Oxygen-centered radicals cyclizations

Zlotorzynska, M., Zhai, H., M. Sammis, G. M. (2008). Chemoselective Oxygen-Centered Radical Cyclizations onto Silyl Enol Ethers. Organic Letters 10(21), 5083. 

Eq. 4.54 shows the reaction of n-heptanol (151) with Pb(OAc)4 under high-pressured carbon monoxide with an autoclave to generate the corresponding 8-lactone (152). This reaction proceeds through the formation of an oxygen-centered radical by the reaction of alcohol (151) with Pb(OAc)4,1,5-H shift, reaction with carbon monoxide to form an acyl radical, oxidation of the acyl radical with Pb(OAc)4, and finally, polar cyclization to provide 8-lactone [142-146]. This reaction can be used for primary and secondary alcohols, while (3-cleavage reaction of the formed alkoxyl radicals derived from tertiary alcohols occurs. 

The first step in the mechanism is the homolysis of the 0-N bond to form an oxygen-centered radical and a nitrogen-centered free radical. Next, the highly reactive alkoxyl radical abstracts a hydrogen atom from the 5-position (5-position) via a quasi chair-like six-atom transition state to generate a new carbon-centered radical that is captured by the initially formed NO free radical. If a competing radical source such as iodine is present, the reaction leads to an iodohydrin, which can cyclize to form a tetrahydrofuran derivative. Occasionally, tetrahydropyran derivatives are obtained in low yields. 

Selectivity in cyclizations of oxygen-centered radicals with the formation of furans 02S1469. 

This cleavage will therefore be discussed first. Several substrates have proven useful for the generation of the pivotal oxiranylcarbinyl radicals. Sharpless epoxides are valuable starting materials for radical precursors [18]. After formation of the oxygen-centered radical, reactions typical for radicals are observed. With a suitably positioned double bond, cyclization occurs as shown in Scheme 10 [19]. It is interesting that the cw-disubstituted carbon-centered radical can react further to yield a bicyclo[2.2.1] system. 

In stark contrast to azoalkanes, azoxy compounds rarely form radicals on heating or irradiation. Furthermore, they are unreactive to alkyl radical attack unless the reaction is intramolecular. For example, P-carbon centered radicals cyclize to azoxy nitrogen or oxygen and produce short-lived aminyl nitroxides that reopen or hydrazyl radicals that undergo fragmentation. The azoxy group is a powerful stabilizer of an adjacent radical center but the chemistry of a-azoxy radicals (hydrazonyloxides) and their dimers is not fully understood. 

Several useful synthetic methodologies are based on the generation of the oxygen-centered radicals from carboxylic acids and the (diacetoxyiodo)benzene-iodine system [613-617]. In particular, a direct conversion of 2-substituted benzoic acids 566 into lactones 567 via oxidative cyclization induced by [bis(acyloxy)iodo]arene/iodine has been reported (Scheme 3.224) [613,614]. 

The applications of such electronic effects extend to radical chemistry. For example, reactions of electrophilic oxygen-centered radicals display excellent chemoselectivity for cyclization onto the electron-rich silyl enol ether when competing with terminal alkene cyclization, 1,5-hydrogen abstraction, and p-fragmentation pathways (Figure 6.115). ... 

Lactone rings have also been constructed using carbonylation of appropriately functionalized compounds by the insertion of carbon monoxide. Ryu, Sonoda et al. have reported the synthesis of 8-lactones from saturated alcohols and carbon monoxide via remote carbonylation [110,111] (Scheme 64). Treatment of saturated alcohol 292 with lead tetraacetate led to oxygen-centered radical 293, which underwent a 1,5-hydrogen transfer reaction to produce carbon-centered radical 294. Trapping of this radical with carbon monoxide and oxidation followed by cyclization gave lactone 297. 

For recent reviews, see (a) Hartung, J., Gottwald, T, and Spehar, K., Selectivity in the chemistry of oxygen-centered radicals the formation of carbon-oxygen bonds. Synthesis, 1469, 2002 (b) Hartung, J., Stereoselective construction of the tetrahydrofuran nucleus by alkoxyl radical cyclizations, Eur. J. Org. Chem., 619, 2001. 

The transition structure trans-42 to fra s-43 TiCp2Cl was also calculated and a barrier of 11.7 kcal mol 1 was obtained for the cyclization. This value is similar to the activation energy for the formation of cis-43 TiCp2Cl, although the distance between the carbon-centered radical and oxygen atom is shorter (2.04 A). 

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