Oximes alkoxy radicals

It was shown by Barton et al. that the photolysis of steroidal nitrites 50 proceeding by formation of alkoxy radicals could result in hydrogen abstrae-tion from suitably situated methyl groups forming earbon-centered radicals, which then reacted with the NO generated to give oximes (equation 79). This permitted the functionalization of the unaetivated centers. 

Other examples of an attack on C from an alkoxy radical at C20 are recorded in the literature for instance, in the progesterone series the oxime (7) obtained from the photolysis of the corresponding nitrite was converted to the nitrile (8) J Oxidation and acid hydrolysis of the nitrile (8) gave 3,20-diketo-4-pregnen-18-oic acid (9) identical with a... 

This conversion has been rationalized33 as depicted in (a) to Id) the alkoxy radical (a) formed during the photolysis of the corresponding nitrite is favorably placed with respect to the 7r-system of the double bond to undergo an intramolecular addition, the resulting intermediate alkyl radical (b) then combines with NO to furnish the oxime (d) via the nitroso compound (c). 

The importance of conformation in selective attack of the 1 l/ -alkoxy radical on C18 and C19 was nicely illustrated by the photolysis of the nitrite 18 derived from the dienone 19. This afforded only C18 attack.7 Treatment of the derived oxime with nitrous acid gave 1-dehydro-aldosterone acetate 20. This is a convenient precursor for labelled aldosterone acetate since selective hydrogenation with tritium gives 1,2-ditritiated aldosterone acetate. 

In the Barton reaction, an alkyl nitrite is converted into an alcohol-oxime. The nitrite is photoexcited to a 1,2-diradical. It fragments to NO and an alkoxy radical (RO-), and the latter abstracts H- from the nearest C-H bond. The resulting alkyl radical then combines with NO to give a nitroso compound, which then tautomerizes to the oxime, probably by a polar stepwise mechanism. The Barton reaction has been used for the remote functionalization of hydrocarbons, especially steroids. 

A range of 0-alkyl thiazolethiones such as (44) have been prepared from 4-chloroacetophenone. Bromination of 4-chloroacetophenone and reaction with hydroxylamine hydrochloride afforded the bromo oxime (42). (42) is then treated with potassium ethyl xanthate and oximino dithiocarbonate, followed by zinc chloride to afford the thiohydroxamic acid (43), which is then alkylated to give (44). These derivatives are a useful source of alkoxy radicals eg, photolysis of (44) leads to the alkoxy radical (45) <97SL848>. 

Examples of heteroatomic radical cyclizations leading to bridged rings will now be described. Oxabicyclic compounds 306 (R = H) have been obtained by photolysis of the nitrites (305) (oxime not isolated) (Scheme 121). When R = Me compounds 307 are obtained and, although yields are modest, this shows that intramolecular addition of an alkoxy radical is possible and that it gives exclusively the (Cy 5) radical in the Cy5/Cy6 case. 

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