Trapping the Oxyallyl Cation Intermediate Derived from the Nazarov Cyclization
were dried over Na2SO4 and then concentrated under re-
duced pressure. Flash chromatography (230–400 mesh silica
gel) of the residue provided the product. The eluting sol-
vents were: for the pyrroles, 10% EtOAc in hexanes with
2.5% triethylamine and then 25% EtOAc in hexanes with
2.5% triethylamine; for the indoles, 10%, increasing to 35%,
EtOAc in hexanes.[11]
7.03 (1H, m), 3.80 (1H, br d, J ꢀ 3 Hz), 3.67 (1H, d, J=
3.0 Hz), 2.34 (3H, s), 1.92 (3H, br s), 1.89 (3H, s); 13C NMR
(125 MHz, CDCl3): d=207.1, 170.4, 145.1, 141.2, 136.9,
135.6, 135.3, 130.1 (3C), 129.3 (2C), 127.8 (2C), 127.6, 127.1
(2C), 125.0, 123.8, 120.2, 120.1, 113.9, 58.1, 53.7, 21.8, 15.8,
8.8; HR-MS (ESI): m/z=478.1424, [C28H25NO3S+Na]+ re-
quires 478.1447.
23b: colorless solid, mp 61–638C (CH2Cl2/pentane); IR
trans-2,3-Dimethyl-4-phenyl-5-(1-phenyl-1H-pyrrol-2-yl)-
cyclopent-2-enone (8): AVK 1 (0.10 g, 0.56 mmol) and 1-
phenylpyrrole (0.16 g, 1.1 mmol) reacted in the presence of
BF3·OEt2 (0.080 mL, 0.62 mmol) to afford 8 as a pale yellow
solid; yield: 0.13 g (67%); mp 132–1338C (CH2Cl2/pentane);
(film): n=1704, 1650, 1601 cmÀ1
;
1H NMR (500 MHz,
CDCl3): d=8.01 (1H, m), 7.75 (2H, d, J=8.4 Hz), 7.31 (4H,
m), 7.25 (2H, d, J=8.4 Hz), 7.19 (2H, m), 7.08 (1H, s), 6.93
(2H, m), 3.79 (1H, d, J=16 Hz), 3.67 (1H, m), 3.28 (1H, d,
J=16 Hz), 2.82 (1H, dd, J=19, 7.2 Hz), 2.36 (s, 3H), 2.34
(1H, dd, J=19, 2.1 Hz), 1.92 (3H, s); 13C NMR (125 MHz,
CDCl3): d=209.3, 171.1, 145.3, 141.8, 138.1, 135.5, 135.4,
130.5, 130.1 (2C), 129.2 (2C), 127.7 (2C), 127.5, 127.0 (2C),
125.2, 124.4, 123.5, 119.3, 117.9, 114.1, 46.7, 44.8, 25.2, 21.8,
8.9; HR-MS (ESI): m/z=478.1431, [C28H25NO3S+Na]+ re-
quires 478.1447.
IR (film): n=1705, 1650, 1599 cmÀ1 1H NMR (500 MHz,
;
CDCl3): d=7.18 (6H, m), 7.12 (2H, m), 6.88 (2H, m), 6.74
(1H, dd, J=3.2, 1.7 Hz), 6.24 (1H, t, J=3.2 Hz), 6.00 (1H,
dd, J=3.2, 1.7 Hz), 3.77 (1H, br d, J ꢀ 3 Hz), 3.55 (1H, d,
J=2.9 Hz), 1.78 (3H, br s), 1.77 (3H, s); 13C NMR
(125 MHz, CDCl3): d=207.4, 170.1, 141.1, 139.9, 135.9,
131.4, 129.1 (2C), 129.0 (2C), 127.6 (4C), 127.3, 127.1, 123.0,
108.7, 107.1, 59.7, 53.9, 15.7, 8.8; HR-MS (ESI): m/z=
350.1513, [C23H21NO+Na]+ requires 350.1515.
2,3-Dimethyl-5-(1-methyl-1H-indol-3-yl)cyclopent-2-
enone (27): AVK 25 (0.075 g, 0.69 mmol) and 1-methylin-
dole (0.17 mL, 1.4 mmol) reacted in the presence of
BF3·OEt2 (0.090 mL, 0.76 mmol) to afford 27 as a colorless
trans-5-(1,2-Dimethyl-1H-indol-3-yl)-2,3-dimethyl-4-phe-
nylcyclopent-2-enone (22a) and 3-[(1,2-dimethyl-1H-indol-3-
yl)methyl]-2-methyl-4-phenylcyclopent-2-enone (22b): AVK
oil; yield: 0.084 g (51%); IR (film): n=1697, 1654 cmÀ1
;
1H NMR (500 MHz, CDCl3): d=7.37 (1H, m), 7.28 (1H,
m), 7.20 (1H, m), 7.05 (1H, m), 6.95 (1H, s), 3.84 (1H, dd,
J=7.3, 2.7 Hz), 3.72 (3H, s), 3.12 (1H, dd, J=18, 7.3 Hz),
3.12 (1H, br dd, J=18, ~3 Hz), 2.11 (3H, s), 1.81 (3H, s);
13C NMR (125 MHz, CDCl3): d=209.8, 168.6, 137.5, 135.7,
127.2, 126.8, 121.9, 119.2, 119.1, 112.9, 109.6, 43.1, 41.2, 32.8,
17.3, 8.4; HR-MS (ESI): m/z=262.1190, [C16H17NO+Na]+
requires 262.1202.
