A facile approach to α,β-unsaturated lactams by ring-closing metathesis

Article abstract of DOI:10.1007/s10593-016-1858-y

[MediaObject not available: see fulltext.]A facile and efficient strategy for the synthesis of α,β-unsaturated lactams through ring-closing metathesis of easily prepared diene amides is being reported here. Reaction conditions were optimized for metathetic cyclization of diene amides to obtain five- to sevenmembered unsubstituted and β-substituted α,β-unsaturated lactams in good to excellent yield.

Full text of DOI:10.1007/s10593-016-1858-y

DOI 10.1007/s10593-016-1858-y
Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
A facile approach to α,β-unsaturated lactams
by ring-closing metathesis
Humaira Yasmeen Gondal1,2*, Didier Buisson2
1 Department of Chemistry, University of Sargodha,
Sargodha-40100, Pakistan; e-mail: hygondal@yahoo.com
2 Museum National d'Histoire Naturelle,
57 Rue Cuvier, Paris 75005, France; e-mail: buisson@mnhn.fr
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2016, 52(3), 183–191
Submitted February 11, 2016
Accepted March 31, 2016
A facile and efficient strategy for the synthesis of α,β-unsaturated lactams through ring-closing metathesis of easily prepared diene
amides is being reported here. Reaction conditions were optimized for metathetic cyclization of diene amides to obtain five- to seven-
membered unsubstituted and β-substituted α,β-unsaturated lactams in good to excellent yield.
Keywords: α,β-unsaturated lactams, Grubbs catalyst, ring-closing metathesis.
Ring-closing metathesis (RCM) proved itself a powerful
technique for crafting variety of heterocycles and carbo-
cycles. It introduces a long range of synthetic applications
which is increasing day by day. Lactams are an important
class of compounds widely distributed among biologically
interesting natural and synthetic compounds.1 They are also
highly versatile intermediates for potential use in organic
synthesis.2 Moreover, α,β-unsaturated lactams are impor-
tant building blocks of numerous natural compounds which
are widely employed to access new molecules by further
chemical modifications.3 Many synthetic efforts for
constructing lactams4 and precisely α,β-unsaturated lactams5
have been reported including ring-closing metathesis.6
The versatility of α,β-unsaturated lactams can be further
extended by the incorporation of different groups at α- and
β-carbon, but reported strategies had certain limitations.7
Therefore development of general methods from simple
and easily available precursors is still the subject of
considerable synthetic interests. Subhash and coworkers
have reported the preparation 4-methyl-3-pyrrolin-2-one
through RCM of a simply prepared diene amide, but not in
good yield.8 We decided to carry out a systematic study to
find the optimal conditions and to extend the scope of this
methodology for the synthesis of unsubstituted and
β-substituted α,β-unsaturated lactams with different size of
cycles. Herein, we report a general, convenient, and efficient
strategy for the synthesis of well-known pyrrolidinones,
pyridinones, and rarely reported azepinones,9 which is also
devoid of the inherent shortcomings.
In this course of study, the key step of ring-closing
metathesis of diene amides 4a–f was attempted with Grubbs
first and second generation catalysts, benzylidenebis-
(tricyclohexylphosphine)dichlororuthenium (Grubbs I) and
benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinyl-
idene]dichloro(tricyclohexylphosphine)ruthenium (Grubbs II)
(Scheme 1). In an effort to optimize reaction conditions,
variations in type and amount of the catalyst, solvent, time,
temperature, and additive were evaluated. The influence of
substituent at β-carbon and nitrogen of amide on meta
cyclization was also studied.
The metathesis precursor diene amides 4a–f were pre-
pared by the condensation of acryloyl chloride with primary
amines 3a–f under basic conditions. Required amines 3b–f
were obtained by nucleophilic displacement of chlorides
1b,e,f or tosylates 1c,d with azide followed by reduction
with triphenylphosphine,8a whereas allylamine (3a) was
commercially available. Diene amides 4a–f were further
treated with Boc2O and FmocCl to provide the N-protected
analogs 5a–f and 6a–f. All of these protected and
unprotected diene amides 4–6 a–f were subjected to ring-
closing metathesis under different conditions (Tables 1, 2)
to furnish α,β-unsaturated lactams 7–9 a–f (Scheme 1).
After obtaining requisite diene amides 4a–f, we focused
on RCM as key step for the preparation of lactams. To
explore the feasibility of this approach, the RCM reaction
of diene amides 4–6 a were selected as model reactions to
examine various conditions for the synthesis of pyrro-
lidinones 7–9 a (Table 1). The Grubbs I catalyst was found
009-3122/16/52(3)-0183©2016 Springer Science+Business Media New York
183

Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
Scheme 1
very sluggish in the reaction with both free and protected
amides 4a and 5a, respectively, where only 17–22%
conversion was accomplished even after 32 h of heating at
80°C in toluene with 10% of catalyst (Table 1, entries 1–3,
10). Thus, Grubbs I catalyst was not further employed for
other molecules. Free diene amide 4a was not successfully
cyclized using the Grubbs II catalyst also, though amount
of catalyst was increased up to 10%. (Table 1, entries 4–7).
The same trend was followed by all other free amides 4c–f
(Table 2, entries 1–4). Yield was increased up to 44% when
a few drops of Ti(O-i-Pr)4 were added as chelating
agent6b,e,h,8b to free amides (Table 1, entry 8). RCM cycli-
zation was found further encouraging with Boc-protected
diene amide 5a. In this reaction, 50% conversion was
observed with 5% Grubbs II catalyst after 14 h (Table 1,
entry 11). To enhance the yield, first we increased reaction
Table 1. Optimization of reaction conditions for the preparation of pyrrolidinones 7–9 a,b by ring-closing metathesis
Grubbs catalyst
generation
Catalyst load,
mol %
Entry
Diene amide
R1
R2
Time, h
Obtained lactam
Yield, %
1
2
H
H
H
H
I
5
7
32
32
32
14
32
32
32
32
32
32
14
32
14
14
14
14
14
14
14
–
Traces
17
4a
4a
4a
4a
4a
4a
4a
4a
4b
5a
5a
5a
5a
5a
5b
5b
6a
6a
6b
7a
7a
7a
7a
7a
7a
7a
7a
7b
8a
8a
8a
8a
8a
8b
8b
9a
9a
9b
I
3
H
H
I
10
5
4
H
H
II
II
II
II
II
II
I
32
5
H
H
5
34
6
H
H
7
36
7
H
H
10
10
7
40
8
H
H
44*
35
9
Me
H
H
10
11
12
13
14
15
16
17
18
19
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Fmoc
Fmoc
Fmoc
10
5
22
H
II
II
II
II
II
II
II
II
II
50
H
5
52
H
7
83
H
7
66**
51
Me
Me
H
5
7
85
5
55
H
7
91
Me
7
90
* Two drops of Ti(O-i-Pr)4 were added.
