The mechanism of the Barton reaction

Abstract

A study of the by-products of the Barton reaction of steroidal nitrites has been made and the mechanisms of formation of these by-products have been elucidated. Epoxy by-products have been shown to' result from the photochemical reaction of a nitroso monomer with nitric oxide. Alcoholic by-products have been shown to arise from intermolecular abstraction of hydrogen by the intermediate alkyl radicals. Ketonic by-products have been shown to be formed by a decomposition of the nitric oxide/alkoxy radical pair. The hyponitrous acid arising from this decomposition has been detected by UV spectroscopy and correlated with the amount of ketone formed. A brief study of solvent effects has demonstrated the unsuitability of aromatic solvents for the 3arton reaction. Reaction parameters have been modified leading to the elimination of epoxy and alcoholic by-products and giving improved yields of oximino products. The ability of the Barton reaction to be triplet sensitised has been ascertained. The Barton reaction in the presence of oxygen, affording nitrate esters, has been extended to 6p -nitrite esters and has been used to synthesise some novel 19- functionalised cholestane derivatives. The existence of a peroxynitrite as an intermediate in this reaction has been looked at and it has been found that the in situ generation of a peroxynitrite by the reaction of a hydro peroxide with nitrosyl chloride and its subsequent re arrangement affords a new synthesis of nitrate esters. A steroidal phosphinate has been prepared in a similar manner by reaction of a hydroperoxide with a chloro-phosphine. The reaction of 17a-hydroperoxyprogesterone with trifluoroacetic anhydride affords a further method of degrading the pregnane side-chain.