Domino Friedel–Crafts-Type Cyclizations of Difluoroalkenes
FULL PAPER
2-Butyl-1,1-difluoro-3-phenylbuta-1,3-diene (9a): 1H NMR (500 MHz,
CDCl3, 258C, TMS): d=0.85 (t, 3JH,H =7.1 Hz, 3H; CH3), 1.23–1.34 (m,
of trifluoromethanesulfonic acid (TfOH, 0.54 mL, 6.1 mmo1). After the
reaction mixture had been stirred at 08C for 15 min, phosphate buffer
(pH 7) was added to quench the reaction. The organic materials were ex-
tracted three times with CH2Cl2. The combined extracts were washed
with brine and dried over anhydrous Na2SO4. After remova1 of the sol-
vent under reduced pressure, the residue was purified by thin layer chro-
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4H; CH2CH2), 2.09 (tdd, JH,H =7.3 Hz, JH,F =2.3, 2.3 Hz, 2H; CH2), 5.25
(s, 1H; =CH2), 5.58 (s, 1H; =CH2), 7.27–7.37 ppm (m, 5H; ArH);
13C NMR (126 MHz, CDCl3, 258C): d=13.8, 22.0, 26.3, 29.6, 92.5 (dd,
3
2JC,F =14, 22 Hz; =C), 116.9, 126.7, 127.9, 128.4, 139.2, 141.4 (d, JC,F
=
3.0 Hz; =C), 154.1 ppm (dd, 1JC,F =288, 289 Hz; =CF2); 19F NMR
(470 MHz, CDCl3, 258C, C6F6): d=70.3 (d, 2JF,F =43 Hz, 1F; =CF2),
72.6 ppm (d, 2JF,F =43 Hz, 1F; =CF2); IR (neat): n˜ =2958, 2929, 1732,
1493, 1252, 777 cmÀ1; HRMS: m/z calcd for C14H16F2 [M]+: 222.1220;
found: 222.1216.
matography (hexane) to give 14a (108 mg, 0.418 mmo1, 96%) as a co1or-
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less solid. 1H NMR (500 MHz, CDCl3, 258C, TMS): d=1.32 (d, JH,H
=
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6.4 Hz, 3H; CH3), 2.47 (s, 3H; CH3), 2,58 (brdd, 2JH,H =16.5 Hz, JH,H
=
10.5 Hz, 1H; CH2), 2.90–2.98 (m, 2H; CH+CH2), 7.29–7.35 (m, 2H;
ArH), 7.37–7.43 (m, 3H; ArH), 7.58 (s, 1H; ArH), 7.74–7.80 (m, 1H;
ArH), 7.85–7.91 (m, 1H; ArH), 8.44–8.48 ppm (m, 1H; ArH); 13C NMR
(126 MHz, CDCl3, 258C): d=18.3, 20.4, 32.6, 34.2, 124.9, 125.0, 125.2,
125.6, 125.7, 127.0, 127.7, 127.8, 128.7, 129.1, 131.5, 133.5, 133.6, 133.9,
135.7, 143.4 ppm; IR (KBr disk): n˜ =3059, 2958, 1736, 1597, 1450, 1379,
1265, 1028, 879, 752 cmÀ1; HRMS: m/z calcd for C20H18 [M]+: 258.1408;
found: 258.1407.
3-Benzyl-2-butyl-1,1-difluorobuta-1,3-diene (9b): 1H NMR (500 MHz,
CDCl3, 258C, TMS): d=0.85 (t, 3JH,H =7.0 Hz, 3H; CH3), 1.17–1.32 (m,
4H; CH2CH2), 2.23–2.08 (m, 2H; CH2), 3.49 (s, 2H; CH2), 5.06 (dd,
3
4JH,H =1.4, 1.4 Hz, 1H; =CH2), 5.10 (s, 1H; =CH2), 7.17 (d, JH,H =7.0 Hz,
3
2H; ArH), 7.20 (dd, 3JH,H =7.3, 7.3 Hz, 1H; ArH), 7.28 ppm (dd, JH,H
=
7.0, 7.3 Hz, 2H; ArH); 13C NMR (126 MHz, CDCl3, 258C): d=13.8, 22.1,
25.9, 29.7 (d, 3JC,F =2 Hz; CH2), 41.7 (d, 4JC,F =2 Hz; CH2), 92.5 (dd,
2JC,F =21, 12 Hz; =C), 117.0 (dd, 4JC,F =5, 3 Hz; =CH2), 126.3, 128.3,
128.9, 138.9, 140.5 (dd, 3JC,F =4, 4 Hz; =C), 153.3 ppm (dd, 1JC,F =286,
291 Hz; =CF2); 19F NMR (470 MHz, CDCl3, 258C, C6F6): d=70.1 (d,
2JF,F =45 Hz, 1F; =CF2), 73.1 ppm (d, 2JF,F =45 Hz, 1F; =CF2); IR (neat):
n˜ =3030, 2958, 1735, 1632, 1497, 1244, 1119, 1018, 908, 700 cmÀ1; HRMS:
m/z calcd for C15H18O [M]+: 236.1376; found: 236.1368.
