3- and 2-Fluoro-8-methoxy-4a,4b,5,6,12,12a-hexahydrochry-
sene-1,4-dione (7a and 7b). 82 mg (13%) of 17a and 17b (91 : 9,
1H NMR) (Found: C, 72.43%; H, 5.11%. C19H17FO3 (312.3)
requires C, 73.06; H, 5.49%); Found (HRMS): M ϩ Naϩ,
335.1098. C19H17FO3 ϩ Naϩ requires 335.1060.
Diels–Alder reaction of 2,3-difluoro-p-benzoquinone (2b) with
Dane’s diene (1)
To Dane’s diene (1) (215 mg, 1.16 mmol) in diethyl ether (8 cm3)
was added 2,3-difluoro-p-benzoquinone (2b) (68 mg, 0.47
mmol). The solution turned red immediately and was stirred at
50 ЊC for 45 min in a glass tube with a Young’s tap. The reaction
was accompanied by precipitation of a yellow solid, which was
filtered after cooling down to room temperature. The residue
(118 mg) contained a share of 90% (19F NMR) of two products
(73 : 27),58 each of which contained two fluorine atoms per
molecule.
1
Compound 7a. H NMR (acetone-d6) δ 1.78–1.88 (m, 1 H,
3 or 2
3 or 2
5-H), 2.27 (ddt,
J
12.9,
J
12.2, 3JH,H 5.2, 1 H, 5-H),
H,H
H,H
2.40–2.60 (m, 2 H, 12-H), 2.62–2.90 (m, 3 H, 6-H, H-4b), 3.29–
3.41 (m, 1 H, 12a-H), 3.71–3.77 (m, 1 H, 4a-H), 3.76 (s, 3 H,
OCH3), 6.09–6.11 (m, 11-H), 6.44 (dd, 4JH,H 1.1, 3JH,F 12.2, 1 H,
2-H), 6.64 (d, 4JH,H 2.6, 1 H, 7-H), 6.71 (dd, 4JH,H 2.6, 3JH,H 8.8,
1 H, 9-H), 7.51 (d, 4JH,H 8.8, 1 H, 10-H); 13C NMR (acetone-d6)
δ 26.5 (t, C-5 or C-6), 27.2 (t, C-5 or C-6), 31.2 (t, C-12), 38.1
(dd, 4JC,F 2.6, C-4b), 48.6 (d, C-12a), 50.0 (dd, 3JC,F 3.8, C-4a),
54.9 (q, OCH3), 113.1 (d, C-7 or C-9), 113.4 (d, C-7 or C-9),
114.6 (d, C-11), 117.2 (dd, 3JC,F 8.9, C-2), 124.9 (d, C-10), 127.2
(s, C-10a), 129.4 (s, C-10b), 138.5 (s, C-6a), 159.2 (s, C-8), 191.9
main product. 19F NMR (CDCl3) δ Ϫ136.4 (d, 3JF, F 5.7, 1 F),
Ϫ139.2 (dd, 4JF, H 5.7, 3JF, F 5.7, 1 F).
minor product. 19F NMR (CDCl3) δ Ϫ136.7 (d, 3JF, F 5.7, 1 F),
Ϫ137.9 (dd, 4JF, H 5.7, 3JF, F 5.7, 1 F).
3
2
(d, JC,F 14.5, C-1), 198.8 (d, JC,F 21.1, C-4);54 19F NMR
2,3-Difluoro-8-methoxy-4b,5,6,12-tetrahydrochrysene-1,4-diol
(14). was obtained as a red solid (93 mg, 60%) on attempted
column-chromatographic separation (after coating crude
product on silica gel; pentane–diethyl ether 10 : 1, 6 : 1) of the
residue. (Found: C, 68.62; H, 4.59. C19H16F2O3 (330.3) requires
(acetone-d6) δ Ϫ111.7 (d, JF, H 12.2); m/z 312 (100%, Mϩ), 297
3
(12, Mϩ Ϫ CH3), 295 (14), 291 (12), 290 (13), 284 (36, 312 Ϫ
CO), 281 (9, Mϩ Ϫ OCH3), 249 (14), 207 (14), 191 (24), 167
(24), 147 (32), 115 (13).55
1
C, 69.08; H, 4.88%); mp 151–152 ЊC (diethyl ether). H NMR
3
3
3
(acetone-d6) δ 1.55 (ddt, JHax,Heq 5.5, JHax,Hax 12.6, JHax,Hax