** Solvent was CH2Cl2 (temperature 40°C), whereas all other experiments were carried out in PhMe at 80°C.
184

Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
Table 2. Experimental conditions for the preparation of α,β-unsaturated lactams 7–9 c–f by ring-closing metathesis*
Grubbs II
catalyst load, mol %
Entry
Diene amide
n
R1
R2
Time, h
Obtained lactam
Yield, %
1
2
2
2
3
3
2
2
2
2
3
3
3
3
2
2
3
3
H
Me
H
H
H
5
5
5
5
5
7
5
7
5
7
5
7
7
7
7
7
14
32
32
32
14
14
14
14
14
14
14
14
14
14
14
14
28
29
20
22
50
84
53
89
53
88
55
87
89
93
90
92
4c
4d
4e
4f
7c
7d
7e
7f
3
H
4
Me
H
H
5
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Fmoc
Fmoc
Fmoc
Fmoc
5c
5c
5d
5d
5e
5e
5f
8c
8c
8d
8d
8e
8e
8f
6
H
7
Me
Me
H
8
9
10
11
12
13
14
15
16
H
Me
Me
H
5f
8f
6c
6d
6e
6f
9c
9d
9e
9f
Me
H
Me
* Solvent was PhMe at 80°C.
time up to 32 h but no significant change was observed
(Table 1, entry 12). The next step was the increase of
catalyst amount and fortunately just 2% further addition
reasonably improved the yield (83%) of the required lactam
8a (Table 1, entry 13). Reaction was also attempted in
DCM at 40°C but unfortunately decrease in yield was
obtained (Table 1, entry 14). Our results are in consistent
with previous reports that increase of steric bulk at nitrogen
atom of amide group facilitates the RCM cyclization.9a
Keeping this in mind, we increase the bulk of amide
protection by Fmoc group, consequently a further raise (up
to 91%) of lactam 9a yield was achieved (Table 1, entry 18).
Our next target was synthesis of 4-methylpyrrolidinones
7–9 b. In reaction catalyzed by 7% of Grubbs II catalyst the
unprotected diene amide 4b formed only 35% of the
required pyrrolidinone 7b along with unreacted amide 4b
(Table 1, entry 9). The yields were enhanced (85–90%) in
the case of protected diene amides 5–6 b using the same
catalyst (Table 1, entries 16 and 19). These results infer
that substitution at the β-carbon of diene amide does not
have any prominent effect, but on the other hand, N-sub-
stitution has significant influence on the ring-closing
metathesis process. Similar conditions were further applied
in the synthesis of pyridinones and azepinones 7–9 c–f
(Table 2). It was observed that unprotected amides 4c–f
could not provide good yield of required lactams 7c–f
(Table 2, entries 1–4). In the case of Boc-protected amides
5c–f only 50–55% yields of the required products were
obtained after 14 h using 5% of Grubbs II catalyst (Table 2,
entries 5, 7, 9, 11). However, when catalyst loading was
increased to 7%, the reactions were completed in 14 h with
good yields (84–89%) (Table 2, entries 6, 8, 10, 12). In the
same conditions Fmoc-protected amides 6c–f were
successfully cyclized to the required lactams 9c–f in 89–
93% yields (Table 2, entries 13–16).
In conclusion, an efficient strategy for the synthesis of
five- to seven-membered α,β-unsaturated lactams was
developed where metathesis cyclization was successfully
employed by using 7% Grubbs II catalyst. Protected diene
amides cyclized more efficiently, whereas substitution at
β-carbon atom does not have any prominent effect. This
ring-closing metathesis strategy offer powerful advantages
over traditional approaches that could be attractive for the
synthetic as well as medicinal chemistry community.
Experimental
IR spectra were registered on a JASCO A-302 spectro-
1
photometer in CHCl3. H and 13C NMR spectra were
registered on a Bruker Avance AM-400 spectrometer (400
and 100 MHz, respectively) in CDCl3, solvent signal was
used as the internal standard. Mass spectra were registered
on a double-focusing mass spectrometer Varian MAT 311 A,
ionization by electron impact (70 eV). High-resolution
mass spectra were registered on a Jeol HX 110 spectro-
meter, with fast atom bombardment ionization using
m-nitrobenzyl alcohol matrix. All the reactions were
monitored by TLC using precoated (silica gel 60F254) alu-
minum sheets, visualization by UV light (254 and 365 nm)
and by locating agent phosphomolybdic acid. Column
chromatography was performed by using Merck silica gel
(0.063–0.200 mm). All reagents and solvents used were of
analytical grades.
Preparation of diene amides 4a–f (General method).
Sodium azide (0.5 g, 8 mmol) was added to the stirred
solution of chlorides 1b,e,f or tosylates 1c,d (6 mmol) in
dry DMSO (8 ml) at room temperature. The reaction
mixture was stirred at 70°C for 15 h, then washed well with
water (3×10 ml) and extracted with CH2Cl2 (2×10 ml).
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Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
Combined organic layers were dried over MgSO4, filtered,
(2H, t, J = 6.8, NHCH2); 4.91 (1H, d, J = 1.8, CH); 5.15
(1H, d, J = 1.8, CH); 5.98 (1H, dd, J = 9.3, J = 15.9, CH);
6.25 (1H, dd, J = 1.6, J = 15.9, CH); 6.41 (1H, dd, J = 1.6,
J = 9.3, CH); 8.54 (1H, br. s, NH). 13C NMR spectrum,
δ, ppm: 21.9; 37.2; 38.5; 112.6; 125.9; 131.2; 142.8; 165.7.
Mass spectrum, m/z (Irel, %): 139 [M]+ (100), 124 (65), 83
(74), 68 (45), 56 (66). Found, m/z: 139.1021 [M]+.
C8H13NO. Calculated, m/z: 139.0997.
and concentrated to obtain the crude azides 2b–f. Resulting
azides were dissolved in Et2O (10 ml), PPh3 (1.6 g, 6 mmol)
was added, the reaction mixture was stirred at 0°C for 1.5 h.
Then water (1 ml) was added and the reaction mixture was
stirred at room temperature overnight. After the comple-
tion, the reaction mixture was poured onto crushed ice and
extracted with CH2Cl2 (3×10 ml). Organic layers were
combined and dried over MgSO4, filtered, and concentrated
under reduced pressure to obtain amines 3b–f. Solution of
amine 3a–f in CH2Cl2 (10 ml) was stirred with K2CO3
(2.2 g, 16 mmol) at 0°C for 15 min. Acryloyl chloride
(0.6 ml, 7 mmol) was added dropwise at 0°C, and the
mixture was stirred at room temperature for 6 h. The
reaction was monitored by TLC. After completion of the
reaction, cold water (10 ml) was added and the mixture was
extracted with CH2Cl2 (3×10 ml). The combined organic
layers were washed with brine, dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The
crude diene amides 4a–f were purified on silica gel column,
eluting with EtOAc–petroleum ether with increasing gradient.
N-(Prop-2-en-1-yl)prop-2-enamide (4a). Yield 62%,
colorless oil. IR spectrum, ν, cm–1: 3326, 3069, 2952, 2930,
1699, 1520, 1357. 1H NMR spectrum, δ, ppm (J, Hz): 4.10
(2H, d, J = 5.7, NHCH2); 5.14–5.22 (2H, m, =CH2); 5.51
(1H, dd, J = 1.7, J = 11.2, CH); 5.90 (1H, ddd, J = 5.8,
J = 9.8, J = 15.9, CH); 6.11 (1H, dd, J = 1.8, J = 16.1, CH);
6.44 (1H, dd, J = 10.9, J = 16.1, CH); 8.60 (1H, br. s, NH).
13C NMR spectrum, δ, ppm: 42.1; 117.0; 127.1; 130.9;
134.6; 167.5. Mass spectrum, m/z (Irel, %): 111 [M]+ (67),
70 (29), 56 (100). Found, m/z: 111.0719 [M]+. C6H9NO.
Calculated, m/z: 111.0684.
