A combinatorial approach towards a library of Chiral γ-lactams and 2,3-disubstituted pyrroles

Article abstract of DOI:10.1055/s-0031-1289584

A library of heterocyclic products with a wide variety of organic residues is produced via a four-component reaction of α,β-unsaturated aldehydes, primary amines, carbon monoxide, and ethylene using a multi-reactor station with an array of 96 autoclaves employing the same high-pressure reaction conditions for all catalytic reactions. In the presence of Ru ₃(CO)₁₂ as a precatalyst, mixtures of chiral γ-lactams and 2,3-disubstituted pyrroles are obtained. This combinatorial approach also enables us for the first time to set up rules relating to the effects of specific substituents in the substrates on the outcome of the respective catalytic reaction. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289584

PAPER
3979
A Combinatorial Approach towards a Library of Chiral g-Lactams and
2,3-Disubstituted Pyrroles
Tobias Biletzki, Wolfgang Imhof*
Friedrich-Schiller-University Jena, Institute of Inorganic and Analytical Chemistry, Humboldtstraße 8, 07743 Jena, Germany
Fax +49(3641)948102; E-mail: Wolfgang.Imhof@uni-jena.de
Received 20 July 2011; revised 4 October 2011
tyric acid derivatives have been investigated with respect
to their potential as psychotropic drugs, as agents against
Alzheimer’s disease, Down’s syndrome, osteoporosis,
and cancer or as constituents of peptide mimetics exhibit-
Abstract: A library of heterocyclic products with a wide variety of
organic residues is produced via a four-component reaction of a,b-
unsaturated aldehydes, primary amines, carbon monoxide, and eth-
ylene using a multi-reactor station with an array of 96 autoclaves
employing the same high-pressure reaction conditions for all cata- ing g-turns.16–22 It has also been demonstrated that incor-
lytic reactions. In the presence of Ru3(CO)12 as a precatalyst, mix-
tures of chiral g-lactams and 2,3-disubstituted pyrroles are obtained.
poration of g-amino acids into protein sequences
considerably enhances their stability against proteases,
This combinatorial approach also enables us for the first time to set
which is an essential prerequisite to use those proteins as
up rules relating to the effects of specific substituents in the sub-
drugs under physiological conditions.23
strates on the outcome of the respective catalytic reaction.
Herein we report the combinatorial reaction of seven a,b-
unsaturated aldehydes with eight different primary
amines in the presence of CO and ethylene to yield the
corresponding pyrrolone and pyrrole derivatives. In order
to afford the same reaction conditions for all catalytic re-
actions we used a multi-reactor station manufactured by
Advanced ChemTech Inc. This multi-reactor station is set
up by 96 autoclaves with a maximum working capacity of
3.5 mL each. The reaction vessel block is covered by a top
clamp plate with a septum and valve membrane sheet and
is connected to a gas mixing facility allowing for the prep-
aration of mixtures of gaseous substrates with different
partial pressures (Figure 1).
Key words: ruthenium, C–H activation, catalysis, g-lactams, pyr-
roles
The direct catalytic activation of C–H bonds with the pur-
pose of establishing new C–C bonds is a highly attractive
synthetic objective in terms of avoiding synthesis and iso-
lation of more reactive intermediates, for example, chlori-
nated compounds. Progress in this field has been
thoroughly reviewed in recent years.1–8
Some of us have developed a reaction of a,b-unsaturated
imines, carbon monoxide, and ethylene (or terminal alk-
enes in general) to produce chiral 1,3-dihydropyrrolones
as the main product in nonpolar solvents. As a side-prod-
uct 2,3-disubstituted pyrroles are formed (Scheme 1).9–15
Ph
Ph
Ru3(CO)12 (cat.)
CO, C2H4
Ph
N
+
Me
O
N
N
3
Me
Me
4
5
Scheme 1 Ruthenium-catalyzed formation of g-lactams and pyr-
roles
The formation of both products obviously proceeds via
the activation of a C–H bond in the b-position relative to
the imine C=N bond. The product ratio is highly depen-
dent on the relative permittivity of the solvent used; with
nonpolar solvents like, for example, hydrocarbons leading
to the quantitative and selective formation of racemic lac-
tams 4, whereas use of more polar solvents or the presence
of traces of water leads to an enhancement of the yield of
the pyrrole 5 (75% in anhyd MeOH).15 g-Lactams or g-bu-
Figure 1 Multi-reactor station (without cover plate)
Initially, we planned to use ionic liquids as reaction media
because we have been able to demonstrate that optimiza-
tion of the reaction conditions of the reaction depicted in
Scheme 1 in [C4mim][BTA] led to milder conditions with
regard to reaction time and partial pressures of the gas-
eous substrates than when performed in classical organic
solvents.24 Beforehand only a limited number of transi-
tion-metal-catalyzed reactions in ionic liquids proceeding
SYNTHESIS 2011, No. 24, pp 3979–3990
x
x.
x
x
.
2
0
1
1
Advanced online publication: 03.11.2011
DOI: 10.1055/s-0031-1289584; Art ID: T71111SS
© Georg Thieme Verlag Stuttgart · New York

3980
T. Biletzki, W. Imhof
PAPER
via C–H activation steps have been reported, including ac-
tivation of methane, dehydrogenation of cyclooctadiene,
isomerization of alkenes, or C–H activation of terminal
alkynes.25–29 Unfortunately, this reaction does not work in
ionic liquids if the multi-reactor station shown in Figure 1
is employed. This is most probably due to the low solubil-
ity of CO in ionic liquids30 in combination with the small
surface, which is caused by the slim layout of the auto-
claves. Nevertheless, combinatoric synthesis of heterocy-
clic compounds was efficiently achieved in toluene as the
solvent.
Table 1 Primary Amines and a,b-Unsaturated Aldehydes Used in
the Experiments
Amines
Aldehydes
2a: benzylamine
2b: aniline
1a: 3-ferrocenylpropenal
1b: trans-cinnamaldehyde
1c: trans-crotonic aldehyde
1d: acrolein
2c: p-toluidine
2d: cyclohexylamine
2e: tert-butylamine
2f: n-butylamine
2g: 4-tert-butylaniline
2h: sec-butylamine
1e: trans-4-fluorocinnamaldehyde
1f: 3-(2-furyl)acrolein
1g: trans-3-(3-pyridyl)acrolein
Table 1 shows the primary amines and a,b-unsaturated al-
dehydes that have been introduced to the catalytic reaction
to form the 1,3-dihydropyrrolones and 2,3-disubstituted
pyrroles, respectively, after reacting with CO and ethylene
in the presence of Ru3(CO)12 as a precatalyst (Scheme 2).
Exploratory analysis at the multi-reactor station showed
that the temperature in the middle of the block differs
about 10 °C from the reaction vessels at the outside of the
block. In order to afford the same reaction conditions for
all catalytic reactions the outer autoclaves were not used.
Thus, eight primary amines were combined with seven
a,b-unsaturated aldehydes. Workup was easily achieved
by removing the solvent under reduced pressure and the
oily residue was used to get an impression of the outcome
which are easily identified by two doublets in the range of
5–7 ppm. Moreover, there was also no signal correspond-
ing to the CH function of imines or even the starting alde-
hyde. Signals in the aliphatic and olefinic region of the
spectrum might be indicative for the formation of oligo-
meric or polymeric products. In contrast, in the case of the
tert-butylamine it is most probably rather a matter of ster-
ic pressure preventing the catalytic reaction. Additional
reactions combining trans-cinnamaldehyde with tert-bu-
tylamine and 2,6-diisopropylphenylamine showed that it
is indeed possible to get the unsaturated imine but not at
all the catalytic reaction products. Other aliphatic amines
give both heterocyclic products 4 and 5 when reacted with
the aldehydes used. In the case of sec-butylamine two dia-
stereomeric pairs of enantiomers are produced, as can be
seen from the NMR data in which signals representing
atoms in close proximity to one of the stereogenic centers
are doubled. Moreover, aromatic amines, for example,
aniline just react with 3-ferrocenylpropenal and 3-(2-fur-
yl)acrolein to a mixture of the corresponding lactam and
pyrrole. Otherwise it can be observed that just the pyrrole
derivative is formed with a yield of about 50%. There is
just one exception for the combination of 3-(2-furyl)ac-
rolein with aniline where also just the pyrrole is formed.
In general, it has to be pointed out that water that is pro-
duced by the condensation reaction of the aldehyde with
the respective amine leads to an enhanced yield of the cor-
responding pyrrole compared to the reaction conditions in
which the pure imine would have been introduced to the
catalytic heterocycle formation in anhydrous toluene.
1
of the products 4 and 5 via H NMR spectroscopy. The
products were finally separated by column chromatogra-
phy and characterized by IR, 1H, and 13C NMR spectros-
copy as well as by mass spectrometry and high-resolution
mass spectrometry (cf. experimental part).
R1
R1
N
O
R2NH2
+
R2
– H2O
3
1a R1 = ferrocenyl 2a R2 = Bn
1b R1 = Ph
2b R2 = Ph
Ru3(CO)12 (cat.)
CO, C2H4
1c R1 = Me
2c R2 = 4-MeC6H4
2d R2 = c-Hex
2e R2 = t-Bu
1d R1 = H
R1
R1
1e R1 = 4-FC6H4
1f R1 = 2-furyl
1g R1 = 3-pyridyl
2f R2 = n-Bu
2g R2 = 4-t-BuC6H4
2h R2 = s-Bu
+
O
N
N
R2
R2
4
5
Scheme 2 Four-component reaction leading to heterocyclic pro-
ducts of type 4 and 5, all combinations of R1 and R2 were used in the
experiments
Table 2 shows the combination of eight amines with sev-
en aldehydes and the yields of the corresponding products
4 and 5. From the entries in Table 2 it can be concluded
that most combinations for the catalytic transformation of
primary amines and unsaturated aldehydes to the hetero-
cyclic products work very well. Acrolein and tert-butyl-
amine are the only substrates examined that did not react
at all. One reason in the case of acrolein might be that it is
too reactive and does not even lead to the intermediate
All amines and aldehydes except 3-ferrocenylpropenal were pur-
chased from Sigma-Aldrich and were used without further purifica-
tion. sec-Butylamine was used as a racemic mixture. 3-Fer-
rocenylpropenal was prepared by alkylation of ferrocene with
1,1,3,3-tetramethoxypropane.31 All catalytic reaction procedures
were carried out under an argon atmosphere in freshly distilled, an-
hydrous solvents.32 The multi-reactor station was purchased from
Advanced ChemTech Inc. Support now is provided by Activotec
Inc. (http://www.activotec.com/). NMR spectra were recorded at
298 K on a Bruker AC 200 spectrometer (1H: 200 MHz; 13C: 50.32
MHz; CDCl3 as internal standard), a Bruker DRX 400 spectrometer
(1H: 400.13 MHz; 13C: 100.62 MHz; CDCl3 as internal standard) or
1
imine after combination with an amine. The resulting H
NMR spectra of crude reaction mixtures showed no sig-
nals indicating the heterocyclic products of type 4 and 5,
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

PAPER
One-Pot g-Lactam Synthesis
3981
Table 2 Used Aldehydes and Amines, Isolated Yields of 4 and 5, and Numbering Scheme of All Products
R2
R1 = Fc
Yield (%)
4
R1 = Ph
R1 = Me
R1 = H
R1 = 4-FC6H4 R1 = 2-furyl
Yield (%) Yield (%)
R1 = 3-pyridyl
Yield (%)
Yield (%)
Yield (%)
Yield (%)
5
4
5
4
5
4
–
–
–
–
–
–
–
5
–
–
–
–
–
–
–
4
5
5
4
5
4
PhCH2 (aa–ga)
Ph (ab–gb)
66
45
45
57
–
30
53
52
42
–
42
–
50
57
47
48
–
22
–
50
57
47
27
–
65
–
28
57
57
34
–
57
–
43
47
55
37
–
59
55
35
46
–
35
45
54
49
–
4-MeC6H4 (ac–gc)
c-Hex (ad–gd)
t-Bu (ae–ge)
–
–
–
40
60
–
46
–
46
–
52
–
n-Bu (af–gf)
67
54
25
44
58
–
40
52
50
–
49
46
55
–
33
54
60
42
36
41
54
64
32
31
4-t-BuC6H4
(ag–gg)
s-Bu (ah–gh)
68
28
51
42
51
27
–
–
41
52
57
38
40
43
a Bruker Ultrashield 600+ (1H: 600.15 MHz; 13C: 150.91 MHz;
CDCl3 as internal standard). Mass spectra were recorded on a Finni-
gan MAT SSQ 710 instrument using direct electron impact (DEI)
techniques. High-resolution mass spectra were recorded on a Finni-
gan MAT 95 XL using EI techniques. IR spectra were recorded at
298 K on a Shimadzu IRAffinity-1 (FTIR) at the laboratory of the
Institute of Organic Chemistry and Macromolecular Chemistry of
Friedrich-Schiller-University of Jena.
13C NMR (50 MHz, CDCl3): d = 9.2, 9.8,, 29.6, 32.9, 43.5, 45.6,
54.2, 65.8, 66.5, 67.2, 67.8, 68.5, 87.9, 113.7, 127.7, 128.1, 128.8,
130.2, 136.7, 179.2.
MS (DEI): m/z (%) = 385 (100, [M+]), 356 (50, [M+ – Et]), 265 (21,
+
[M+ – C9H12]), 91 (30, [C7H7 ]).
HRMS: m/z calcd for C23H2354FeNO: 383.11759; found: 383.11679,
D = 0.80 mmu.
N-Benzyl-2-ethyl-3-ferrocenylpyrrole (5aa)
Yield: 110 mg (30%); eluent: light petroleum–CH2Cl2 (70:30).
