Benzophenone steroid esters

Photochemical functionalizations with synthetic potential have been achieved using benzophenone esters of steroids (Scheme 10). In some cases attack occurs on several hydrogens for instance, a mixture of and A -alkenes is produced on irradiation of (2). However, with compound (3) photolysis produces only (4) as a new steroid. The yield of 55% involves some photoreduction of the benzophenone unit by solvent, so the other significant product is starting material with a reduced ketone group. Many other photolyses of benzophenone steroid esters have been studied they lead to useful infoimation about conformations, but not the directed single-site functionalizations that would make them synthetically useful. 

The introduction of a 9(11) double bond into steroids is of practical interest, since such olefins can be converted to the 9-fluoro-l 1 -hydroxy grouping found in most useful corticosteroids. Ester 6 had a benzophenone-4-hexanoic acid tethered to the hydroxyl group of androstan-17/3-ol that curled under the steroid ring and photochemically inserted into the C-9 a-hydrogen, forming product 7 with a 9(11) double bond after lead tetraacetate cleavage of the carbinol product and hydrolytic cleavage of the tether (Scheme 6-3) [33]. A product with a 14,15 double bond was also produced. 

In a full paper describing this and other functionalizations of steroids tethered to benzophenones [34], it was revealed that the 3a-cholestanol ester 8 of benzophenone-4-acetic acid afforded, after hydrolytic removal of the tether, A " -3a-cholestenol 4 as the product along with the diphenylcarbinol from reduction of the benzophenone. The short tether did not permit insertion into the C-14-H bond, so after the oxygen atom of excit-... 

We have largely been describing reactions on steroid substrates, which are conforma-tionally rigid and permit selective functionalizations by appropriate tethered templates. However, when the templates are linked to flexible chains, the results can be used to learn about the conformational preferences of such flexible chains. In one study [56], we examined the positional selectivities of insertion reactions into flexible chains by attached benzophenone units, a process we had also examined earlier [31], and compared the results with those from the intramolecular chlorination of such flexible chains by attached aryliodine dichlorides. The results were complementary. In another study [57] we used long-chain alkyl esters of nicotinic acid in radical relay chlorination, and saw some interesting selectivities reflecting conformational preferences in these nominally flexible cases. 

Similar regioselectivities have been achieved with intramolecular oxidation of long-chain esters. Benzophenone forms biradicals upon UV irradiation, which eliminate hydrogen atoms from saturated hydrocarbons. Benzophenone esters prefer intramolecular attack, and a cetylester is oxidized at C14 in 66% yield (Scheme 2.4.4). The general scheme of this remote oxidation procedure has been applied even more successfully to rigid steroid skeletons (see Scheme 3.4.3). 

The remote photochemical oxidation by means of a rigid benzophenone reagent attached to a hydroxy-group" has been further investigated with the cholestanol ester (314) as well as other steroid molecules (see Chapter 1, ref. 360). " ... 

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