=
=
1
Compound 7b. H NMR (acetone-d6) δ 1.78–1.88 (m, 1 H,
2JH,H 12.2, 1 H, 5-Hax), 2.80 (ddt, JHeq,Hax 6.2, JHeq,Hax
3
3
3 or 2
3 or 2
5-H), 2.27 (ddt,
J
12.9,
J
12.2, 3JH,H 5.2, 1 H, 5-H),
3JHeq,Heq 1.9, JH,H 12.2, 1 H, 5-Heq), 2.88 (dd, JHeq,Hax 6.0,
H,H
H,H
2
3
2.40–2.60 (m, 2 H, 12-H), 2.62–2.90 (m, 3 H, 6-H, H-4b), 3.29–
3.41 (m, 1 H, 12a-H), 3.71–3.77 (m, 1 H, 4a-H), 3.76 (s, 3 H,
OCH3), 6.09–6.11 (m, 11-H), 6.50 (d, 3JH,F 12.2, 1 H, 3-H), 6.64
(d, 4JH,H 2.6, 1 H, 7-H), 6.71 (dd, 4JH,H 2.6, 3JH,H 8.8, 1 H, 9-H),
7.53 (d, 4JH,H 9.1, 1 H, 10-H); 19F NMR (acetone-d6) δ Ϫ115.6
2JH,H 17.3, 1 H, 6-Heq), 3.14 (ddd, JHax,Hax 12.6, JHax,Heq 6.0,
3
3
2JH,H 17.3, 1 H, 6-Hax), 3.43 (dm, JH,H 3.7, 1 H, 12-H), 3.52–
3
3.62 (m, 1 H, 4b-H), 3.77 (s, 3 H, 13-H), 6.01 (t, 3JH,H 3.7, 1 H,
11-H), 6.67 (d, 4JH,H 2.6, 1 H, 7-H), 6.73 (dd, 4JH,H 2.6, 3JH,H 8.6,
3
1 H, 7-H), 7.38 (d, JH,H 8.6, 10-H), 8.09 (s, 1 H, OH), 8.19 (s,
4
3
(dd, JF, H 5.7, JF, H 12.2); m/z 312 (100%, Mϩ), 297 (26, Mϩ
Ϫ
1 H, OH); 13C NMR (acetone-d6) δ 25.3 (dt, JC,F 2.5, C-12),
4
CH3), 295 (23), 291 (13), 284 (4, 312 Ϫ CO), 263 (36), 249 (23),
4
30.5 (t, C-5 or C-6), 32.2 (t, C-5 or C-6), 35.7 (dd, JC,F 2.5,
220 (24), 207 (23), 167 (28), 109 (22), 88 (27).55
C-4b), 54.9 (q, C-13), 112.6, 113.5, 114.7 (each d, C-7, C-9,
3
3
C-11), 118.2 (d, JC,F 2.5, C-4a or C-12a), 122.3 (d, JC,F 2.5,
C-4a or C12a), 125.7 (d, C-10), 130.3 (s, C-10a), 135.3 (d, 2JC,F
11.4, C-1 or C-4), 135.8 (s, C-10b), 136.2 (d, JC,F 11.4, C-1 or
C-4), 137.6 (s, C-6a), 139.6 (dd, JC,F 15.3, JC,F 239.1, C-2
3- and 2-Fluoro-8-methoxy-4a,5,6,11,12,12a-hexahydrochry-
sene-1,4-dione (8a and 8b). 72 mg (0.23 mmol, 11%)56 of 8a and
8b (92 : 8, 1H NMR) (Found: C, 72.54%; H, 5.22%. C19H17FO3
(312.3) requires C, 73.06; H, 5.49%); m/z (ESI) 313 (100%, M ϩ
Hϩ), 285 (8, 313 Ϫ CO), 186 (92, C13H14Oϩ; retro-Diels–Alder
after tautomerisation), 161 (28), 155 (27), 121 (13). Found
(HRMS): M ϩ Naϩ, 335.1084. C19H17FO3 ϩ Naϩ requires
335.1060.
2
2
1
2
1
or C-3), 140.1 (dd, JC,F 15.3, JC,F 239.1, C-2 or C-3), 159.4
(s, C-8); 19F NMR (acetone-d6) δ Ϫ163.9 (d, 3JF, F 21.0), Ϫ164.2
(d, 3JF, F 21.0); m/z 330 (100%, Mϩ), 326 (25), 315 (19, Mϩ–CH3),
302 (32, Mϩ–CO after tautomerisation), 299 (10, Mϩ Ϫ OCH3),
279 (15), 265 (15), 253 (22), 209 (18, Mϩ Ϫ COHC2F2COH Ϫ
H), 207 (21), 185 (22, C13H14Oϩ Ϫ H; retro Diels–Alder after
tautomerisation), 158 (18, 185 Ϫ C2H3), 147 (22), 145 (23,
C6H2F2O2ϩ ϩ H; retro Diels–Alder after tautomerisation), 121
(23), 102 (20), 66 (21), 40 (92). Found (HRMS): Mϩ, 331.1149.
