A convenient 1,3-dipolar cycloaddition approach to pyridylpyrroles

Article abstract of DOI:10.1016/j.tetlet.2011.05.111

A variety of 2-, 3-, and 4-pyridylpyrroles were synthesized in good to excellent yields via the 1,3-dipolar cycloaddition of symmetrical and unsymmetrical muenchnones and nitroalkenes. The unsymmetrical muenchnones show moderate to excellent regioselectiv

Full text of DOI:10.1016/j.tetlet.2011.05.111

Tetrahedron Letters 52 (2011) 4106–4108
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A convenient 1,3-dipolar cycloaddition approach to pyridylpyrroles
⇑
Justin M. Lopchuk, Gordon W. Gribble
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of 2-, 3-, and 4-pyridylpyrroles were synthesized in good to excellent yields via the 1,3-dipolar
cycloaddition of symmetrical and unsymmetrical münchnones and nitroalkenes. The unsymmetrical
münchnones show moderate to excellent regioselectivity.
Received 7 April 2011
Revised 23 May 2011
Accepted 24 May 2011
Available online 12 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Münchnone
1,3-Dipolar cycloaddition
Regioselectivity
Nitroalkene
Henry reaction
The synthesis of biheteroaryl compounds remains an active area
of research particularly as it relates to medicinal1 and materials2
applications. Although somewhat rare in natural products, pyridyl-
pyrroles frequently populate the patent literature3 which gives an
indication of the sustained interest in these structures. The most
common method for the synthesis of biheteroaryl compounds re-
mains palladium-catalyzed cross-coupling4 (e.g., Suzuki, Stille).
Despite some recent success5 with improving these reactions for
nitrogen-based heterocycles, challenges still remain, especially
when coupling at the 2-position of pyridine. Other methods used
to generate these compounds include cycloadditions with TosMIC,
isocyanides, and oxazolidines.6
NO2
CHO
i, ii or iii
N
N
1: 2-pyridyl
5 (i) 61%
2
3
: 2-quinolyl
: 3-pyridyl
6
7
(i) 63%
(ii) 38%
4: 4-pyridyl
8 (iii) 55%
(i) a) CH3NO2, TMG; b) MsCl, triethylamine
(ii) CH3NO2, methylamine, Na2CO3
(iii) a) CH3NO2, K2CO3; b) Ac2O, NaOAc
Scheme 1. Synthesis of nitroalkenes.
During the course of our investigations into the 1,3-dipolar
cycloaddition of nitroindoles7 and nitrovinylindoles8 with münch-
nones, we became interested in developing a similar approach to a
variety of pyridylpyrroles which would allow aryl substitution at
any position of the pyridine core. Nitroalkenes 5 and 6 were ac-
cessed via a modified Henry reaction reported by Hills9 which uses
a catalytic amount of 1,1,3,3-tetramethylguanidine (TMG) to gen-
erate the b-nitro alcohol which is then trapped and dehydrated
with methanesulfonyl chloride (MsCl) and triethylamine. A more
traditional nitroaldol reaction10 was enlisted to synthesize nitroal-
kenes 7 and 8 (Scheme 1).
R1
O
R2
O
DIPC
THF
O
N
R1
N
CO2H
Bn
13
Bn
R2
9
: R1 = R2 = Me
10: R1 = R2 = Ph
11
: R1 = R2 = Me
14: R1 = R2 = Ph
: R1 = Ph, R2 = Me
12: R1 = Me, R2 = Ph
15
: R1 = Ph, R2 = Me
16: R1 = Me, R2 = Ph
Symmetrical and unsymmetrical münchnones 13–16 were pre-
pared as previously reported7 and generated in situ with N,N0-
diisopropylcarbodiimide (DIPC) (Scheme 2).
Scheme 2. Symmetrical and unsymmetrical münchnones.