One-Pot Synthesis of g-Lactams and Pyrroles; General Proce-
dure
1H NMR (200 MHz, CDCl3): d = 1.12 (t, J = 7.6 Hz, 3 H), 2.68 (q,
J = 7.6 Hz, 2 H), 4.07 (s, 5 H), 4.18 (t, J = 1.8 Hz, 2 H), 4.43 (t,
J = 1.8 Hz, 2 H), 5.04 (s, 2 H), 6.30 (d, J = 2.8 Hz, 1 H), 6.54 (d,
J = 2.8 Hz, 1 H), 6.99–7.31 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 14.9, 18.1, 50.2, 66.7, 67.2, 69.1,
83.2, 108.0, 117.1, 120.2, 126.2, 127.3, 128.7, 131.0, 138.8.
Each reaction vessel was charged with a primary amine 2 (1 mmol),
an a,b-unsaturated aldehyde 1 (1 mmol) as well as Ru3(CO)12 (19
mg, 0.03 mmol) and anhyd, freshly distilled toluene (1.5 mL). Af-
terwards, the multi-reactor station was pressurized with CO (12 bar)
and ethylene (8 bar), and heated up to 140 °C for a reaction time of
16 h. After the autoclaves had cooled to r.t., the reaction mixtures
were transferred to Schlenk tubes. The solvent was removed in vac-
uo and the remaining oily residue was used to determine yields of
the products 4 and 5 by 1H NMR spectroscopy. If resonances corre-
sponding to the respective products were observed, the solvent used
for the 1H NMR spectroscopic investigation was removed under re-
duced pressure. Preparative separation of 4 and 5 was achieved by
column chromatography (10 × 2 cm, silica gel). Using a mixture of
light petroleum (bp 40–60 °C) and CH2Cl2, depending on the reac-
tion mixture, led to elution of 5, whereas 4 was obtained by using
EtOH as eluent. The exact ratio of solvents for the elution of all de-
rivatives of 4 and 5 are specified in connection with the physical
data of each compound (vide infra). Analytical data of 4ba and 5ba
are in accordance with values published earlier by us.13 All com-
pounds were either light yellow (R1 = aliphatic moiety) or yellow-
orange (R1 = aromatic) oils.
MS (DEI): m/z (%) = 369 (100, [M+]), 354 (6, [M+ – Me]), 278 (9,
+
[M+ – C7H7]), 263 (22, [M+ – C8H10]), 91 (22, [C7H7 ]).
HRMS: m/z calcd for C23H2354FeN: 367.12267; found: 367.12247,
D = 0.2 mmu.
3-Ethyl-3-ferrocenyl-N-phenyl-1,3-dihydropyrrol-2-one (4ab)
Yield: 166 mg (45%); eluent: EtOH.
IR (neat): 2955 (m), 2924 (vs), 2855 (m), 1717 (s), 1701 (s), 1597
(m), 1501 (s), 1458 (m), 1385 (m), 1273 (s), 1211 (m), 1072 (m),
741 (vs), 691 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.80 (t, J = 7.4 Hz, 3 H), 1.86 (q,
J = 7.4 Hz, 2 H), 4.05 (s, 5 H), 4.11–4.55 (m, 4 H), 5.66 (d, J = 5.2
Hz, 1 H), 6.99 (d, J = 5.2 Hz, 1 H), 7.10–7.58 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 8.3, 32.7, 54.1, 65.4, 67.3, 67.5,
N-Benzyl-3-ethyl-3-ferrocenyl-1,3-dihydropyrrol-2-one (4aa)
Yield: 253 mg (66%); eluent: EtOH.
86.5, 113.4, 120.3, 124.5, 128.2, 129.6, 136.0, 176.8.
MS (DEI): m/z (%) = 371 (100, [M+]), 342 (58, [M+ – Et]), 314 (6,
IR (neat): 3090 (w), 2967 (w), 2932 (w), 2874 (w), 2021 (m), 1952
(m), 1694 (s), 1605 (m), 1354 (s), 1103 (s), 999 (s), 818 (vs), 698
cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.74 (t, J = 7.4 Hz, 2 H), 1.16 (t,
J = 7.5 Hz, 1 H), 1.83 (q, J = 7.4 Hz, 1.3 H), 2.23 (q, J = 7.6 Hz, 0.6
H), 4.09–4.47 (m, 4 H), 4.65 (AB spin system, J = 14.8, 51.3 Hz, 2
H), 5.45 (d, J = 4.8 Hz, 1 H), 6.44 (d, J = 4.8 Hz, 1 H), 7.28–7.31
(m, 5 H).
+
[M+ – Et – CO]), 121 (6, [FeC5H5 ]), 77 (7, [Ph+]).
HRMS: m/z calcd for C22H2154FeNO: 369.10194; found: 369.10251,
D = 0.57 mmu.
2-Ethyl-3-ferrocenyl-N-phenylpyrrole (5ab)
Yield: 188 mg (53%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.98 (t, J = 7.4 Hz, 3 H), 2.74 (q,
J = 7.4 Hz, 2 H), 4.13 (s, 5 H), 4.22 (t, J = 1.8 Hz, 2 H), 4.46 (t,
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

3982
T. Biletzki, W. Imhof
PAPER
J = 1.8 Hz, 2 H), 6.38 (d, J = 3.0 Hz, 1 H), 6.68 (d, J = 3.0 Hz, 1 H),
7.32– 7.50 (m, 5 H).
(s, 5 H), 4.16 (t, J = 1.6 Hz, 2 H), 4.38 (t, J = 1.6 Hz, 2 H), 6.25 (d,
J = 3.2 Hz, 1 H), 6.61 (d, J = 3.2 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 14.7, 18.2, 67.1, 67.3, 69.1, 83.0,
109.1, 117.8, 121.1, 126.4, 127.1, 129.0, 131.6, 140.5.
13C NMR (100 MHz, CDCl3): d = 15.4, 17.9, 25.5, 26.1, 34.9, 54.7,
67.0, 69.0, 83.8, 107.9, 115.1, 115.5, 130.1.
MS (DEI): m/z (%) = 355 (100, [M+]), 340 (14, [M+ – Me]), 170
MS (DEI): m/z (%) = 361 (100, [M+]), 331 (2, [M+ – C2H6]), 279 (3,
(10, [M+ – C10H9Fe]).
[M+ – C6H10]), 264 (6, [M+ – C7H13]), 83 (11, [C6H11+]).
HRMS: m/z calcd for C22H2154FeN: 353.10702; found: 353.10452,
D = 2.50 mmu.
HRMS: m/z calcd for C22H2754FeN: 359.15397; found: 359.15152,
D = 2.45 mmu.
3-Ethyl-3-ferrocenyl-N-p-tolyl-1,3-dihydropyrrol-2-one (4ac)
Yield: 174 mg (45%); eluent: EtOH.
N-Butyl-3-ethyl-3-ferrocenyl-1,3-dihydropyrrol-2-one (4af)
Yield: 236 mg (67%); eluent: EtOH.
IR (neat): 2963 (w), 2924 (m), 2855 (w), 1956 (w), 1709 (s), 1612
(m), 1512 (vs), 1454 (m), 1385 (s), 1204 (s), 999 (m), 814 (vs), 702
cm–1 (m).
IR (neat): 2959 (w), 2932 (w), 2874 (vw), 1967 (vw), 1694 (vs),
1454 (m), 1377 (m), 1261 (m), 1107 (s), 999 (s), 818 (vs), 691
cm–1 (m).
1H NMR (200 MHz, CDCl3): d = 0.80 (t, J = 7.4 Hz, 3 H), 1.85 (q,
J = 7.4 Hz, 2 H), 2.34 (s, 3 H), 4.05 (s, 5 H), 4.11–4.56 (m, 4 H),
5.66 (d, J = 5.0 Hz, 1 H), 6.95 (d, J = 5.0 Hz, 1 H), 7.22 (dd, J = 2.0
Hz, J = 6.7 Hz, 2 H), 7.43 (dd, J = 2.0, 6.7 Hz, 2 H).
1H NMR (200 MHz, CDCl3): d = 0.72 (t, J = 7.4 Hz, 3 H), 0.93 (t,
J = 7.2 Hz, 3 H), 1.33–1.37 (m, 2 H), 1.56–1.60 (m, 2 H), 1.77 (q,
J = 7.4 Hz, 2 H), 3.28–3.64 (m, 2 H), 4.03 (s, 5 H), 4.05–4.43 (m, 4
H), 5.44 (d, J = 5.0 Hz, 1 H), 6.50 (d, J = 5.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 9.3, 20.9, 33.7, 55.0, 66.0, 68.0,
68.5, 87.5, 114.1, 120.3, 129.7, 130.9, 134.4, 135.3, 177.8.
13C NMR (50 MHz, CDCl3): d = 9.2, 13.7, 20.0, 31.1, 33.0, 41.5,
54.3, 65.9, 66.6, 67.1, 67.8, 68.5, 88.0, 113.3, 130.8, 179.3.
MS (DEI): m/z (%) = 385 (100, [M+]), 356 (25, [M+ – Et]), 328 (4,
MS (DEI): m/z (%) = 351 (100, [M+]), 322 (63, [M+ – Et]), 280 (9,
+
+
[M+ – Et – CO]), 121 (4, [FeC5H5 ]).
[M+ – C5H11]), 121 (5, [FeC5H5 ]).
HRMS: m/z calcd for C23H2354FeNO: 383.11759; found: 383.11799,
D = 0.40 mmu.
HRMS: m/z calcd for C20H2554FeNO (349.13324): 349.13138,
D = 1.86 mmu.
2-Ethyl-3-ferrocenyl-N-p-tolylpyrrole (5ac)
Yield: 192 mg (52%); eluent: light petroleum–CH2Cl2 (70:30).
N-Butyl-2-ethyl-3-ferrocenylpyrrole (5af)
Yield: 84 mg (25%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.99 (t, J = 7.4 Hz, 3 H), 2.43 (s,
3 H), 2.72 (q, J = 7.4 Hz, 2 H), 4.13 (s, 5 H), 4.21 (t, J = 1.8 Hz, 2
H), 4.46 (t, J = 1.8 Hz, 2 H), 6.37 (d, J = 2.8 Hz, 1 H), 6.65 (d,
J = 2.8 Hz, 1 H), 7.24 (s, 4 H).
13C NMR (50 MHz, CDCl3): d = 14.7, 18.2, 21.1, 67.1, 67.3, 69.1,
83.1, 108.8, 117.4, 121.1, 126.3, 129.6, 131.7, 137.0, 138.0.
1H NMR (200 MHz, CDCl3): d = 0.97 (t, J = 7.2 Hz, 3 H), 1.22 (t,
J = 7.4 Hz, 3 H), 1.39–1.43 (m, 2 H), 1.72–1.76 (m, 2 H), 2.74 (q,
J = 7.4 Hz, 2 H), 3.79 (t, J = 7.4 Hz, 2 H), 4.08 (s, 5 H), 4.17 (t,
J = 1.8 Hz, 2 H), 4.40 (t, J = 1.8 Hz, 2 H), 6.24 (d, J = 3.0 Hz, 1 H),
6.53 (d, J = 3.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 13.8, 15.0, 17.9, 20.1, 33.7, 46.2,
66.9, 67.1, 69.1, 83.6, 107.7, 116.1, 118.7, 130.2.
MS (DEI): m/z (%) = 369 (100, [M+]), 354 (9, [M+ – Me]), 339 (4,
+
+
[M+ – C2H6]), 185 (4, [FeC10H9 ]), 121 (7, [FeC5H5 ]).
MS (DEI): m/z (%) = 335 (100, [M+]), 320 (9, [M+ – Me]), 306 (4,
[M+ – Et]), 291 (2, [M+ – C3H8]), 186 (3, [FeC10H10]).
HRMS: m/z calcd for C23H2354FeN: 367.12267; found: 367.12031,
D = 2.36 mmu.
HRMS: m/z calcd for C20H2554FeN: 333.13832; found: 333.13537,
D = 2.95 mmu.
N-Cyclohexyl-3-ethyl-3-ferrocenyl-1,3-dihydropyrrol-2-one
(4ad)
N-(4-tert-Butylphenyl)-3-ethyl-3-ferrocenyl-1,3-dihydropyrrol-
2-one (4ag)
Yield: 216 mg (57%); eluent: EtOH.
Yield: 230 mg (54%); eluent: EtOH.
IR (neat): 3094 (w), 2932 (m), 2855 (w), 1967 (w), 1686 (s), 1605
(m), 1450 (m), 1377 (s), 1254 (m), 999 (s), 818 (vs), 752 (vs), 691
cm–1 (s).
IR (neat): 2962 (m), 2365 (s), 2330 (m), 1697 (vs), 1616 (m), 1516
(vs), 1454 (s), 1389 (s), 1204 (s), 999 (s), 818 (vs), 706 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 0.69 (t, J = 7.2 Hz, 3 H), 1.12–
1.70 (m, 10 H), 1.80 (q, J = 7.2 Hz, 2 H), 3.94–3.98 (m, 1 H), 4.03
(s, 5 H), 4.05–4.47 (m, 4 H), 5.43 (d, J = 4.8 Hz, 1 H), 6.60 (d,
J = 5.0 Hz, 1 H).
1H NMR (200 MHz, CDCl3): d = 0.79 (t, J = 7.4 Hz, 3 H), 1.31 (s,
9 H), 1.85 (q, J = 7.4 Hz, 2 H), 4.05 (s, 5 H), 4.02–4.56 (m, 4 H),
5.63 (d, J = 5.2 Hz, 1 H), 6.96 (d, J = 5.2 Hz, 1 H), 7.45 (d, J = 3.8
Hz, 4 H).
13C NMR (100 MHz, CDCl3): d = 9.1, 25.4, 32.0, 32.3, 33.5, 50.3,
13C NMR (50 MHz, CDCl3): d = 8.3, 30.3, 32.7, 33.5, 54.0, 64.9,
65.8, 66.1, 67.0, 68.5, 86.6, 113.2, 120.0, 125.1, 129.8, 133.4,
147.6, 176.8.
