Barton reaction

[2] The Barton reaction involves a homolytic RO–NO cleavage, followed by δ-hydrogen abstraction, free radical recombination, and tautomerization to form an oxime.

Due to its unique property at the time to change otherwise inert substrates, Barton used this reaction extensively in the 1960s to create a number of unnatural steroid analogues.

[5] The unusual alkyl nitrite starting material of the Barton reaction is prepared by attack of an alcohol on a nitrosylium cation generated in situ by dehydration of doubly protonated nitrous acid.

[6] This series of steps is mechanistically identical to the first half of the mechanism formation of the more well-known aryl and alkyl diazonium salts.

The Barton reaction commences with a photochemically induced cleavage of the nitrite O-N bond, typically using a high pressure mercury lamp.

[14] Most commonly, including steroidal systems, the hydrogen atom is abstracted from a methyl group that has a 1,3 diaxial relationship with the alkoxyl radical.

[17] In certain cases, particularly nitrites derived from cyclopentyl alcohols, the oxygen-centered radical prefers to react via C-C bond cleavage as opposed to H-atom abstraction.

This intermediate is trapped by the nitrosyl radical and then isomerizes to give a δ-nitrate ester which, while both acid- and base-stable, can be reduced to the corresponding alcohol under mild conditions.

[22] In a publication immediately proceeding Barton's initial disclosure of the methodology in the Journal of the American Chemical Society, a synthesis of aldosterone acetate is demonstrated.

Subsequently, irradiation under inert atmosphere followed by treatment with aqueous sodium nitrite selectively gives the desired oxime.

In the process of preparing a series of derivatives of the triterpenoid allobetulin, Dehan and coworkers observed a remarkable transformation resulting from two consecutive 1,5-hydrogen atom transfers.