Alkoxylation-lactonization

SCHEME 15.16. Intramolecular Pd-catalyzed alkoxylation-lactonization as the key step in the synthesis of trani -kumausyne according to Boukouvalas et al. ... 

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 results described herein demonstrate that the )9-fragmentation reaction of alkoxyl radicals generated under oxidative or reductive conditions is well suited for the synthesis of medium-sized and macro ketones and lactones. The system hyper-... 

Oxidation Reactions. Hypoiodite intermediates may be generated from the reaction of simple alcohols with NIS. When conducted under photochemical irradiation, the products of Barton-type or fragmentation reactions of alkoxyl radical intermediates may be obtained. Aldehydes are oxidized to methyl esters via hemiacetal intermediates by reaction with NIS in methanol at rt. However, such conditions are not effective for the oxidation of simple alcohols. The combination of NIS and Tetrabutylammonium Iodide in dichloromethane has been developed for the oxidation of a variety of alcohols to the corresponding carbonyl corrpounds (eq 8). This reagent system is most widely used for the oxidation of lactols to lactones, in which near-quantitative yields are generally obtained under mild conditions (eq 9). ... 

Since acyloxyl radicals add more readily intermolecularly to double bonds than do alkoxyl radicals one could hope to obtain lactones from... 

The bromo-alkoxylation route for the synthesis of crown ethers (6,189 5,178) has been adapted to allow the preparation of substituted mono- and di-thia-crown systems (Scheme 49). Once again, one of these sequences uses the cyclization that is effected by a sulphonyl chloride and a base, as does a recently reported preparation of oxo-crown ethers e.g. Scheme 50 for the mono-oxo-series. Studies here imply activation of the carboxy- rather than of the alkoxy-terminus by the sulphonyl chloride. The ester functions reduce the complexing ability of these macrocycles with respect to normal crown ethers. The reduction of oxo-crowns to cyclic ethers, rather than to the diols that might be expected from reduction of a lactone, by LiAlHi has been studied the crown system seems to be necessary, and the involvement of lithium complexes has been suggested. 

Miscellaneous Reactions.—a-Alkoxylated a-lithioacetates may be alkylated,may react with ketones (the products from which cyclize to f3-lactones, themselves precursors of enol ethers by CO2 elimination" ), and may be condensed with lactones, as applied in a synthesis of natural product derivatives.The trianion derived from PhCH(0H)C02H is. C-alkylated but only in mediocre yield.The anions PhSCHCO and PhSCHC02Me react efficiently with electrophiles however, the former adds 1,2 to a, 8-unsaturated ketones, whereas the latter adds 1,4- ... 

New General Synthesis of medium-ring lactones via a Regioselective -Fragmentation of Alkoxyl Radicals Generated from Catacondensed Lactols... 

---