1
(0.10 g, 0.56 mmol) and 1,2-dimethylindole (0.16 g,
1.1 mmol) reacted in the presence of BF3·OEt2 (0.080 mL,
0.62 mmol). Flash chromatography of the product mixture
provided 22a (yield: 0.11 g, 62%) and 22b (yield: 0.052 g,
28%).
22a: pale yellow solid, mp 164–1668C (CH2Cl2/pentane);
IR (film): n=1702, 1648, 1602 cmÀ1 1H NMR (500 MHz,
;
CDCl3): d=7.31 (2H, m), 7.25 (2H, m), 7.12 (1H, m), 7.06
(2H, m), 6.97 (2H, m), 3.90 (1H, br d, Jꢀ3 Hz), 3.65 (1H,
d, J=3.2 Hz), 3.61 (3H, s), 2.03 (3H, s), 1.97 (3H, br s),
1.94 (3H, s); 13C NMR (125 MHz, CDCl3): d=209.3, 169.9,
142.1, 137.4, 137.2, 135.0, 129.1 (2C), 127.7 (2C), 127.1,
126.1, 120.9, 119.1, 118.2, 109.0, 108.0, 58.6, 54.9, 29.8, 15.7,
10.5, 8.9; HR-MS (ESI): m/z=352.1667, [C23H23NO+Na]+
requires 352.1672.
Acknowledgements
We are grateful to the Natural Sciences and Engineering
Council of Canada and the Killam Foundation for financial
support.
22b: pale yellow solid, mp 199–2018C (CH2Cl2/pentane);
IR (film): n=1698, 1641, 1602 cmÀ1 1H NMR (500 MHz,
;
CDCl3): d=7.25 (4H, m), 7.16 (1H, m), 7.12 (1H, m), 7.01
(1H, m), 6.86 (2H, m), 3.92 (1H, d, J=16 Hz), 3.62 (1H,
m), 3.61 (3H, s), 3.37 (1H, d, J=16 Hz), 2.74 (1H, dd, J=
19, 7.4 Hz), 2.24 (1H, dd, J=19, 2.2 Hz), 2.04 (3H, s), 1.85
(3H, s); 13C NMR (125 MHz, CDCl3): d=209.9, 174.5,
142.7, 137.1, 136.8, 134.4, 128.9 (2C), 127.8, 127.6 (2C),
127.0, 121.0, 119.2, 118.0, 108.8, 105.9, 46.2, 45.1, 29.8, 25.0,
10.0, 8.9; HR-MS (ESI): m/z=352.1676, [C23H23NO+Na]+
requires 352.1672.
References
[1] For reviews on the Nazarov reaction, see: a) K. L. Hab-
ermas, S. E. Denmark, T. K. Jones, Org. React. 1994,
45, 1–158; b) H. Pellissier, Tetrahedron 2005, 61, 6479–
6517; c) A. J. Frontier, C. Collison, Tetrahedron 2005,
61, 7577–7606; d) M. A. Tius, Eur. J. Org. Chem. 2005,
2193–2206; e) W. Nakanishi, F. G. West. Curr. Opin.
Drug Discovery Dev. 2009, 12, 732–751.
[2] For some recent examples of the development of Naza-
rov reaction methodology and applications in synthesis,
see: a) C. J. Rieder, K. J. Winberg, F. G. West, J. Am.
Chem. Soc. 2009, 131, 7504–7505; b) J. A. Malona, K.
Cariou, A. J. Frontier, J. Am. Chem. Soc. 2009, 131,
7560–7561; c) R. Singh, M. K. Parai, G. Panda, Org.
Biomol. Chem. 2009, 7, 1858–1867; d) A. Y. Bitar, A. J.
Frontier, Org. Lett. 2009, 11, 49–52; e) N. Shimada,
B. O. Ashburn, A. K. Basak, W. F. Bow, D. A. Vicic,
M. A. Tius, Chem. Commun. 2010, 46, 3774–3775;
f) M. Wang, F. Han, H. Yuan, Q. Liu. Chem. Commun.
trans-2,3-Dimethyl-4-phenyl-5-(1-tosyl-1H-indol-3-yl)cy-
clopent-2-enone (23a) and 2-methyl-4-phenyl-3-[(1-tosyl-
1H-indol-3-yl)methyl]cyclopent-2-enone (23b): AVK
1
(0.10 g, 0.56 mmol) and 1-(toluenesulfonyl)indole (0.30 g,
1.1 mmol) reacted in the presence of InCl3 (0.24 g,
1.1 mmol). Flash chromatography of the product mixture
provided 23a (yield: 0.064 g, 25%) and 23b (yield: 0.061 g,
24%).
23a: colorless solid, mp 76–788C (CH2Cl2/pentane); IR
(film): n=1708, 1650, 1605 cmÀ1
;
1H NMR (500 MHz,
CDCl3): d=7.94 (1H, m), 7.74 (2H, d, J=8.5 Hz), 7.33 (4H,
m), 7.27 (1H, m), 7.22 (2H, d, J=8.5 Hz), 7.08 (3H, m),
Adv. Synth. Catal. 2011, 353, 64 – 68
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
67