The Journal of Organic Chemistry
Article
afforded the title compound 1p (1.44 g, 3.23 mmol, 99%) as a clear
colorless oil after purification via column chromatography (n-
pentane/EtOAc = 50:1). Rf = 0.70 (n-pentane/EtOAc = 10:1, UV);
1H NMR (300 MHz, CDCl3) δ 7.33 (d, J = 8.6 Hz, 1H), 7.01 (dd, J =
(s), 578 (m), 548 (m), 506 (m), 487 (w), 475 (w), 443 (m). The
analytical data is in accordance with that reported in the literature.43
( 8 R , 9 S , 1 3 S , 1 4 S ) - 3 - ( D i m e t h y l a m i n o ) - 1 3 - m e t h y l -
6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]-
phenanthren-17-one (3q). Following general procedure B, the use of
(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca-
hydro-6H-cyclopenta[a]phenanthren-3-yl trifluoromethanesulfonate
(1q, 0.532 mmol) afforded the title compound 3q (87%, 138 mg,
0.463 mmol, free base) as a white solid after purification via column
chromatography (n-pentane/EtOAc = 20:1). Rf = 0.44 (n-pentane/
8.6, 2.8 Hz, 1H), 6.96 (d, J = 2.7 Hz, 1H), 4.01−3.83 (m, 4H), 2.92−
2.84 (m, 2H), 2.38−2.18 (m, 2H), 2.09−1.71 (m, 5H), 1.70−1.22
(m, 6H), 0.88 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 147.6,
141.1, 139.7, 127.3, 121.2, 119.4, 118.9 (q, J = 320.7 Hz), 118.2, 65.4,
64.7, 49.4, 46.1, 43.9, 38.6, 34.3, 30.7, 29.6, 26.7, 26.0, 22.5, 14.4. 19F
NMR (282 MHz, CDCl3) δ −72.97. MS (EI): m/z (relative
intensity) 446 (6), 384 (15), 99 (100), 86 (12), 84 (10), 28 (35).
HRMS (EI, m/z): calcd for C21H25O5F3S1[M]+ 446.1369, found
446.1370. IR (ATR, neat, cm−1): 2973 (w), 2938 (w), 2872 (w),
1739 (w), 1606 (w), 1583 (w), 1489 (m), 1456 (w), 1418 (s), 1381
(w), 1339 (w), 1308 (w), 1274 (w), 1248 (m), 1204 (s), 1182 (m),
1163 (m), 1139 (s), 1118 (s), 1105 (m), 1075 (w), 1060 (m), 1044
(m), 1032 (m), 1013 (m), 984 (w), 963 (m), 948 (m), 915 (s), 882
(m), 849 (m), 836 (m), 818 (m), 780 (m), 765 (w), 751 (w), 718
(w), 704 (w), 657 (w), 603 (s), 565 (m), 548 (w), 535 (w), 511 (m),
491 (w), 477 (w), 453 (w), 422 (w), 404 (w). The analytical data is
in accordance with that reported in the literature.42
1
EtOAc = 10:1, UV) free base; H NMR (300 MHz, CDCl3) δ 7.19
(d, J = 8.7 Hz, 1H), 6.63 (dd, J = 8.6, 2.8 Hz, 1H), 6.52 (d, J = 2.8 Hz,
1H), 2.98−2.88 (m, 7H), 2.59−1.89 (m, 7H), 1.74−1.37 (m, 6H),
1.28 (s, 1H), 0.92 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 221.2,
149.0, 137.0, 128.3, 126.0, 113.2, 111.1, 50.4, 48.1, 44.0, 40.9, 38.6,
35.9, 31.7, 30.0, 26.8, 26.0, 21.6, 13.9. MS (EI): m/z (relative
intensity) 298 (22), 297 (100), 296 (12), 212 (20), 173 (38), 172
(12). HRMS (EI, m/z): calcd for C20H27NO [M]+ 298.2171, found
298.2167. IR (ATR, neat, cm−1): 2972 (w), 2921 (m), 2870 (m),
2808 (m), 1610 (m), 1561 (w), 1509 (s), 1469 (m), 1458 (m), 1436
(m), 1409 (w), 1376 (m), 1354 (m), 1337 (m), 1299 (m), 1275 (m),
1224 (s), 1195 (m), 1180 (m), 1157 (s), 1120 (s), 1103 (s), 1074
(m), 1059 (s), 1045 (s), 1031 (s), 1010 (m), 1001 (m), 985 (m), 955
(s), 934 (m), 918 (m), 884 (m), 856 (m), 836 (m), 803 (m), 773 (s),
747 (m), 713 (m), 696 (m), 650 (m), 629 (m), 587 (m), 572 (m),
525 (m), 511 (m), 483 (m), 443 (m), 420 (m), 406 (m). Crystal data
of 3q (CCDC1981523): C20H27NO, M = 297.42, orthorhombic,
space group P212121, a = 8.2340(2), b = 12.4121(4), c = 16.2533(5)
Å, V = 1661.11(8) Å3, T = 150(2) K, Z = 4, 9416 reflections
measured, 2923 independent reflections (Rint = 0.0317), final R values
(I > 2σ(I)): R1 = 0.0442, wR2 = 0.1217, final R values (all data): R1 =
0.0453, wR2 = 0.1234, 202 parameters.