N-(Pent-4-en-1-yl)prop-2-enamide (4e). Yield 61%,
colorless oil. IR spectrum, ν, cm–1: 3267, 3074, 2965, 1704,
1
1520, 1305. H NMR spectrum, δ, ppm (J, Hz): 1.96–2.10
(2H, m, CH2); 2.28 (2H, t, J = 6.7, CH2); 3.26 (2H, t,
J = 7.0, NHCH2); 5.06 (1H, dd, J = 1.8, J = 9.7, CH); 5.12
(1H, dd, J = 1.8, J = 15.4, CH); 5.63 (1H, dd, J = 1.8,
J = 15.6, CH); 5.89 (1H, dd, J = 9.7, J = 15.5, CH); 6.10
(1H, d, J = 16.1, CH); 6.52 (1H, dd, J = 1.8, J = 15.6, CH);
8.30 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 29.8;
32.5; 42.1; 116.6; 125.7; 130.9; 137.8; 169.3. Mass spectrum,
m/z (Irel, %): 139 [M]+ (100), 85 (64), 71 (59), 70 (25), 56
(77). Found, m/z: 139.1029 [M]+. C8H13NO. Calculated,
m/z: 139.0997.
N-(4-Methylpent-4-en-1-yl)prop-2-enamide (4f). Yield
62%, colorless oil. IR spectrum, ν, cm–1: 3310, 3045, 2987,
1712, 1525, 1298. 1H NMR spectrum, δ, ppm (J, Hz): 1.78
(3H, s, CH3); 2.29 (2H, t, J = 6.4, CH2); 1.69–1.74 (2H, m,
CH2); 3.23 (2H, t, J = 6.8, NHCH2); 4.97 (1H, d, J = 1.7,
CH); 5.21 (1H, d, J = 1.7, CH); 5.66 (1H, dd, J = 1.7,
J = 15.2, CH); 6.09 (1H, dd, J = 9.6, J = 15.2, CH); 6.42
(1H, dd, J = 1.7, J = 9.6, CH); 7.80 (1H, br. s, NH).
13C NMR spectrum, δ, ppm: 22.1; 28.6; 36.8; 41.2; 111.7;
126.9; 132.2; 145.1; 167.8. Mass spectrum, m/z (Irel, %):
153 [M]+ (100), 138 (64), 97 (88), 82 (51), 56 (61). Found,
m/z: 139.1021 [M]+. C9H15NO. Calculated, m/z: 153.1154.
Preparation of Boc-protected diene amides 5a–f
(General method). A solution of DMAP (13 mg, 0.1 mmol)
in dry MeCN (2 ml) was added dropwise to a mixed
solution of diene amides 4a–f (1 mmol) and Boc2O
(263 mg, 1.2 mmol) in MeCN (4 ml) at room temperature
under inert atmosphere, and the reaction mixture was
stirred for 2 h. After completion of the reaction, the mixture
was concentrated under reduced pressure and the residue
was diluted with water (5 ml) and extracted with CH2Cl2
(3×10 ml). The combined organic layers were dried over
anhydrous MgSO4, filtered, concentrated at low pressure,
and purified on silica gel column using EtOAc–petroleum
ether as eluent.
N-(2-Methylprop-2-en-1-yl)prop-2-enamide (4b).8a Yield
60%, colorless oil. IR spectrum, ν, cm–1: 3338, 3075, 2973,
2921, 1704, 1516, 1328. 1H NMR spectrum, δ, ppm
(J, Hz): 1.79 (3H, s, CH3); 3.66 (2H, s, NHCH2); 5.09 (1H,
d, J = 1.9, CH); 5.25 (1H, d, J = 1.9, CH); 5.62 (1H, dd,
J = 1.7, J = 9.6, CH); 6.11 (1H, dd, J = 9.6, J = 15.9, CH);
6.29 (1H, dd, J = 1.7, J = 15.9, CH); 8.11 (1H, br. s, NH).
13C NMR spectrum, δ, ppm: 21.0; 46.1; 112.3; 125.9;
132.4; 142.8; 168.2. Mass spectrum, m/z (Irel, %): 125 [M]+
(100), 110 (32), 71 (41), 57 (45), 56 (89). Found, m/z:
125.0869 [M]+. C7H11NO. Calculated, m/z: 125.0840.
N-(But-3-en-1-yl)prop-2-enamide (4c). Yield 61%,
colorless oil. IR spectrum, ν, cm–1: 3298, 3075, 2989, 2936,
1
1701, 1527, 1374. H NMR spectrum, δ, ppm (J, Hz): 2.29–
2.33 (2H, m, CH2); 3.29 (2H, t, J = 6.8, NHCH2); 4.96 (1H,
dd, J = 1.8, J = 9.6, CH); 5.05 (1H, dd, J = 1.8, J = 15.7,
CH); 5.64 (1H, dd, J = 2.0, J = 16.1, CH); 5.86–5.93 (1H,
m, CH); 6.11 (1H, dd, J = 16.1, J = 9.6, CH); 6.49 (1H, dd,
J = 2.0, J = 9.6, CH); 8.31 (1H, br. s, NH). 13C NMR
spectrum, δ, ppm: 34.2; 41.5; 117.1; 125.9; 132.4; 136.3;
167.2. Mass spectrum, m/z (Irel, %): 125 [M]+ (78), 117
(100), 99 (74), 69 (35), 56 (63). Found, m/z: 125.0874 [M]+.
C7H11NO. Calculated, m/z: 125.0840.
tert-Butyl N-acryloyl-N-(prop-2-en-1-yl)carbamate (5a).
Yield 81%, colorless oil. IR spectrum, ν, cm–1: 2984, 1731,
1
1686, 1611, 1422. H NMR spectrum, δ, ppm (J, Hz): 1.41
(9H, s, C(CH3)3); 5.01 (2H, m, NCH2); 5.24 (1H, dd, J = 1.6,
J = 9.4, CH); 5.30 (1H, d, J = 1.7, CH); 5.61 (1H, dd, J = 1.8,
J = 9.4, CH); 5.71–5.74 (1H, m, CH); 6.15 (1H, dd, J = 9.4,
J = 16.1, CH); 6.48 (1H, dd, J = 1.8, J = 16.1, CH).
13C NMR spectrum, δ, ppm: 29.1; 43.9; 81.5; 119.3; 128.2;
132.6; 132.9; 163.3; 176.1. Mass spectrum, m/z (Irel, %):
211 [M]+ (37), 111 (100), 100 (51), 56 (63). Found, m/z:
211.1216 [M]+. C11H17NO3. Calculated, m/z: 211.1208.
tert-Butyl N-acryloyl-N-(2-methylprop-2-en-1-yl)carbamate
(5b).8 Yield 83%, colorless oil. IR spectrum, ν, cm–1:
N-(3-Methylbut-3-en-1-yl)prop-2-enamide (4d). Yield
63%, colorless oil. IR spectrum, ν, cm–1: 3352, 3080, 2978,
2932, 1701, 1521, 1366. 1H NMR spectrum, δ, ppm
(J, Hz): 1.79 (3H, s, CH3); 2.32 (2H, t, J = 6.8, CH2); 3.37
186

Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
1
2978, 1737, 1679, 1605, 1427. H NMR spectrum, δ, ppm
(J, Hz): 1.45 (9H, s, C(CH3)3); 1.80 (3H, s, CH3); 4.25 (2H,
s, NCH2); 5.22 (1H, d, J = 1.9, CH); 5.35 (1H, d, J = 1.8,
CH); 5.57 (1H, dd, J = 1.9, J = 9.1, CH); 6.11 (1H, dd,
J = 1.9, J = 15.9, CH); 6.50 (1H, dd, J = 9.1, J = 15.9, CH).