54.6, 65.8, 66.5, 67.1, 67.8, 68.5, 87.9, 113.3, 127.8, 178.6.
MS (DEI): m/z (%) = 377 (100, [M+]), 348 (54, [M+ – Et]), 266 (16,
[M+ – C8H15]), 83 (30, [C6H11+]).
MS (DEI): m/z (%) = 427 (100, [M+]), 398 (55, [M+ – Et]), 370 (2,
[M+ – Et – CO]), 313 (2, [M+ – Et – CO – C4H9]), 121 (11,
HRMS: m/z calcd for C22H2754FeNO: 375.14889; found: 375.14465,
D = 4.24 mmu.
+
[FeC5H5 ]).
HRMS: m/z calcd for C26H2954FeNO: 425.16454; found: 425.16345,
D = 1.09 mmu.
N-Cyclohexyl-2-ethyl-3-ferrocenylpyrrole (5ad)
Yield: 153 mg (42%); eluent: light petroleum–CH2Cl2 (70:30).
N-(4-tert-Butylphenyl)-2-ethyl-3-ferrocenylpyrrole (5ag)
Yield: 180 mg (44%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (400 MHz, CDCl3): d = 1.20 (t, J = 7.6 Hz, 3 H), 1.38–
2.03 (m, 10 H), 2.76 (q, J = 7.6 Hz, 2 H), 3.74–3.82 (m, 1 H), 4.09
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

PAPER
One-Pot g-Lactam Synthesis
3983
1H NMR (400 MHz, CDCl3): d = 1.00 (t, J = 7.6 Hz, 3 H), 1.38 (s,
9 H), 2.72 (q, J = 7.6 Hz, 2 H), 4.13 (s, 5 H), 4.21 (t, J = 1.6 Hz, 2
H), 4.46 (t, J = 1.6 Hz, 2 H), 6.37 (d, J = 2.8 Hz, 1 H), 6.66 (d,
J = 2.8 Hz, 1 H), 7.26 (d, J = 2.8 Hz, 2 H), 7.45 (d, J = 2.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 14.8, 18.2, 31.4, 34.6, 67.1, 67.3,
69.1, 83.2, 108.8, 117.4, 121.1, 125.8, 126.0, 131.7, 137.9, 150.2.
1H NMR (200 MHz, CDCl3): d = 0.93 (t, J = 7.4 Hz, 3 H), 2.43 (s,
3 H), 2.76 (q, J = 7.4 Hz, 2 H), 6.37 (d, J = 2.8 Hz, 1 H), 6.73 (d,
J = 2.8 Hz, 1 H), 7.22–7.49 (m, 9 H).
13C NMR (50 MHz, CDCl3): d = 14.7, 18.1, 21.1, 108.5, 121.6,
122.4, 125.3, 126.4, 128.1, 128.3, 129.6, 131.8, 137.3, 137.4, 138.0.
MS (DEI): m/z (%) = 261 (100, [M+]), 246 (82, [M+ – Me]), 168 (4,
MS (DEI): m/z (%) = 411 (100, [M+]), 396 (6, [M+ – Me]), 339 (4,
[M+ – C7H9]), 154 (4, [M+ – C8H11]), 91 (7, [C7H7 ]).
+
+
[M+ – C5H12]), 266 (10, [C11H13+]), 121 (6, [FeC5H5 ]).
HRMS: m/z calcd for C19H19N: 261.15175; found: 261.15148 (M+),
D = 0.27 mmu.
HRMS: m/z calcd for C26H2954FeN: 409.16962; found: 409.16677,
D = 2.85 mmu.
N-Cyclohexyl-3-ethyl-3-phenyl-1,3-dihydropyrrol-2-one (4bd)
N-sec-Butyl-3-ethyl-3-ferrocenyl-1,3-dihydropyrrol-2-one
Yield: 125 mg (46%); eluent: EtOH.
(4ah)
IR (neat): 2924 (s), 2855 (m), 1967 (w), 1700 (m), 1601 (w), 1447
(m), 1377 (m), 1253 (m), 752 (s), 698 cm–1 (vs).
Yield: 239 mg (68%); eluent: EtOH.
IR (neat): 3094 (vw), 2967 (w), 2932 (vw), 2874 (vw), 1967 (w),
1686 (vs), 1605 (m), 1454 (m), 1381 (s), 1258 (s), 999 (s), 818 (vs),
752 cm–1 (s).
1H NMR (200 MHz, CDCl3): d = 0.78 (t, J = 7.4 Hz, 3 H), 1.11–
1.78 (m, 10 H), 1.99 (q, J = 7.4 Hz, 2 H), 3.86–3.93 (m, 1 H), 5.57
(d, J = 5.0 Hz, 1 H), 6.61 (d, J = 5.0 Hz, 1 H), 7.18–7.45 (m, 5 H).
1H NMR (600 MHz, CDCl3): d = 0.69 (t, J = 7.2 Hz, 3 H), 0.84 (t,
J = 7.6 Hz, 3 H), 1.13 (d, J = 6.7 Hz, 1.8 H), 1.20 (d, J = 6.9 Hz, 1.2
H), 1.52–1.57 (m, 2 H), 1.69–1.88 (m, 2 H), 3.98–4.02 (m, 1 H),
4.00–4.04 (m, 2 H), 4.03 (s, 5 H), 4.23–4.27 (m, 2 H), 5.40 (d,
J = 4.8 Hz, 0.6 H), 5.43 (d, J = 4.8 Hz, 0.4 H), 6.49 (d, J = 4.8 Hz,
0.6 H), 6.50 (d, J = 4.8 Hz, 0.4 H).
13C NMR (500 MHz, CDCl3): d = 9.0, 25.4, 31.0, 31.7, 32.1, 50.4,
58.8, 113.3, 126.6, 126.8, 128.3, 128.4, 140.2, 179.1.
MS (DEI): m/z (%) = 269 (100, [M+]), 240 (59, [M+ – Et]), 187 (13,
[M+ – C6H10]), 172 (12, [M+ –C7H13]), 158 (48, [M+ – C8H15]), 77
(5, [Ph+]).
13C NMR (150 MHz, CDCl3): d = 8.0, 8.4, 9.8, 10.0, 18.4, 18.6,
27.5, 27.8, 31.3, 32.2, 47.1, 47.6, 53.7, 53.8, 64.8, 64.9, 65.3, 65.6,
66.1, 66.4, 66.7, 66.8, 67.5, 87.2, 87.8, 112.7, 113.0, 126.2, 126.6,
178.1, 178.2.
HRMS: m/z calcd for C18H23NO: 269.17796; found: 269.17795,
D = 0.01 mmu.
N-Cyclohexyl-2-ethyl-3-phenylpyrrole (5bd)
Yield: 122 mg (48%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 1.24 (t, J = 7.4 Hz, 3 H), 1.34–
2.07 (m, 10 H), 2.74 (q, J = 7.4 Hz, 2 H), 3.77–3.92 (m, 1 H), 6.27
(d, J = 3.0 Hz, 1 H), 6.71 (d, J = 3.0 Hz, 1 H), 7.18–7.41 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 15.6, 17.8, 25.5, 26.1, 35.0, 55.0,
107.7, 115.8, 120.8, 125.0, 128.0, 128.2, 130.1, 137.8.
MS (DEI): m/z (%) = 351 (100, [M+]), 323 (18, [M+ – CO]), 322
+
(73, [M+ – Et]), 266 (18, [M+ – C6H13]), 121 (12, [FeC5H5 ]).
HRMS: m/z calcd for C20H2554FeNO: 349.13324; found: 349.13179,
D = 1.45 mmu.
N-sec-Butyl-2-ethyl-3-ferrocenylpyrrole (5ah)
Yield: 94 mg (28%); eluent: light petroleum–CH2Cl2 (70:30).
MS (DEI): m/z (%) = 253 (100, [M+]), 238 (18, [M+ – Me]), 224 (4,
[M+ – Et]), 170 (3, [M+ – C6H11]), 156 (8, [M+ – C7H13]).
1H NMR (600 MHz, CDCl3): d = 0.76 (t, J = 7.2 Hz, 3 H), 1.12 (t,
J = 7.2 Hz, 3 H), 1.32 (d, J = 7.2 Hz, 3 H), 1.67 (q, J = 7.2 Hz, 2 H),
2.67–2.75 (m, 2 H), 3.88 (q, J = 7.2 Hz, 1 H), 3.99 (s, 5 H), 4.10 (d,
J = 7.2 Hz, 2 H), 4.33 (d, J = 7.2 Hz, 2 H), 6.17 (d, J = 3.0 Hz, 1 H),
6.47 (d, J = 3.0 Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 10.0, 14.3, 16.9, 21.2, 30.2, 51.2,
65.9, 66.1, 68.1, 82.9, 107.0, 113.4, 114.3, 129.7.
HRMS: m/z calcd for C18H23N: 253.18305; found: 253.18344,
D = 0.39 mmu.
N-Butyl-3-ethyl-3-phenyl-1,3-dihydropyrrol-2-one (4bf)
Yield: 142 mg (58%); eluent: EtOH.
IR (neat): 2959 (w), 2932 (w), 2874 (vw), 1686 (s), 1447 (w), 1373
(w), 1261 (m), 1076 (m), 1015 (m), 791 (m), 698 cm–1 (vs).
1H NMR (600 MHz, CDCl3): d = 0.80 (t, J = 7.2 Hz, 3 H), 0.90 (t,
J = 7.2 Hz, 3 H), 1.30 (q, J = 7.2 Hz, 2 H), 1.50–1.56 (m, 2 H), 2.00
(q, J = 7.2 Hz, 2 H), 3.32–3.48 (m, 2 H), 5.61 (d, J = 5.4 Hz, 1 H),
6.52 (d, J = 5.4 Hz, 1 H), 7.20–7.44 (m, 5 H).
MS (DEI): m/z (%) = 335 (100, [M+]), 320 (6, [M+ – Me]), 306 (2,
[M+ – Et]), 278 (2, [M+ – C4H9]).
HRMS: m/z calcd for C20H2554FeN: 333.13832; found: 333.13618,
D = 2.14 mmu.
13C NMR (150 MHz, CDCl3): d = 9.2, 13.6, 20.0, 31.0, 31.3, 41.7,
58.5, 113.2, 126.7, 126.9, 128.4, 131.5, 140.2, 179.6.
2-Ethyl-N,3-diphenylpyrrole (5bb)
Yield: 140 mg (57%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.92 (t, J = 7.4 Hz, 3 H), 2.78 (q,
J = 7.4 Hz, 2 H), 6.39 (d, J = 2.8 Hz, 1 H), 6.76 (d, J = 2.8 Hz, 1 H),
7.35–7.50 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 14.3, 17.7, 108.5, 121.3, 122.3,
125.1, 126.3, 127.1, 127.8, 128.0, 128.8, 131.4, 137.1, 140.2.
MS (DEI): m/z (%) = 243 (100, [M+]), 214 (76, [M+ – Et]), 200 (17,
[M+ – C3H7]), 186 (4, [M+ – C4H9]), 172 (50, [M+ – C3H7 – CO]).
HRMS: m/z calcd for C16H21NO: 243.16231; found: 243.16213,
D = 0.18 mmu.
MS (DEI): m/z (%) = 247 (100, [M+]), 232 (83, [M+ – Me]), 141 (5,
N-Butyl-2-ethyl-3-phenylpyrrole (5bf)
Yield: 91 mg (40%); eluent: light petroleum–CH2Cl2 (70:30).
[M+ – C8H10]), 91 (15, [C7H7 ]), 77 (22, [Ph+]).
+
1H NMR (600 MHz, CDCl3): d = 0.90 (t, J = 7.2 Hz, 3 H), 1.24 (t,
J = 7.2 Hz, 3 H), 1.42 (dt, J = 7.2 Hz, 2 H), 1.76–1.81 (m, 2 H), 2.75
(q, J = 7.2 Hz, 2 H), 3.85 (t, J = 7.2 Hz, 2 H), 6.26 (d, J = 3.0 Hz, 1
H), 6.63 (d, J = 3.0 Hz, 1 H), 7.19–7.41 (m, 5 H).
13C NMR (150 MHz, CDCl3): d = 12.8, 14.2, 16.8, 19.2, 32.8, 45.3,
106.6, 118.3, 120.4, 124.0, 126.9, 127.2, 129.7, 136.8.
HRMS: m/z calcd for C18H17N: 247.13610; found: 247.13522 (M+),
D = 0.88 mmu.
2-Ethyl-3-phenyl-N-p-tolylpyrrole (5bc)
Yield: 122 mg (47%); eluent: light petroleum–CH2Cl2 (70:30).
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

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T. Biletzki, W. Imhof
PAPER
MS (DEI): m/z (%) = 227 (100, [M+]), 212 (72, [M+ – Me]), 198
MS (DEI): m/z (%) = 215 (100, [M+]), 186 (11, [M+ – Et]), 149 (38,
(27, [M+ – Et]), 184 (26, [M+ – C3H7]), 170 (19, [M+ – C4H9]).
[M+ – C5H6]), 91 (72, [C7H7 ]), 65 (8, [C5H5 ]).
+
+
HRMS: m/z calcd for C16H21N: 227.16740; found: 227.16754,
D = 0.14 mmu.
HRMS: m/z calcd for C14H17NO: 215.13101; found: 215.13078,
D = 0.23 mmu.
N-4-tert-Butylphenyl-2-ethyl-3-phenylpyrrole (5bg)
Yield: 158 mg (52%); eluent: light petroleum–CH2Cl2 (70:30).
N-Benzyl-2-ethyl-3-methylpyrrole (5ca)
Yield: 100 mg (50%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 1.35 (t, J = 7.4 Hz, 3 H), 1.41 (s,
9 H), 2.80 (q, J = 7.4 Hz, 2 H), 6.40 (d, J = 3.0 Hz, 1 H), 6.77 (d,
J = 3.0 Hz, 1 H), 7.29–7.53 (m, 9 H).