Symmetrical münchnones 13 and 14 were tested first and found
to react smoothly with each of the nitroalkenes giving pyridylpyr-
roles 17–24 in high yields (Table 1).11 Phenyl-substituted münch-
none 14 was generally higher yielding compared to 13 which is
consistent with our previous observations.8
⇑
Corresponding author. Tel.: +1 603 646 3118; fax: +1 603 646 3946.
E-mail address: ggribble@dartmouth.edu (G.W. Gribble).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.111

J. M. Lopchuk, G. W. Gribble / Tetrahedron Letters 52 (2011) 4106–4108
4107
Table 1
A mechanistic rationale for this cycloaddition is illustrated in
Scheme 3.
Reaction of symmetrical münchnones with nitroalkenes13–20
In summary, we report a protocol which allows for the efficient
construction of a variety of 2-, 3-, and 4-pyridylpyrroles in high
yield. The regioselectivity of unsymmetrical münchnones was
found to be good to excellent especially for the 2-pyridyl and 2-
quinolyl nitroalkenes. Further synthetic and computational studies
are underway and will be reported in due course.
R1
O
B
N
n
O
N
R1
R2
NO2
Bn
R2
H
DIPC, THF
reflux
N
N
Acknowledgments
Entry
Nitroalkene
Münchnone 13
Münchnone 14
Product
Yielda
This work was supported by the Donors of the Petroleum Re-
search Fund (PRF), administered by the American Chemical Society,
and by Wyeth. The authors wish to thank Ms. Mia Song for the
preparation of nitroalkene 7.
Product
Yielda
1
2
3
4
5
7
8
6
17
18
19
20
91
81
87
69
21
22
23
24
97
89
96
96
References and notes
a
Yields are for isolated products after column chromatography.
1. For recent examples, see: (a) Perri, V.; Rochais, C.; Cresteil, T.; Dallemagne, P.;
Rault, S. Bioorg. Med. Chem. 2009, 17, 7783–7788; (b) Hong, S.; Lee, S.; Kim, B.;
Lee, H.; Hong, S.-S.; Hong, S. Bioorg. Med. Chem. Lett. 2010, 20, 7212–7215; (c)
Ferlin, M. G.; Bortolozzi, R.; Brun, P.; Castagliuolo, I.; Hamel, E.; Basso, G.; Viola,
G. ChemMedChem 2010, 5, 1373–1385; (d) Wang, K.; Dömling, A. Chem. Biol.
Drug Des. 2010, 75, 277–283.
2. For recent examples, see: (a) Panzella, L.; Pezzella, A. M.; Manini, P.;
Napolitano, A.; d’Ischia, M. Tetrahedron 2009, 65, 2032–2036; (b) Gandhi, V.;
Thompson, M. L.; Lash, T. D. Tetrahedron 2010, 66, 1787–1799.
3. (a) For recent examples in the patent literature, see: Ripka, A.; Shapiro, G.;
Chesworth, R. PCT Int. Appl. WO 2009158473, 2009.; (b) Ackermann, P.;
Bobbio, C.; Corsi, C.; Ehrenfreund, J.; McGinley, A. M. U. S. Patent 2010/
0292258, 2010.; (c) Gray, N. S.; Janne, P.; Eck, M. J. PCT Int. Appl. WO
2010129053, 2010.; (d) Corsi, C.; Wendeborn, S. V.; Bobbio, C.; Kessabi, J.;
Schneiter, P.; Grasso, V.; Haas, J. U. PCT Int. Appl. WO 2010069879, 2010.; (e)
Kim, T-S.; Lee, E.; Kim, D.; Park, B-M.; Park, J.; Joo, J. PCT Int. Appl. WO
2010044543, 2010.
