Dialdehydes radical cyclization

Di-0-benzyl-3,4-0-isopropylidene-D-mannitol was ring closed to afford a 9 1 cis/trans mixture of 189 in high yield by (Swern) oxidation and radical cyclization of the dialdehyde using samarium iodide in fcrf-butanol. The cis-diastereoisomer was selectively converted into a cis-cyclic sulfate which underwent cleavage upon treatment with potassium tert-butoxide to afford a cyclo-... 

A section on cardenolides would not be complete without mentioning the total synthesis of (+)-digitoxinin by Stork and his co-workers. Protected Wieland-Miescher ketone 66 was converted into compound 67 via formation of the trimethylsilyl enol ether ozonolysis of the enol ether gave a mixture of hydroxyketones, which was reduced to the corresponding diol and then cleaved with sodium periodate to yield dialdehyde intermediate 67. Compound 67 was then elaborated into Diels-Alder precursor 68 in two steps. After completion of the Diels-Alder reaction, four additional steps led to the preparation of intermediate 69, which was ideally set up for a vinyl radical cyclization. Key intermediate 70 was then elegantly converted into (+)-digitoxinin (71). 

Scheme 9.178. A representation of the radical cyclization of 1,5-pentanedial (glutaric dialdehyde) to cw-l,2-dihydroxycyclopentane on treatment with tributyltin hydride (catalyzed by AIBN).

Intramolecular pinacol coupling reactions are known, giving cyclic 1,2-diols. Dialdehydes have been cyclized by reaction with TiCls to give cyclic 1,2-diols in good yield. ° A radical-induced coupling of an a,03-dialdehyde led to cw-l,2-cyclo-pentanediol when treated with BuaSnH and AIBN. or induced photochemically. ... 

Aldehydes form O-stannyl ketyls with the BujSn radical. A /3-alkoxyacrylate unit five bonds away from the ketyl is well positioned to be involved in a radical transfer process therefore, cyclization ensues. Fused oxacycles of well-defined stereochemistry are assembled by this reaction. Heterocyclic 1,2-amino alcohols are similarly procured from dialdehyde monooxime ethers. ... 

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