1H NMR (200 MHz, CDCl3): d = 1.01 (t, J = 7.6 Hz, 3 H), 2.10 (s,
3 H), 2.52 (q, J = 7.6 Hz, 2 H), 5.03 (s, 2 H), 6.01 (d, J = 2.8 Hz, 1
H), 6.53 (d, J = 2.8 Hz, 1 H), 7.01–7.38 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 14.4, 17.8, 31.1, 34.6, 108.3,
120.3, 120.8, 121.3, 122.0, 125.0, 125.7, 127.7, 128.0, 131.5, 137.4,
150.1.
13C NMR (50 MHz, CDCl3): d = 11.3, 14.6, 17.4, 50.4, 108.7,
114.6, 119.3, 126.3, 126.7, 127.2, 128.6, 130.9.
MS (DEI): m/z (%) = 199 (52, [M+]), 184 (62, [M+ – Me]), 91 (100,
MS (DEI): m/z (%) = 303 (100, [M+]), 288 (40, [M+ – Me]), 244 (7,
[C7H7 ]), 65 (13, [C5H5 ]).
+
+
[M+ – C4H11]), 232 (22, [M+ – C5H11]).
HRMS: m/z calcd for C14H17N: 199.13610; found: 199.13673,
D = 0.63 mmu.
HRMS: m/z calcd for C22H25N: 303.19870; found: 303.19795,
D = 0.75 mmu.
2-Ethyl-3-methyl-N-phenylpyrrole (5cb)
N-sec-Butyl-3-ethyl-3-phenyl-1,3-dihydropyrrol-2-one (4bh)
Yield: 106 mg (57%); eluent: light petroleum–CH2Cl2 (70:30).
Yield: 124 mg (51%); eluent: EtOH.
1H NMR (200 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H), 2.12 (s,
3 H), 2.56 (q, J = 7.4 Hz, 2 H), 6.08 (d, J = 2.8 Hz, 1 H), 6.64 (d,
J = 2.8 Hz, 1 H), 7.26–7.47 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 11.3, 14.5, 17.6, 109.8, 115.5,
120.2, 126.1, 126.8, 128.9, 131.5, 140.8.
IR (neat): 2967 (m), 2916 (m), 2851 (w), 2361 (w), 1971 (w), 1686
(s), 1601 (m), 1454 (m), 1377 (s), 1253 (m), 907 (m), 752 (vs), 698
cm–1 (vs).
1H NMR (600 MHz, CDCl3): d = 0.70–0.83 (m, 6 H), 1.09 (d,
J = 6.8 Hz, 1.5 H), 1.13 (d, J = 6.8 Hz, 1.5 H), 1.45–1.52 (m, 2 H),
1.94–1.98 (m, 2 H), 4.00 (q, J = 6.6 Hz, 1 H), 5.54 (d, J = 5.4 Hz,
0.5 H), 5.56 (d, J = 5.4 Hz, 0.5 H), 6.51 (d, J = 5.4 Hz, 1 H), 7.15
(m, 1 H), 7.22 (m, 2 H), 7.39 (m, 2 H).
MS (DEI): m/z (%) = 185 (78, [M+]), 170 (100, [M+ – Me]), 77 (15,
[Ph+]).
HRMS: m/z calcd for C13H15N: 185.12045; found: 185.11962,
D = 0.83 mmu.
13C NMR (50 MHz, CDCl3): d = 9.1, 9.3 10.7, 10.8, 19.5, 19.6,
28.5, 29.7, 31.0, 31.2, 48.4, 59.0, 113.5, 113.7, 126.6, 126.7, 126.8,
127.9, 128.0, 128.4, 128.8, 140.2, 179.4.
2-Ethyl-3-methyl-N-p-tolylpyrrole (5cc)
Yield: 94 mg (47%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H), 2.12 (s,
3 H), 2.40 (s, 3 H), 2.55 (q, J = 7.4 Hz, 2 H), 6.06 (d, J = 2.8 Hz, 1
H), 6.61 (d, J = 2.8 Hz, 1 H), 7.14–7.24 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 11.3, 14.5, 17.6, 21.0, 109.5,
115.2, 120.2, 126.0, 129.5, 131.6, 136.7, 138.3.
MS (DEI): m/z (%) = 243 (100, [M+]), 214 (93, [M+ – Et]), 186 (17,
[M+ – C4H9]), 158 (43, [M+ – C4H9 – CO]), 77 (8, [Ph+]).
HRMS: m/z calcd for C16H21NO: 243.16231; found: 243.16212,
D = 0.19 mmu.
N-sec-Butyl-2-ethyl-3-phenylpyrrole (5bh)
Yield: 95 mg (42%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.89 (t, J = 3.7 Hz, 3 H), 1.26 (t,
J = 7.0 Hz, 3 H), 1.43 (d, J = 6.6 Hz, 3 H), 1.78 (q, J = 7.4 Hz, 2 H),
2.73 (q, J = 7.6 Hz, 2 H), 4.03 (q, J = 7.0 Hz, 1 H), 6.29 (d, J = 3.0
Hz, 1 H), 6.66 (d, J = 3.0 Hz, 1 H), 7.18–7.38 (m, 5 H).
MS (DEI): m/z (%) = 199 (100, [M+]), 184 (80, [M+ – Me]), 154
+
(18, [M+ – C2H6 – Me+]), 91 (17, [C7H7 ]), 77 (5, [Ph+]).
HRMS: m/z calcd for C14H17N: 199.13610; found: 199.13607 (M+),
D = 0.03 mmu.
N-Cyclohexyl-3-ethyl-3-methyl-1,3-dihydropyrrol-2-one (4cd)
Yield: 96 mg (46%); eluent: CH2Cl2.
13C NMR (50 MHz, CDCl3): d = 11.1, 15.6, 17.7, 22.3, 31.2, 52.5,
109.0, 115.0, 120.6, 124.9, 128.0, 128.2, 130.7, 137.9.
IR (neat): 2928 (vs), 2855 (m), 1971 (m), 1937 (m), 1674 (vs), 1450
(s), 1377 (s), 1258 (s), 1188 (s), 1138 (s), 895 (m), 691 cm–1 (m).
1H NMR (200 MHz, CDCl3): d = 0.66 (t, J = 7.4 Hz, 3 H), 1.09 (s,
3 H), 1.53 (q, J = 7.4 Hz, 2 H), 1.20–1.75 (m, 10 H), 3.80–3.86 (m,
1 H), 5.17 (d, J = 5.0 Hz, 1 H), 6.43 (d, J = 5.0 Hz, 1 H).
MS (DEI): m/z (%) = 227 (100, [M+]), 212 (97, [M+ – Me]), 198
(28, [M+ – Et]), 156 (48, [M+ – C5H11]).
HRMS: m/z calcd for C16H21N: 227.16740; found: 227.16730,
D = 0.10 mmu.
13C NMR (50 MHz, CDCl3): d = 8.8, 21.9, 25.3, 25.4, 31.7, 32.1,
N-Benzyl-3-ethyl-3-methyl-1,3-dihydropyrrol-2-one (4ca)
Yield: 47 mg (22%); eluent: light petroleum–CH2Cl2 (50:50).
50.0, 51.2, 115.0, 127.3, 181.5.
MS (DEI): m/z (%) = 207 (68, [M+]), 192 (7, [M+ – Et]), 178 (100,
IR (neat): 2959 (w), 2928 (m), 2859 (w), 1705 (vs), 1454 (s), 1396
(m), 1273 (s), 1072 (m), 698 cm–1 (vs).
[M+ – Et]).
1H NMR (200 MHz, CDCl3): d = 0.75 (t, J = 7.4 Hz, 3 H), 1.19 (s,
3 H), 1.63 (q, J = 7.4 Hz, 2 H), 4.60 (AB spin system, J = 15.2, 20.1
Hz, 2 H), 5.24 (d, J = 5.0 Hz, 1 H), 6.29 (d, J = 5.0 Hz, 1 H), 7.18–
7.32 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 9.1, 23.8, 38.8, 45.5, 68.2, 115.5,
126.3, 127.7, 128.7, 130.8, 137.0, 177.5.
HRMS: m/z calcd for C13H21NO: 207.16231; found: 207.16278,
D = 0.47 mmu.
N-Cyclohexyl-2-ethyl-3-methylpyrrole (5cd)
Yield: 51 mg (27%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 1.11 (t, J = 7.4 Hz, 3 H), 1.25–
1.94 (m, 10 H), 2.05 (s, 3 H), 2.58 (q, J = 7.4 Hz, 2 H), 3.68–3.83
(m, 1 H), 5.96 (d, J = 2.8 Hz, 1 H), 6.58 (d, J = 2.8 Hz, 1 H).
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

PAPER
One-Pot g-Lactam Synthesis
3985
13C NMR (50 MHz, CDCl3): d = 11.2, 15.0, 17.4, 25.5, 26.1, 35.0,
MS (DEI): m/z (%) = 181 (50, [M+]), 152 (100, [M+ – Et]), 124 (30,
54.9, 108.4, 113.2, 114.5, 130.0.
[M+ – C4H9]), 110 (7, [M+ – C5H11]), 96 (42, [M+ – C6H13]), 57 (11,
+
[C4H9 ]).
MS (DEI): m/z (%) = 191 (88, [M+]), 176 (100, [M+ – Me]), 162
(29, [M+ – Et]).
HRMS: m/z calcd for C11H19NO: 181.14666; found: 181.14699,
D = 0.33 mmu.
HRMS: m/z calcd for C13H21N: 191.16740; found: 191.16732,
D = 0.08 mmu.
N-sec-Butyl-2-ethyl-3-methylpyrrole (5ch)
Yield: 45 mg (27%); eluent: light petroleum–CH2Cl2 (70:30).
N-Butyl-3-ethyl-3-methyl-1,3-dihydropyrrol-2-one (4cf)
Yield: 90 mg (50%); eluent: light petroleum–CH2Cl2 (50:50).
1H NMR (200 MHz, CDCl3): d = 0.84 (t, J = 7.4 Hz, 3 H), 1.10 (t,
J = 7.6 Hz, 3 H), 1.37 (d, J = 6.8 Hz, 3 H), 1.66–1.81 (m, 2 H), 2.05
(s, 3 H), 2.57 (q, J = 7.6 Hz, 2 H), 3.93 (q, J = 6.8 Hz, 1 H), 5.98 (d,
J = 3.0 Hz, 1 H), 6.53 (d, J = 3.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 11.0, 11.2, 15.0, 17.3, 22.2, 31.1,
52.4, 108.6, 112.9, 113.8, 130.5.
IR (neat): 2963 (m), 2928 (m), 2874 (w), 1694 (vs), 1458 (m), 1362
(m), 1265 (m), 1192 (m), 1111 (m), 741 (m), 691 cm–1 (s).
1H NMR (200 MHz, CDCl3): d = 0.68 (t, J = 7.4 Hz, 3 H), 0.87 (t,
J = 7.2 Hz, 3 H), 1.10 (s, 3 H), 1.20–1.31 (m, 2 H), 1.41–1.66 (m, 4
H), 3.31–3.38 (m, 2 H), 5.19 (d, J = 5.0 Hz, 1 H), 6.33 (d, J = 5.0
Hz, 1 H).
MS (DEI): m/z (%) = 165 (85, [M+]), 150 (100, [M+ – Me]), 136
(40, [M+ – Et]), 122 (19, [M+ –C3H7]), 108 (18, [M+ – C4H9]), 94
13C NMR (50 MHz, CDCl3): d = 8.9, 13.6, 19.8, 22.0, 29.9, 30.9,
41.4, 50.9, 114.9, 130.3, 182.0.
+
(64, [M+ – C5H11]), 57 (25, [C4H9 ]).
HRMS: m/z calcd for C11H19N: 165.15175; found: 165.15098,
D = 0.77 mmu.
MS (DEI): m/z (%) = 181 (58, [M+]), 166 (11, [M+ – Me]), 152
(100, [M+ – Et]), 138 (22, [M+ – C3H7]), 110 (62, [M+ – C5H11]), 96
(17, [M+ – C6H13]).
N-Benzyl-3-ethyl-3-(4-fluorophenyl)-1,3-dihydropyrrol-2-one
(4ea)
Yield: 193 mg (65%); eluent: EtOH.
HRMS: m/z calcd for C11H19NO: 181.14666; found: 181.14621,
D = 0.45 mmu.
IR (neat): 2967 (w), 2932 (w), 1967 (w), 1682 (s), 1601 (s), 1508
(vs), 1393 (m), 1358 (s), 1227 (vs), 1157 (s), 1076 (m), 833 (vs),
729 (vs), 698 cm–1 (vs).
1H NMR (600 MHz, CDCl3): d = 0.74 (t, J = 7.2 Hz, 2.25 H), 1.10
(t, J = 7.6 Hz, 0.75 H), 1.94 (q, J = 7.2 Hz, 1.5 H), 2.16 (q, J = 7.6
Hz, 0.5 H), 4.52 (AB spin system, J = 15.0, 85.1 Hz, 2 H), 5.54 (d,
J = 4.8 Hz, 1 H), 6.39 (d, J = 4.8 Hz, 1 H), 6.91–7.39 (m, 9 H).
13C NMR (150 MHz, CDCl3): d = 9.3, 9.9, 29.7, 31.6, 43.6, 45.8,
57.8, 113.3, 115.3, 127.8, 128.8, 128.3, 131.3, 135.6, 136.7, 138.4,
162.0, 179.5.
