14-Methyl steroids. Part 2. Total synthesis of (±)-14α-methyl-19-norsteroids

Cycloaddition route to 14,17-ethano- and 14-alkyl-19-norsteroids

“…Osmylation of (36) afforded a ca. 1 : 2 mixture of the diols (37) and (38); predictably, the proportions and distinctive characteristics of (37) and (38) were similar to those of the corresponding 3-methoxy compounds (16) and (17).…”

“…3 600, 3 430br, 3 055, 1 030, and 850 cm-'; 6H(500 MHz) 0.9 (3 H, s, 13P-Me), 1.03 and 1.28 (each 1 H, ddd, J 6. 1,1.5,and 1.2 Hz,16-and 17'-H), 1.45 and 1.49 (each 1 H, dd, J 10.0 and 1.2 Hz, C-14), 43.0 (d, C-9), 37.0 (s, C-13), 35.4 (d, C-8), 36.9,34.9,29.9,28. 5,27.1, and 23.6 (each t, C-6, C-7, C-11, C-12, C-15, and C-172), 15.2 and 12.9 (each d, C-16 and C-17'), and 14.4 (9, C-18) (Found: C, 81.2; H, 8.7%; M + , 310.…”

“…In an effort to develop a more versatile synthetic approach to 14-alkyl-19-norsteroids, we sought a method which would ensure the desired stereoselectivity and, at the same time, generate functionality at C-14 and C-17 which could be elaborated in different ways. Our conceptual approach (Scheme 1) was based upon Diels-Alder addition of an ethylene equivalent to a steroidal 14,16-diene (A), followed by oxidative cleavage of the residual olefinic bond in the cycloadduct (B).6 In this way, the ring D system (C) could be restored, with concomitant introduction of a 14a-formyl group, and with 17-substitution patterns determined by the choice of 16-and 17-substituents in the starting diene. Implicit in the approach was that an oxygen function at C-17 would also allow extended oxidative cleavage, leading to the 14a-formyl-17-ketone (D).…”

Steroid reactions and partial synthesis

“…The cycloaddition of phenylvinylsulfolene to the ring D diene of 3-methoxy-16-methylestra-1,3,5( 10),14,16-pentaen-17-yl acetate (49) and some transformations of the products have been described. 49 The major products (50) and ( 51) arise from…”

14-Methyl steroids. Part 5. Structural features influencing stereoselectivity of 14-methylation of 15-oxo-19-norsteroids: synthesis of 14α-methyl-19-norprogesterone

“…3,l 52-Dihydroxy-19-norpregna-1,3,5( lO)-trien-20-one (12) was converted sequentially into the 3-methyl ether (13) and the derived 20,20-ethylenedioxy compound (14), which underwent oxidation with pyridinium chlorochromate in buffered medium at 0 'C to give the desired 15-ketone (15). 3,l 52-Dihydroxy-19-norpregna-1,3,5( lO)-trien-20-one (12) was converted sequentially into the 3-methyl ether (13) and the derived 20,20-ethylenedioxy compound (14), which underwent oxidation with pyridinium chlorochromate in buffered medium at 0 'C to give the desired 15-ketone (15).…”