13C NMR spectrum, δ, ppm: 21.6; 29.2; 49.7; 81.7; 114.1;
126.4; 132.5; 139.2; 153.9; 174.3. Mass spectrum, m/z (Irel, %):
225 [M]+ (39), 210 (22), 195 (17), 125 (100), 117 (39), 110
(32), 71 (46). Found, m/z: 225.1406 [M]+. C12H19NO3.
Calculated, m/z: 225.1365.
101 (21), 97 (76). Found, m/z: 253.1706 [M]+. C14H23NO3.
Calculated, m/z: 253.1678.
Preparation of Fmoc-protected diene amides 6a–f
(General method). Solution of dieneamides 4a–f (1 mmol)
in dioxane (2 ml) was stirred with 10% Na2CO3 solution
(2 ml) and cooled at 0°C. 9-Fluorenylmethyl chloroformate
(540 mg, 1.4 mmol) was added slowly and the resulting
mixture was stirred at 0°C for 2 h and kept at room
temperature overnight. Reaction mixture was diluted with
H2O and extracted with EtOAc (2×7 ml). The organic layer
was washed with NaHCO3 solution and acidified with 10%
HCl, then extracted with EtOAc (3×7 ml). The combined
organic layers were dried over anhydrous MgSO4 and
concentrated under reduced pressure. The resulting residue
was purified on silica gel column using 5% EtOAc in
hexane as eluent.
tert-Butyl N-acryloyl-N-(but-3-en-1-yl)carbamate (5c).
Yield 80%, colorless oil. IR spectrum, ν, cm–1: 2968, 1732,
1660, 1598, 1412. 1H NMR spectrum, δ, ppm (J, Hz): 1.44
(9H, s, C(CH3)3); 2.35 (2H, m, CH2); 4.42 (2H, d, J = 7.2,
NCH2); 5.11 (1H, dd, J = 1.9, J = 10.5, CH); 5.19 (1H, dd,
J = 1.9, J = 16.3, CH); 5.62 (1H, dd, J = 1.7, J = 9.8, CH);
5.79–5.84 (1H, m, CH); 6.13 (1H, dd, J = 1.7, J = 16.1,
CH); 6.45 (1H, dd, J = 1.7, J = 16.1, CH). 13C NMR
spectrum, δ, ppm: 29.2; 34.6; 49.1; 83.4; 117.6; 128.5;
132.3; 137.9; 158.2; 173.5. Mass spectrum, m/z (Irel, %):
225 [M]+ (100), 211 (19), 125 (78), 117 (69), 99 (53), 56
(64). Found, m/z: 225.1389 [M]+. C12H19NO3. Calculated,
m/z: 225.1365.
(9H-Fluoren-9-yl)methyl N-acryloyl-N-(prop-2-en-1-yl)-
carbamate (6a). Yield 87%, colorless oil. IR spectrum, ν, cm–1:
1
2984, 1735, 1667, 1595, 1411. H NMR spectrum, δ, ppm
(J, Hz): 4.37 (1H, t, J = 6.4, CH); 4.65 (2H, d, J = 6.4,
OCH2); 5.11 (2H, d, J = 6.1, NCH2); 5.24 (1H, dd, J = 1.9,
J = 8.7, CH); 5.29 (1H, dd, J = 1.9, J = 15.9, CH); 5.61
(1H, dd, J = 1.8, J = 9.8, CH); 5.88 (1H, dd, J = 8.7,
J = 15.9, CH); 6.12 (1H, dd, J = 9.8, J = 15.9, CH); 6.41
(1H, dd, J = 1.9, J = 15.9, CH); 7.28–7.33 (2H, m, H Ar);
7.36–7.41 (2H, m, H Ar); 7.56 (2H, ddd, J = 7.2, J = 2.1,
J = 0.7, H Ar); 7.90 (2H, ddd, J = 7.1, J = 2.6, J = 0.7,
H Ar). 13C NMR spectrum, δ, ppm: 45.3; 48.1; 69.2; 118.7;
121.5; 125.9; 126.4; 126.9; 131.6; 132.3; 144.1; 153.4;
172.9. Mass spectrum, m/z (Irel, %): 333 [M]+ (39), 315
(19) 303 (26), 279 (64), 211 (28), 206 (32), 179 (100), 164
(87), 125 (33), 117 (34). Found, m/z: 333.1387 [M]+.
C21H19NO3. Calculated, m/z: 333.1365.
tert-Butyl N-acryloyl-N-(3-methylbut-3-en-1-yl)carbamate
(5d). Yield 81%, colorless oil. IR spectrum, ν, cm–1: 2978,
1737, 1679, 1605, 1427. 1H NMR spectrum, δ, ppm
(J, Hz): 1.45 (9H, s, C(CH3)3); 1.79 (3H, s, CH3); 2.34 (2H,
t, J = 6.8, CH2); 4.59 (2H, t, J = 6.8, NCH2); 5.03 (1H, d,
J = 1.9, CH); 5.14 (1H, d, J = 1.9, CH); 5.64 (1H, dd,
J = 1.7, J = 9.6, CH); 6.16 (1H, dd, J = 9.6, J = 16.0, CH);
6.41 (1H, dd, J = 1.7, J = 16.0, CH). 13C NMR spectrum,
δ, ppm: 23.1; 29.3; 37.5; 45.2; 83.6; 112.2; 127.8; 132.5;
142.1; 156.3; 172.4. Mass spectrum, m/z (Irel, %): 239 [M]+
(84), 139 (100), 124 (37), 100 (23), 68 (51). Found, m/z:
239.1576 [M]+. C13H21NO3. Calculated, m/z: 239.1521.
tert-Butyl N-acryloyl-N-(pent-4-en-1-yl)carbamate (5e).
Yield 82%, colorless oil. IR spectrum, ν, cm–1: 2994, 1736,
1683, 1597, 1432. 1H NMR spectrum, δ, ppm (J, Hz): 1.46
(9H, s, C(CH3)3); 1.81 (2H, m, CH2); 2.37 (2H, m, CH2);
4.43 (2H, t, J = 6.8, NCH2); 5.03 (1H, dd, J = 1.9, J = 9.6,
CH); 5.12 (1H, dd, J = 1.9, J = 16.0, CH); 5.62 (1H, dd,
J = 1.7, J = 9.8, CH); 5.87 (1H, dd, J = 9.8, J = 16.0, CH);
6.11 (1H, dd, J = 1.7, J = 16.0, CH); 6.48 (1H, dd, J = 1.7,
J = 9.8, CH). 13C NMR spectrum, δ, ppm: 27.5; 28.1; 32.6;
44.7; 84.5; 119.3; 127.4; 132.8; 138.4; 153.7; 172.8. Mass
spectrum, m/z (Irel, %): 239 [M]+ (61), 139 (100), 100 (68),
85 (33), 71 (45). Found, m/z: 239.1569 [M]+. C13H21NO3.
Calculated, m/z: 239.1521.
(9H-Fluoren-9-yl)methyl N-acryloyl-N-(2-methylprop-
2-en-1-yl)carbamate (6b). Yield 84%, colorless oil.