N-Butyl-2-ethyl-3-methylpyrrole (5cf)
Yield: 81 mg (49%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.94 (t, J = 7.4 Hz, 3 H), 1.11 (t,
J = 7.4 Hz, 3 H), 1.30–1.41 (m, 2 H), 1.62–1.77 (m, 2 H), 2.04 (s, 3
H), 2.55 (q, J = 7.4 Hz, 2 H), 3.85 (t, J = 7.4 Hz, 2 H), 5.91 (d,
J = 2.8 Hz, 1 H), 6.47 (d, J = 2.8 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 11.2, 13.7, 14.7, 17.3, 20.1, 33.9,
46.3, 108.1, 113.8, 118.0, 130.4.
MS (DEI): m/z (%) = 165 (66, [M+]), 150 (100, [M+ – Me]), 136
(30, [M+ – Et]), 122 (20, [M+ – C3H7]), 108 (31, [M+ – C4H9]), 94
MS (DEI): m/z (%) = 295 (100, [M+]), 280 (4, [M+ – Me]), 266 (49,
+
(22, [M+ – C5H11]), 28 (24, [C2H4 ]).
+
[M+ – Et]), 204 (3, [M+ – C7H7]), 91 (62, [C7H7 ]).
HRMS: m/z calcd for C11H19N: 165.15175; found: 165.15189,
D = 0.14 mmu.
HRMS: m/z calcd for C19H18FNO: 295.13724; found: 295.13726,
D = 0.02 mmu.
N-(4-tert-Butylphenyl)-2-ethyl-3-methylpyrrole (5cg)
Yield: 111 mg (46%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.98 (t, J = 7.4 Hz, 3 H), 1.36 (s,
9 H), 2.12 (s, 3 H), 2.56 (q, J = 7.4 Hz, 2 H), 6.06 (d, J = 2.8 Hz, 1
H), 6.63 (d, J = 2.8 Hz, 1 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.43 (d,
J = 8.0 Hz, 2 H).
N-Benzyl-2-ethyl-3-(4-fluorophenyl)pyrrole (5ea)
Yield: 78 mg (28%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 1.12 (t, J = 7.6 Hz, 3 H), 2.65 (q,
J = 7.6 Hz, 2 H), 5.10 (s, 2 H), 6.26 (d, J = 2.8 Hz, 1 H), 6.61 (d,
J = 2.8 Hz, 1 H), 7.00–7.36 (m, 9 H).
13C NMR (150 MHz, CDCl3): d = 14.1, 16.8, 49.4, 107.0, 114.8,
119.6, 125.4, 126.4, 127.7, 128.3, 129.4, 130.1, 132.6, 137.4, 159.3.
13C NMR (50 MHz, CDCl3): d = 11.3, 14.6, 17.6, 31.4, 34.6, 109.5,
115.2, 120.2, 125.7, 125.8, 131.6, 138.2, 149.8.
MS (DEI): m/z (%) = 279 (100, [M+]), 264 (22, [M+ – Me]), 188 (6,
MS (DEI): m/z (%) = 241 (100, [M+]), 226 (72, [M+ – Me]), 196
+
[M+ – C7H7]), 91 (95, [C7H7 ]).
+
(10, [M+ – C3H9]), 170 (31, [M+ – C5H11]), 57 (7, [C4H9 ]).
HRMS: m/z calcd for C19H18FN: 279.14233; found: 279.14283,
D = 0.50 mmu.
HRMS: m/z calcd for C17H23N: 241.18305; found: 241.18335,
D = 0.30 mmu.
2-Ethyl-3-(4-fluorophenyl)-N-phenylpyrrole (5eb)
Yield: 150 mg (57%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 7.4 Hz, 3 H), 2.72 (q,
J = 7.4 Hz, 2 H), 6.32 (d, J = 2.8 Hz, 1 H), 6.74 (d, J = 2.8 Hz, 1 H),
7.01–7.43 (m, 9 H).
13C NMR (50 MHz, CDCl3): d = 14.6, 18.0, 108.8, 115.1, 121.6,
126.6, 127.5, 129.1, 129.4, 129.6, 131.6, 133.4, 140.5, 163.6.
N-sec-Butyl-3-ethyl-3-methyl-1,3-dihydropyrrol-2-one (4ch)
Yield: 93 mg (51%); eluent: CH2Cl2.
IR (neat): 2967 (m), 2928 (w), 1694 (vs), 1454 (m), 1381 (m), 1258
(s), 1069 (m), 745 (m), 691 cm–1 (s).
1H NMR (200 MHz, CDCl3): d = 0.63–0.83 (m, 6 H), 1.10 (s, 1.8
H), 1.08–1.13 (m, 1.8 H), 1.13 (s, 1.2 H), 1.10–1.16 (m, 1.2 H),
1.41–1.71 (m, 4 H), 4.02 (q, J = 7.0 Hz, 1 H), 5.21 (d, J = 5.0 Hz, 1
H), 6.38 (d, J = 5.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 8.9, 9.1, 10.6, 10.7, 19.5, 19.7,
22.2, 22.2, 28.4, 28.5, 29.9, 47.9, 48.1, 51.3, 51.4, 115.3, 126.7,
126.8, 181.9.
MS (DEI): m/z (%) = 265 (89, [M+]), 250 (100, [M+ – Me]), 235 (4,
[M+ – C2H6]), 77 (8, [Ph+]), 28 (3, [C2H4]).
HRMS: m/z calcd for C18H16FN: 265.12668: found: 265.12490
(M+), D = 1.78 mmu.
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

3986
T. Biletzki, W. Imhof
PAPER
2-Ethyl-3-(4-fluorophenyl)-N-p-tolylpyrrole (5ec)
Yield: 140 mg (50%); eluent: light petroleum–CH2Cl2 (70:30).
N-Butyl-2-ethyl-3-(4-fluorophenyl)pyrrole (5ef)
Yield: 82 mg (33%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H), 2.41 (s,
3 H), 2.70 (q, J = 7.4 Hz, 2 H), 6.31 (d, J = 2.8 Hz, 1 H), 6.71 (d,
J = 2.8 Hz, 1 H), 7.00–7.40 (m, 8 H).
13C NMR (50 MHz, CDCl3): d = 14.3, 17.7, 20.7, 108.2, 114.7,
121.3, 125.6, 126.1, 129.2, 129.3, 131.4, 133.1, 137.0, 137.6, 160.8.
1H NMR (600 MHz, CDCl3): d = 0.97 (t, J = 7.2 Hz, 3 H), 1.20 (t,
J = 7.2 Hz, 3 H), 1.40 (q, J = 7.2 Hz, 2 H), 1.70–1.79 (m, 2 H), 2.70
(q, J = 7.2 Hz, 2 H), 3.83 (t, J = 7.2 Hz, 2 H), 6.19 (d, J = 3.0 Hz, 1
H), 6.61 (d, J = 3.0 Hz, 1 H), 7.03 (t, J = 9.0 Hz, 2 H), 7.31 (t,
J = 4.2 Hz, 2 H).
13C NMR (150 MHz, CDCl3): d = 12.8, 14.2, 16.7, 19.1, 32.8, 45.3,
106.5, 114.0, 118.3, 119.4, 128.3, 129.6, 132.8, 160.00.
MS (DEI): m/z (%) = 279 (100, [M+]), 264 (82, [M+ – Me]), 91 (6,
+
[C7H7 ]).
MS (DEI): m/z (%) = 245 (100, [M+]), 230 (74, [M+ – Me]), 216
HRMS: m/z calcd for C19H18FN: 279.14233; found: 279.14268,
D = 0.35 mmu.
(28, [M+ – Et]), 202 (28, [M+ – C3H7]), 188 (26, [M+ – C4H9]).
HRMS: m/z calcd for C16H20FN: 245.15798; found: 245.15760,
D = 0.38 mmu.
N-Cyclohexyl-3-ethyl-3-(4-fluorophenyl)-1,3-dihydropyrrol-2-
one (4ed)
Yield: 148 mg (52%); eluent: EtOH.
N-(4-tert-Butylphenyl-2-ethyl-3-(4-fluorophenyl)pyrrole (5eg)
Yield: 174 mg (54%); eluent: light petroleum–CH2Cl2 (70:30).
IR (neat): 2963 (m), 2932 (m), 1967 (w), 1686 (m), 1601 (m), 1508
(s), 1381 (m), 1261 (vs), 1223 (s), 1161 (m), 1096 (vs), 1015 (vs),
802 (vs), 690 cm–1 (s).
1H NMR (600 MHz, CDCl3): d = 0.77 (t, J = 7.2 Hz, 3 H), 1.11–
1.81 (m, 10 H), 1.95 (q, J = 7.2 Hz, 2 H), 3.85–3.91 (m, 1 H), 5.56
(d, J = 5.4 Hz, 1 H), 6.62 (d, J = 5.2 Hz, 1 H), 6.96 (t, J = 8.4 Hz, 2
H), 7.40 (t, J = 4.2 Hz, 2 H).
1H NMR (200 MHz, CDCl3): d = 1.26 (t, J = 7.4 Hz, 3 H), 1.37 (s,
9 H), 2.71 (q, J = 7.4 Hz, 2 H), 6.31 (d, J = 2.8 Hz, 1 H), 6.72 (d,
J = 2.8 Hz, 1 H), 7.01–7.48 (m, 8 H).
13C NMR (50 MHz, CDCl3): d = 14.7, 18.0, 31.4, 34.7, 108.5,
115.1, 121.6, 126.0, 126.0, 126.1, 129.4, 131.8, 133.5, 137.8, 150.6,
163.6.
13C NMR (150 MHz, CDCl3): d = 9.1, 25.4, 25.5, 31.6, 32.1, 50.5,
58.2, 113.0, 115.1, 128.3, 128.6, 136.0, 161.9, 179.0.
MS (DEI): m/z (%) = 321 (100, [M+]), 306 (36, [M+ – Me]), 250
(12, [M+ – C5H11]), 132 (4, [C10H12+]), 57 (6, [C4H9 ]).
+
MS (DEI): m/z (%) = 287 (100, [M+]), 258 (50, [M+ – Et]), 204 (3,
HRMS: m/z calcd for C22H24FN: 321.18928; found: 321.18829,
D = 0.99 mmu.
[M+ – C6H11]), 176 (9, [M+ – C6H11 – C2H4]), 109 (4, [M+ – C6H11
C6H4F]).
–
N-sec-Butyl-3-ethyl-3-(4-fluorophenyl)-1,3-dihydropyrrol-2-
one (4eh)
Yield: 108 mg (41%); eluent: EtOH.
HRMS: m/z calcd for C18H22FNO: 287.16854; found: 287.16825,
D = 0.29 mmu.
N-Cyclohexyl-2-ethyl-3-(4-fluorophenyl)pyrrole (5ed)
Yield: 92 mg (34%); eluent: light petroleum–CH2Cl2 (70:30).
IR (neat): 2967 (m), 2932 (w), 1694 (s), 1508 (s), 1381 (m), 1258
(vs), 1161 (m), 1015 (vs), 791 (vs), 694 cm–1 (m).
1H NMR (600 MHz, CDCl3): d = 1.21 (t, J = 7.2 Hz, 3 H), 1.40–
2.04 (m, 10 H), 2.70 (q, J = 7.2 Hz, 2 H), 3.80–3.84 (m, 1 H), 6.22
(d, J = 3.0 Hz, 1 H), 6.69 (d, J = 3.0 Hz, 1 H), 7.03 (t, J = 8.4 Hz, 2
H), 7.31 (dd, J = 3.0, 5.4 Hz, 2 H).
13C NMR (150 MHz, CDCl3): d = 14.6, 16.7, 24.5, 25.1, 34.0, 54.0,
106.7, 113.9, 114.8, 118.9, 128.4, 129.0, 132.8, 160.0.
1H NMR (200 MHz, CDCl3): d = 0.70–0.89 (m, 6 H), 1.12 (d,
J = 6.8 Hz, 1.5 H), 1.17 (d, J = 6.8 Hz, 1.5 H), 1.41–1.61 (m, 2 H),
1.96 (q, J = 7.4 Hz, 1 H), 1.96 (q, J = 7.4 Hz, 1 H), 4.03 (m, 1 H),
5.57 (d, J = 3.1 Hz, 0.5 H), 5.60 (d, J = 3.1 Hz, 0.5 H), 6.57 (d,
J = 5.0 Hz, 1 H), 6.95 (t, J = 8.8 Hz, 2 H), 7.37–7.45 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 9.0, 9.2, 10.6, 10.7, 19.4, 19.6,
28.4, 31.3, 31.4, 48.4, 58.2, 113.1, 113.3, 114.8, 115.3, 128.1,
128.2, 128.3, 135.9, 159.3, 164.2, 179.2.
MS (DEI): m/z (%) = 271 (100, [M+]), 256 (25, [M+ – Me]), 242 (4,
[M+ – Et]), 188 (7, [M+ – C6H11]), 83 (3, [C6H11+]).
MS (DEI): m/z (%) = 261 (100, [M+]), 246 (3, [M+ – Me]), 232 (96,
HRMS: m/z calcd for C18H22FN: 271.17363; found: 271.17367,
D = 0.04 mmu.
[M+ – Et]), 204 (20, [M+ – C4H9]), 190 (4, [M+ – C5H11]), 176 (52,
+
[M+ – C6H13]), 57 (9, [C4H9 ]), 29 (18, [Et+]).
N-Butyl-3-ethyl-3-(4-fluorophenyl)-1,3-dihydropyrrol-2-one
(4ef)
Yield: 144 mg (55%); eluent: EtOH.
HRMS: m/z calcd for C16H20FNO: 261.15289; found: 261.15237,
D = 0.52 mmu.
N-sec-Butyl-2-ethyl-3-(4-fluorophenyl)pyrrole (5eh)
Yield: 128 mg (52%); eluent: light petroleum–CH2Cl2 (70:30).
IR (neat): 2963 (w), 2932 (w), 2874 (vw), 1967 (vw), 1686 (s), 1601
(m), 1508 (vs), 1369 (m), 1261 (w), 1223 (vs), 1161 (m), 833 (vs),
691 cm–1 (w).
