A variety of new approaches for the total synthesis of modified steroids, involving en enamine reaction in the critical step of the synthetic plan, have been recently reported from this laboratory (la-e). This communication describes a facile transformation of the enamine derived from 6-methoxytetralone-1 to certain ring C modified steroids.
The morpholine enamine of 6-methoxytetralone-1 (1) was conveniently prepared (SO$) by the method of White and Weingarten ( 2); [b.p. 13S-140Β°/2x10-5 mm; ~2:~ 1620 cm" (N-C=C); bcDc13 5.12t (lH, C=C-H)]. Acyletion of enamine 1 with the aoid chloride of monomethyl succinate, using two equival_ents of 1, followed by acidic hydrolysis, yielded diketc acid 2; m.p. 165-166 0 ; structure of 2 was attested by it8 spectral date; vm8x lCBr 2400-2700 (carboxyl O-H and C=C-OH), 1705 (oarboxyl C=O) end 1610, 1600, 1560 cm-'; b (pentadeuteropyridine) 2.5-2.8 m (4H, C3 and C4 methylene protona),2.95 s (4H, CO-CH2CH2COOH), 3.72 '8 (3H, ocH3), 6.8 d (lH, C5-H, J=2 O/B), 6.87 2 doublets (lH, 7 C -H, J=2 c/a; J=t3.5 o/e) and 8.0, d (IH, Cg-H, J=8.5 c/8). 2 naa eaterified smoothly to the corresponding ethyl eater with ethenol and HCl. When the latter wae refluxed (24 h) with one equivalent of guanidine carbonate in P-ethoxyethanol, the tricyclic system 3 was obtained in good yield: m.p. 104-107', vmax KBr 3500, 3390 (NS,), 1722 (eater C=O) 8nd 1630, 1610, 1595, 1555 (pyrimidine). Reduction of 3 in an aqueous acidic solution (pH 3-4) over lC$ Pd/C, under pressure (3 atmospheres), gave 11,13-diasesteroid 4, m.p. 2050(aeo.), in 70 p.c. yield. Its moleoular structure followed from its epectroanalyticel dSt8; mol.&. (MS) Foundi