Remote intramolecular hydrogen abstraction

Remote photocyclization of (dibenzylamino)ethyl benzoylacetate. Intramolecular hydrogen abstraction through a ten-membered cyclic transition state. Journal of the Chemical Society, Chemical Communications, 363-364. 

Hydrogen abstraction can occur intramolecularly and is useful for functionalizing rather remote unactivated sites. With freely rotating alkyl systems, there is a great preference for a five- or six-membered cyclic transition state. With rigid or conformationally restricted systems, molecular models are necessary to predict the site of intramolecular hydrogen abstraction. 

Intramolecular hydrogen abstraction by a photochemically generated alkoxyl radical has been employed in remote functionalisation of non-activated carbon atoms,and the stereoisomeric a-iodo epoxides (128) are formed by irradiation of 5-hydroxy-5/3-cholest-3-ene (129) in benzene containing mercury(II) oxide and iodine. 

Intramolecular hydrogen abstraction by excited nitrobenzene derivatives may lead to the introduction of an oxidized functional group in a remote part of the molecule, as previously reported by Scholl and Van De Mark.63 Japanese workers have now extended this reaction to the preparation of some oxidized derivatives of the triterpene dammaranediol.64... 

Photoinduced remote cyclization of amino ketones provides modest yields of mixtures of the cis and trans isomers of oxazocinones (79 R = H, = H, Ph, R = H, Ph R = Me, R = R = Ph) (Scheme 21), resulting from intramolecular hydrogen abstraction by the photoexcited ketone in a ten-membered transition state <85CC363,90JCS(Pl)90l). 

Both substitution and addition reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic utility, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. The preference for a six-membered cyclic transition state in the hydrogen-abstraction step imparts considerable selectivity to these intramolecular hydrogen abstractions. An important example of this... 

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). °... 

Hasegawa, X, Miyata, K., Ogawa, T., Yoshihara, N., and Yoshioka, M., Remote photocychsation of (dibenzylamino) ethyl benzoylacetate. Intramolecular hydrogen abstraction through a ten-mem-bered cyclic transition state, /. Chem. Soc., Chem. Commun., 363, 1985. 

The billiard reaction, a second intramolecular hydrogen abstraction from a 1,3-diaxially located methyl group by a carbon-centered radical, initially generated by an alkoxyl radical was observed in the remote functionalization of certain triterpenoids and diterpenoids by a thermal hypoiodite reaction with lead tetraacetate-iodine by Wenkert and Milari in 1967. Recent work by Suarez indicates that similar results can be achieved by the photolysis of hypoiodites in the presence of (diacetoxyiodo)benzene-iodine (Scheme 21). Scheme 22 outlines the reaction path. 

There is only one limitation of general scope, namely the possibility for more remote hydrogen abstraction, especially from carbons next to strong electron donors, and for competing intramolecular Paterno-Buchi reaction with appropriately located double bonds. Chapters 3 and 4 cover these processes and may provide the information necessary to determine the likelihood of such reactions competing with y-hydrogen abstraction in a particular compound. 

Several different elegant studies have been concerned with the availability of remote hydrogens for intramolecular abstraction by a triplet benzoyl group. Breslow and Winnik first reported remote hydrogen abstraction from para-substituted benzophenones 79). Winnik has shown that the accessibility of... 

The selectivity observed in most intramolecular functionalizations depends on the preference for a six-membered transition state in the hydrogen-atom abstraction step. Appropriate molecules can be constmcted in which steric or conformational effects dictate a preference for selective abstraction of a hydrogen that is more remote from the reactive radical. 

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