Barton reaction intramolecular functionalization

Intramolecular hydrogen abstraction is an important synthetic reaction because it provides a method of introducing a functional group at a saturated carbon bonded to only hydrogen and other carbons, a difficult task to accomplish by other means.196 The abstracting radical need not be carbon the Barton reaction (Scheme 15) is a standard method in which the abstracting radical is oxygen.197 This technique has been used extensively for selective introduction of functionality in steroid synthesis.198... 

The best known intramolecular free radical reactions probably are the 1,5-hydrogen abstractions by alkoxyl or aminium radicals used in selective functionalization. The first, known as the Barton reaction, has been reviewed, " as has the second one, the Hofmann-Loffler-Freytag reaction. Synthetic uses and mechanistic aspects of intramolecular homolytic aromatic substitution have also been reviewed recently. " ... 

Section 12.5 in Part A describes some additional reactions that are of synthetic value and involve intramolecular hydrogen abstraction at unactivated groups. Of particular note is a method, known as the Barton reaction, in which nitrite esters of alcohols are photolyzed. Nearby hydrocarbon groups, including methyl groups, can be functionalized by this method, and the reaction has been applied to remote functionalization in steroids. 

Remote Oxidation.—Remote oxidation reactions generally involve intramolecular hydrogen abstraction. The best known example is the Barton reaction (photolysis of nitrite esters). "- One of the most important applications of this reaction was to the synthesis of aldosterone acetate. The yield of this reaction has been substantially improved (55%) by irradiating the dienone nitrite ester (172) in which the extended conjugation ensures that sufficient separation between C-19 and the 11/3-oxygen atom exists to suppress functionalization at C-19 in favour of attack at C-18. Another recent application of the Barton reaction occurred in the synthesis of perhydrohistrionicotoxin (175), where the key step was the stereoselective formation of the oxime (174) from the nitrite ester (173). °... 

The photolysis of nitrite esters for intramolecular hydrogen abstraction reactions, a procedure that has become known as the Barton reaction, is a useful process for functionalization of unactivated sites. The carbon radical thus generated may be quenched by a variety of reagents (i- ii), D. H. R. Barton, J. M. Beaton, L. E. Geller, M. M. Pechet, J. Amer. Chem. Soc., 83, 4076 (1961) M. Akhtar, D. H. R. Barton and P. G. Sammes, J. Amer. Chem. Soc., 87, 4601 (1965). 

Musso has reported the synthesis of diasterane (tricyclo-[3.1.1.I2 4]octane) 15. For this first member of the series of asteranes, the decarboxylation of 16b -> 16c was best achieved via the photolysis of the Barton ester of 16a in the presence of BuSH, as shown in Scheme 5.14 Fukumoto has accomplished asymmetric total synthesis of atisine 17, where the bridged pentacyclic intermediate 18, a precursor for atisine, was synthesized via an intramolecular double Michael reaction starting with 19, Scheme 6.15 Barton protocol was favored during the late stages of the synthesis and the presence of various functionalities was easily accommodated. 

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