Steroidal, from silyl enol ethers

Trimethylsiloxycyclopropanes, readily available from silyl enol ethers and carbene or carbenoid species, constitute, now, very useful synthetic intermediates . Thus, they undergo acid-, base-inducedor thermal ring-opening into a-methylated aldehydes and ketones in very good yields. The reaction is highly regiospecific in the case of an unsymmetrical ketone, monomethylation can be oriented either to the a- or a -position (equation 58) °°. This sequence has been applied to ethylenic ketones and in the steroid field . ... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

While fluoroxy compounds react well with enol derivatives, fluorine in general does not. However, there are various reports where such reactions are described and in certain cases even with decent yields. In 1982 it was reported that pyruvates with a dominant enolic form react well with fluorine, to give the corresponding fluoro derivatives l.78 Several silyl enol ethers 2 and 379 including ones made from 1,3-dicarbonyl derivatives 480 react quite satisfactorily with fluorine to give the expected a-fluoro ketones. Steroidal 16-enol acetates react with fluorine to form mainly 16a-fluoro-17-oxo steroids e.g. 5.81... 

Fluoropyridinium triflate (la) exhibits high selectivity in fluorinations. In a steroid 8 with two reaction sites, a conjugated and a nonconjugated vinyl acetate moiety, 1-fluoropyridinium triflate (la) reacts at the conjugated site only. On the other hand, steroid 9 with a silyl enol ether and a conjugated acetate moiety affords the product resulting from reaction at the former site only.44,52... 

The fluorination of 12, easily prepared from the corresponding triketo steroid, with an equimolar amount of 1 (Scheme 2) shows the remarkable ability of 1 to distinguish di-substituted from tri-substituted enol silyl ethers. The 9a-fluoro steroid 13 is produced in 51% yield (78% based on recovered triketo steroid) and the combined yield of the other fluorinated products is only 4.6%.17 it thus is apparent that 1 reacts almost exclusively with the trisubstituted enol ether moiety. The new, selective direct fluorination at the 9a-position holds considerable promise as a means to prepare biologically important 9a-fiuoro steroids.18... 

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