Unsymmetrical münchnones 15 and 16 proved to be signifi-
cantly more regioselective compared to what we observed with a
variety of nitrovinylindoles.8 Nitroalkenes 5 and 6, which have
the aromatic pyridine nitrogen ortho to the nitrovinyl group, are al-
most completely regioselective with only a trace of the minor reg-
ioisomer observable by NMR. When the pyridine nitrogen is moved
to the meta position (Table 2, entry 2) regioselectivity is excellent
with münchnone 15 but decreases substantially with münchnone
16. Finally, when the pyridine nitrogen is moved para to the nitro-
vinyl group (Table 2, entry 3) regioselectivity is found to be mod-
erate for both münchnones. Given these results it is possible the
pyridine nitrogen either helps to direct the approach of the münch-
none or stabilizes the transition state of the major isomer.12
4. For examples of the synthesis of arylpyrroles via palladium-catalyzed cross
coupling, see: (a) Alvarez, A.; Guzman, A.; Ruiz, A.; Velarde, E. J. Org. Chem.
Table 2
Reaction of unsymmetrical münchnones with nitroalkenes21–28
R1
O
Bn
N
Bn
N
O
N
Ph
Me
Me
Ph
NO2
Bn
R2
H
+
H
DIPC, THF
reflux
N
N
N
"syn"
"anti"
Entry
Nitroalkene
Münchnone 15
Münchnone 16
Prod
Yielda
S:Ab
Prod
Yielda
S:Ab
1
2
3
4
5
7
8
6
25:26
27:28
29:30
31:32
98
91
97
86
>99:1
>99:1
87:13
>99:1
25:26
27:28
29:30
31:32
61
94
91
78
1:>99
29:71
30:70
2:98
a
Yields are for isolated products after column chromatography.
S:A refers to the ratio of ‘syn’ to ‘anti’ products. Isomeric ratios were determined by NOE and NMR integration.
b
Scheme 3. Mechanism for the 1,3-dipolar cycloaddition.

4108
J. M. Lopchuk, G. W. Gribble / Tetrahedron Letters 52 (2011) 4106–4108
1992, 57, 1653–1656; (b) Wang, J.; Scott, A. I. Tetrahedron Lett. 1996, 37, 3247–
1.5 Hz), 7.47–7.04 (m, 15H), 6.70–6.67 (m, 2H), 6.62 (s, 1H), 5.13 (s, 2H); 13C
NMR (300 MHz, CDCl3) d 149.1, 146.5, 139.1, 136.3, 134.6, 133.3, 133.2, 132.7,
132.3, 131.4, 129.4, 128.9, 128.8, 128.5, 128.4, 127.7, 127.2, 126.2, 123.24,
120.0, 109.2, 48.8; HRMS (ESI+) m/z calcd for C28H23N2 (MH+) 387.1861, found
387.1862.
3250; (c) Ghosez, L.; Franc, C.; Denonne, F.; Cuisinier, C.; Touillaux, R. Can. J.
Chem. 2001, 79, 1827–1839; (d) Stockman, V.; Eriksen, K. L.; Fiksdahl, A.
Tetrahedron 2008, 64, 11180–11184; (e) Stockman, V.; Bakke, J. M.; Bruheim, P.;
Fiksdahl, A. Tetrahedron 2009, 65, 3668–3672; (f) Fall, Y.; Doucet, H.; Santelli,
M. ChemSusChem 2009, 2, 153–157.
19. 4-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)pyridine (23): Pale yellow solid, mp
141–142 °C; 1H NMR (300 MHz, CDCl3) d 8.34 (d, 2H, J = 6.1 Hz), 7.45–7.08 (m,
15H), 6.70–6.68 (m, 3H), 5.10 (s, 2H); 13C NMR (300 MHz, CDCl3) d 149.8, 144.0,
138.8, 136.4, 134.2, 133.1, 132.7, 131.3, 129.4, 129.0, 128.8, 128.7, 128.6, 127.9,
127.2, 126.2, 124.1, 121.9, 120.5, 109.1, 48.7; HRMS (ESI+) m/z calcd for
5. (a) Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew. Chem., Int. Ed.
2006, 45, 3484–3488; (b) Billingsley, K. L.; Buchwald, S. L. J. Am. Chem. Soc.