IR spectrum, ν, cm–1: 2979, 1739, 1678, 1602, 1430.
1H NMR spectrum, δ, ppm (J, Hz): 1.83 (3H, s, CH3); 4.21
(2H, s, CH2); 4.39 (1H, t, J = 6.1, CH); 4.67 (2H, d, J = 6.1,
CH2); 5.17 (1H, d, J = 1.7, CH); 5.24 (1H, d, J = 1.7, CH);
6.09 (1H, dd, J = 9.4, J = 16.0, CH); 6.37 (1H, dd, J = 1.7,
J = 9.4, CH); 6.44 (1H, dd, J = 1.7, J = 16.0, CH); 7.25–
7.31 (2H, m, H Ar); 7.38–7.45 (2H, m, H Ar); 7.55 (2H,
ddd, J = 7.4, J = 2.2, J = 0.8, H Ar); 7.89 (2H, ddd, J = 7.2,
J = 2.6, J = 0.8, H Ar). 13C NMR spectrum, δ, ppm: 21.3;
49.6; 68.2; 113.8; 120.6; 125.4; 126.7; 127.1; 132.5; 138.9;
141.7; 142.4; 153.2; 171.9. Mass spectrum, m/z (Irel, %):
347 [M]+ (45), 329 (26), 206 (39), 125 (76), 179 (87), 164
(100), 110 (19), 71 (23). Found, m/z: 347.1578 [M]+.
C22H21NO3. Calculated, m/z: 347.1521.
(9H-Fluoren-9-yl)methyl N-acryloyl-N-(but-3-en-1-yl)-
carbamate (6c). Yield 89%, yellowish oil. IR spectrum,
ν, cm–1: 2992, 1737, 1660, 1598, 1412. 1H NMR spectrum,
δ, ppm (J, Hz): 2.26–2.29 (2H, m, CH2); 4.42 (1H, t, J = 6.3,
CH); 4.79 (2H, d, J = 6.3, CH2); 4.57 (2H, t, J = 7.0, CH2);
5.01 (1H, d, J = 1.8, CH); 5.08 (1H, d, J = 1.8, CH);
5.83–5.87 (1H, m, CH); 5.79 (1H, dd, J = 9.5, J = 16.0,
CH); 6.18 (1H, dd, J = 1.8, J = 9.5, CH); 6.44 (1H, dd,
J = 1.8, J = 16.0, CH); 7.27–7.31 (2H, m, H Ar); 7.34–7.39
(2H, m, H Ar); 7.58 (2H, dd, J = 7.8, J = 2.1, H Ar);
tert-Butyl N-acryloyl-N-(4-methylpent-4-en-1-yl)carbamate
(5f). Yield 80%, colorless oil. IR spectrum, ν, cm–1: 2985,
1
1734, 1667, 1601, 1413. H NMR spectrum, δ, ppm (J, Hz):
1.47 (9H, s, C(CH3)3); 1.65–1.68 (2H, m, CH2); 1.79 (3H,
s, CH3); 2.23–2.27 (2H, m, CH2); 4.35 (2H, t, J = 7.1,
NCH2); 4.98 (1H, d, J = 1.8, CH); 5.21 (1H, d, J = 1.8,
CH); 5.64 (1H, dd, J = 1.9, J = 9.6, CH); 6.16 (1H, dd,
J = 9.6, J = 16.0, CH); 6.47 (1H, dd, J = 1.9, J = 16.0, CH).
13C NMR spectrum, δ, ppm: 22.9; 25.3; 28.7; 37.2; 45.5;
82.4; 111.7; 126.1; 132.4; 145.1; 153.2; 172.5. Mass
spectrum, m/z (Irel, %): 253 [M]+ (63), 153 (100), 138 (44),
187

Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
7.79 (2H, dd, J = 7.2, J = 2.1, H Ar). 13C NMR spectrum,
The Grubbs I catalyst (5–10 mol %) was added to a
degassed homogeneous solution of diene amides 4a, 5a
(1 mmol) in dry PhMe (5 ml) under inert atmosphere, and
reaction mixture was heated at 80°C for 32 h. The reaction
mixture was concentrated and purified by column chro-
matography, yielding a small amount of required lactams
along with major part of starting diene amides.
δ, ppm: 31.6; 47.3; 47.8; 68.2; 117.5; 121.2; 124.9; 126.7;
127.1; 132.2; 137.4; 142.2; 143.6; 153.4; 171.7. Mass
spectrum, m/z (Irel, %): 347 [M]+ (22), 329 (17), 179 (42),
167 (55), 164 (28), 152 (65), 125 (100), 99 (31). Found, m/z:
347.1586 [M]+. C22H21NO3. Calculated, m/z: 347.1521.
(9H-Fluoren-9-yl)methyl N-acryloyl-N-(3-methylbut-
3-en-1-yl)carbamate (6d). Yield 85%, colorless oil.
IR spectrum, ν, cm–1: 2987, 1733, 1662, 1589, 1438.
1H NMR spectrum, δ, ppm (J, Hz): 1.78 (3H, s, CH3); 2.39
(2H, t, J = 6.8, CH2); 4.47 (1H, t, J = 6.4, CH); 4.54 (2H, t,
J = 6.8, CH2); 4.73 (2H, d, J = 6.4, CH2); 4.98–5.02 (1H,
m, CH); 5.16 (1H, d, J = 1.3, CH); 5.60 (1H, dd, J = 9.6,
J = 15.8, CH); 6.29 (1H, dd, J = 1.9, J = 9.6, CH); 6.38
(1H, dd, J = 1.9, J = 15.8, CH); 7.26–7.29 (2H, m, H Ar);
7.37–7.42 (2H, m, H Ar); 7.55 (2H, dd, J = 7.2, J = 1.9,
H Ar); 7.71 (2H, dd, J = 7.3, J = 2.2, H Ar). 13C NMR
spectrum, δ, ppm: 23.1; 37.4; 44.9; 46.8; 68.3; 110.7;
121.2; 124.9; 125.3; 125.2; 126.8; 132.5; 142.8; 143.2;
152.1; 172.3. Mass spectrum, m/z (Irel, %): 361 [M]+ (58),
343 (14), 330 (43), 206 (19), 179 (33), 166 (100), 164 (45),
139 (84). Found, m/z: 361.1703 [M]+. C23H23NO3.
Calculated, m/z: 361.1678.
Method II (Grubbs II catalyst). Solution of diene amides
4–6 a–f (1 mmol) in dry PhMe (5 ml) was degassed well,
and Grubbs II catalyst (5–10 mol %) was added under inert
atmosphere. The resulting mixture was stirred at 80°C for
14 or 32 h. The reaction mixture was concentrated and
purified on silica gel column using EtOAc–petroleum ether
as eluent.
1,5-Dihydro-2H-pyrrol-2-one (7a).10 Colorless oil.
IR spectrum, ν, cm–1: 3437, 2979, 1689, 1450, 1293, 1178.
1H NMR spectrum, δ, ppm: 4.11–4.17 (2H, m, CH2); 6.14–
6.20 (1H, m, CH); 7.11–7.16 (1H, m, CH); 8.01 (1H, br. s,
NH). 13C NMR spectrum, δ, ppm: 51.64; 114.7; 137.5;
176.2. Mass spectrum, m/z (Irel, %): 83 [M]+ (100), 61 (45),
57 (39). Found, m/z: 83.0389 [M]+. C4H5NO. Calculated,
m/z: 83.0365.
