Remote functionalization, alkoxyl radicals

H. Suginome, Remote functionalization hy alkoxyl radicals generated hy the photolysis of nitrite esters The Barton reaction and related reactions of nitrite esters in CR. Handbook of Organic Photochemistry and Photobiology, 2nd Edition,... 

TBS-Protected 7-lactol is obtained through the formation of hypoiodite, followed by the formation of an alkoxyl radical, 1,5-H shift, and then formation of 8-iodoalcohol, and finally polar cyclization. The Fenton system with ROOH and Fe2+ also generates alkoxyl radical, RO. These reactions indicate that the Barton (-type) reactions are remote functionalization of non-activated C-H bonds at the 8- or e-position. 

The generation of alkoxyl radicals from alcohols is an important process which has been used for remote functionalization via hydrogen atom abstraction and for rearrangement via -fragmentation. Hypervalent organoiodine compounds have been applied with success in this type of chemistry. More recently, tetravalent selenium compounds have been used for the same purpose [120]. An efficient way of making ether linkage from non-functionalized alcohols has been developed. The conversion of the alcohol 158 to the ether 159 is a key step in the synthesis of (-l-)-8-deoxyvernolepin [Eq. (51)] [121]. This transformation is best... 

Suginome, H., Remote Functionalization by Alkoxyl Radicals Generated by the Photolysis of Nitrite Esters the Barton Reaction and Related Reactions of Nitrite Esters. In Horspool, W. M., Lenci, F. (eds), CRC Handbook of Organic Photochemistry and Photobiology, 2nd edn, CRC Press LLC, Boca Raton, FL, 2004, Chapter 102, pp. 1 16. 

The Barton nitrite ester photolysis is undeniably one of the most popular and useful reactions in radical chemistry for the functionalization of remote and inactivated positions within steroids (Scheme 19). Photolysis of nitrite esters gives nitric oxide and an alkoxyl radical that abstracts an ideally positioned hydrogen atom (1,5-hydrogen atom abstraction). The resulting alkyl radical reacts with nitric oxide in a solvent cage to afford the nitroso-alcohol derivative that is finally isolated as an oxime [53]. Related cyclizations of alkoxyl radicals have been reported by Surzur photolysis of y,(5-alkenyl nitrite esters leads to alkoxyl radicals that undergo subsequent tandem 5-exo cyclization followed by NO-trapping [54, 55]. 

Remote Functionalization by Alkoxyl Radicals Generated by the Photolysis of Nitrite Esters The Barton Reaction and Related Reactions of Nitrite Esters... 

Among the numerous results reported by the Swiss group, two typical examples of remote functionalization with this reagent are outlined in Schemes 16 and 17. The products of the remote functionalization of steroids by the hypoiodite reaction are either the five-membered oxide (Scheme 16) or the a-lactol acetate (Scheme 17), depending on the relative disposition between the relevant alkoxyl radical and the iodine attached to CIS or C19 of a conformer of the first-formed intermediate monoiodide. Thus, the five-membered oxide is an exclusive product in the example outhned in Scheme 16, because the iodo-methyl group can adopt an orientation that is appropriate for an S 2 or S 2 displacement of the iodine by the 6P-alkoxyl radical or ion, to give the observed oxide, as shown in Scheme 18. On the other hand, the a-lactol acetate is an exclusive product in the example outlined in Scheme 17, because the preferred orientation of the iodomethyl group with respect to the 4P-hydroxyl in the first-formed intermediate... 

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. 

These results indicate that hypoiodite photolysis with mercury (11) oxide and iodine reagent is a powerful method that is applicable to even remote functionalization involving a many-membered transition state, because alkoxyl radicals are considered to be repeatedly generated from the regenerated hypoiodites in a solution containing an excess of the reagent. 

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