2007, 129, 3358–3366; (c) Billingsley, K. L.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2008, 47, 4695–4698.
6. For examples with TosMIC, see: (a) Pavri, N. P.; Trudell, M. L. J. Org. Chem. 1997,
62, 2649–2651; (b) Smith, N. D.; Huang, D.; Cosford, N. D. P. Org. Lett. 2002, 4,
3537–3539. and references therein; For an example with isocyanides, see:
Lygin, A. V.; Larionov, O. V.; Korotkov, V. S.; de Meijere, A. Chem. Eur. J. 2009, 15,
227–236; For an example with oxazolidines, see: Deprez, P.; Royer, J.; Husson,
H-P. Synthesis 1991, 759–762; For other methods, see: (a) Katritzky, A. R.; Zhu,
L.; Lang, H.; Denisko, O.; Wang, Z. Tetrahedron 1995, 51, 13271–13276; (b)
Hoemann, M. Z.; Melikian-Badalian, A.; Kumaravel, G.; Hauske, J. R. Tetrahedron
Lett. 1998, 39, 4749–4752; (c) Nishiwaki, N.; Yamashita, K.; Azuma, M.; Adachi,
T.; Tamura, M.; Ariga, M. Synthesis 2004, 1996–2000; (d) Braun, R. U.; Muller, T.
J. J. Synthesis 2004, 2391–2406.
C
28H23N2 (MH+) 387.1861, found 387.1863.
20. 2-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)quinoline (24): Off-white solid, mp
163–165 °C; 1H NMR (300 MHz, CDCl3) d 8.14 (d, 1H, J = 8.8 Hz), 7.75 (d, 1H,
J = 8.8 Hz), 7.69–7.65 (m, 2H), 7.57–7.55 (d, 2H, J = 6.8 Hz), 7.44–7.32 (m, 9H),
7.22 (s, 1H), 7.12–7.10 (m, 3H), 6.99 (d, 1H, J = 8.5 Hz), 6.72–6.69 (m, 2H), 5.20
(s, 2H); 13C NMR (300 MHz, CDCl3) d 155.5, 148.7, 138.9, 136.6, 135.4, 133.6,
133.2, 131.6, 130.0, 129.5, 129.5, 129.3, 128.9, 128.8, 128.5, 128.2, 127.6, 127.6,
127.1, 126.4, 125.5, 124.6, 121.5, 110.7, 48.9; HRMS (ESI+) m/z calcd for
C
32H25N2 (MH+) 437.2018, found 437.2017.
21. 2-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)pyridine (25): yellow oil; 1H
NMR (300 MHz, CDCl3) d 8.45 (d, 1H, J = 4.9 Hz), 7.60 (dd, 1H, J = 7.8, 1.5 Hz),
7.42–7.19 (m, 8H), 6.92–6.87 (m, 3H), 6.76 (d, 1H, J = 8.1 Hz), 6.68 (s, 1H), 4.95
(s, 2H), 2.18 (s, 3H); 13C NMR (300 MHz, CDCl3) d 155.3, 149.3, 138.8, 135.8,
133.4, 132.5, 131.4, 130.9, 128.8, 128.7, 128.5, 128.3, 127.2, 126.7, 121.8, 120.0,
107.9, 47.7, 12.7; HRMS (ESI+) m/z calcd for C23H21N2 (MH+) 325.1705, found
325.1705.
7. Gribble, G. W.; Pelkey, E. T.; Simon, W. E.; Trujillo, H. A. Tetrahedron 2000, 56,
10133–10140.
8. Lopchuk, J. M.; Gribble, G. W. Heterocycles 2011, 82, 1617–1631.
9. Nomland, A.; Hills, I. D. Tetrahedron Lett. 2008, 49, 5511–5514.
10. (a) Bourguignon, J.; Le Nard, G.; Queguiner, G. Can. J. Chem. 1985, 63, 2354–
2361; (b) Krafft, E. A.; Kurt, A.; Maier, A.; Thomas, A. W.; Zimmerli, D. Synthesis
2005, 3245–3252.