(8R,9S,13S,14S)-N,N,13-Trimethyl-6,7,8,9,11,12,13,14,15,16-dec-
ahydrospiro [Cyclopenta[a]phenanthrene-17,2′-[1,3]dioxolan]-3-
amine (3p). Following general procedure B, the use of
(8R,9S,13S,14S)-13-methyl-6,7,8,9,11,12,13,14,-15,16-decahydrospiro
[cyclopenta[a]phenanthrene-17,2′-[1,3]dioxolan]-3-yl trifluorome-
thanesulfonate (1p, 0.365 mmol) afforded the title compound 3p
(110 mg, 0.322 mmol, 88%, free base) as a white solid after
purification via column chromatography (n-pentane/EtOAc = 4:1). Rf
1
= 0.08 (n-pentane/EtOAc = 8:1, UV) free base; m.p. = 90.3 °C; H
NMR (400 MHz, CDCl3) δ 7.19 (d, J = 8.6 Hz, 1H), 6.64 (d, J = 7.4
Hz, 1H), 6.53 (s, 1H), 4.02−3.84 (m, 4H), 2.91 (s, 6H), 2.89−2.77
(m, 2H), 2.37−2.17 (m, 2H), 2.09−1.98 (m, 1H), 1.94−1.71 (m,
4H), 1.69−1.59 (m, 1H), 1.57−1.26 (m, 5H), 0.88 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 137.5, 126.2, 119.6, 113.7, 111.4, 77.4,
65.4, 64.7, 49.5, 46.4, 43.7, 41.3, 39.4, 34.4, 30.9, 30.2, 27.3, 26.3,
22.5, 14.5. MS (EI): m/z (relative intensity) 341 (49), 240 (17), 186
(12), 172 (19), 158 (17), 129 (12), 99 (100), 86 (14), 55 (15), 43
(16). HRMS (EI, m/z): calcd for C20H26O3[M]+ 341.2349, found
341.2368. IR (ATR, neat, cm−1): 2972 (w), 2921 (m), 2870 (m),
2808 (m), 1610 (m), 1561 (w), 1509 (s), 1469 (m), 1458 (m), 1436
(m), 1409 (w), 1376 (m), 1354 (m), 1337 (m), 1299 (m), 1275 (m),
1224 (s), 1195 (m), 1180 (m), 1157 (s), 1120 (s), 1103 (s), 1074
(m), 1059 (s), 1045 (s), 1031 (s), 1010 (m), 1001 (m), 985 (m), 955
(s), 934 (m), 918 (m), 884 (m), 856 (m), 836 (m), 803 (m), 773 (s),
747 (m), 713 (m), 696 (m), 650 (m), 629 (m), 587 (m), 572 (m),
525 (m), 511 (m), 483 (m), 443 (m), 420 (m), 406 (m).
4-Acetylphenyl Trifluoromethanesulfonate (1r). Following gen-
eral procedure A, the use of 1-(4-hydroxyphenyl)ethan-1-one (11.02
mmol) at 0 °C instead of −78 °C and triethylamine as the base
afforded the title compound 1r (2.82 g, 10.51 mmol, 95%) as a clear
colorless oil after purification via column chromatography (n-
pentane/EtOAc = 5:1). Rf = 0.27 (n-pentane/EtOAc = 5:1, UV);
1H NMR (300 MHz, CDCl3) δ 8.04 (d, J = 8.9 Hz, 2H), 7.36 (d, J =
8.8 Hz, 2H), 2.61 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 196.1,
152.5, 136.9, 130.6, 121.7, 118.7 (q, J = 320.8 Hz), 26.7. 19F NMR
(282 MHz, CDCl3) δ −73.03 (dd, J = 10.0, 4.8 Hz). MS (EI): m/z
(relative intensity) 268 (17), 253 (100), 95 (12). HRMS (EI, m/z):
calcd for C9H7O4F3S [M]+ 268.0012, found 268.0005. IR (ATR, neat,
cm−1): 1690 (m), 1594 (w), 1497 (w), 1423 (m), 1409 (m), 1360
(w), 1301 (w), 1263 (m), 1250 (m), 1205 (s), 1132 (s), 1077 (w),
1014 (w), 960 (w), 879 (s), 842 (s), 787 (m), 762 (w), 672 (m), 632
(m), 607 (s), 585 (s), 571 (m), 524 (m), 471 (w), 422 (w).
