Radical cyclisation strategies to bridged systems. Regioselective construction of chiral bicyclo [2.2.2] and [3.2.1] octanes via 6-exo trig and 5-exo trig radical cyclisation reactions

Abstract

Radical cyclisation reaction of the bromoenones 6̲ and 7̲, obtained from (R)-phenyl carvone 3̲, gave a mixture of bicyclo [2.2.2] and [3.2.1] octanones via competitive 6-exo trig and 5-exo trig modes. On the other hand, radical cyclisation reaction of the alcohol 12̲ furnished the bicyclo[3.2.1]-octanol 15̲ as the major cyclised product, where as the alcohol 13̲ furnished the bicyclo[2.2.2]octanol 18̲ as the major cyclised product. An explanation based on conformational rigidity due to the intramolecular hydrogen bonding between the hydroxy and methoxy groups is proposed, and proved by the formation of bicyclo[2.2.2]octanes as major cyclised products with the corresponding acetates 19̲ and 20̲.