22. 2-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)pyridine (26): pale orange oil; 1
H
NMR (300 MHz, CDCl3) d 8.64 (d, 1H, J = 3.9 Hz), 7.66 (t, 1H), 7.52 (d, 1H,
J = 7.8 Hz), 7.41–7.26 (m, 9H), 7.08–7.03 (d, 2H), 6.71 (s, 1H), 5.22 (s, 2H), 2.54
(s, 3H); 13C NMR (300 MHz, CDCl3) d 156.4, 149.4, 138.8, 136.4, 134.8, 133.6,
130.0, 129.1, 128.7, 127.4, 127.3, 126.0, 121.7, 120.0, 108.6, 48.1, 12.1; HRMS
(ESI+) m/z calcd for C23H21N2 (MH+) 325.1705, found 325.1697.
11. Sample procedure:
(60 mg, 0.40 mmol, 1 equiv), münchnone precursor
3 equiv) and anhydrous THF (10 mL, distilled from sodium/benzophenone
immediately prior to use). DIPC (186 L, 1.2 mmol, 3 equiv) was added via
A
round bottom flask was charged with nitroalkene
5
9
(266 mg, 1.2 mmol,
l
syringe and the mixture was refluxed under nitrogen for 24 h. Once TLC
indicated complete consumption of the nitroalkene the reaction was cooled to
room temperature and concentrated in vacuo. The remaining residue was
dissolved in CH2Cl2 and purified by flash chromatography (silica gel, 15% ethyl
acetate in hexanes) to yield pyridylpyrrole 17 (95 mg, 91%).13
23. 3-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)pyridine (27): pale orange oil; 1
H
NMR (300 MHz, CDCl3) d 8.52 (d, 1H, J = 1.5 Hz), 8.29 (dd, 1H, J = 4.8, 1.7 Hz),
7.42–7.18 (m, 9H), 7.05–7.00 (m, 1H), 6.91 (d, 2H, J = 6.8 Hz), 6.32 (s, 1H), 4.99
(s, 2H), 2.19 (s, 3H); 13C NMR (300 MHz, CDCl3) d 149.0, 146.2, 138.8, 134.5,
132.9, 132.7, 131.3, 130.1, 129.1, 129.0, 129.0, 128.7, 128.6, 128.5, 128.3, 128.2,
128.0, 127.6, 127.3, 107.2, 47.8, 12.7; HRMS (ESI+) m/z calcd for C23H21N2
(MH+) 325.1705, found 325.1700.
12. Computational studies designed to study this regioselectivity will be reported
separately in a full account of this work.
13. 2-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)pyridine (17): White solid, mp 82–
83 °C; 1H NMR (300 MHz, CDCl3) d 8.61 (d, 1H, J = 4.2 Hz), 7.62 (t, 1H), 7.44
(d, 1H, J = 8.1 Hz), 7.34–7.23 (m, 3H), 7.03–6.97 (m, 3H), 6.36 (s, 1H), 5.10 (s,
2H), 2.55 (s, 3H), 2.21 (s, 3H); 13C NMR (300 MHz, CDCl3) d 156.8, 149.3, 138.2,
136.2, 129.0, 128.4, 127.9, 127.4, 126.0, 121.4, 120.2, 119.5, 106.4, 47.0, 12.6,
11.8; HRMS (ESI+) m/z calcd for C18H19N2 (MH+) 263.1548, found 263.1547.
14. 3-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)pyridine (18): Pale yellow oil; 1H NMR
(300 MHz, CDCl3) d 8.69 (d, 1H, J = 2.0 Hz), 8.42 (dd, 1H, J = 4.9, 1.5 Hz), 7.69 (dt,
1H, J = 7.8, 3.9 Hz), 7.35–7.25 (m, 4H), 6.95 (d, 2H, J = 7.1 Hz), 6.12 (s, 1H), 5.09
(s, 2H), 2.27 (s, 3H), 2.21 (s, 3H); 13C NMR (300 MHz, CDCl3) d 149.3, 146.3,
138.2, 135.0, 133.5, 129.2, 128.8, 127.5, 125.9, 123.5, 117.6, 106.4, 47.2, 12.5,
11.4; HRMS (ESI+) m/z calcd for C18H19N2 (MH+) 263.1548, found 263.1541.