Palladium carbon (25 wt%, 15 mg, 10 mol%) was added to a solution of
14a (60 mg, 0.23 mmol) in mesitylene. The reaction mixture was stirred
for 15 h under reflux. The mixture was filtered, and the organic materials
were extracted three times with CH2Cl2. The combined extracts were
washed with water and dried over anhydrous Na2SO4. After removal of
the solvent under reduced pressure, the residue was purified by thin layer
chromatography (hexane) to give 16 (55 mg, 0.22 mmol, 96%) as a color-
less solid.
5,7-Dimethylbenzo[c]phenanthrene (16): 1H NMR (500 MHz, CDCl3,
258C, TMS): d=2.80 (s, 3H; CH3), 2.85 (s, 3H; CH3), 7.53–7.60 (m, 2H;
ArH), 7.65–7.68 (m, 2H; ArH), 7.71 (s, 1H; ArH), 7.87 (s, 1H; ArH),
7.89–7.92 (m, 1H; ArH), 8.26–8.30 (m, 1H; ArH), 8.96 (d, 3JH,H =7.6 Hz,
1H; ArH), 9.07–9.12 ppm (m, 1H; ArH); 13C NMR (126 MHz, CDCl3,
258C): d=20.1, 20.4, 122.9, 124.2, 125.1, 125.4, 125.5, 125.8, 126.7, 127.4,
127.6, 128.0, 128.9, 129.3, 130.4, 130.5, 131.9, 132.6, 132.8, 133.0 ppm; IR
(KBr disk): n˜ =3066, 2918, 1736, 1603, 1439, 1396, 1255, 1032, 879,
754 cmÀ1; HRMS: m/z calcd for C20H16 [M]+: 256.1252; found: 256.1245.
1,1-Difluoro-3-methyl-2-(2-phenylpropyl)buta-1,3-diene (10a): 1H NMR
(500 MHz, CDCl3, 258C, TMS): d=1.24 (d, 3JH,H =6.7 Hz, 3H; CH3),
1.85–1.89 (s, 3H; CH3), 2.36–2.44 (m, 2H; CH2), 2.84 (tq, 3JH,H =7.3,
2
6.7 Hz, 1H; CH), 4.94 (d, 2JH,H =0.6 Hz, 1H; =CH2), 5.06 (d, JH,H
=
0.6 Hz, 1H; =CH2), 7.15–7.22 (m, 3H; ArH), 7.28 ppm (dd, 3JH,H =7.6,
7.6 Hz, 2H; ArH); 13C NMR (126 MHz, CDCl3, 258C): d=21.0, 22.3 (dd,
2
J
C,F =5, 2 Hz), 34.9 (d, JC,F =2 Hz), 37.9 (d, JC,F =2 Hz), 92.3 (dd, JC,F
=
4
20, 12 Hz; =C), 115.6 (dd, JC,F =5, 3 Hz; =CH2), 126.2, 126.9, 128.3, 136.8
(dd, 3JC,F =3, 3 Hz; =C), 146.5, 154.0 ppm (dd, 1JC,F =277, 293 Hz; =CF2);
19F NMR (470 MHz, CDCl3, 258C, C6F6): d=72.0 (d, 2JF,F =42 Hz, 1F; =
CF2), 74.4 ppm (d, 2JF,F =42 Hz, 1F; =CF2); IR (neat): n˜ =2964, 1731,
1704, 1604, 1494, 1454, 1240, 1118, 1008, 902, 761, 700 cmÀ1; HRMS: m/z
calcd for C15H18F2 [M]+: 2022.1220; found: 222.1225.