1H NMR (600 MHz, CDCl3): d = 0.77 (t, J = 7.2 Hz, 3 H), 0.78 (t,
J = 7.2 Hz, 3 H), 0.89 (t, J = 7.2 Hz, 3 H), 1.28 (q, J = 7.2 Hz, 2 H),
1.48–1.55 (m, 2 H), 1.95 (q, J = 7.2 Hz, 2 H), 3.69 (q, J = 7.2 Hz, 2
H), 5.58 (d, J = 4.8 Hz, 1 H), 6.53 (d, J = 4.8 Hz, 1 H), 6.96 (t,
J = 9.0 Hz, 1 H), 7.42 (dd, J = 5.4 Hz, J = 8.4 Hz, 2 H).
1H NMR (200 MHz, CDCl3): d = 0.84 (t, J = 7.4 Hz, 3 H), 1.19 (t,
J = 7.4 Hz, 3 H), 1.41 (d, J = 6.6 Hz, 3 H), 1.77 (q, J = 7.6 Hz, 2 H),
2.67 (q, J = 7.6 Hz, 2 H), 3.99 (q, J = 6.8 Hz, 1 H), 6.21 (d, J = 3.0
Hz, 1 H), 6.63 (d, J = 3.0 Hz, 1 H), 6.96–7.05 (m, 2 H), 7.23–7.32
(m, 2 H).
13C NMR (50 MHz, CDCl3): d = 11.0, 15.5, 17.6, 22.3, 31.1, 52.6,
107.9, 114.9, 119.7, 129.3, 129.4, 130.6, 133.9, 160.9.
MS (DEI): m/z (%) = 245 (100, [M+]), 230 (32, [M+ – Me]), 216
(13, [M+ – Et]), 188 (6, [M+ – C4H9]), 174 (20, [M+ – C5H11]), 95 (3,
[C6H4F]).
13C NMR (150 MHz, CDCl3): d = 9.2, 13.6, 19.9, 30.9, 31.6, 41.8,
57.8, 112.8, 115.2, 128.4, 131.7, 135.9, 162.7, 179.5.
MS (DEI): m/z (%) = 261 (100, [M+]), 232 (49, [M+ – Et]), 218 (6,
[M+ – C3H7]), 204 (4, [M+ –C4H9]), 190 (16, [M+ – C5H11]).
HRMS: m/z calcd for C16H20FN: 245.15798; found: 245.15786,
D = 0.12 mmu.
HRMS: m/z calcd for C16H20FNO: 261.15289; found: 261.15165,
D = 1.24 mmu.
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

PAPER
One-Pot g-Lactam Synthesis
3987
N-Benzyl-3-ethyl-3-furyl-1,3-dihydropyrrol-2-one (4fa)
Yield: 151 mg (57%); eluent: EtOH.
HRMS: m/z calcd for C17H17NO2: 267.12593; found: 267.12564,
D = 0.29 mmu.
IR (neat): 2970 (w), 2932 (w), 2878 (w), 2361 (w), 2021 (m), 1952
(m), 1667 (s), 1605 (m), 1497 (s), 1454 (s), 1354 (s), 1258 (m), 1076
(m), 1011 (s), 729 (vs), 689 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.84 (t, J = 7.4 Hz, 1.5 H), 1.16 (t,
J = 7.6 Hz, 1.5 H), 2.06 (q, J = 7.4 Hz, 1 H), 2.23 (q, J = 7.6 Hz, 1
H), 4.52 (AB spin system, J = 7.8, 36.6 Hz, 2 H), 5.46 (d, J = 2.8
Hz, 1 H), 6.19 (dd, J = 0.8, 3.2 Hz, 1 H), 6.30 (dd, J = 1.8, 3.3 Hz,
1 H), 6.41 (d, J = 2.8 Hz, 1 H), 7.21–7.32 (m, 5 H), 7.35 (dd, J = 0.8,
1.8 Hz, 1 H).
2-Ethyl-3-furyl-N-p-tolylpyrrole (5fc)
Yield: 139 mg (55%); eluent: light petroleum–CH2Cl2 (60:40).
1H NMR (200 MHz, CDCl3): d = 1.05 (t, J = 7.4 Hz, 3 H), 2.42 (s,
3 H), 2.77 (q, J = 7.4 Hz, 2 H), 6.27 (dd, J = 0.8, 3.2 Hz, 1 H), 6.43
(dd, J = 1.8, 3.4 Hz, 1 H), 6.46 (d, J = 2.8 Hz, 1 H), 6.67 (d, J = 3.0
Hz, 1 H), 7.18–7.28 (m, 4 H), 7.39 (dd, J = 0.8, 1.8 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 14.1, 18.3, 20.7, 102.4, 106.3,
110.6, 112.4, 121.4, 121.4, 126.1, 129.3, 132.0, 137.2, 139.6, 151.6.
13C NMR (50 MHz, CDCl3): d = 8.5, 9.5, 28.2, 29.3, 43.2, 43.4,
55.2, 58.0, 105.6, 109.8, 111.3, 126.0, 127.1, 127.4, 128.4, 131.5,
141.8, 152.2, 177.2.
MS (DEI): m/z (%) = 251 (100, [M+]), 236 (98, [M+ – Me]), 222
+
(17, [M+ – Et]), 208 (17, [M+ – C3H7]), 91 (8, [C7H7 ]).
HRMS: m/z calcd for C17H17NO: 251.13101; found: 251.13079,
D = 0.22 mmu.
MS (DEI): m/z (%) = 267 (100, [M+]), 238 (39, [M+ – Et]), 200 (11,
+
[M+ – C4H3O]), 176 (6, [M+ – C7H7]), 91 (52, [C7H7 ]).
N-Cyclohexyl-3-ethyl-3-furyl-1,3-dihydropyrrol-2-one (4fd)
Yield: 155 mg (60%); eluent: EtOH.
HRMS: m/z calcd for C17H17NO2: 267.12593; found: 267.12572,
D = 0.21 mmu.
IR (neat): 2932 (m), 2855 (w), 1967 (w), 1694 (s), 1605 (m), 1450
(m), 1381 (m), 1254 (m), 1011 (s), 730 (vs), 694 cm–1 (s).
N-Benzyl-2-ethyl-3-furylpyrrole (5fa)
Yield: 109 mg (43%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.79 (t, J = 7.4 Hz, 3 H), 1.12–
1.80 (m, 10 H), 2.00 (q, J = 7.4 Hz, 2 H), 3.87–3.94 (m, 1 H), 5.43
(d, J = 5.0 Hz, 1 H), 6.15 (dd, J = 0.8, 3.2 Hz, 1 H), 6.26 (dd,
J = 2.0, 3.2 Hz, 1 H), 6.59 (d, J = 5.0 Hz, 1 H), 7.31 (dd, J = 1.0, 1.8
Hz, 1 H).
1H NMR (200 MHz, CDCl3): d = 1.11 (t, J = 7.6 Hz, 3 H), 2.78 (q,
J = 7.6 Hz, 2 H), 5.08 (s, 2 H), 6.24 (dd, J = 0.8, 3.2 Hz, 1 H), 6.43
(d, J = 2.8 Hz, 1 H), 6.43 (dd, J = 0.8, 3.2 Hz, 1 H), 6.60 (d, J = 2.8
Hz, 1 H), 7.03–7.33 (m, 5 H), 7.38 (dd, J = 0.8, 1.8 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 14.0, 18.1, 49.9, 102.0, 105.8,
110.6, 120.6, 126.0, 127.1, 128.4, 131.4, 138.0, 139.4, 151.8.
13C NMR (50 MHz, CDCl3): d = 8.6, 25.4, 28.5, 31.8, 32.1, 50.5,
55.9, 105.7, 110.1, 111.2, 129.4, 142.0, 152.9, 177.0.
MS (DEI): m/z (%) = 251 (100, [M+]), 236 (38, [M+ – Me]), 160 (7,
MS (DEI): m/z (%) = 259 (100, [M+]), 230 (44, [M+ – Et]), 177 (21,
[M+ – C6H10]), 148 (62, [M+ – C6H11 – C2H4]), 120 (7, [M+ – C6H11
– C2H4 – CO]).
+
[M+ – C7H7]), 91 (73, [C7H7 ]).
HRMS: m/z calcd for C17H17NO: 251.13101; found: 251.13106,
D = 0.05 mmu.
HRMS: m/z calcd for C16H21NO2: 259.15723; found: 259.15696,
D = 0.27 mmu.
2-Ethyl-3-furyl-N-phenylpyrrole (5fb)
Yield: 111 mg (47%); eluent: light petroleum–CH2Cl2 (70:30).
N-Cyclohexyl-2-ethyl-3-furylpyrrole (5fd)
Yield: 90 mg (37%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 1.06 (t, J = 7.4 Hz, 3 H), 2.80 (q,
J = 7.4 Hz, 2 H), 6.29 (dd, J = 0.8, 3.4 Hz, 1 H), 6.39 (dd,
J = 1.8, 3.2 Hz, 1 H), 6.49 (d, J = 3.0 Hz, 1 H), 6.70 (d, J = 3.0 Hz,
1 H), 7.35 (dd, J = 0.8, 1.8 Hz, 1 H), 7.31–7.47 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 14.4, 18.6, 102.9, 106.8, 110.9,
113.2, 121.7, 126.6, 127.5, 129.1, 132.3, 140.0, 151.8.
1H NMR (200 MHz, CDCl3): d = 1.20 (t, J = 7.4 Hz, 3 H), 1.39–
2.02 (m, 10 H), 2.84 (q, J = 7.4 Hz, 2 H), 3.80–3.85 (m, 1 H), 6.18
(dd, J = 0.8, 3.4 Hz, 1 H), 6.35 (d, J = 3.0 Hz, 1 H), 6.39 (dd,
J = 1.8, 3.4 Hz, 1 H), 6.65 (d, J = 3.0 Hz, 1 H), 7.35 (dd, J = 0.8, 1.8
Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 14.9, 18.3, 25.5, 26.1, 34.8, 54.8,
102.2, 105.9, 110.8, 111.2, 116.1, 130.8, 139.6, 152.3.
MS (DEI): m/z (%) = 237 (100, [M+]), 222 (70, [M+ – Me]), 208 (2,
+
[M+ – Et]), 91 (3, [C7H7 ]), 77 (5, [Ph+]).
MS (DEI): m/z (%) = 243 (100, [M+]), 228 (35, [M+ – Me]), 214 (5,
HRMS: m/z calcd for C16H15NO: 237.11536; found: 237.11537
(M+), D = 0.01 mmu.
[M+ – Et]), 161 (9, [M+ – C6H10]), 146 (30, [M+ – C6H11 – Me]).
HRMS: m/z calcd for C16H21NO: 243.16231; found: 243.16212,
D = 0.19 mmu.
3-Ethyl-3-furyl-N-p-tolyl-1,3-dihydropyrrol-2-one (4fc)
Yield: 108 mg (40%); eluent: EtOH.
N-Butyl-3-ethyl-3-furyl-1,3-dihydropyrrol-2-one (4ff)
Yield: 140 mg (60%); eluent: EtOH.
IR (neat): 2963 (w), 2928 (m), 2859 (w), 1717 (vs), 1612 (m), 1512
(vs), 1458 (m), 1385 (vs), 1277 (s), 1207 (s), 1072 (s), 1015 (s), 864
(s), 813 (vs), 736 (vs), 706 cm–1 (s).
1H NMR (200 MHz, CDCl3): d = 0.89 (t, J = 7.4 Hz, 3 H), 2.11 (q,
J = 7.4 Hz, 2 H), 2.32 (s, 3 H), 5.63 (d, J = 5.0 Hz, 1 H), 6.24 (dd,
J = 0.8, 3.4 Hz, 1 H), 6.30 (dd, J = 1.8, 3.2 Hz, 1 H), 6.93 (d, J = 5.0
Hz, 1 H), 7.15–7.36 (m, 4 H), 7.50 (dd, J = 3.6, 5.6 Hz, 1 H).
IR (neat): 2959 (m), 2920 (m), 2851 (m), 1701 (w), 1462 (m), 1377
(w), 1258 (vs), 1080 (s), 1015 (vs), 864 (m), 794 (vs), 729 cm–1 (m).
1H NMR (200 MHz, CDCl3): d = 0.85 (t, J = 7.2 Hz, 3 H), 0.89 (t,
J = 7.2 Hz, 3 H), 1.24–1.29 (m, 2 H), 1.49–1.55 (m, 2 H), 2.02 (q,
J = 7.2 Hz, 2 H), 3.35–3.42 (m, 2 H), 5.45 (d, J = 5.0 Hz, 1 H), 6.15
(dd, J = 0.8, 3.2 Hz, 1 H), 6.26 (dd, J = 1.8, 3.2 Hz, 1 H), 6.49 (d,
J = 5.0 Hz, 1 H), 7.31 (dd, J = 0.8, 1.8 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 8.7, 13.6, 19.8, 28.5, 30.9, 41.7,
55.6, 105.7, 110.1, 111.2, 132.3, 142.0, 152.8, 177.5.
MS (DEI): m/z (%) = 233 (93, [M+]), 204 (86, [M+ – Et]), 190 (11,
[M+ – C3H7]), 162 (39, [M+ – C3H7 – CO]), 151 (100, [M+ – C4H3O
– Me]), 148 (26, [M+ – C6H13]).
13C NMR (50 MHz, CDCl3): d = 8.8, 20.9, 30.4, 56.2, 106.1, 110.2,
112.1, 121.5, 128.8, 129.6, 132.5, 135.6, 142.2, 152.4, 176.0.
MS (DEI): m/z (%) = 267 (80, [M+]), 252 (2, [M+ – Me]), 238 (100,
[M+ – Et]), 223 (7, [M+ – C3H8]), 210 (17, [M+ – CO – Et]), 91 (23,
+
[C7H7 ]).
