Barton-photolysis

Table 32 Summary of the results obtained during the Barton photolysis of 277...

Cekovic has examined the addition of electron-deficient olefins to 3-hydroxy radicals [164]. Addition to acrylonitrile of the carbon-centered radicals resulting from the Barton photolysis of alkyl nitrite 173 and subsequent 1,5-hydrogen transfer, yielded a-oximino nitrile 174 (63%, Scheme 57) [165]. 

Barton photolysis of the nitrite (80) introduces further functionality to give (81). The ester (82) was prepared from (83) by a route which required selective benzoylation of the diol (83). Further -ray analyses of products... 

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

Scheme 19. Nitrite ester photolysis the Barton reaction.

Another related reaction is the Barton reaction, by which a methyl group in the 0 position to an OH group can be oxidized to a CHO group. The alcohol is first converted to the nitrite ester. Photolysis of the nitrite results in conversion of the nitrite group to the OH group and nitrosation of the methyl group. Hydrolysis of the oxime tautomer gives the aldehyde, for example,... 

Photolysis of 2-propylnitrite, in which intramolecular hydrogen abstraction cannot occur via a six-membered transition state, results in a 30% yield of 2-propanone. As we shall see, this intramolecular hydrogen abstraction has been extensively applied to steroid syntheses by D. H. R. Barton and hence is commonly referred to as the Barton reaction. 

Radical migration of hydrogen is also known, though only over longer distances than 1,2-shifts, e.g. a 1,5-shift to oxygen via a 6-membered cyclic T.S. in the photolysis of the nitrite ester (129)—an example of the Barton reaction ... 

A very elegant application of 1,3-diaxial interactions is found in Barton s partial synthesis of aldosterone (38) [14], in which an axial methyl group at C(13) is functionalised (37) by photolysis of a nitrite at C(11) which is also axially oriented [15] (Scheme 8.10). 

Barton, D. H. R. Beaton, J. M. Geller, L. E. Pechet, M. M. J. Am. Chem. Soc. 1960, 82, 2640. In 1960, Derek Barton took a vacation in Cambridge, Massachusetts he worked in a small research institute called the Research Institute for Medicine and Chemistry. In order to make the adrenocortical hormone aldosterol. Barton invented the Barton nitrite photolysis by simply writing down on a piece of paper what he thought would be an ideal process. His skilled collaborator. Dr. John Beaton, was able to reduce it to practice. They were able to make 40 to 50 g of aldosterol at a time when the total world supply was only about 10 mg. Barton considered it his most satisfying piece of work. 

The photolysis of nitrites which do not contain g-hydrogen atoms usually results in the elimination of nitric oxide and the formation of hydroxy and carbonyl compounds. When g-hydrogen atoms are present than the product is an oxime or the corresponding nitroso dimer. This reaction is known as Barton S reaction. 

Some examples of radical nonchain reactions are shown in Figure 4.8. In the Barton reaction (hrst example in Fig. 4.8), photolysis of a nitrite ester gives an... 

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. 

Recently, Kabasakalian et al.138-140 have reported the nitroso dimer formation in the photolysis of primary and secondary nitrites. Both this reaction and the Barton reaction16 are explained in terms of reactions of alkoxy radicals. 

Photolysis of primary, secondary, and tertiary alkyl nitrites in benzene indicated that a minimum chain length of five carbon atoms attached to the nitrite grouping is required for appreciable yields of secondary nitroso dimers via the Barton reaction. In the case of primary and secondary nitrites, a chain of length of four carbon atoms or more attached to the nitrite grouping is required for formation of the six-membered intermediate (e.g., A) involved in the Barton reaction.139140... 

In a similar manner, 11/3-nitrites, on photolysis, attack Ci to furnish the corresponding oximes which, upon nitrous acid treatment, gave 18-oxygenated steroids. The most spectacular application of the Barton reaction has been a three-step synthesis of aldosterone.12 Irradiation of corticosterone-11-nitrite (27, R = NO), followed by nitrous acid treatment, gave aldosterone (29) in 15% overall yield. Comparable conversions of 11/3-hydroxyprogesterone to 21-desoxyaldosterone12 and A1-corticosterone to A aldosterone14 have also been achieved. 

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