I.-I. Radu et al. / Tetrahedron Letters 43 (2002) 7617–7619
7619
In conclusion, we developed a novel strategy for the
synthesis of a C-18 aminosteroid. Distinct advantages
of our approach over the classical procedure are the
easy preparation of estrone-triflate as starting material,
and the absence of non-desirable secondary products in
its palladium(0)-catalysed amination reaction. The pro-
cedure is particularly useful because of its simplicity,
the readily available starting materials and ease of
reaction conditions, as well as its applicability to the
synthesis of other non-natural C-18 aminosteroids, in
addition to the biologically relevant 3-aminoestrone. To
our knowledge, to date there is no mention in the
literature of such an application of this type of palla-
dium(0)-catalysed amination reaction in the case of
C-18 steroid triflates.
16. Morrow, D. F.; Hofer, R. M. J. Med. Chem. 1966, 9,
249–251.
17. Conrow, R. B.; Bernstein, S. Steroids 1968, 11, 151–164.
18. Tschitschibabin, A. E.; Jeletzky, N. P. Chem. Ber. 1924,
57, 1158–1161.
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22. Reverse-phase C-18 Nova-Pak C18 column (100×40 mm
i.d.). Mixture of CH3CN:MeOH:H2O/40:35:25 as eluent
at a flow rate of 25 mL/min, UV detection at 205 nm.
23. Wolfe, J. P.; Ahman, J.; Sadighi, J. P.; Singer, R. A.;
Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6367–6370.
24. Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buch-
wald, S. L. J. Org. Chem. 2000, 65, 1158–1174.
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26. Procedure for the synthesis of 6: In a Schlenk tube purged
with argon, Pd2(dba)3 (27 mg, 3% mol), S-(−)-BINAP (28
mg, 4.5% mol), Cs2CO3 (456 mg, 1.4 mmol) in 2 mL
toluene were added and stirring began. To the resulting
solution, 5 (403 mg, 1 mmol) and benzophenone imine
(201 mL, 1.2 mmol) were added and heated at 120°C for
3 days. The dark colour mixture was then cooled to room
temperature and diluted with 25 mL Et2O and filtered
over Celite and then evaporated under reduced pressure.
The crude solid was purified by silica gel flash chro-
matography using gradient elution with CH2Cl2 to 3%
Et2O/CH2Cl2 to afford 32 mg (8%) of starting material 5
and 321 mg (74%) of imine 6 as a yellow solid. Mp
151–153°C. [h]D +88.80° (c 1.00, CHCl3). IR (KBr): 1739
(CꢀO); 1597 (CꢀN) cm−1. 1H NMR (300 MHz, CDCl3): l
0.90 (s, 18-CH3); 1.30–1.67 (m, 6H); 1.88–2.26 (m, 5H);
2.27–2.38 (m, 1H); 2.50 (dd, J1=19.50 Hz, J2=8.45 Hz,
16b-CH); 2.72–2.81 (m, 6-CH2); 6.47 (dd, J1=8.20 Hz,
J2=1.70 Hz, 2-CH); 6.55 (s, 4-CH); 7.02 (d, J=8.20 Hz,
1-CH); 7.09–7.20 (m, 2H); 7.23–7.32 (m, 3H); 7.33–7.53
(m, 3H); 7.72 (d, J=7.14 Hz, 2H) ppm. 13C NMR (75.5
MHz, CDCl3): l 13.86; 21.54; 25.65; 26.48; 29.25; 31.55;
35.82; 38.11; 44.09; 47.95; 50.47; 118.59; 121.86; 125.25;
127.93; 128.14; 129.58; 134.90; 136.56; 139.61; 148.09;
167.93; 220.90 ppm. MS for C31H32NO [M+H]+: 434.40
m/z.
Acknowledgements
We would like to thank FCAR (Fonds pour la Forma-
tion de Chercheurs et l’Aide a` la Recherche) for the
scholarships of I.-I.R. We are also grateful to Dr.
Fernand Labrie and Endorecherche for providing
chemical and biological facilities.
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