D
J. M. Lopchuk et al.
Special Topic
Synthesis
13C NMR (75 MHz, CDCl3): δ = 138.9, 133.3, 131.8, 129.1, 129.0, 129.0,
128.8, 128.7, 128.6, 128.6, 127.5, 127.3, 125.9, 122.6, 122.5, 108.7,
48.2, 11.8
1′-Benzyl-5′-methyl-2′-phenyl-1-(phenylsulfonyl),1H′-2,3-bipyr-
role (29)
Yield: 155 mg (69%); a 77:23 mixture of diastereomers 29 and 30
(Table 1, entry 7); pale yellow oil.
HRMS (ESI): m/z [M + H]+ calcd for C22H20NS: 330.1316; found:
1H NMR (500 MHz, CDCl3): δ = 7.69 (dd, J = 8.6, 1.2 Hz, 2 H), 7.43 (dd,
J = 3.4, 1.7 Hz, 1 H), 7.41–7.25 (m, 6 H), 7.15–7.05 (m, 3 H), 6.92 (d, J =
7.6 Hz, 2 H), 6.63 (dd, J = 8.4, 1.2 Hz, 2 H), 6.14–6.12 (m, 2 H), 5.76 (dd,
J = 3.4, 1.7 Hz, 1 H), 5.02 (s, 2 H), 2.20 (fd, J = 1.0 Hz, 3 H).
330.1315.
1-Benzyl-3-(furan-2-yl)-5-methyl-2-phenyl-1H-pyrrole (25)
Yield: 144 mg (92%); a 78:22 mixture of diastereomers 25 and 26
13C NMR (125 MHz, CDCl3): δ = 139.6, 138.9, 134.1, 133.7, 132.4,
130.9, 130.6, 129.1, 128.9, 128.5, 128.1, 127.8, 127.5, 127.3, 126.2,
122.8, 116.5, 111.8, 111.7, 111.4, 47.9, 12.8
(Table 1, entry 3); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 7.35–7.21 (m, 9 H), 6.88 (d, J = 6.6 Hz, 2
H), 6.37 (fd, J = 1.0 Hz, 1 H), 6.22 (dd, J = 3.3, 1.76 Hz, 1 H), 5.67 (dd, J =
3.4, 0.7 Hz, 1 H), 4.93 (s, 2 H), 2.16 (fd, J = 1.0 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C28H25N2O2S: 453.1637; found
13C NMR (75 MHz, CDCl3): δ = 139.8, 138.8, 131.4, 129.6, 129.1, 128.8,
128.8, 128.7, 128.6, 128.6, 128.2, 127.2, 125.9, 111.0, 105.4, 102.6,
47.7, 12.7.
453.1627.
1′-Benzyl-2′-methyl-5′-phenyl-1-(phenylsulfonyl),1H′-2,3-bipyr-
role (30)
HRMS (ESI): m/z [M + H]+ calcd for C22H20NO: 314.1545; found
Yield: 151 mg (67%); an 82:28 mixture of diastereomers 30 and 29
314.1543.
(Table 1, entry 8); pale yellow oil.
1-Benzyl-3-(furan-2-yl)-2-methyl-5-phenyl-1H-pyrrole (26)
1H NMR (500 MHz, CDCl3): δ = 7.56 (dd, J = 8.6, 1.3 Hz, 2 H), 7.54 (dd,
J = 3.4, 1.7 Hz, 1 H), 7.42–7.25 (m, 11 H), 7.06 (d, J = 7.7 Hz, 2 H), 6.36
(t, J = 3.4 Hz, 1 H), 6.23 (s, 1 H), 6.16 (dd, J = 3.4, 1.7 Hz, 1 H), 5.15 (s, 2
H), 1.74 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 139.3, 138.8, 133.5, 133.5, 133.4,
131.4, 130.8, 129.1, 129.0, 128.9, 128.8, 127.6, 127.5, 127.2, 126.1,
123.3, 116.1, 112.5, 111.8, 111.4, 48.2, 10.9.
Yield: 132 mg (84%); a 60:40 mixture of diastereomers 26 and 25
(Table 1, entry 4); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 7.41 (dd, J = 2.0, 0.7 Hz, 1 H), 7.34–7.25
(m, 9 H), 6.99 (d, J = 6.8 Hz, 1 H), 6.52 (s, 1 H), 6.45 (dd, J = 3.3, 1.7 Hz,
1 H), 6.27 (dd, J = 3.4, 0.7 Hz, 1 H), 5.16 (s, 2 H), 2.34 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 140.2, 138.8, 131.4, 129.6, 129.1, 129.0,
128.8, 128.7, 128.7, 128.6, 128.2, 127.3, 125.9, 111.2, 106.8, 103.3,
48.0, 11.8.
