Nitrite esters, photolysis

Cycloalkoxy radical intermediates are readily generated from a parent alcohol by various methods (e.g., nitrite ester photolysis, hypohalite thermolysis, lead tetraacetate oxidation) (83MI1). Once formed, reactive cycloalkoxy radicals undergo /3-scission to produce a carbonyl compound and a new carbon-centered radical. 

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,... 

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-... 

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

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]. 

The relatively high yields of cyclic products, often even better than with carbon radicals, observed in the Cy5/Cy6 case is somewhat surprising when one recalls that the intermolecular addition of alkoxyl radicals to olefins is a very unfavorable process. One possible reason that this is so when the alkoxyl radicals are generated by nitrite ester photolysis is that scavenging of the cyclized (Cy 5) radical by NO (Scheme 33) is a very fast process, so that competitive reactions are minor ones. But it is also necessary to postulate that the cyclization process is very fast in the Cy5/Cy6 case. Actually, photolysis of... 

A unique method for the degradation of 17-hydroxy-20-oxygenated pregnanes to 17-ketoandrostanes involves the photolysis of the corresponding nitrite esters.While this generally is equivalent to bismuthate or periodate oxidations, it is the only mild method for the conversion of a 17-hydroxy-... 

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. 

Alkoxy radicals are also the active hydrogen-abstracting species in a procedure that involves photolysis of nitrite esters. This reaction was originally developed as a method for functionalization of methyl groups in steroids.379... 

The photolysis of nitrite esters has been found to be of considerable synthetic utility, particularly in functionalizing steroid methyl groups. The most spectacular application of this reaction has been a three-step synthesis of aldosterone.<59) Irradiation of corticosterone-11-nitrite (30) followed by nitric acid treatment gave aldosterone (32) in a 15% overall yield ... 

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 ... 

For the substitution of the angular methyl groups in steroids five methods are known (a) homolysis of N-chloramines [Loffier-Freytag reaction (only C-18)] (b) oxidation of alcohols with lead tetraacetate (c) photolysis of nitrite esters (d) homolysis of hypochlorites (e) the hypoiodite 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... 

Peroxynitrite is an important cytotoxin that results in vivo from the direct reaction of superoxide and nitric oxide. There are several methods to synthesize peroxynitrite, including the solid-state photolysis of KNOs, the ozonation of sodium azide, or the alkaline reaction of nitrite esters with hydrogen peroxide. Perhaps the most common peroxynitrite synthesis involves treating an acidified solution of hydrogen peroxide with nitrite, followed by an immediate quench with base. Although this synthesis is facile, quick, and affordable, it results in... 

Formation of hydroxamic acids has been reported during the photolysis of steroidal C-17 fl-nitrite esters,227 of ether dl-bornyl ether, and of dl-isobornyl nitrite.144... 

Nitrosamines, unlike nitrite esters, do not undergo cyclizations or other radical reactions upon photolysis in neutral conditions (73ACR354). Pre-... 

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,... 

Photolysis of the nitrite ester (49a), which was derived from isojervine, gave the isoxazolines (51a) and (52a) in a ratio of 3 1. The structures of these products were determined by spectroscopic studies, and were confirmed, in the case of isoxazoline (51a), by X-ray diffraction studies on the derived iodomethyl compound (51c).55 The 5,6-dihydro-derivative (49b) similarly gave isoxazolines (51b) and (52b) on irradiation.56 In each case, the isoxazolines isolated appear to be secondary products which are formed by cyclization of the initially formed unstable formyloxime derivatives (50) during chromatography on silica gel.55 56... 

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