From carbohydrates to the discovery of pronounced heteroatomic effects on anionically accelerated [3,3]-sigmatropic rearrangements

The (Z)-(iodovinyl)oxetane 12 was prepared from d-glucose and the acyclic a nalog 18 was obtained from d-mannitol. Following the generation of their li thium derivatives by halogen-metal exchange, coupling to the enantiopure vi nyl-substituted norbornanones 20, 23, and 29 proceeded exclusively via endo attack to deliver the targeted exo-carbinols. The anionic oxy-Cope rearran gements of 21 and 24 were seen to differ appreciably in rate. While the sul fur derivative 24 experiences [3,3] sigmatropy with a half-life of less tha n a minute at -78 degrees C, its oxygen analogue 21 proved unreactive below -20 degrees C under entirely comparable conditions. This phenomenon is cri tically examined in a synthetic context involving 26 and 30, where the heav ily functionalized acyclic side chain involved previously is supplanted by an oxetane assembly. in the sulfur example, isomerization occurs very rapid ly as before with 100% transfer of chirality. The kinetic response of vinyl ether 26 now proved to be entirely comparable. However, the pathway follow ed in this instance was intramolecular nucleophilic attack by the "naked" a lkoxide at the less substituted C-O bond of the oxetane with ring cleavage and formation of alcohol 28. The global findings provide a glimpse of the s ubtle way in which [3,3]-sigmatropic transpositions can be modulated by het eroatomic substitution.