HRMS (ESI): m/z [M + H]+ calcd for C28H25N2O2S: 453.1637; found:
453.1639.
HRMS (ESI): m/z [M + H]+ calcd for C22H20NO: 314.1545; found:
314.1547.
Acknowledgment
1′-Benzyl-1,5′-dimethyl-2′-phenyl-1H,1H′-2,3-bipyrrole (27)
J.M.L. acknowledges support from the Department of Education
GAANN fellowship. G.W.G. acknowledges support from the Donors of
the Petroleum Research Fund, administered by the American Chemi-
cal Society, and by Wyeth.
Yield: 93 mg (57%); an 87:23 mixture of diastereomers 27 and 28
(Table 1, entry 5); yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.35–7.11 (m, 8 H), 6.96 (d, J = 8.3 Hz, 2
H), 6.52 (fd, J = 1.0 Hz, 1 H), 6.10 (d, J = 17.3 Hz, 2 H), 5.95 (dd, J = 3.5,
1.7 Hz, 1 H), 5.10 (s, 2 H), 3.24 (s, 3 H), 2.18 (fd, J = 1.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 139.2, 133.4, 132.1, 130.4, 129.3,
129.0, 128.7, 128.5, 127.2, 127.1, 125.9, 121.3, 114.1, 109.8, 108.7,
107.2, 48.1, 34.5, 12.7.
References
(1) Bergman, J.; Janosik, T. Comprehensive Heterocyclic Chemistry
III; Vol. 3; Katritzky, A. R.; Ramsden, C.; Scriven, E. F. V.; Taylor,
R. J. K., Eds.; Elsevier: Oxford, 2008, 269–351.
HRMS (ESI): m/z [M + H]+ calcd for C23H23N2: 327.1861; found
327.1858.
(2) (a) Young, I. S.; Thornton, P. D.; Thompson, A. Nat. Prod. Rep.
2010, 27, 1801. (b) Welsch, M. E.; Snyder, S. A.; Stockwell, B. R.
Curr. Opin. Chem. Biol. 2010, 14, 347. (c) Horton, D. A.; Bourne,
G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893.
(3) (a) Bhardwaj, V.; Gumber, D.; Abbot, V.; Dhiman, S.; Sharma, P.
RSC Adv. 2015, 5, 15233. (b) Li, J. J. Pyrroles, In Heterocyclic
Chemistry in Drug Discovery; Li, J. J., Ed.; Wiley: Hoboken, 2013,
Chap. 2, 18.
(4) (a) Sathyamoorthi, G.; Soong, M. L.; Ross, T. W.; Boyer, J. H. Het-
eroat. Chem. 1993, 4, 603. (b) Grimsdale, A. C.; Chan, K. L.;
Martin, R. E.; Jokisz, P. G.; Holmes, A. B. Chem. Rev. 2009, 109,
897. (c) Panzella, L.; Pezzella, A.; Arzillo, M.; Manini, P.;
Napolitano, A.; d’Ischia, M. Tetrahedron 2009, 65, 2032.
(5) (a) Yurovskaya, M. A.; Alekseyev, R. S. Chem. Heterocycl. Compd.
2014, 49, 1400. (b) Ferreira, V. F.; de Souza, M. C. B. V.; Cunha, A.
C.; Pereira, L. O. R.; Ferreira, M. L. G. Org. Prep. Proced. Int. 2001,
33, 411.
1′-Benzyl-1,2′-dimethyl-5′-phenyl-1H,1H′-2,3-bipyrrole (28)
Yield: 95 mg (58%); a 24:86 mixture of diastereomers 28 and 27
(Table 1, entry 6); yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.35–7.11 (m, 9 H), 6.99 (d, J = 8.8 Hz, 2
H), 6.71 (dd, J = 3.4, 0.7 Hz, 1 H), 6.32 (s, 1 H), 6.21 (dd, J = 3.4, 0.7 Hz,
1 H), 5.20 (s, 2 H), 3.64 (s, 3 H), 2.14 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 139.1, 134.1, 133.5, 129.3, 129.0,
128.9, 128.7, 127.3, 127.1, 125.9, 125.8, 121.8, 113.7, 110.0, 108.4,
107.3, 48.3, 34.8, 11.4.
HRMS (ESI): m/z [M + H]+ calcd for C23H23N2: 327.1861; found:
327.1856.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–E