
4.2.10. 3-Phenyl-1-(1-phenylethyl)-4-pyridin-4-ylazetidin-2-one
17
Total yield 61%. (ꢀ)-(3R,4S,10R)-17: Yield 69 mg, 21%, yellow oil;
½
a 2D8:2
ꢁ
¼ ꢀ93:3 (c 0.01, CHCl3); FT-IR (CHCl3) 3032, 3005, 2959,
2928, 2854, 1748, 1601, 1454 cmꢀ1 1H NMR (400.13 MHz, CDCl3)
;
d 1.87 (d, J = 7.2 Hz, 3H), 4.07 (d, J = 2.1 Hz, 1H), 4.27 (d, J = 2.1 Hz,
1H), 4.50 (q, J = 7.2 Hz, 1H), 7.06 (d, J = 5.7 Hz, 2H), 7.20–7.37 (m,
10H), 8.53 (d, J = 5.7 Hz, 2H); 13C NMR (100.62 MHz, CDCl3) d
19.7, 54.7, 61.7, 64.2, 121.3, 126.9, 127.3, 127.9, 128.3, 128.5,
128.7, 129.1, 134.4, 147.0, 150.3, 167.7; GC–MS (70 eV) m/z 328
[M+] (<1), 181 (100), 180 (71), 152 (9), 105 (15); HRMS-ESI calcd
for C22H20N2O 328.16553; found 328.16562. (+)-(3S,4R,10R)-17:
4.2.13. 4-Benzothiazol-2-yl-3-phenyl-1-(1-phenylethyl)-
azetidin-2-one 20
Total yield 52%. (ꢀ)-(3R,4S,10R)-20: Yield 100 mg, 26%, yellow
solid; mp = 126–129 °C, n-hexane; ½a D28:0
¼ ꢀ72:5 (c 0.015, CHCl3);
ꢁ
Yield 49 mg, 15%, yellow oil; ½a D29:4
ꢁ
¼ þ103:3 (c 0.012, CHCl3); FT-
FT-IR (CHCl3) 3066, 3009, 2927, 2855, 1757, 1456, 1304 cmꢀ1 1H
;
IR (CHCl3) 3032, 3006, 2960, 2928, 2855, 1748, 1602, 1454 cmꢀ1
;
NMR (400.13 MHz, CDCl3) d 1.93 (d, J = 7.2 Hz, 3H), 4.47 (d,
J = 2.2 Hz, 1H), 4.63 (q, J = 7.2 Hz, 1H), 4.83 (d, J = 2.2 Hz, 1H),
7.20–7.36 (m, 10H), 7.43 (t, J = 8.0 Hz, 1H), 7.51 (t, J = 8.2 Hz, 1H),
7.88 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H); 13C NMR
(100.62 MHz, CDCl3) d 20.1, 55.7, 60.1, 63.6, 121.8, 123.4, 125.6,
126.4, 126.9, 127.3, 127.4, 127.9, 128.1, 128.7, 129.0, 134.0,
135.0, 140.7, 167.6, 169.3; GC–MS (70 eV) m/z 384 [M+] (<1), 236
(100), 237 (49), 204 (4), 105 (10); HRMS-ESI calcd for C24H20N2OS
384.13763; found 384.13769. (+)-(3S,4R,10R)-20: Yield 87,5 mg,
1H NMR (400.13 MHz, CDCl3) d 1.45 (d, J = 7.2 Hz, 3H), 4.08 (d,
J = 2.4 Hz, 1H), 4.17 (d, J = 2.4 Hz, 1H), 5.14 (q, J = 7.2 Hz, 1H),
7.05 (d, J = 5.9 Hz, 2H), 7.19–7.35 (m, 10H), 8.60 (d, J = 5.9 Hz,
2H); 13C NMR (100.62 MHz, CDCl3) d 18.8, 53.0, 62.1, 64.3, 121.5,
127.0, 127.3, 127.9, 128.1, 128.8, 129.0, 134.3, 140.5, 148.4,
150.3, 167.5; GC–MS (70 eV) m/z 328 [M+] (<1), 181 (100), 180
(68), 152 (12), 105 (14); HRMS-ESI calcd for C22H20N2O
328.16553; found 328.16559. 2-Phenyl-N-[(1R)-phenylethyl]acet-
amide 22:36 Yield 58 mg, 24.4%.
22,8%, yellow solid; mp = 97-100 °C, n-hexane; ½a D31:0
¼ þ86:1 (c
ꢁ
0.013, CHCl3); FT-IR (CHCl3) 3066, 3012, 2927, 2855, 1753, 1455,
4.2.11. 3-Phenyl-1-(1-phenylethyl)-4-pyridin-3-ylazetidin-2-one
1304 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 1.53 (d, J = 7.2 Hz,
;
18
3H), 4.49 (d, J = 2.4 Hz, 1H), 4.81 (d, J = 2.4 Hz, 1H), 5.20 (q,
J = 7.2 Hz, 1H), 7.10–7.12 (m, 2H), 7.22–7.36 (m, 8H), 7.43 (t,
J = 8.1 Hz, 1H), 7.52 (t, J = 8.3 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 8.02
(d, J = 8.3 Hz, 1H); 13C NMR (100.62 MHz, CDCl3) d 18.6, 53.1,
60.2, 63.9, 121.9, 123.4, 125.8, 126.5, 127.3, 127.4, 127.9, 128.1,
128.8, 128.9, 133.9, 135.0, 139.6, 153.0, 168.0, 170.2; GC–MS
(70 eV) m/z 384 [M+] (2), 237(52), 236 (100), 204 (5), 105 (12);
HRMS-ESI calcd for C24H20N2OS 384.13763; found 384.13768. 2-
Phenyl-N-[(1R)-phenylethyl]acetamide 22:36 Yield 7 mg, 3%.