4-Methyl-1,5-dihydro-2H-pyrrol-2-one (7b).10b,c Color-
(9H-Fluoren-9-yl)methyl
N-acryloyl-N-(pent-4-en-
less oil. IR spectrum, ν, cm–1: 3448, 2980, 1678, 1447,
1
1-yl)carbamate (6e). Yield 87%, colorless oil. IR spectrum,
ν, cm–1: 2987, 1733, 1662, 1589, 1438. 1H NMR spectrum,
δ, ppm (J, Hz): 1.79–1.83 (2H, m, CH2); 2.19–2.24 (2H, m,
CH2); 4.31 (2H, t, J = 6.9, CH2); 4.44 (1H, t, J = 6.5, CH);
4.75 (2H, d, J = 6.5, CH); 5.03 (1H, d, J = 1.4, CH); 5.08
(1H, d, J = 1.4, CH); 5.71 (1H, dd, J = 8.9, J = 16.1, CH);
5.78–5.86 (1H, m, CH); 6.22 (1H, dd, J = 1.7, J = 8.9, CH);
6.41 (1H, dd, J = 1.7, J = 16.1, CH); 7.26–7.31 (2H, m,
H Ar); 7.36–7.41 (2H, m, H Ar); 7.59 (2H, ddd, J = 7.1,
J = 2.6, J = 0.9, H Ar); 7.86 (2H, ddd, J = 7.3, J = 2.2,
J = 0.9, H Ar). 13C NMR spectrum, δ, ppm: 27.8; 32.2;
44.5; 48.3; 68.1; 116.7; 121.4; 125.5; 126.7; 127.1; 132.5;
137.2; 142.9; 143.6; 153.2; 171.9. Mass spectrum, m/z (Irel, %):
361 [M]+ (44), 343 (19), 206 (27), 166 (95), 164 (100), 139
(77), 85 (53). Found, m/z: 361.1711 [M]+. C23H23NO3.
Calculated, m/z: 361.1678.
1293, 1164. H NMR spectrum, δ, ppm (J, Hz): 2.05 (3H,
s, CH3); 3.99 (2H, d, J = 15.6, NHCH2); 5.88 (1H, s, CH);
7.81 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 15.18;
51.67; 104.7; 122.6; 176.4. Mass spectrum, m/z (Irel, %): 97
[M]+ (100), 82 (35), 58 (24). Found, m/z: 97.0574 [M]+.
C5H7NO. Calculated, m/z: 97.0528.
5,6-Dihydropyridin-2(1H)-one (7c).11 Colorless oil.
IR spectrum, ν, cm–1: 3429, 2977, 1686, 1435, 1267, 1089.
1H NMR spectrum, δ, ppm (J, Hz): 2.36–2.44 (2H, m,
CH2); 4.13–4.18 (2H, m, CH2); 6.26 (1H, d, J = 9.2, CH);
6.61–6.65 (1H, m, CH); 7.79 (1H, br. s, NH). 13C NMR
spectrum, δ, ppm: 35.4; 51.4; 105.6; 123.0; 176.8. Mass
spectrum, m/z (Irel, %): 97 [M]+ (100), 74 (65), 61 (45).
Found, m/z: 97.0534 [M]+. C5H7NO. Calculated, m/z:
97.0528.
4-Methyl-5,6-dihydropyridin-2(1H)-one (7d). Light-
(9H-Fluoren-9-yl)methyl N-acryloyl-N-(4-methylpent-
4-en-1-yl)carbamate (6f). Yield 84%, colorless oil.
IR spectrum, ν, cm–1: 2993, 1735, 1678, 1607, 1432. 1H NMR
spectrum, δ, ppm (J, Hz): 1.79 (3H, s, CH3); 1.65 (2H, m,
CH2); 2.19 (2H, t, J = 6.9, CH2); 4.41 (2H, t, J = 7.0, CH2);
4.48 (1H, t, J = 6.6, CH); 4.66 (2H, d, J = 6.6, CH2); 4.97
(1H, d, J = 1.8, CH); 5.10 (1H, d, J = 1.8, CH); 5.57 (1H,
dd, J = 9.4, J = 15.9, CH); 6.11 (1H, dd, J = 1.9, J = 9.4,
CH); 6.49 (1H, dd, J = 1.9, J = 15.9, CH); 7.23–7.27 (2H,
m, H Ar); 7.33–7.38 (2H, m, H Ar); 7.61 (2H, dd, J = 7.1,
J = 2.3, H Ar); 7.85 (2H, dd, J = 7.0, J = 2.2, H Ar).
13C NMR spectrum, δ, ppm: 23.4; 25.7; 36.9; 45.2; 48.3;
68.0; 110.4; 120.9; 125.5; 126.4; 126.3; 127.1; 132.6;
141.8; 143.4; 144.2; 151.8; 172.2. Mass spectrum, m/z (Irel, %):
375 [M]+ (39), 357 (23), 206 (35), 179 (100), 164 (87), 153
(61), 139 (17). Found, m/z: 375.1869 [M]+. C23H23NO3.
Calculated, m/z: 375.1834.
yellow oil. IR spectrum, ν, cm–1: 3416, 2968, 1681, 1465,
1
1291, 1144. H NMR spectrum, δ, ppm (J, Hz): 2.05 (3H,
s, CH3); 2.37 (2H, t, J = 6.1, CH2); 3.89 (2H, t, J = 6.0,
CH2); 5.88 (1H, s, CH); 7.81 (1H, br. s, NH). 13C NMR
spectrum, δ, ppm: 15.1; 36.7; 51.7; 102.9; 123.2; 168.9.
Mass spectrum, m/z (Irel, %): 111 [M]+ (100), 96 (72), 74
(49). Found, m/z: 111.0690 [M]+. C6H9NO. Calculated, m/z:
111.0678.
1,5,6,7-Tetrahydro-2H-azepin-2-one (7e).12 Colorless
oil. IR spectrum, ν, cm–1: 3398, 2942, 1669, 1436, 1281,
1
1155. H NMR spectrum, δ, ppm (J, Hz): 1.87–2.11 (2H,
m, CH2); 2.47–2.52 (2H, m, CH2); 3.87–3.91 (2H, m, CH2);
5.98 (1H, d, J = 9.6, CH); 6.4 (1H, m, NH). 13C NMR
spectrum, δ, ppm: 29.8; 34.5; 52.6; 106.2; 129.4; 174.1.
Mass spectrum, m/z (Irel, %): 111 [M]+ (100), 95 (21), 74
(32). Found, m/z: 111.0684 [M]+. C6H9NO. Calculated, m/z:
111.0678.
Ring-closing metathesis reaction of diene amides
4–6 a–f (General method). Method I (Grubbs I catalyst).
4-Methyl-1,5,6,7-tetrahydro-2H-azepin-2-one (7f). Yel-
lowish oil. IR spectrum, ν, cm–1: 3445, 2976, 1674, 1467,
188

Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
1288, 1174. 1H NMR spectrum, δ, ppm: 1.75 (3H, s, CH3);
1.91 (3H, s, CH3); 2.19–2.22 (2H, m, CH2); 4.71 (2H, t,
J = 6.9, CH2); 6.13 (1H, s, CH). 13C NMR spectrum,
δ, ppm: 22.9; 27.3; 28.5; 36.2; 49.6; 81.8; 121.0; 148.4;
152.3; 164.1. Mass spectrum, m/z (Irel, %): 225 [M]+ (84),
212 (66), 174 (43), 142 (51), 125 (100), 110 (37). Found,
m/z: 225.1367 [M]+. C12H19NO3. Calculated, m/z: 225.1359.