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

3988
T. Biletzki, W. Imhof
PAPER
HRMS: m/z calcd for C14H19NO2: 233.14158; found: 233.14188,
D = 0.30 mmu.
13C NMR (50 MHz, CDCl3): d = 8.6, 8.9, 10.6, 10.8, 19.4, 19.7,
28.3, 28.4, 28.6, 48.4, 48.6, 56.0, 56.1, 105.7, 110.1, 111.5, 111.7,
128.7, 128.9, 142.0, 153.0, 177.4.
N-Butyl-2-ethyl-3-furylpyrrole (5ff)
Yield: 79 mg (36%); eluent: light petroleum–CH2Cl2 (80:20).
MS (DEI): m/z (%) = 233 (100, [M+]), 204 (75, [M+ – Et]), 190 (3,
[M+ – C3H7]), 176 (15, [M+ – C4H9]), 148 (24, [M+ – C4H9 – CO]),
1H NMR (200 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H), 1.21 (t,
J = 7.4 Hz, 3 H), 1.34–1.43 (m, 2 H), 1.70–1.78 (m, 2 H), 2.82 (q,
J = 7.4 Hz, 2 H), 3.82 (t, J = 7.4 Hz, 2 H), 6.19 (dd, J = 0.8, 3.4 Hz,
1 H), 6.33 (d, J = 3.0 Hz, 1 H), 6.40 (dd, J = 1.8, 3.4 Hz, 1 H), 6.55
(d, J = 3.0 Hz, 1 H), 7.36 (dd, J = 0.8, 1.8 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 13.7, 14.5, 18.3, 20.0, 33.7, 46.2,
102.1, 105.6, 110.8, 111.8, 119.6, 131.2, 139.6, 152.3.
MS (DEI): m/z (%) = 217 (100, [M+]), 202 (72, [M+ – Me]), 188
(16, [M+ – Et]), 174 (7, [M+ – C3H7]), 160 (18, [M+ – C4H9]), 146
(14, [M+ – C5H12]).
57 (3, [C4H9 ]).
+
HRMS: m/z calcd for C14H19NO2: 233.14158; found: 233.14174,
D = 0.16 mmu.
N-sec-Butyl-2-ethyl-3-furylpyrrole (5fh)
Yield: 82 mg (38%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.84 (t, J = 7.4 Hz, 3 H), 1.19 (t,
J = 7.4 Hz, 3 H), 1.40 (d, J = 6.8 Hz, 2 H), 1.76 (t, J = 7.4 Hz, 3 H),
2.83 (q, J = 7.4 Hz, 2 H), 4.01 (q, J = 7.0 Hz, 1 H), 6.18 (dd, J = 0.8,
3.4 Hz, 1 H), 6.37 (d, J = 3.0 Hz, 1 H), 6.39 (dd, J = 1.8, 3.4 Hz, 1
H), 6.60 (d, J = 3.0 Hz, 1 H), 7.35 (dd, J = 0.8, 1.8 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 10.9, 14.8, 18.2, 22.3, 30.9, 52.4,
102.1, 106.2, 110.8, 111.1, 115.3, 131.3, 139.6, 152.4.
HRMS: m/z calcd for C14H19NO: 217.14666; found: 217.14699,
D = 0.33 mmu.
N-(4-tert-Butylphenyl)-3-ethyl-3-furyl-1,3-dihydropyrrol-2-one
(4fg)
Yield: 131 mg (42%); eluent: light petroleum–CH2Cl2 (70:30).
MS (DEI): m/z (%) = 217 (100, [M+]), 202 (50, [M+ – Me]), 188
+
(10, [M+ – Et]), 146 (31, [M+ - C5H11]), 57 (6, [C4H9 ]).
HRMS: m/z calcd for C14H19NO: 217.14666; found: 217.14709,
D = 0.43 mmu.
IR (neat): 2959 (m), 2928 (m), 2870 (w), 1717 (vs), 1609 (m), 1516
(s), 1462 (m), 1385 (s), 1269 (m), 1211 (s), 1072 (m), 1015 (m), 864
(m), 833 (s), 729 (vs), 702 cm–1 (s).
1H NMR (200 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H), 1.30 (s,
9 H), 2.12 (q, J = 7.4 Hz, 2 H), 5.64 (d, J = 5.0 Hz, 1 H), 6.25 (dd,
J = 0.8, 3.2 Hz, 1 H), 6.31 (dd, J = 1.8, 3.2 Hz, 1 H), 6.95 (d, J = 5.0
Hz, 1 H), 7.38 (s, 4 H), 7.36 (dd, J = 0.8, 2.0 Hz, 1 H).
N-Benzyl-3-ethyl-3-(3-pyridyl)-1,3-dihydropyrrol-2-one (4ga)
Yield: 163 mg (59%); eluent: EtOH.
IR (neat): 2967 (w), 2932 (w), 2874 (w), 1670 (m), 1420 (m), 1261
(m), 1026 (m), 806 (m), 748 (s), 698 cm–1 (vs).
1H NMR (400 MHz, CDCl3): d = 0.81 (t, J = 7.6 Hz, 3 H), 2.05 (q,
J = 7.6 Hz, 2 H), 4.59 (AB spin system, J = 15.2, 53.9 Hz, 2 H),
5.64 (d, J = 5.2 Hz, 1 H), 6.49 (d, J = 5.2 Hz, 1 H), 7.17–7.30 (m, 5
H), 7.91–8.60 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 9.2, 31.5, 45.8, 56.7, 112.0,
123.5, 127.8, 128.3, 128.7, 131.9, 134.5, 135.7, 136.4, 148.3, 148.4,
178.9.
13C NMR (50 MHz, CDCl3): d = 8.7, 29.7, 31.3, 34.5, 56.3, 106.1,
110.2, 112.1, 121.1, 126.0, 132.4, 142.2, 148.8, 152.4, 176.0.
MS (DEI): m/z (%) = 309 (100, [M+]), 294 (12, [M+ – Me]), 280
(46, [M+ – Et]), 266 (7, [M+ – C3H7]), 252 (17, [M+ – CO – Et]), 133
+
(4, [C10H13+]), 57 (14, [C4H9 ]).
HRMS: m/z calcd for C20H23NO2: 309.17288; found: 309.17227,
D = 0.61 mmu.
MS (DEI): m/z (%) = 278 (25, [M+]), 249 (25, [M+ – Et]), 221 (2,
+
[M+ – Et – CO]), 91 (100, [C7H7 ]), 77 (7, [Ph+]).
N-(4-tert-Butylphenyl-2-ethyl-3-furylpyrrole (5fg)
Yield: 121 mg (41%); eluent: light petroleum–CH2Cl2 (70:30).
HRMS: m/z calcd for C18H18N2O: 278.14191; found: 278.14185,
D = 0.06 mmu.
1H NMR (200 MHz, CDCl3): d = 1.08 (t, J = 7.4 Hz, 3 H), 1.38 (s,
9 H), 2.79 (q, J = 7.4 Hz, 2 H), 6.28 (dd, J = 0.8, 3.2 Hz, 1 H), 6.44
(dd, J = 1.8, 3.2 Hz, 1 H), 6.48 (d, J = 3.0 Hz, 1 H), 6.69 (d, J = 3.0
Hz, 1 H), 7.25 (d, J = 8.8 Hz, 2 H), 7.40 (dd, J = 0.8, 1.8 Hz, 1 H),
7.47 (d, J = 8.8 Hz, 2 H).
13C NMR (50 MHz, CDCl3): d = 14.5, 18.6, 31.4, 34.7, 102.7,
106.6, 110.9, 112.8, 121.7, 126.0, 126.1, 132.4, 137.4, 139.9, 150.6,
151.9.
N-Benzyl-2-ethyl-3-(3-pyridyl)pyrrole (5ga)
Yield: 91 mg (35%); eluent: light petroleum–CH2Cl2 (40:60).
1H NMR (400 MHz, CDCl3): d = 1.15 (t, J = 7.6 Hz, 3 H), 2.65 (q,
J = 7.6 Hz, 2 H), 5.10 (s, 2 H), 6.31 (d, J = 2.8 Hz, 1 H), 6.64 (d,
J = 2.8 Hz, 1 H), 7.03–7.33 (m, 5 H), 7.25–8.67 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 15.1, 17.9, 50.5, 107.9, 121.3,
126.4, 127.6, 127.9, 128.3, 128.8, 132.0, 133.6, 134.7, 138.1, 146.4,
148.9.
MS (DEI): m/z (%) = 293 (100, [M+]), 278 (71, [M+ – Me]), 222
(15, [M+ – C5H11]).
MS (DEI): m/z (%) = 262 (100, [M+]), 247 (50, [M+ – Me]), 234 (3,
HRMS: m/z calcd for C20H23NO: 293.17796; 293.17873, D = 0.77
mmu.
+
[M+ – C2H4]), 91 (47, [C7H7 ]).
HRMS: m/z calcd for C18H18N2: 262.14700; found: 262.14649,
D = 0.51 mmu.
N-sec-Butyl-3-ethyl-3-furyl-1,3-dihydropyrrol-2-one (4fh)
Yield: 134 mg (57%); eluent: EtOH.
3-Ethyl-3-(3-pyridyl)-N-phenyl-1,3-dihydropyrrol-2-one (4gb)
Yield: 146 mg (55%); eluent: EtOH.
IR (neat): 2967 (w), 2936 (w), 2878 (vw), 2045 (w), 1971 (w), 1695
(vs), 1609 (m), 1462 (m), 1377 (s), 1254 (s), 1219 (s), 1011 (s), 802
(m), 735 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.77–0.86 (m, 6 H), 1.15 (d,
J = 2.1 Hz, 1.5 H), 1.19 (d, J = 2.1 Hz, 1.5 H), 1.53 (m, 2 H), 2.02
(q, J = 7.4 Hz, 2 H), 4.07 (m, 1 H), 5.46 (d, J = 2.4 Hz, 0.5 H), 5.47
(d, J = 2.4 Hz, 0.5 H), 6.14 (m, 1 H), 6.26 (m, 1 H), 6.54 (d, J = 5.0
Hz, 1 H), 7.13 (t, J = 0.8 Hz, 1 H).
IR (neat): 2963 (vw), 2928 (vw), 1705 (w), 1597 (m), 1497 (s), 1385
(m), 1026 (m), 806 (m), 752 (s), 691 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.89 (t, J = 7.4 Hz, 3 H), 2.11 (q,
J = 7.4 Hz, 2 H), 5.84 (d, J = 5.2 Hz, 1 H), 7.04 (d, J = 5.2 Hz, 1 H),
7.28–7.47 (m, 5 H), 7.28–7.47 (m, 1 H), 7.96 (dt, J = 2.0, 8.0 Hz, 1
H), 8.44–8.51 (m, 1 H), 8.63–8.70 (m, 1 H).
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

PAPER
One-Pot g-Lactam Synthesis
3989
13C NMR (50 MHz, CDCl3): d = 9.1, 31.9, 57.5, 112.7, 121.5,
123.5, 126.0, 129.2, 132.3, 134.6, 136.7, 140.2, 148.2, 148.5, 177.5.
13C NMR (50 MHz, CDCl3): d = 8.57, 24.86, 25.03, 31.3, 31.7,
50.3, 56.7, 111.3, 123.0, 129.1, 134.1, 135.7, 147.8, 178.0.
MS (DEI): m/z (%) = 264 (91, [M+]), 235 (100 [M+ – Et]), 77 (19,
MS (DEI): m/z (%) = 270 (100, [M+]), 255 (2, [M+ – Me]), 241 (48,
[Ph+]).
[M+ – Et]), 188 (17, [M+ – C6H10]), 84 (10, [C6H12+]).
HRMS: m/z calcd for C17H16N2O: 264.12626; found: 264.12627,
D = 0.01 mmu.
HRMS: m/z calcd for C17H22N2O: 270.17321; found: 270.17314,
D = 0.07 mmu.
2-Ethyl-N-phenyl-3-(3-pyridyl)pyrrole (5gb)
Yield: 111 mg (45%); eluent: light petroleum–CH2Cl2 (50:50).
N-Cyclohexyl-2-ethyl-3-(3-pyridyl)pyrrole (5gd)
Yield: 52 mg (20%); eluent: CH2Cl2.
1H NMR (200 MHz, CDCl3): d = 0.86 (t, J = 7.4 Hz, 3 H), 2.72 (q,
J = 7.4 Hz, 2 H), 6.37 (d, J = 3.0 Hz, 1 H), 6.77 (d, J = 3.0 Hz, 1 H),
7.32–7.53 (m, 5 H), 7.70 (m, 2 H), 8.38–8.45 (m, 1 H), 8.62–8.67
(m, 1 H).
13C NMR (50 MHz, CDCl3): d = 14.1, 18.1, 108.6, 122.2, 126.6,
127.7, 128.8, 129.2, 129.8, 130.9, 132.5, 135.0, 140.1, 146.6, 149.1.
1H NMR (200 MHz, CDCl3): d = 1.12 (t, J = 7.6 Hz, 3 H), 1.30–
2.03 (m, 10 H), 2.70 (q, J = 7.6 Hz, 2 H), 3.78–3.85 (m, 1 H), 6.25
(d, J = 3.0 Hz, 1 H), 6.72 (d, J = 3.0 Hz, 1 H), 7.20–7.26 (m, 1 H),
7.63 (dt, J = 2.0, 8.0 Hz, 1 H), 8.35–8.42 (m, 1 H), 8.60–8.65 (m, 1
H).
13C NMR (50 MHz, CDCl3): d = 15.6, 17.8, 25.4, 26.1, 34.9, 55.1,
107.6, 116.5, 117.1, 123.2, 128.7, 133.5, 134.9, 146.2, 149.0.
MS (DEI): m/z (%) = 248 (100, [M+]), 233 (47, [M+ – Me]), 77 (7,
[C6H7 ]).
MS (DEI): m/z (%) = 254 (100, [M+]), 239 (13, [M+ – Me]), 156
+
(10, [M+ – C7H14]), 29 (18, [Et+]).