Total yield 78%. (ꢀ)-(3R,4S,10R)-18: Yield 138 mg, 42%, yellow
oil; ½a 2D7:2
¼ ꢀ79:9 (c 0.012, CHCl3). FT-IR (CHCl3) 3033, 3009,
ꢁ
2928, 2855, 1745, 1379 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d
;
1.85 (d, J = 7.1 Hz, 3H), 4.13 (d, J = 2.3 Hz, 1H), 4.33 (d, J = 2.3 Hz,
1H), 4.51 (q, J = 7.1 Hz, 1H), 7.20–7.36 (m, 11H), 7.49 (dd, J = 7.9,
1.8 Hz, 1H), 8.41 (d, J = 1.8 Hz, 1H), 8.53 (dd, J = 1.5, 4.8 Hz, 1H);
13C NMR (100.62 MHz, CDCl3) d 19.6, 54.3, 60.5, 64.2, 123.7,
126.9, 127.3, 127.8, 128.4, 128.7, 129.0, 133.4, 133.8, 134.5,

374
L. Troisi et al. / Tetrahedron: Asymmetry 20 (2009) 368–374
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6. Otani, T.; Oie, S.; Matsumoto, H.; Tempest, M.; Micetich, R. G.; Singh, R.;
Yamashita, T.; WO 01,109, 1994; Chem. Abstr. 1994, 121, 57497.
7. Alpigiani, M.; Bissolino, P.; Perrone, E.; Pesenti, E.; WO 02,603, 1995; Chem.
Abstr. 1995, 122, 205179.
4.2.14. 3-(4-Methoxyphenyl)-1-(1-phenylethyl)-4-pyridin-2-yl-
azetidin-2-one 21
Total yield 89%. (ꢀ)-(3R,4S,10R)-21: Yield 207 mg, 58%, yellow
solid; mp = 59–62 °C, n-hexane; ½a D24:9
¼ ꢀ205:0 (c 0.012, CHCl3);
ꢁ
FT-IR (CHCl3) 3065, 3010, 2953, 2936, 1743, 1514, 1249, 1179,
8. Veinberg, G.; Vorona, M.; Shestakova, I.; Kanepe, I.; Zharkova, O.; Mezapuke, R.;
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16. Bose, A. K.; Spiegelman, G.; Manhas, M. S. Tetrahedron Lett. 1971, 3167–
3170.
1036 cmꢀ1 1H NMR (400.13 MHz, CDCl3) d 1.83 (d, J = 7.1 Hz,
;
3H), 3.78 (s, 3H), 4.27 (d, J = 2.0 Hz, 1H), 4.45 (d, J = 2.0 Hz, 1H),
4.57 (q, J = 7.1 Hz, 1H), 6.85–6.87 (m, 2H), 7.00 (d, J = 7.8 Hz, 1H),
7.15–7.20 (m, 8H), 7.54 (t, J = 7.8 Hz, 1H), 8.56 (d, J = 4.4 Hz, 1H);
13C NMR (100.62 MHz) d 19.8, 54.4, 55.2, 61.9, 63.6, 114.2, 121.6,
121.9, 127.0, 127.2, 127.5, 128.5, 128.6, 136.5, 140.9, 149.8,
157.4, 159.0, 168.6; GC–MS (70 eV) m/z 358 [M+] (2), 211 (40),
210 (100), 195 (5), 167 (10); HRMS-ESI calcd for C23H22N2O2
358.17609; found 358.17617. (+)-(3S,4R,10R)-21: Yield 111 mg,
31%, yellow oil; ½a D25:7
ꢁ
¼ þ110:0 (c 0.012, CHCl3); FT-IR (film)
3063, 3031, 2976, 2933, 1747, 1514, 1250, 1179, 1033 cmꢀ1
;
1H
17. Manhas, M. S.; Banik, B. K.; Mathur, A.; Vincent, J. E.; Bose, A. K. Tetrahedron
NMR (400.13 MHz) d 1.35 (d, J = 7.1 Hz, 3H), 3.75 (s, 3H), 4.33 (d,
J = 2.0 Hz, 1H), 4.38 (d, J = 2.0 Hz, 1H), 5.14 (q, J = 7.1 Hz, 1H),
6.80 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 8.6 Hz, 2H), 7.19 (d, J = 7.6 Hz,
1H), 7.23–7.34 (m, 6H), 7.64 (t, J = 7.6 Hz, 1H), 8.62 (d, J = 4.6 Hz,
1H); 13C NMR (100.62 MHz) d 18.5, 52.3, 55.2, 61.8, 63.9, 114.2,
121.8, 123.2, 127.2, 127.6, 127.7, 128.5, 128.6, 136.7, 140.1,
149.9, 158.3, 159.0, 168.9; GC–MS (70 eV) m/z 358 [M+] (2), 211
(35), 210 (100), 195 (5), 167 (12); HRMS-ESI calcd for
C23H22N2O2 358.17609; found 358.17619.
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Acknowledgements
We would like to thank the University of Salento and the C.I.N.
M.P.I.S. (Consorzio Interuniversitario Nazionale Metodologie e Pro-
cessi Innovativi di Sintesi) for the financial support.
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