Spectral data for other cyclization products of 1,1-difluoroalka-1,3-dienes
(ketones, phenols, and fluorenes).
2-Butyl-3-methyl-1H-inden-1-one (11a): 1H NMR (500 MHz, CDCl3,
258C, TMS): d=0.91 (t, 3JH,H =7.3 Hz, 3H; CH3), 1.29–1.38 (m, 2H;
CH2), 1.40–1.48 (m, 2H; CH2), 2.11 (s, 3H; CH3), 2.27 (t, 3JH,H =7.5 Hz,
(E)-3-Ethyl-1,1-difluoro-2-(2-phenylpropyl)hexa-1,3-diene
(10b):
1H NMR (500 MHz, CDCl3, 258C, TMS): d=0.91 (t, 3JH,H =7.6 Hz, 3H;
CH3), 0.98 (t, 3JH,H =7.6 Hz, 3H; CH3), 1.22 (d, 3JH,H =7.0 Hz, 3H; CH3),
2.08 (m, 2H; CH2), 2.02–2.19 (m, 2H; CH2), 2.24–2.35 (m, 2H; CH2),
2H; CH2), 7.01 (d, 3JH,H =7.4 Hz, 1H; ArH), 7.16 (dd, 3JH,H =7.4, 7.4 Hz,
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1H; ArH), 7.32 (dd, 3JH,H =7.4, 7.4 Hz, 1H; ArH), 7.36 ppm (d, JH,H
=
7.4 Hz, 1H; ArH); 13C NMR (126 MHz, CDCl3, 258C): d=11.5, 13.9,
22.5, 22.7, 31.2, 118.5, 121.5, 128.0, 130.9, 133.2, 135.2, 146.4, 153.8,
198.2 ppm; IR (neat): n˜ =2960, 2940, 1710, 1610, 1460, 1390, 760, 715,
670 cmÀ1; elemental analysis (%) calcd for C14H16O: C 83.96; H 8.05;
found: C 83.71; H 7.86.
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2.74 (tq, JH,H =7.0, 7.0 Hz, 1H; CH), 5.24 (t, JH,H =7.3 Hz, 1H; =CHEt),
3
7.17 (d, JH,H =7.6 Hz, 2H; ArH), 7.18 (dd, 3JH,H =7.6, 7.6 Hz, 1H; ArH),
3
7.28 ppm (dd, JH,H =7.6, 7.6 Hz, 2H; ArH); 13C NMR (126 MHz, CDCl3,
258C): d=13.2, 14.3, 21.1, 21.2, 21.6 (d, JC,F =2 Hz), 34.3, 37.7 (d, JC,F
=
2 Hz), 92.3 (dd, 2JC,F =20, 15 Hz; =C), 126.1, 127.0, 128.3, 132.1 (dd,
3JC,F =4, 12 Hz; =C), 132.8 (dd, 4JC,F =3, 3 Hz; =CHEt), 146.7, 154.2 ppm
(dd, 1JC,F =286, 286 Hz; =CF2); 19F NMR (470 MHz, CDCl3, 258C, C6F6):
2-Butyl-3-methyl-1-naphthol (11b): 1H NMR (500 MHz, CDCl3, 258C,
TMS): d=0.97 (t, 3JH,H =7.3 Hz, 3H; CH3), 1.47 (tq, 3JH,H =7.3, 7.3 Hz,
2H; CH2), 1.57 (m, 2H; CH2), 2.46 (d, 4JH,H =0.9 Hz, 3H; CH3), 2.76 (t,
3JH,H =7.9 Hz, 2H; CH2), 5.16 (s, 1H; OH), 7.26 (s, 1H; ArH), 7.37–7.41
(m, 2H; ArH), 7.68–7.70 (m, 1H; ArH), 8.00–8.04 ppm (m, 1H; ArH);
13C NMR (126 MHz, CDCl3, 258C): d=14.0, 20.4, 23.1, 26.4, 31.6, 120.7,
120.8, 121.7, 123.1, 124.5, 125.5, 127.0, 132.8, 135.4, 148.2 ppm; IR (neat):
n˜ =3340, 2950, 1465, 1365, 1280, 1110, 865, 745 cmÀ1; HRMS: m/z calcd
for C15H18O 214.1358 [M]+; found: 214.1357.