(9H-Fluoren-9-yl)methyl 2-oxo-2,5-dihydro-1H-pyrrole-
1-carboxylate (9a). White powder. Mp 54–55°C.
IR spectrum, ν, cm–1: 2988, 1736, 1661, 1597, 1442.
1H NMR spectrum, δ, ppm (J, Hz): 4.11 (2H, d, J = 6.1,
CH2); 4.41 (2H, t, J = 6.5, CH2); 4.71 (2H, d, J = 6.5, CH2);
6.31 (1H, d, J = 8.7, CH2); 6.93–6.98 (1H, m, CH); 7.24–
7.30 (4H, m, H Ar); 7.59 (2H, d, J = 6.4, J = 2.3, H Ar);
7.90 (2H, d, J = 6.7, J = 2.1, H Ar) . 13C NMR spectrum,
δ, ppm: 47.1; 52.3; 66.5; 119.5; 122.1; 123.9; 125.4; 126.2;
129.7; 133.6; 141.5; 149.1; 153.4; 174.8. Mass spectrum,
m/z (Irel, %): 305 [M]+ (45), 179 (100), 123 (84), 83 (66).
Found, m/z: 305.1046 [M]+. C19H15NO3. Calculated, m/z:
305.1052.
2.10–2.15 (2H, m, CH2); 2.39–2.42 (2H, m, CH2); 3.76–
3.81 (2H, m, CH2); 5.74 (1H, s, CH). 13C NMR spectrum,
δ, ppm: 18.3; 27.6; 31.4; 52.1; 104.9; 123.7; 176.5. Mass
spectrum, m/z (Irel, %): 125 [M]+ (64), 118 (59), 110 (100),
74 (45), 61 (28). Found, m/z: 125.0871 [M]+. C7H11NO.
Calculated, m/z: 125.0835.
tert-Butyl 2-oxo-2,5-dihydro-1H-pyrrole-1-carboxy-
late (8a).5e Colorless oil. IR spectrum, ν, cm–1: 2957, 1740,
1691, 1556, 1482. 1H NMR spectrum, δ, ppm (J, Hz): 1.41
(9H, s, C(CH3)3); 4.29 (2H, d, J = 6.6, NHCH2); 6.21 (1H,
d, J = 10.1, CH); 6.43 (1H, dd, J = 6.6, J = 10.1, CH).
13C NMR spectrum, δ, ppm: 28.2; 53.5; 81.7; 121.6; 146.9;
153.8; 171.3. Mass spectrum, m/z (Irel, %): 183 [M]+ (43),
111 (62), 83 (100), 73 (35), 58 (86). Found, m/z: 183.0913
[M]+. C9H13NO3. Calculated, m/z: 183.0899.
tert-Butyl
4-methyl-2-oxo-2,5-dihydro-1H-pyrrole-
1-carboxylate (8b).8 Colorless oil. IR spectrum, ν, cm–1:
1
2996, 1738, 1686, 1544, 1423. H NMR spectrum, δ, ppm:
1.44 (9H, s, C(CH3)3); 1.98 (3H, s, CH3); 4.17 (2H, s,
CH2); 5.93 (1H, s, CH). 13C NMR spectrum, δ, ppm: 16.1;
27.5; 53.1; 82.4; 122.1; 148.8; 157.2; 169.7. Mass
spectrum, m/z (Irel, %): 197 [M]+ (54), 182 (44), 97 (95), 82
(100), 74 (26). Found, m/z: 197.1073 [M]+. C10H15NO3.
Calculated, m/z: 197.1046.
(9H-Fluoren-9-yl)methyl 4-methyl-2-oxo-2,5-dihydro-
1H-pyrrole-1-carboxylate (9b). White powder. Mp 57–
58°C. IR spectrum, ν, cm–1: 2993, 1741, 1670, 1535, 1428.
1H NMR spectrum, δ, ppm (J, Hz): 1.76 (3H, s, CH3); 4.18
(2H, s, CH2); 4.41 (1H, t, J = 6.4, CH); 4.65 (2H, d, J = 6.4,
CH2); 6.33 (1H, s, CH); 7.29–7.35 (4H, m, H Ar); 7.57
(2H, dd, J = 6.7, J = 2.2, H Ar); 7.83 (2H, dd, J = 6.6,
J = 2.5, H Ar). 13C NMR spectrum, δ, ppm: 21.3; 46.8;
51.9; 66.4; 119.2; 122.0; 123.6; 124.9; 126.1; 134.7; 136.8;
141.3; 149.6; 151.1; 170.4. Mass spectrum, m/z (Irel, %):
319 [M]+ (65), 180 (19), 179 (87), 123 (100), 97 (35), 83
(46). Found, m/z: 319.1223 [M]+. C20H17NO3. Calculated,
m/z: 319.1202.
(9H-Fluoren-9-yl)methyl 2-oxo-5,6-dihydropyridine-
1(2H)-carboxylate (9c). White powder. Mp 51–53°C.
IR spectrum, ν, cm–1: 2975, 1739, 1658, 1546, 1457.
1H NMR spectrum, δ, ppm (J, Hz): 2.25–2.28 (2H, m,
CH2); 3.66 (2H, t, J = 6.6, CH2); 4.41 (1H, t, J = 6.7, CH);
4.73 (2H, d, J = 6.7, CH2); 6.23 (1H, d, J = 8.7, CH); 6.35–
6.39 (1H, m, CH); 7.28–7.34 (4H, m, H Ar); 7.56 (2H, dd,
J = 6.2, J = 2.3, H Ar); 7.88 (2H, dd, J = 6.6, J = 2.5,
H Ar). 13C NMR spectrum, δ, ppm: 26.1; 45.9; 47.4; 66.8;
121.8; 123.3; 124.5; 127.4; 128.8; 140.8; 143.7; 147.2;
153.4; 167.8. Mass spectrum, m/z (Irel, %): 319 [M]+ (45),
179 (64), 164 (100), 97 (53). Found, m/z: 319.1219 [M]+.
C20H17NO3. Calculated, m/z: 319.1202.
tert-Butyl 2-oxo-5,6-dihydropyridine-1(2H)-carboxy-
late (8c).13 Colorless oil. IR spectrum, ν, cm–1: 2984, 1738,
1684, 1573, 1461. 1H NMR spectrum, δ, ppm (J, Hz): 1.46
(9H, s, C(CH3)3); 2.27–2.30 (2H, m, CH2); 3.62 (2H, t,
J = 6.9, NHCH2); 6.11 (1H, d, J = 9.4, CH); 6.35–6.39 (1H,
m, CH). 13C NMR spectrum, δ, ppm: 24.7; 28.2; 45.5; 81.3;
126.2; 147.0; 153.8; 167.1. Mass spectrum, m/z (Irel, %):
197 [M]+ (31), 174 (63), 158 (41), 125 (19), 118 (32), 110
(42), 97 (100). Found, m/z: 197.1061 [M]+. C10H15NO3.
