466G
L-01. 53
C O M M U N I C A T I O N S TO THE E D I T O R
TABLEI IL.S
\
110
I
11, R'=H III? K ' = C H 3
progesterone by Oppenauer oxidation. Only about 20% of the "normal" product, the corresponding I 7a,20-dimethyl-5-pregnene-3P,20-diol, carbinol was formed and conveniently separated by chromatography. Analogously, the 3a,Cia epoxide obtained by peracetic acid treatment of I, m.p. 1TO-1'71", [ a ] D - 67.2, gave in similar yields 3fl,3a-dihydroxy-G@,lia-dimethylpregnan-2O-one, m.p. lSS-192",which was directly oxidized by chromic acid to the 3,20dione, n1.p. 230-233", and converted by niethanolic sodium hydroxide to 6 a ,17-dimethylprogesterone, ~ Am,, 239 mp, log E 4.2. 1n.p. 137-140°, [ a ]+90.3, The latter substance, and the corresponding B-dehydro derivative, m.p. 143-14(j0, [ @ I D +87.1, Amax 292 mp, log e 4.4, obtained by chloranil dehydrogenation, were orally a t least as active, in the Clauand berg test, as 19-nor-lia-ethynyltestosterone, twenty times more active than 170-methylprogesterone. KOTEADDEDIS P~uo~.-ij,l7-Dimethy~-6-dehJ.droprogesterone is as active orally as Ba-rneth~-l-17-acetoxyprogesterone. It is devoid of any androgenic properties.
Treatment of I with ethylmagnesium iodide in anisole gave lTa,21-dimethylpregnenolone 111, m.p. 145-14So,with no detectable amount of carbinol being formed. Oppenauer oxidation gave 1ia,21-dimethylprogesterone,m.p. 1S7-l~59°, [ a ] D +1Oi.i, A,, 2-1-1 m p , log E 4.2' in 705; over-all yield. Further transformations of these methylated steroids together with a report on their G-halogenated derivatives3will be presented in a more detailed paper. .ail new compounds ( 2 ) All rotations in 1'; chloroiurm solution had satisfactory elemental analysis We are indebted t o l)r. G. Papineau-Couture and his associates for the analytical data and t o Drs C . Chappel and C.Kevesz for the bioassays. f ~ 3 )Prepared by Dr. Y. Lefebvre of these laboratories
CONTRIBUTION KO.2738 FREDKAPLAN GATESAND CRELLIN LABORATORIES OF CHEMISTRY .\"ERST RESEARCH LABORATORIES CALIFORNIA INSTITUTE O F TECHNOLOGY l i . I)EGHESGHI PASADESA, CALIFORNIA JOHX L). ROBERTS I). 0. Box 6115 R . GAUDRY MONTREAL, P. Q., CANADA RECEIVED AUGCST9, 1961 RECEIVED SEPTEMBER 20, 1961 STERICALLY CONTROLLED GRIGNARD REACTIONS. A NEW SIMPLE ROUTE TO METHYLATED STEROID ANALOGS
17a-
Say:
INERTIAL EFFECTS OF SUBSTITUENTS ON HOT ATOM CAPTURE'
Sir:
We wish to report a convenient new synthesis of Hot hydrogen atoms can replace hydrogen and 17a-methylated steroid derivatives which has made other atoms and groups with high collision effipossible the preparation of highly active proges- ciency.2 The course of these reactions has been terone homologs When the readily available shown to be largely controlled by steric factors.' (I) was However certain results, particularly on alkyl remethyl 3~-hydroxy-l7a-methyl-5-etienate refluxed in anisole for one hour in presence of placement, have not found explanation. This excess niethyhagnesium bromide, the correspond- letter reports a remarkable new effect in the hot ing sterically hindered ketone, 17a-methylpregnenol- hydrogen displacement of halogen atoms from one 11' was obtained in 70yoyield. The latter sub(1) Studies supported by the U. S . Atomic Energy Commissivll. stance was converted to the known' 17a-methyl- Contribution S o . lBS1 from the Sterling Chemistry Laboratory. ( 1 ) PI. 4 Plattner, H H r u s v r P Th H e r z i g , 32, 270 ( l Y l %
Hell
Chrin A r l o
(2) D. Urch and K. Tb-olfgang.,J . d i n . Chem Soc., 83, 2982 (1961). This paper contains references t o t h e earlier literature