15. 4-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)pyridine (19): Yellow solid, mp 83–
85 °C; 1H NMR (300 MHz, CDCl3) d 8.50 (d, 2H, J = 4.6 Hz), 7.36–7.23 (m, 5H),
6.92 (d, 2H, J = 7.3 Hz), 6.17 (s, 1H), 5.07 (s, 2H), 2.30 (s, 3H), 2.19 (s, 3H); 13C
NMR (300 MHz, CDCl3) d 149.8, 145.4, 137.9, 129.2, 129.1, 128.6, 127.5, 126.7,
125.8, 125.6, 122.3, 118.4, 106.2, 47.2, 12.5, 11.8; HRMS (ESI+) m/z calcd for
24. 3-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)pyridine (28): pale orange oil; 1
H
NMR (300 MHz, CDCl3) d 8.74 (d, 1H, J = 1.5 Hz), 8.46 (dd, 1H, J = 4.9, 1.7 Hz),
7.75 (dt, 1H, J = 8.1, 4.1 Hz), 7.40–7.16 (m, 9H), 7.00 (d, 2H, J = 8.1 Hz), 6.45 (s,
1H), 5.20 (s, 2H), 2.27 (s, 3H); 13C NMR (300 MHz, CDCl3) d 149.4, 146.6, 138.7,
135.2, 133.3, 133.2, 131.3, 129.1, 129.0, 128.9, 128.8, 128.2, 127.5, 125.9, 123.5,
108.5, 48.3, 11.6; HRMS (ESI+) m/z calcd for C23H21N2 (MH+) 325.1705, found
325.1703.
25. 4-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)pyridine (29): pale orange oil; 1
H
NMR (300 MHz, CDCl3) d 8.30 (d, 2H, J = 4.2 Hz), 7.34–7.19 (m, 8H), 7.04 (d, 2H,
J = 6.1 Hz), 6.88 (d, 2H, J = 6.6 Hz), 6.37 (d, 1H, J = 1.0 Hz), 4.95 (s, 2H), 2.18 (d,
3H, J = 0.7 Hz); 13C NMR (300 MHz, CDCl3) d 149.5, 144.5, 138.5, 133.2, 132.9,
132.6, 131.3, 130.3, 129.7, 129.2, 129.1, 129.0, 128.8, 128.8, 128.7, 128.7, 128.6,
127.9, 127.4, 126.9, 126.8, 125.9, 121.8, 118.9, 107.0, 47.7, 12.7; HRMS (ESI+)
m/z calcd for C23H21N2 (MH+) 325.1705, found 325.1708.
26. 4-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)pyridine (30): orange oil; 1H
NMR (300 MHz, CDCl3) d 8.49 (d, 2H, J = 5.9 Hz), 7.43–7.12 (m, 10H), 6.92 (d,
2H, J = 7.3 Hz), 6.57 (s, 1H), 5.23 (s, 2H), 2.27 (s, 3H); 13C NMR (300 MHz, CDCl3)
d 157.5, 150.3, 144.5, 139.1, 135.0, 133.3, 131.5, 130.3, 129.6, 129.5, 129.3,
129.3, 129.1, 128.9, 127.9, 127.8, 126.2, 126.1, 122.3, 119.5, 108.7, 47.9, 12.3;
HRMS (ESI+) m/z calcd for C23H21N2 (MH+) 325.1705 found 325.1702.