HRMS: m/z calcd for C17H16N2: 248.13135; found: 248.13104,
D = 0.31 mmu.
HRMS: m/z calcd for C17H22N2: 254.17830; found: 254.17875,
D = 0.45 mmu.
3-Ethyl-3-(3-pyridyl)-N-p-tolyl-1,3-dihydropyrrol-2-one (4gc)
Yield: 98 mg (35%); eluent: EtOH.
N-Butyl-3-ethyl-3-(3-pyridyl)-1,3-dihydropyrrol-2-one (4gf)
Yield: 133 mg (54%); eluent: EtOH.
IR (neat): 2955 (w), 2920 (m), 2851 (w), 1709 (s), 1512 (vs), 1385
(s), 1026 (s), 810 (vs), 714 cm–1 (vs).
IR (neat): 2959 (m), 2932 (m), 2874 (w), 1694 (vs), 1670 (vs), 1655
(vs), 1547 (m), 1416 (m), 1373 (m), 1261 (m), 1026 (m), 806 (s),
714 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.79 (t, J = 7.4 Hz, 1.5 H), 0.88 (t,
J = 7.2 Hz, 1.5 H), 0.89 (t, J = 7.2 Hz, 1.5 H), 1.12 (t, J = 7.6 Hz,
1.5 H), 1.24–1.31 (m, 2 H), 1.44–1.50 (m, 2 H), 1.98 (q, J = 7.4 Hz,
1 H), 2.16 (q, J = 7.6 Hz, 1 H), 3.18–3.24 (m, 1 H), 3.34–3.42 (m, 1
H), 5.63 (d, J = 5.0 Hz, 1 H), 6.57 (d, J = 5.0 Hz, 1 H), 7.22 (q,
J = 4.8 Hz, 1 H), 7.89 (dt, J = 2.0, 8.0 Hz, 1 H), 8.39–8.43 (m, 1 H),
8.52–8.59 (m, 1 H).
13C NMR (50 MHz, CDCl3): d = 9.1, 9.9, 13.6, 13.7, 19.8, 20.0,
29.8, 30.9, 31.4, 31.7, 39.2, 41.8, 56.8, 111.6, 123.5, 132.4, 134.6,
136.5, 148.2, 178.9.
MS (DEI): m/z (%) = 245 (100, [M+ + 1]), 244 (68, [M+]), 215 (41,
[M+ – Et]), 201 (4, [M+ – C3H7]), 173 (23, [M+ – C5H11]), 27 (60,
[Et+]).
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 7.4 Hz, 3 H), 2.05–
2.14 (m, 2 H), 2.32 (s, 3 H), 5.82 (d, J = 5.0 Hz, 1 H), 6.99 (d,
J = 5.0 Hz, 1 H), 7.17 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.4 Hz, 2 H),
7.51–7.60 (m, 1 H), 7.96 (dt, J = 2.0, 8.4 Hz, 1 H), 8.45–8.51 (m, 1
H), 8.62–8.69 (m, 1 H).
13C NMR (150 MHz, CDCl3): d = 9.2, 20.9, 31.9, 57.4, 112.5,
121.6, 123.5, 129.7, 132.1, 132.6, 134.2, 134.6, 135.9, 148.3, 148.5,
177.5.
MS (DEI): m/z (%) = 278 (100, [M+]), 249 (87, [M+ – Et]), 221 (15,
+
[M+ – Et – CO]), 91 (10, [C7H7 ]).
HRMS: m/z calcd for C18H18N2O: 278.14191; found: 278.14141,
D = 0.50 mmu.
2-Ethyl-3-(3-pyridyl)-N-p-tolylpyrrole (5gc)
Yield: 142 mg (54%); eluent: CH2Cl2.
HRMS: m/z calcd for C15H20N2O: 244.15756; found: 244.15759,
D = 0.03 mmu.
1H NMR (200 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H), 2.41 (s,
3 H), 2.70 (q, J = 7.4 Hz, 2 H), 6.35 (d, J = 3.0 Hz, 1 H), 6.73 (d,
J = 3.0 Hz, 1 H), 7.03–7.38 (m, 4 H), 7.72 (dt, J = 2.0, 8.0 Hz, 1 H),
8.34–8.71 (m, 3 H).
13C NMR (50 MHz, CDCl3): d = 14.7, 18.1, 21.1, 108.3, 118.6,
120.8, 122.3, 123.3, 126.5, 129.7, 130.3, 132.6, 134.9, 137.7, 146.5,
149.1.
N-Butyl-2-ethyl-3-(3-pyridyl)pyrrole (5gf)
Yield: 72 mg (32%); eluent: light petroleum–CH2Cl2 (70:30).
1H NMR (200 MHz, CDCl3): d = 0.95 (t, J = 7.2 Hz, 3 H), 1.20 (t,
J = 7.4 Hz, 3 H), 1.40 (q, J = 7.2 Hz, 2 H), 1.68–1.75 (m, 2 H), 2.69
(q, J = 7.4 Hz, 2 H), 3.83 (t, J = 7.2 Hz, 2 H), 6.22 (d, J = 2.8 Hz, 1
H), 6.63 (d, J = 2.8 Hz, 1 H), 7.50 (dd, J = 3.2, 5.8 Hz, 1 H), 7.64
(dt, J = 2.0, 8.0 Hz, 1 H), 8.34–8.41 (m, 1 H), 8.56–8.63 (m, 1 H).
MS (DEI): m/z (%) = 262 (100, [M+]), 247 (53, [M+ – Me]), 91 (4,
+
[C7H7 ]).
13C NMR (50 MHz, CDCl3): d = 13.8, 15.2, 17.8, 20.1, 33.7, 46.4,
107.4, 119.9, 123.1, 123.6, 128.8, 130.9, 134.8, 146.0, 148.8.
HRMS: m/z calcd for C18H18N2: 262.14700; found: 262.14701,
D = 0.01 mmu.
MS (DEI): m/z (%) = 228 (100, [M+]), 213 (19, [M+ – Me]), 185 (7,
N-Cyclohexyl-3-ethyl-3-(3-pyridyl)-1,3-dihydropyrrol-2-one
(4gd)
Yield: 146 mg (54%); eluent: EtOH.
[M+ – C3H7]), 157 (8, [M+ – C5H11]), 149 (14, [M+ – C5H5N]), 57 (6,
+
[C4H9 ]), 29 (20, [Et+]).
HRMS: m/z calcd for C15H20N2: 228.16265; found: 228.16302,
D = 0.37 mmu.
IR (neat): 2932 (m), 2855 (w), 1686 (vs), 1605 (m), 1381 (s), 1254
(s), 1196 (m), 1138 (m), 810 (m), 694 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.72 (t, J = 7.4 Hz, 3 H), 1.24–
1.75 (m, 10 H), 1.92 (q, J = 7.4 Hz, 2 H), 3.78–3.82 (m, 1 H), 5.54
(d, J = 5.0 Hz, 1 H), 6.61 (d, J = 5.0 Hz, 1 H), 7.19 (dd, J = 4.8, 8.0
Hz, 1 H), 7.81 (dt, J = 1.8, 8.0 Hz, 1 H), 8.37 (d, J = 3.6 Hz, 1 H),
8.68 (d, J = 1.8 Hz, 1 H).
N-(4-tert-Butylphenyl)-3-ethyl-3-(3-pyridyl)-1,3-dihydropyr-
rol-2-one (4gg)
Yield: 204 mg (64%); eluent: EtOH.
IR (neat): 2920 (vs), 2851 (s), 1709 (w), 1462 (m), 1261 (w), 1022
(w), 802 (m), 718 cm–1 (w).
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York

3990
T. Biletzki, W. Imhof
PAPER
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 7.4 Hz, 3 H), 1.29 (s,
9 H), 2.10 (q, J = 7.4 Hz, 2 H), 5.81 (d, J = 5.0 Hz, 1 H), 7.01 (d,
J = 5.0 Hz, 1 H), 7.33–7.43 (m, 4 H), 7.50 (dd, J = 3.4, 5.8 Hz, 1 H),
7.96 (dt, J = 1.8, 8.0 Hz, 1 H), 8.47–8.52 (m, 1 H), 8.59–8.64 (m, 1
H).
HRMS: m/z calcd for C15H20N2: 228.16265; found: 228.16293,
D = 0.28 mmu.
Acknowledgment
13C NMR (50 MHz, CDCl3): d = 9.1, 31.3, 31.8, 34.5, 57.4, 112.6,
121.2, 123.3, 126.1, 130.9, 132.5, 134.1, 134.6, 148.3, 148.5, 149.1,
177.7.
The authors gratefully thank the Deutsche Bundesstiftung Umwelt
(DBU) for financial support.
MS (DEI): m/z (%) = 320 (100, [M+]), 305 (42, [M+ – Me]), 291
References
(61, [M+ – Et]), 277 (22, [M+ – C3H7]), 134 (95, [C10H14+]), 57 (14,
+
[C4H9 ]).
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HRMS: m/z calcd for C21H24N2O: 320.18886; found: 320.18865,
D = 0.21 mmu.
N-(4-tert-Butylphenyl)-2-ethyl-3-(3-pyridyl)pyrrole (5gg)
Yield: 93 mg (31%); eluent: CH2Cl2.
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1H NMR (200 MHz, CDCl3): d = 0.94 (t, J = 7.4 Hz, 3 H), 1.36 (s,
9 H), 2.72 (q, J = 7.4 Hz, 2 H), 5.35 (d, J = 3.0 Hz, 1 H), 6.75 (d,
J = 3.0 Hz, 1 H), 6.95–7.03 (m, 2 H), 7.32–7.39 (m, 2 H), 7.37–7.43
(m, 1 H), 8.32–8.38 (m, 1 H), 8.54–8.67 (m, 2 H).
13C NMR (150 MHz, CDCl3): d = 14.1, 19.2, 31.3, 34.4, 108.3,
114.9, 119.4, 122.3, 126.3, 128.9, 132.4, 130.9, 134.1, 134.9, 146.5,
148.0, 148.7.
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MS (DEI): m/z (%) = 304 (100, [M+]), 289 (68, [M+ – Me]), 233
+
(21, [M+ – C5H11]), 57 (14, [C4H9 ]).
HRMS: m/z calcd for C21H24N2: 304.19395; found: 304.19406,
D = 0.11 mmu.
N-sec-Butyl-3-ethyl-3-(3-pyridyl)-1,3-dihydropyrrol-2-one
(4gh)
Yield: 98 mg (40%); eluent: EtOH.
IR (neat): 2967 (w), 2932 (vw), 2878 (vw), 1694 (vs), 1609 (m),
1458 (m), 1381 (s), 1258 (s), 1219 (s), 1026 (m), 910 (m), 806 (m),
714 cm–1 (vs).
1H NMR (200 MHz, CDCl3): d = 0.66–0.86 (m, 6 H), 1.10 (d,
J = 6.8 Hz, 1.5 H), 1.15 (d, J = 6.8 Hz, 1.5 H), 1.44–1.51 (m, 2 H),
1.96 (q, J = 7.4 Hz, 2 H), 3.96–4.08 (m, 1 H), 5.59 (d, J = 3.0 Hz,
0.5 H), 5.62 (d, J = 3.0 Hz, 0.5 H), 6.59 (d, J = 5.2 Hz, 1 H), 7.19
(q, J = 4.8 Hz, 1 H), 7.79–7.83 (m, 1 H), 8.41 (dd, J = 1.4, 4.8 Hz,
1 H), 8.54 (d, J = 2.2 Hz, 1 H).
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13C NMR (100 MHz, CDCl3): d = 8.9, 9.2, 10.6, 10.7, 19.4, 19.5,
28.3, 28.4, 31.1, 31.2, 48.6, 48.6, 57.1, 57.2, 111.9, 112.0, 123.4,
128.8, 128.9, 134.3, 134.4, 135.9, 136.0, 148.2, 178.6.
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MS (DEI): m/z (%) = 244 (100, [M+]), 229 (3, [M+ – Me]), 215 (89,
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Forster, R. Angew. Chem. Int. Ed. 2007, 46, 7281.
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[M+ – Et]), 201 (2, [M+ – C3H7]), 187 (24, [M+ – C4H9]), 173 (6, [M+
+
– C5H11]), 159 (76, [M+ – C6H13]), 57 (8, [C4H9 ]).
HRMS: m/z calcd for C15H20N2O: 244.15756; found: 244.15763,
D = 0.07 mmu.
N-sec-Butyl-2-ethyl-3-(3-pyridyl)pyrrole (5gh)
Yield: 97 mg (43%); eluent: CH2Cl2.
1H NMR (200 MHz, CDCl3): d = 0.84 (t, J = 7.4 Hz, 3 H), 1.22 (t,
J = 7.4 Hz, 3 H), 1.42 (d, J = 6.8 Hz, 3 H), 1.77 (q, J = 7.4 Hz, 2 H),
2.69 (q, J = 7.6 Hz, 2 H), 4.02 (q, J = 6.8 Hz, 1 H), 6.27 (d, J = 3.0
Hz, 1 H), 6.67 (d, J = 3.0 Hz, 1 H), 7.24 (dq, J = 0.8, 4.8 Hz, 1 H),
7.64 (dt, J = 2.0, 7.8 Hz, 1 H), 8.39 (dd, J = 1.6, 4.8 Hz, 1 H), 8.63
(dd, J = 0.8, 2.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 11.0, 15.5, 17.7, 22.3, 31.1, 52.7,
107.8, 115.7, 116.9, 123.2, 131.4, 133.5, 134.9, 146.1, 149.0.
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MS (DEI): m/z (%) = 228 (100, [M+]), 213 (78, [M+ – Me]), 199
(24, [M+ – Et]), 157 (41, [M+ – C5H11]).
Synthesis 2011, No. 24, 3979–3990 © Thieme Stuttgart · New York