Radical reactions Barton nitrite photolysis

To explain the high chemical yield in the transformation A - D, coupled with the fact that the quantum yield for the photodecomposition of nitrites is less than unity, it was suggested that the Barton reaction might take place through a radical "cage mechanism.2 However, recent studies at the Institute on the mechanism of nitrite photolysis have shown this not to be so. Photolysis of an equimolecular mixture of 3/3-acetoxy-androstan-6/8-yl nitrite (102) and 3/8-acetoxy-cholestan-6/8-yf nitrite containing 98% of nitrogen as N16 (103) in iso-octane or toluene... 

H. Suginome, Remote functionalization hy alkoxyl radicals generated hy the photolysis of nitrite esters The Barton reaction and related reactions of nitrite esters in CR. Handbook of Organic Photochemistry and Photobiology, 2nd Edition,... 

The book explores the invention of new chemical reactions for use in the synthesis of biologically and economically important compounds. It begins with a mechanistic study of the industrial importance of the pyrolysis of chlorinated alkanes. It continues with a theory on the biosynthesis of phenolate derived alkaloids involving phenolate radical coupling. Included in the book is a description of the work on nitrite photolysis (the Barton Reaction) which involved the invention of new radical chemistry leading to a simple synthesis of the hormone, aldosterone. In two final chapters Dr Shyamal Parekh views Professor Barton s pioneering work from the modern perspective, with a review of recent applications in industry and research. 

Akhtar, M., Barton, D. H. R., Sammes, P. G. Some radical exchange reactions during nitrite ester photolysis. J. Am. Chem. Soc. 1965, 87,... 

Suginome, H., Remote Functionalization by Alkoxyl Radicals Generated by the Photolysis of Nitrite Esters the Barton Reaction and Related Reactions of Nitrite Esters. In Horspool, W. M., Lenci, F. (eds), CRC Handbook of Organic Photochemistry and Photobiology, 2nd edn, CRC Press LLC, Boca Raton, FL, 2004, Chapter 102, pp. 1 16. 

The Barton nitrite ester photolysis is undeniably one of the most popular and useful reactions in radical chemistry for the functionalization of remote and inactivated positions within steroids (Scheme 19). Photolysis of nitrite esters gives nitric oxide and an alkoxyl radical that abstracts an ideally positioned hydrogen atom (1,5-hydrogen atom abstraction). The resulting alkyl radical reacts with nitric oxide in a solvent cage to afford the nitroso-alcohol derivative that is finally isolated as an oxime [53]. Related cyclizations of alkoxyl radicals have been reported by Surzur photolysis of y,(5-alkenyl nitrite esters leads to alkoxyl radicals that undergo subsequent tandem 5-exo cyclization followed by NO-trapping [54, 55]. 

Remote Functionalization by Alkoxyl Radicals Generated by the Photolysis of Nitrite Esters The Barton Reaction and Related Reactions of Nitrite Esters... 

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 ... 

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... 

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. 

The involvement of an intramolecular hydrogen abstraction in the Barton reaction is not necessarily limited to those molecules with rigid stereochemistry. In fact, simple aliphatic nitrites undergo the Barton reaction with equal ease. Thus, the principal product obtained from the photolysis of ra-octyl nitrite20 in benzene solution is the dimer of 4-nitroso-l-octanol however, photolysis of n-octyl nitrite in n-heptane20 produced a mixture of 7/-nitroso heptanes in addition to 4-nitroso-l-octanol in the ratio l 4.5,f respectively. The formation of y-nitroso heptane obviously results from an attack of the intermediate alkoxy radical on the solvent molecule. The intermediate alkyl radical then collapses, according to eq. 2. For the sake of convenience we have indi-... 

The photolysis of n-octyl nitrite in n-heptane provides a favorable situation for comparing the tendency of an alkoxyl radical to undergo the Barton-type intramolecular reaction or, alternatively, the intermolecular reaction as indicated in eqs. 1 and 2. Calculations23 reveal that both intramolecular and intermolecular hydrogen abstraction involving a second-... 

Alkoxyl radicals can be generated by a variety of methods including peroxide reduction, nitrite ester photolysis, hypohalite thermolysis, and fragmentation of epoxyalkyl radicals (for additional examples of alkoxyl radical generation, see Section 4.2.S.2). Hypohalites are excellent halogen atom donors to carbon-centered radicals, and a recent example of this type of cyclization from the work of Kraus is illustrated in Scheme 43.182 Oxidation of the hemiketal (57) presumably forms an intermediate hypoiodite, which spontaneously cyclizes to (58) by an atom transfer mechanism. Unfortunately, the direct application of the Barton method for the generation of alkoxyl radicals fails because the intermediate pyridine-thione carbonates are sensitive to hydrolytic reactions. However, in a very important recent development, Beckwith and Hay have shown that alkoxyl radicals are formed from N-alkoxypyridinethiones.183 Al-... 

The photolysis of organic nitrites of appropriate constitution and conformation in solvents such as benzene or acetonitrile transforms them into A-nitroso alcohols via the sequence (1) a homolytic fission of the O-N bond of their nitrosoxy group (2) an intramolecular d-hydrogen abstraction of the resulting alkoxyl radicals to generate a d-carbon radical and (3) formation of d-nitroso alcohols by combining of the d-carbon radical with the generated nitric oxide. The nitroso alcohols are isolated as d-hydroxyimino alcohols as a result of spontaneous thermal isomerization or as nitroso-dimers [1] (Scheme 1). This transformation has been named the Barton reaction [2, 3],... 

Schemes 5 and 6 outline the functionalization of a 10/1-Me by a steroidal 6/f-ol [1] and a 2/3-61 nitrite [6], Functionalization of 13/i-Me by a 20a-ol nitrite [7] and functionalization in the terpenoid field [8] are outlined in Schemes 7 and 8. The last example involves a 7-membered cyclic transition state that seldom occurs. Scheme 9 outlines a recent application of the Barton reaction in the synthesis of a biologically active carbacepham [9]. The photolysis of acyclic 5-phenyl-1-pentanol nitrite gives, preferentially, a nitroso dimer arising as a result of the abstraction of a hydrogen attached to the d-carbon, rather than the e-carbon from which the better stabilized benzyl radical can be generated (Scheme 10) [10].

A functionalization that converts C—H bonds to C— NO bonds occurs when nitrite esters are photo-lyzed (the Barton reaction Scheme 4). Again an alkoxyl radical abstracts a 8-hydrogen, and the resulting carbon radical picks up NO. The product nitroso compounds convert easily to oximes. Particularly valuable examples have bMn studied in the steroid field. If the photolysis is performed in the presence of copperfll) acetate the intermediate carbon radical can be oxidized to an alkene, rather than capture NO. If the alcohol whose nitrite ester is photolyzed is part of a cyanohydrin, then the Heusler-Kalvoda reaction occurs, and the product is a ketone with a migrated cyano group (Scheme 5) ... 

When a free radical is formed and held tightly within a molecule, reactions of quite high site specificity (regioselectivity) may be observed. The free radical may be generated from another functional group in the molecule, but the result is the substitution at a centre that in a formal sense has the characteristics of a hydrocarbon. Such reactions are observed in the photolysis of nitrite esters (RONO) (the Barton reaction), the... 

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