27. 2-(1-Benzyl-5-methyl-2-phenyl-1H-pyrrol-3-yl)quinoline (31): Pale yellow oil;
1H NMR (300 MHz, CDCl3) d 8.12 (d, 1H, J = 8.8 Hz), 7.73 (d, 1H, J = 8.5 Hz),
7.67–7.63 (m, 2H), 7.43–7.23 (m, 9H), 6.98–6.91 (m, 4H), 5.05 (s, 2H), 2.25 (s,
3H); 13C NMR (300 MHz, CDCl3) d 155.8, 148.7, 138.7, 135.2, 133.5, 133.4,
131.5, 130.3, 129.4, 129.2, 128.9, 128.4, 127.5, 127.3, 126.5, 126.0, 125.3, 123.1,
121.3, 108.5, 47.8, 12.8; HRMS (ESI+) m/z calcd for C27H23N2 (MH+) 375.1861,
found 375.1861.
C
18H19N2 (MH+) 263.1548, found 263.1546.
16. 2-(1-Benzyl-2,5-dimethyl-1H-pyrrol-3-yl)quinoline (20): Pale orange oil; 1H
NMR (300 MHz, CDCl3) d 8.07 (d, 2H, J = 8.5 Hz), 7.75 (d, 1H, J = 7.8 Hz), 7.65
(t, 2H), 7.43 (t, 1H), 7.36–7.24 (m, 3H), 7.02 (d, 2H, J = 7.1 Hz), 6.49 (s, 1H), 5.13
(s, 2H), 2.71 (s, 3H), 2.24 (s, 3H); 13C NMR (300 MHz, CDCl3) d 156.8, 148.6,
138.1, 135.9, 129.4, 129.3, 129.2, 129.1, 128.5, 127.6, 127.4, 126.2, 126.0, 125.1,
120.9, 120.3, 106.8, 47.0, 12.7, 12.1; HRMS (ESI+) m/z calcd for C22H21N2 (MH+)
313.1705, found 313.1707.
17. 2-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)pyridine (21): Bright yellow solid, mp
122–124 °C; 1H NMR (300 MHz, CDCl3) d 8.60 (d, 1H, J = 3.9 Hz), 7.52–7.49 (m,
2H), 7.38–7.25 (m, 9H), 7.11–7.07 (m, 3H), 7.04 (s, 1H), 6.97–6.92 (m, 1H), 6.82
(d, 1H, J = 8.1 Hz), 6.68–6.65 (m, 2H), 5.12 (s, 2H); 13C NMR (300 MHz, CDCl3) d
155.1, 149.6, 139.0, 136.4, 135.7, 134.4, 133.6, 133.2, 131.4, 129.4, 128.9, 128.7,
128.5, 128.3, 127.5, 127.1, 126.3, 124.0, 122.0, 120.3, 110.2, 48.9; HRMS (ESI+)
m/z calcd for C28H23N2 (MH+) 387.1861, found 387.1853.
28. 2-(1-Benzyl-2-methyl-5-phenyl-1H-pyrrol-3-yl)quinoline (32): Pale orange oil;
1H NMR (300 MHz, CDCl3) d 8.13–8.09 (m, 2H), 7.79–7.65 (m, 4H), 7.48–7.26
(m, 8H), 7.08 (d, 2H, J = 6.8 Hz), 6.84 (s, 1H), 5.25 (s, 2H), 2.71 (s, 3H); 13C NMR
(300 MHz, CDCl3) d 156.5, 148.6, 138.6, 136.0, 134.9, 133.5, 131.4, 129.4, 129.3,
129.2, 129.1, 128.8, 127.7, 127.4, 126.3, 126.0, 125.3, 121.8, 120.9, 109.0, 48.1,
12.4; HRMS (ESI+) m/z calcd for C27H23N2 (MH+) 375.1861, found 375.1864.
18. 3-(1-Benzyl-2,5-diphenyl-1H-pyrrol-3-yl)pyridine (22): White solid, mp 116–
117 °C; 1H NMR (300 MHz, CDCl3) d 8.57 (d, 1H, J = 2.0 Hz), 8.32 (dd, 1H, J = 4.9,