4-Methyl-2-(1-methylethylidene)-a-tetralone (12a): 1H NMR (500 MHz,
CDCl3, 258C, TMS): d=1.30 (d, 3JH,H =7.0 Hz, 3H; CH3), 1.95 (s, 3H;
CH3), 2.24 (s, 3H; CH3), 2.71 (dd, 2JH,H =14.0 Hz, 3JH,H =5.5 Hz, 1H;
CH2), 2.84 (dd, 2JH,H =14.0 Hz, 3JH,H =3.1 Hz, 1H; CH2), 3.08–3.16 (m,
2
2
d=68.1 (d, JF,F =48 Hz, 1F; =CF2), 68.7 ppm (d, JF,F =48 Hz, 1F; =CF2);
IR (neat): n˜ =3033, 2966, 1732, 1545, 1377, 1225, 1117, 1070, 762,
698 cmÀ1
;
HRMS: m/z calcd for C17H22F2 [M]+: 264.1689; found:
264.1678.
1,1-Difluoro-3-phenyl-2-(2-phenylpropyl)buta-1,3-diene (13b): 1H NMR
(500 MHz, CDCl3, 258C, TMS): d=1.21 (d, 3JH,H =6.8 Hz, 3H; CH3),
2.28–2.40 (m, 2H; CH2), 2.75 (tq, 3JH,H =6.8, 6.8 Hz, 1H; CH), 5.15 (s,
1H; =CH2), 5.54 (s, 1H; =CH2), 7.08 (d, 3JH,H =7.0 Hz, 2H; ArH), 7.16
(dd, 3JH,H =7.0, 7.0 Hz, 1H; ArH), 7.24 (d, 3JH,H =7.3 Hz, 2H; ArH),
7.25–7.34 ppm (m, 5H; ArH); 13C NMR (126 MHz, CDCl3, 258C): d=
21.4, 34.9, 37.8, 91.4 (dd, 2JC,F =15, 22 Hz; =C), 117.5 (dd, 4JC,F =3, 3 Hz;
=CH2), 126.2, 126.8, 127.0, 127.9, 128.3, 128.4, 139.0, 141.1 (dd, 3JC,F =2,
2 Hz; =C), 146.2, 154.8 ppm (dd, 1JC,F =288, 290 Hz; =CF2); 19F NMR
(470 MHz, CDCl3, 258C, C6F6): d=71.3 (d, 2JF,F =43 Hz, 1F; =CF2),
73.5 ppm (d, 2JF,F =43 Hz, 1F; =CF2); IR (neat): n˜ =2962, 1732, 1603,
1495, 1454, 1246, 1119, 1003, 908, 700 cmÀ1; HRMS (FAB): m/z calcd for
C19H18F2 [M]+: 284.1376; found: 284.1368.
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1H; CH), 7.25 (d, JH,H =7.3 Hz, 1H; ArH), 7.31 (ddd, JH,H =7.3, 7.3 Hz,
4JH,H =0.9 Hz, 1H; ArH), 7.46 (ddd, JH,H =7.3, 7.3 Hz, JH,H =1.2 Hz, 1H;
ArH), 8.08 ppm (dd, 3JH,H =7.3 Hz, 4JH,H =1.2 Hz, 1H; ArH); 13C NMR
(126 MHz, CDCl3, 258C): d=21.2, 23.1, 23.5, 34.1, 35.7, 126.6, 127.1,
127.9, 128.5, 132.7, 134.0, 147.0, 148.2, 189.8 ppm; IR (neat): n˜ =2923,
1664, 1600, 1457, 1305, 1270, 1226, 927, 757 cmÀ1; HRMS: m/z calcd for
C14H16O [M]+: 200.1201; found: 200.1191.
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Domino cyclizations of 1,1-difluoroalka-1,3-dienes: The synthesis of 16 is
described as a typical procedure. Compound 13a (130 mg, 0.436 mmo1)
in HFIP (0.5 mL) was added at 08C over 1 h to an HFIP solution (4 mL)
2-(1-Ethylbutylidene)-4-methyl-a-tetralone (12b, 52:48): 1H NMR
(500 MHz, CDCl3, 258C, TMS): d=0.99 (t, 3JH,H =7.3 Hz, 3Hꢂ0.48;
Chem. Eur. J. 2011, 17, 12175 – 12185
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12183