巴顿反应

title: 反应机理和区域选择性.
content: The Barton reaction commences with a photochemically induced cleavage of the nitrite O-N bond, typically using a high pressure mercury lamp. This produces an alkyoxyl radical which immediately abstracts a hydrogen atom from the δ-carbon. In the absence of other radical sources or other proximal reactive groups, the alkyl radical recombines with the nitrosyl radical. The resultant nitroso compounds undergoes 互变异构 to the isolated oxime product. The carbon centered radical can be intercepted by other radical sources such as iodine or 丙烯腈. The first instance results in the δ-hydrogen being replaced with iodine, then subsequent 环化 to a 四氢呋喃 by an SN2反应. The second example results in a chain elongation product with the oxime formed 2 carbon units further from the oxygen than normal.  This mechanistic hypothesis is supported by 动力学同位素效应 experiments. Isotopic labeling of the nitrite with 15N has shown the mechanism non-‘caged’ and that the nitrosyl radical formed from a given nitrite recombines randomly with other alkyl radicals. However, recombination of the nitrosyl radical with the alkoxyl radical (a reversal of the homolytic cleavage) has been shown to proceed without scrambling of isotope labels. This lack of tight radical pairing is also supported by the observation that alkyl radicals generated by Barton conditions can undergo radical cyclization while analogous intermediates generated by 四乙酸铅 oxidation do not.  In rare cases, it appears that the alkoxyl radical may epimerize before hydrogen atom abstraction.  Most commonIy, including steroidal systems, the hydrogen atom is abstracted from a methyl group that has a 1,3 diaxial relationship with the alkoxyl radical. In the absence of a hydrogen on the δ-carbon, or when the particular conformation of the substrate orients the ε-carbon close together, 1,6-hydrogen atom transfer is the favored process. However, these reactions tend to be an order of magnitude slower than the corresponding 1,5-hydrogen atom transfer.  Computational studies have shown that this preference for 1,5-hydrogen atom transfer over 1,6-hydrogen atom transfer appears to be entropically favored rather than a result of a particular stable ‘chair-like’ transition state. In fact, it has been calculated that the 1,6-hydrogen atom transfer proceeds through a transition that is about 0.8 kcal/mol lower than that of the 1,5.  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. For example, when subjected to Barton conditions, cyclopentyl nitrite forms glutaraldehyde monoxime. This is also observed in cases where the radical intermediate formed by fragmentation is particularly stable, such as the allylic radical formed by the fragmentation of isopulegol nitrite.
title: 变体.
content: In rigid systems such as aldosterone, the 1,5-hydrogen atom transfer is exceedingly fast, with a rate constant on the order of 10^7 s-1. Similar intermolecular H-atom transfer can be up to 100 times slower. Furthermore, the hydrogen atom transfer benefits from the formation of a stronger O-H bond at the expense of a weaker C-H bond. For the formation of a primary, second, or tertiary alkyl radical from an alkoxyl radical, there is a driving force of 3 kcal/mol, 5 kcal/mol, and 9 kcal/mol, respectively.  The alkyl radical formed after hydrogen atom transfer is susceptible to standard radical reactions when scavengers are present in sufficient excess to outcompete the nitrosyl radical. Soon after their initial disclosure, Barton and co-workers reported the trapping of the radical with I and CClBr (as Iodine and Bromine radical sources, respectively) to form the δ-halo-alcohol. These halohydrin species can be cyclized to the corresponding 四氢吡喃 derivates under basic conditions.  In the presence of oxygen, the alkyl radical is trapped and forms an organic peroxy radical. This intermiediate 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.
title: 在复杂分子合成中的应用.

Summary: 巴顿反应(Barton反应)以英国化学家德里克·巴顿命名,也称为巴顿亚硝酸酯反应反应中亚硝酸酯光解生成δ-亚硝基醇。反应经由RO–NO键均裂,氧自由基夺氢,而后自由基结合的机理。

Barton reaction: The Barton reaction, also known as the Barton nitrite ester reaction, is a photochemical reaction that involves the photolysis of an alkyl nitrite to form a δ-nitroso alcohol.