A. L. WILDS,JAMES A .
5324
JOI-INSON, JR., AND
REID E. SUTTON
Vol. 72
[CONTRIBUrION FROM TlIC r,ABOR4TC)RY O F O R G A N I C CHEMISrRY O F THE U N I V E R S T Y OF WISCONSIN]
The Stereochemical Course of Hydrogenation of Ring D-Unsaturated Equilenane Derivatives BY A. L. WILDS,JAMES A. JOHNSON:, In several communications from this Laboratory, we have reported on a method for synthesizing the steroid ring system by way o€ AI4-]?unsaturated 16-keto derivatives such as I.3 The final step of these syntheses has involved a selective hydrogenation to ketones such as 16-equilenone (11), in which the C:D ring configuration may become cis or trans. Since most of the natural steroids have these rings in the trans configuration, it has been of considerable interest to study the stereochemical course of this reduction and possible methods €orits control. Significant progress has now been made in this direction. Hydrogenation of I with palladium-on-carbon catalyst in dioxane was reported3b to give predominately one stereoisomer of 11, m. p. 168.5169'. By reduction of the ketone group this isomer was converted into a hydrocarbon (Pequilenane) identical with that obtained from P-17-equilenone ; this isomer of I1 is therefore presumed to be tranr by analogy to eqt~ilenin.~J
JR..'
C H d
\XI)REID E.
SUTTON~
.r$J 111
1\'
yield material melting a t 1i1-t72°. This, however, proved to be the stereoisomer of the above ketone, since a mixture of the two showed a large melting point depression. Similarly, alkaline reduction of the phenolic ketone corresponding to I11 gave a different isomer from that obtained under neutral conditions, but identical with that prepared by demethylation of this new isomer of IV. I n order to establish the configuration of these isomers, the 16-carbonyl group was reduced using the technique of H~ang-Minlon.~The 169.5171O isomer of IV gave trans-3-methoxyequilenane (VIII) identical with a sample prepared by reducing the 17-keto group of &equilenin methyl ether. The 171-172' isomer of IV gave cis-3niethoxyequilenane identical with that from (11-isoequilenin methyl ether. Thus, the alkaline hydrogenation of I11 had led to the cis isomer of IV in excellent yield, while both isomers were I I1 formed under neutral conditions with the trans Since it is well-known that alkali or acid isomer apparently predominating. When the frequently will alter the stereochemical course of a hydrogenation was carried out in dioxane solution reduction,6 the effect was tested in the present containing a trace of acetic acid, the pro ortion case. Potassium hydroxide accelerated the palla- of trans-isomer was increased, so that 3 8 4 could dium-catalyzed hydrogenation of I and Ied to a readily be In acetic acid alone as the Since solvent, the hydrogenation with palladium became different isomer of 11, m. p. 94.5-95'. Clemmensen reduction gave a-equilenane, iden- less selective, leading to considerable reduction tical with the hydrocarbon from cu-l7-equilenone, of the ketone group as well as the double bond. the new isomer is considered to be the cis form. The similar behavior of ketones I and I11 on Neutral hydrogenation of the methoxyl sub- alkaline hydrogenation, leading to the C :D stituted ketone I11 was found to give 3-methoxy- configurations of a-equilenone and isoequilenin, 16-equilenone (IV) as a difficultly separable niix- respectively, provides another excellent analogy ture of isomers from which one, m. p. 169.5- in support of the similar cis configuration for each. l i l ' , could be isolated in 24-2970 ~ i e l d . ~ cAlkaIt could be demonstrated that the alkaline line hydrogenation has now afforded in excellent effect, in promoting cis hydrogenation, involved (1) Wisconsin Alumni Research Foundation Research Assistsnt, the ketone group rather than the catalyst. Wolff1946-1947, Eli Lilly Fellow. 19'4-1 ioiit\,ern Keiearch IiiKishner reduction of the desoxy ketone I gave stitute, Birnungham, Ala 14,15-dehydroequilenane (V) in excellent yield. (2) Research Laboratory, Shell 011Co , Wood River I11 (3) (a) Wilds, Tnrs J o r i R ~ n l . ,64, 1-121 (1942), (b) Wilds rud That the double bond remained in conjugation Beck, i b i d , 66, 1688 (1944); ( c ) n i l d s and Close, ebrd, 69, 3079 with the ring was shown by the ultraviolet ab(1947); (d) Wilds and T. L Johnson, zbzd , 70, 1166 (1948) (4) Wilds, Beck and T L Johrisoii 1 (5) The recent work of Rrchm~rriiA I 1329 (1950),and Bachrnaiin .rnd Krtiiirrt i b r d , 71, 2273 11949), provides new evidence i n supim t I r t ! t i t I I 5 1 , - i r itiguratio,i i