Calculated, m/z: 197.1046.
tert-Butyl 4-methyl-2-oxo-5,6-dihydropyridine-1(2H)-
carboxylate (8d). Colorless oil. IR spectrum, ν, cm–1:
1
2969, 1733, 1677, 1584, 1462. H NMR spectrum, δ, ppm
(J, Hz): 1.41 (9H, s, C(CH3)3); 1.96 (3H, s, CH3); 2.26 (2H,
t, J = 6.8, CH2); 3.62 (2H, t, J = 6.8, NHCH2); 6.01 (1H, s,
CH). 13C NMR spectrum, δ, ppm: 20.4; 27.5; 30.2; 42.8;
81.4; 120.1; 150.8; 157.3; 165.7. Mass spectrum, m/z (Irel, %):
211 [M]+ (42), 175 (37), 142 (56), 128 (21), 110 (100), 99
(43). Found, m/z: 211.1217 [M]+. C11H17NO3. Calculated, m/z:
211.1202.
tert-Butyl 7-oxo-2,3,4,7-tetrahydro-1H-azepine-1-carb-
oxylate (8e). Yellowish oil. IR spectrum, ν, cm–1: 2977,
1739, 1683, 1578, 1449. 1H NMR spectrum, δ, ppm (J, Hz):
1.43 (9H, s, C(CH3)3); 1.66 (2H, m, CH2); 1.97–2.11 (2H,
m, CH2); 4.71 (2H, t, J = 6.6, NHCH2); 6.25 (1H, d, J = 9.5,
CH); 6.32–6.37 (1H, m, CH). 13C NMR spectrum, δ, ppm:
27.3; 29.2; 32.4; 47.7; 81.4; 122.8; 142.6; 153.1; 164.3.
Mass spectrum, m/z (Irel, %): 211 [M]+ (58), 125 (41), 117
(34), 111 (100), 99 (65), 74 (39). Found, m/z: 211.1221
[M]+. C11H17NO3. Calculated, m/z: 211.1202.
(9H-Fluoren-9-yl)methyl 4-methyl-2-oxo-5,6-dihydro-
pyridine-1(2H)-carboxylate (9d). White powder. Mp 56–
57°C. IR spectrum, ν, cm–1: 2968, 1741, 1673, 1581, 1429.
1H NMR spectrum, δ, ppm (J, Hz): 1.78 (3H, s, CH3); 2.25
(2H, t, J = 6.7, CH2); 3.73 (2H, t, J = 6.6, CH2); 4.42 (1H, t,
J = 6.1, CH); 4.71 (2H, d, J = 6.1, CH2); 6.19 (1H, s, CH);
7.27–7.34 (4H, m, H Ar); 7.53 (2H, dd, J = 6.5, 2.2, H Ar);
7.71 (2H, dd, J = 6.4, 1.9, H Ar). 13C NMR spectrum,
δ, ppm: 21.4; 46.3; 52.7; 64.8; 103.4; 117.6; 122.0; 123.6;
125.3; 127.2; 128.1; 134.8; 136.4; 142.1; 147.0; 153.4;
173.6. Mass spectrum, m/z (Irel, %): 333 [M]+ (58), 179
(64), 178 (100), 154 (19), 111 (32), 110 (49), 97 (68).
Found, m/z: 333.1371 [M]+. C21H19NO3. Calculated, m/z:
333.1359.
tert-Butyl 5-methyl-7-oxo-2,3,4,7-tetrahydro-1H-azepine-
1-carboxylate (8f). Colorless oil. IR spectrum, ν, cm–1:
1
2983, 1730, 1658, 1582, 1439. H NMR spectrum, δ, ppm
(J, Hz): 1.47 (9H, s, C(CH3)3); 1.61–1.66 (2H, m, CH2);
189

Chemistry of Heterocyclic Compounds 2016, 52(3), 183–191
Kamano, Y.; Herald, C. L.; Fujii, Y.; Kizu, H.; Boyd, M. R.;
(9H-Fluoren-9-yl)methyl 7-oxo-2,3,4,7-tetrahydro-1H-
azepine-1-carboxylate (9e). White powder. Mp 52–53°C.
IR spectrum, ν, cm–1: 2994, 1732, 1660, 1593, 1449.
1H NMR spectrum, δ, ppm (J, Hz): 1.66–1.69 (2H, m,
CH2); 2.14–2.18 (2H, m, CH2); 4.75 (2H, t, J = 6.1, CH2);
4.45 (1H, t, J = 6.4, CH); 4.75 (2H, d, J = 6.4, CH2); 6.21
(1H, d, J = 9.2, CH); 6.33–6.38 (1H, m, CH); 7.26–7.31
(4H, m, H Ar); 7.60 (2H, dd, J = 6.7, J = 2.2, H Ar); 7.89
(2H, dd, J = 6.4, J = 2.2, H Ar). 13C NMR spectrum,
δ, ppm: 29.2; 34.1; 46.8; 50.0; 67.1; 122.3; 123.9; 125.5;
127.2; 126.4; 129.3; 139.5; 141.8; 142.5; 143.2; 152.4;
168.2. Mass spectrum, m/z (Irel, %): 333 [M]+ (42), 179
(64), 179 (100), 111 (41), 97 (56). Found, m/z: 333.1374
[M]+. C21H19NO3. Calculated, m/z: 333.1359.
Boettner, F. E.; Doubek, D. L.; Schmidt, J. M.; Chapuis, J.-C.;
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(9H-Fluoren-9-yl)methyl 4-methyl-7-oxo-2,3,4,7-tetra-
hydro-1H-azepine-1-carboxylate (9f). White powder.
Mp 58–59°C. IR spectrum, ν, cm–1: 2989, 1737, 1667,
3. (a) Fodor, G. B.; Colasanti, B. In Alkaloids: Chemical and
Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New
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In The Alkaloids; Cordell, G. A., Ed.; Academic Press: San
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Gauthier, D.; Skouta, R.; Dory, Y. L. Chem.–Eur. J. 2007,
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1
1573, 1445. H NMR spectrum, δ, ppm (J, Hz): 1.78 (3H,
s, CH3); 1.69–1.73 (2H, m, CH2); 2.10–2.14 (2H, m, CH2);
4.43 (1H, t, J = 6.2, CH); 4.72 (2H, d, J = 6.2, CH2); 4.80
(2H, t, J = 6.5, CH2); 6.19 (1H, s, CH); 7.30–7.36 (4H, m,
H Ar); 7.60 (2H, dd, J = 6.6, J = 2.4, H Ar); 7.89 (2H, dd,
J = 6.5, J = 2.2, H Ar). 13C NMR spectrum, δ, ppm: 22.4;
27.8; 40.2; 46.8; 49.3; 68.1; 120.6; 122.0; 125.6; 126.3;
142.1; 143.4; 147.0; 153.4; 166.6. Mass spectrum, m/z (Irel, %):
347 [M]+ (32), 179 (87), 164 (100), 125 (57), 111 (32), 110
(61). Found, m/z: 347.1527 [M]+. C22H21NO3. Calculated,
m/z: 347.1515.
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Kobayashi, K.; Kusuda, S.; Tatsumi, T.; Murota, M.;
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Napier, R. M.; Neve, P.; Shipman, M. Org. Biomol. Chem.
2015, 13, 7655. (d) Fürstner, A.; Langemann, K. Synthesis
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Soc. 1997, 119, 9130. (f) Benedetti, E.; Lomazzi, M.;
Tibiletti, F.; Goddard J.-P.; Fensterbank, L.; Malacria, M.;
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(g) Fürstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J.;
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H. Y. Gondal is thankful to Embassy of France in
Pakistan for the financial support for postdoctoral studies
at MNHN, Paris, France.
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