Steroidal double bonds

The 17-keto group in 19 is hydrogenated over W-4 Raney nickel in preference to a double bond (Eqn. 15.14)46 but not the A 2 enol acetate, 20, over palladium (Eqn. 15.15).22 The saturation of a 3P hydroxy A steroid is accomplished more readily after conversion to the 3P acetate.42 

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While the foregoing concepts have been utilized to rationalize the product distribution obtained on hydrogenation of a number of monocyclic olefins, it should be noted that the effect of pressure on the stereochemistry of hydrogenation of steroidal double bonds has not been critically evaluated. 

Olefins are normally hydrogenated more readily than any other functional group except acetylenes. However, because of steric differences, a considerable variation exists in the ease of saturation of steroidal double bonds. 

In general the rates of hydrogenation of steroidal double bonds can be roughly classified as follows a) readily hydrogenated A, A, A", A , A14 A diene, A , A ° and 19-vinyl (Z>) moderately difficult ... 

Deuterioboration is one of the most important recent additions to the array of methods for saturating double bonds with deuterium. The easy accessibility of metal deuterides (lithium aluminum deuteride or sodium borodeuteride) facilitates the in situ preparation of deuteriodiborane which reacts with steroidal double bonds with a high degree of site and/or stereospecificity, depending on the location of the double bond. " ... 

The hydroboration step, being very sensitive to steric effects, yields only secondary alkylboranes from trisubstituted double bonds, whereas the less hindered alkylborane is formed predominantly from disubstituted steroidal double bonds. The diborane attack occurs usually towards the a-side and hence results in overall a-hydration of double bonds after alkaline hydrogen peroxide oxidation. ... 

In analogy with the peracid attack on steroidal double bonds, the formation of the bromonium ion, e.g., (81a), occurs from the less hindered side (usually the a-side of the steroid nucleus) to give in the case of the olefin (81) the 9a-bromo-l l -ol (82). Base treatment of (82) provides the 9 5,1 l S-oxide (83). Similarly, reaction of 17/3-hydroxyestr-5(10)-en-3-one (9) with A -bromosuccinimide-perchloric acid followed by treatment with sodium hydroxide and sodium borohydride furnishes the 3, 17 5-dihydroxy-5a,l0a-oxirane. As mentioned previously, epoxidation of (9) with MPA gives the 5, 10 -oxirane. °... 

Since many steroidal double bonds will react with peracids, these must be protected before the enol acetylation step. Chlorination is generally satisfactory for this purpose. ... 

Raney nickel, 119, 132, 134, 135, 138 Rates of hydrogenation of steroidal double bonds, 119... 

In general the rates of hydrogenation of steroidal double bonds can be roughly classified as follows (a) readily hydrogenated A1, A2, A3, A4, A6, A14, A15 A14 16 diene, A16, A17(20), A20 and 19-vinyl (b) moderately difficult A5 > A22 and (c) difficult to hydrogenate A8 > A9(11) > A7 > A8(14). The data for the hydrogenation of A7-steroids is obscurred by the fact that this olefin is isomerized readily to the 8(14) position. Double bond isomerization does not occur with A7-9/ -steroids.18,23,39,54... 

The addition of trifluoromethyl hypofluorite to steroid double bonds has been investigated mainly by Barton and co-workers.3s6,406.4i 4.415.445 examples of these reactions are given by the formation of 5,383-385 g 3S3-385.406 384.386... 

Early studies indicated that dichloro- and dibromocarbene (generated from halo-form) do not react with hindered steroidal double bonds. However, Bond and Cornelia76 report that if phenyl(trihalomethyl)mercury precursors are used addition can be effected to A7-, A5-, andA6-double bonds. 

Generation of difluorocarbene. In an early study1 of the reaction of difluoro-carbene with steroidal double bonds, the methylenation was conducted by portion wise addition of an excess of dry sodium chlorodifluoroacetate to a diglyme solution of the substrate at temperatures of 120-150°. The same laboratory (Syntex)2 now reports that the reaction is improved by addition of a solution of the salt in diglyme to a refluxing diglyme solution of the substrate. The reaction with A4-6- and AI 4 a-3-ketosteroids results mainly in addition to the Afi-double bond to give 6a,7a-difluoromethylene-A4- and A -4-3-ketones, respectively. 

Steroid double bond isomerase (1 x 10 with A -androstene -3,17- dione)... 

This finding has been verified by several experiments phases with polar properties show a good steric selectivity (see Fig. 6). Thus, isomeric steroids (double-bond isomerism) cannot be separated selectively using hydrophobic phases (co-elution of peaks 2 and 3 in the upper and middle chromatograms), but they can if polar groups are present on the surface of the stationary phase, as in the lower chromatogram in Fig. 6. The stationary phase is Resolve, a non-endcapped material. 

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