Ketyl 8-endo cyclizations

An intramolecular ketyl/alkyne coupling method has been employed in a synthetic approach to erigerol [91], wherein a reasonably complex tricyclic system was created in high yield (Eq. 80), and in the synthesis of isocarbacyclin (Eq. 81) [92]. Finally, the analogous >-endo cyclization process has also been applied with some success [83], creating functionalized cyclooctenols in modest yield (Eq. 82). 

Molander GA, George KM, Monovich JG. Total synthesis of (+)-isoschizandrin utiUziug a samarium(II) iodide-promoted 8-endo ketyl-olefin cyclization. J. Org. Chem. 2003 68 (25) 9533 9540. 

The major product of the keto olefin cyclizations often corresponds to what one would predict, assuming the intermediate ketyl behaves like the corresponding monoradical (Eq. 34). For example, given an option between a 5-exo and a 6-endo-trig cyclization, the former predominates in radical cyclizations [51], and constitutes the exclusive cyclization path in the electrochemical counterpart, 110 - 112 [47]. In addition, the stereochemical outcome parallels that of the radical... 

A novel application of the radical cascade for construction of the indolizidinone skeleton focused on the initial formation of (9-stannyl ketyls. The tributyl tin radical was found to react with the carbonyl group of 507 to give ketyl 508 (Scheme 87) (04T8181). Consecutive 6-endo- and 5-exo-trig cyclizations then furnished stannyl enol ether 510. Eventual hydrolysis of the enol ether provided indolizidinone 511 in 36% yield as a Id-mixture of diastereomers. Again, the predominant isolation of the thermodynamic favored products derived from a 6-endo-trig cyclization can be... 

Samarium diiodide-induced ketyl couplings are of significant synthetic interest, and Reissig el al. have reported an elegant application of the reaction in the case of the precursor 18. Reaction of 18 with 2 equivalents of samarium diodide and HMPA gave the 2-benzazepine 19 from an S-endo-dig cyclization reaction of the ketyl radical from the... 

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