(8R,9S,13S)-13-Methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca-
hydro-6H-cyclopenta[a]phenanthren-3-yl Trifluoromethanesulfo-
nate (1q). Following general procedure A, the use of estrogen
(3.70 mmol) and NEt3 as the base afforded the title compound 1q
(1.46 g, 19.24 mmol, 98%) as a white solid after purification via
column chromatography (n-pentane/EtOAc = 5:1). Rf = 0.30 (n-
1-(4-(Dimethylamino)phenyl)ethan-1-one Hydrochloride (3r·
HCl). Following general procedure B, the use of 4-formyl-2-
methoxyphenyl trifluoromethanesulfonate (1r) afforded the title
compound 3r (15 mg, 0.092 mmol, 18%) as a white solid after
purification via column chromatography (n-pentane/EtOAc = 10:1)
and treatment with 2 M HCl in Et2O. Rf = 0.20 (n-pentane/EtOAc =
1
pentane/EtOAc = 5:1, UV); m.p. = 91.3 °C; H NMR (300 MHz,
1
CDCl3) δ 7.34 (d, J = 8.5 Hz, 1H), 7.03 (dd, J = 8.6, 2.8 Hz, 1H),
6.99 (d, J = 2.6 Hz, 1H), 2.94 (dd, J = 8.7, 4.3 Hz, 2H), 2.59−2.46
(m, 1H), 2.45−2.36 (m, 1H), 2.30 (td, J = 10.4, 9.9, 4.1 Hz, 1H),
2.23−1.91 (m, 4H), 1.73−1.38 (m, 6H), 0.92 (s, 3H). 13C{1H} NMR
(75 MHz, CDCl3) δ 220.5, 147.7, 140.4, 139.4, 127.3, 121.4, 118.9 (q,
J = 320.8 Hz), 118.4, 50.5, 48.0, 44.2, 37.9, 35.9, 31.6, 29.5, 26.2, 25.8,
21.7, 13.9. 19F NMR (282 MHz, CDCl3) δ −72.97. MS (EI): m/z
(relative intensity) 402 (60), 358 (35), 345 (22), 292 (11), 251 (17),
225 (22), 213 (35), 185 (14), 157 (17), 129 (24), 128 (23), 115
(39), 91 (22), 69 (100), 55 (24), 41 (24). HRMS (EI, m/z): calcd for
C21H25O5F3S1[M]+ 402.1107, found 402.1105. IR (ATR, neat, cm−1):
2966 (w), 2931 (w), 2869 (w), 1736 (s), 1604 (w), 1488 (w), 1455
(w), 1418 (s), 1405 (m), 1373 (w), 1338 (w), 1275 (w), 1249 (m),
1207 (s), 1137 (s), 1085 (m), 1054 (m), 1007 (m), 983 (w), 951
(w), 916 (s), 901 (m), 879 (m), 848 (m), 836 (s), 820 (m), 785 (m),
766 (w), 723 (w), 714 (w), 702 (m), 654 (w), 639 (w), 620 (m), 605
5:1, UV) free base; H NMR (300 MHz, CDCl3) δ 7.94−7.84 (m,
1H), 6.73−6.59 (m, 1H), 3.07 (s, 3H), 2.52 (s, 2H). 13C{1H} NMR
(75 MHz, CDCl3) δ 196.4, 153.4, 130.5, 125.4, 110.7, 40.1, 26.0. MS
(EI): m/z (relative intensity) 163 (30), 148 (100), 118 (10), 104
(12), 91 (11), 78 (10), 77 (23), 74 (13), 63 (13), 51 (13), 50 (11),
43 (29), 42 (39). HRMS (ESI-TOF, m/z): calcd for C10H13NO [M +
H]+ 164.1075, found 164.1075. IR (ATR, neat, cm−1): 2901 (w),
2822 (w), 2651 (w), 1649 (m), 1586 (m), 1547 (w), 1522 (w), 1429
(m), 1413 (m), 1356 (m), 1313 (m), 1282 (m), 1229 (m), 1187 (m),
1130 (m), 1067 (m), 1018 (m), 943 (m), 814 (s), 654 (m), 592 (m),
560 (m), 498 (m). The analytical data is in accordance with that
reported in the literature.44
4-Allyl-2-methoxyphenyl Trifluoromethanesulfonate (1s). Fol-
lowing general procedure A, the use of 4-allyl-2-methoxyphenol (3.50
mmol) and 2,6-dimethylpyridine as the base afforded the title
compound 1s (830 mg, 2.67 mmol, 76%) as a colorless oil after
H
J. Org. Chem. XXXX, XXX, XXX−XXX