Arkivoc 2018, iv, 13-22
Valdez-Garcia, R. M. et al.
Experimental Section
General. Reactions were monitored by TLC on ALUGRAM SIL G/UV254 plates from MACHEREY-NAGEL. TLC
plates were sprayed with a 1% solution of vanillin in 50% HClO4 and heated until color developed. Melting
points were measured on a Melt-Temp II apparatus. NMR spectra were recorded in CDCl3 solutions in a Varian
INOVA 400 spectrometer using the solvent signal as reference. NMR signals assignments were carried out with
1
the aid of combined 1D and 2D NMR techniques that included H, 13C, COSY, Nuclear Overhauser Effect
Spectroscopy (NOESY), Heteronuclear Single Quantum Correlation (HSQC) and Heteronuclear Multiple Bond
Correlation (HMBC). High resolution mass spectra were registered in a Jeol, AccuTOF JMS-T100LC
spectrometer. The starting alkynones 4a and 4b were obtained following our previously described protocols
(vide supra Scheme 1).8,9,12 Previously obtained physical and NMR data for 4a and 4b are provided for
comparison purposes.
1
17-Acetoxy-4,5-epoxy-5-androstan-3-one (4a).12 Mp 140–142 °C (from EtOAc) H NMR (400 MHz, CDCl3)
ppm: 4.59 (dd, J 9.2, 7.8 Hz, 1H, H-17), 2.51 (ddd, J 14.5, 6.3, 6.3 Hz, 1H, H-6 ax.), 2.26 (ddd, J 14.7, 4.5, 2.4
Hz, 1H, H-6 eq.), 1.91 (m, 1H, H-4), 2.03 (s, 3H, CH3 acetyl), 1.07 (s, 3H, H-19), 0.84 (s, 3H, H-18). 13C NMR
(CDCl3 100 MHz) ppm: 33.5 C-1, 13.7 C-2, 84.9 C-3, 68.1 C-4, 214.1 C-5, 37.9 C-6, 30.5 C-7, 34.6 C-8, 47.3 C-9,
50.7 C-10, 21.0 C-11, 36.2 C-12, 42.5 C-13, 50.2 C-14, 23.5 C-15, 27.4 C-16, 82.3 C-17, 12.0 C-18, 20.5 C-19,
21.1 CH3 acetyl, 171.1 C=O acetyl.
1
4,5-secocholest-3-yn-5-one (4b).8 Transparent oil. H NMR (CDCl3, 400 MHz): δ ppm: 2.51 (td, J 14.5, 6.4 Hz,
1H, H-6ax.), 2.25 (ddd, J 14.5, 4.5, 2.3 Hz, 1H, H-6eq.), 1.92 (t, J 2.4 Hz, 1H, H-4), 2.12 (m, 2H, H-2) 1.08 (s, 3H,
H-19), 0.91 (d, J 6.5 Hz, 3H, H-21), 0.87 (d, J 1.8 Hz, 3H, H-26), 0.85 (d, J 1.8 Hz, 3H, H-27), 0.72 (s, 3H, H-18). 13C
NMR (CDCl3, 100 MHz) δ ppm: 33.6 C-1, 13.7 C-2, 85.1 C-3, 67.9 C-4, 214.7 C-5, 38.2 C-6, 31.2 C-7, 34.8 C-8,
47.4 C-9, 50.7 C-10, 21.5 C-11, 39.3 C-12, 42.5 C-13, 55.8 C-14, 23.8 C-15, 28.1 C-16, 56.0 C-17, 12.0 C-18, 20.6
C-19, 35.7 C-20, 18.6 C-21, 36.1 C-22, 24.2 C-23, 39.5 C-24, 28.0 C-25, 22.8 C-26, 22.5 C-27.
Method A (Eglinton coupling): A solution of the alkynone 4a, 4b (1 mmol) and Cu(OAc)2•H2O (280 mg, 1.40
mmol) in CH3OH/pyridine (10 mL, 1:1) was refluxed for 6 h. The mixture was cooled to 0 °C and poured
carefully into chilled concentrated HCl (4 mL) and extracted with EtOAc (2 x 30 mL). The organic layer was
washed with H2O (3 x 20 mL), 10% aq. CuSO4, H2O (2 x 30 mL), dried (Na2SO4) and evaporated to produce an
oil that was purified in a column packed with silica gel (15 g) employing hexane-EtOAc 15/1 as eluent to afford
the desired dimeric compound (See Table 1 for yields).
Method B (Pd catalyzed coupling): A mixture of the alkynone (1 mmol), Pd(PPh3)4 (9.6 mg, 0.0083 mmol) and
CuI (3.2 mg, 0.0166 mmol in Et3N (3 mL) was stirred at rt for 2 h under an oxygen atmosphere. EtOAc (50 mL)
was added and the mixture was washed with H2O (5 × 20 mL) dried (anh. Na2SO4) and evaporated. The
residue produced was purified in a chromatographic column packed with silica gel (15 g) that was eluted with
→
hexane/EtOAc mixture (10/0 10/3) to afford the desired dimer (See Table 1 for yields).
1
4,4´-Bis-(4,5-secoandrost-3-yn-5-one) (5a). Oil. NMR H (CDCl3, 400 MHz) δ (ppm): 4.59 (dd, J 9.2, 7.7 Hz, 2H,
H-17, H-17'), 2.50 (ddd, J 15.0, 14.5, 6.3 Hz, 2H, H-6 ax. H-6'ax.), 2.27 (ddd, J 15.0, 4.6, 2.4 Hz, 1H, H-6 eq. H-
6'eq.), 2.15 (m, 4H, H-2 H-2'), 2.04 (s, 6H 2x CH3 acetyl), 1.07 (s, 6H, H-19 H-19'), 0.84 (s, 6H, H-18 H-18') 13C
NMR (CDCl3, 100.53 MHz) δ (ppm): 33.3 C-1 C-1', 14.5 C-2 C-2', 77.8 C-3 C-3', 65.3 C-4 C-4', 214.1 C-5 C-5', 37.9
C-6 C-6', 30.5 C-7 C-7', 34.6 C-8 C-8', 47.4 C-9 C-9', 50.7 C-10 C-10', 21.1 C-11 C-11', 36.22 C-12 C-12', 42.5 C-13
C-13', 50.1 C-14 C-14', 23.5 C-15 C-15', 27.4 C-16 C-16', 82.4 C-17 C-17', 12.1 C-18 C-18', 20.5 C-19 C-19' 171.0
2 x C=O acetyl, 21.1 2 x CH3 acetyl. HRMS (FAB) Estimated for C42H59O6 (MH+) 659.4312, observed 659.4312.
Page 19
©ARKAT USA, Inc