C19H16F2O3 ϩ Hϩ (331.3) requires 331.1146.55
Compound 8a. 1H NMR (CDCl3) δ 1.95–2.14 (m, 2 H, 11-H),
2.15–2.38 (m, 2 H, 5-H), 2.40–2.65 (m, 2 H, 12-H), 2.66–2.94
(m, 2 H, 6-H), 3.08–3.17 (m, 12a-H), 3.64–3.70 (m, 4a-H),
4
3
3.76 (s, 3 H, OMe), 6.37 (dd, JH,H 0.7, JH,F 11.2, 1 H, 2-H),
6.68–6.74 (m, 2 H, 7-H, 9-H), 7.09–7.14 (m, 1 H, 10-H); 13C
NMR (CDCl3) δ 24.2 (t, C-12), 25.2 (t, C-11), 27.7 (t, C-5), 28.3
Diels–Alder reaction of 2,6-difluoro-p-benzoquinone (2c) with
Dane’s diene (1)
3
(t, C-6), 48.4 (d, C-12a), 52.4 (dd, JC,F 3.9, C-4a), 55.3 (q,
OCH3), 111.1 (d, C-9), 113.5 (d, C-7), 118.7 (dd, 2JC,F 7.7, C-2),
123.5 (d, C-10), 125.0 (d, 4JC,F 1.8, C-4b), 127.9 (s, C-10a), 129.4
3,4a- and 2,12a-Difluoro-8-methoxy-4a,4b,5,6,12,12a-hexa-
hydrochrysene-1,4-dione (15a and 15b). Dane’s diene (1) (173
mg, 0.93 mmol) and 2,6-difluoro-p-benzoquinone (2c) (146 mg,
1.01 mmol) were dissolved in diethyl ether (6 cm3) and stirred
for 12.5 h at rt. The solution turned bright-red immediately
and the formation of a yellow precipitate was observed. The
product mixture was concentrated under reduced pressure
(water bath of rotary evaporator not exceeding 40 ЊC) and the
regioisomeric mixture of cycloadducts (315 mg, quantitative)
15a and 15b (93 : 7, 19F NMR) was furnished as a green
foam, showing a purity of 95% (19F NMR; also 1H NMR
just indicated minor impurities). 15a,b. m/z (ESI) 353 (28%,
M ϩ Naϩ), 331 (13, M ϩ Hϩ).
1
(s, C-10b), 137.6 (s, C-6a), 158.9 (s, C-8), 162.8 (d, JC,F 297.7,
2
3
C-3), 191.1 (d, JC,F 19.2, C-4), 198.9 (d, JC,F 14.4, C-1); 19F
NMR (CDCl3) δ Ϫ109.1 (d, 3JF, H 11.2).55
Compound 8b. 1H NMR (CDCl3) δ 1.95–2.14 (m, 2 H, 11-H),
2.15–2.38 (m, 2 H, 5-H), 2.40–2.65 (m, 2 H, 12-H), 2.66–2.94
(m, 2 H, 6-H), 3.08–3.17 (m, 12a-H), 3.64–3.70 (m, 4a-H), 3.76
3
(s, 3 H, OMe), 6.41 (d, JH,F 11.0, 1 H, 3-H), 6.68–6.74 (m,
2 H, 7-H, 9-H), 7.09–7.14 (m, 1 H, 10-H); 13C NMR (CDCl3)
δ 24.0 (t, C-12), 24.8 (t, C-11), 27.7 (t, C-5), 28.3 (t, C-6), 46.5
(dd, 3JC,F 3.3, C-12a), 54.0 (d, C-4a), 55.3 (q, OCH3), 111.1 (d,
C-9), 113.1 (d, C-7), 119.2 (dd, 2JC,F 7.9, C-3), 123.4 (d, C-10),
128.0 (s, C-10a), 130.0 (s, C-10b), 137.6 (s, C-6a), 158.8 (s, C-8),
Compound 15a. 1H NMR (CDCl3) δ 1.86–1.96 (m, 2 H, 5-H),
2.55–2.93 (m, 5 H, 4b-H, 6-H, 12-H), 3.39 (dt, 3JH,F 10.7, 3JH,H
6.4, 1 H, 12a-H), 3.76 (s, 3 H, OMe), 6.02–6.07 (m, 1 H, 11-H),
6.47 (d, 3JH,F 10.7, 1 H, 2-H), 6.57 (d, 4JH,H 2.6, 1 H, 7-H), 6.71
1
2
162.0 (d, JC,F 296.4, C-2), 192.5 (d, JC,F 18.3, C-1), 197.2 (d,
3JC,F = 12.4, C-4);57 19F NMR (CDCl3) δ Ϫ110.6 (dd, JF, H 3.8,
4
3JF, H 11.0).55
2726
J. Chem. Soc., Perkin Trans. 1, 2002, 2719–2728