Heterocycle Synthesis Based on Allylic Alcohol Transposition Using Traceless Trapping Groups

Abstract

Allylic alcohols undergo transposition reactions in the presence of Re2O7 whereby the equilibrium can be dictated by trapping one isomer with a pendent electrophile. Additional ionization can occur when the trapping group is an aldehyde or ketone, thus leading to cyclic oxocarbenium ion formation. Terminating the process through bimolecular nucleophilic addition into the intermediate provides a versatile method for the synthesis of diverse oxygen‐containing heterocycles. Understanding the relative rates of the steps in the sequence leads to the design of reactions which create multiple stereocenters with good to excellent levels of control.

Re2O7‐Mediated Dehydrative Cyclization Reactions: Total Synthesis of Herboxidiene and Its 12‐Desmethyl Analogue

“…We have been exploring [9] the use of Re 2 O 7 -catalyzed allylic alcohol transposition reactions [10] in complex molecule synthesis. These processes, in which allylic alcohols react with Re 2 O 7 to form allylic perrhenate esters that rearrange and cleave to form isomeric allylic alcohols, employ appended electrophiles to dictate the regioselectivity of the transposition reaction.…”

“…These processes, in which allylic alcohols react with Re 2 O 7 to form allylic perrhenate esters that rearrange and cleave to form isomeric allylic alcohols, employ appended electrophiles to dictate the regioselectivity of the transposition reaction. However we observed [9c] that allylic alcohols can also serve as precursors to allylic cations (Scheme 1) during an investigation of epoxides as electrophilic traps. This result is consistent with calculations that show substantial charge separation in the transition states of perrhenate ester rearrangements [11] and with the generation of highly stabilized carbocations from allylic alcohols in bimolecular processes.…”

“…Exposing 1 to Re 2 O 7 •SiO 2 [9c] (5 mol%) at rt generated diastereomeric tetrahydropyrans 3 in <10 min through the putative carbocation intermediate 2 . While the diastereoselectivity improved at prolonged reaction times the epimerization proved to be too sluggish at ambient temperature for practical purposes.…”

Re2O7‐Mediated Dehydrative Cyclization Reactions: Total Synthesis of Herboxidiene and Its 12‐Desmethyl Analogue

“…We have been exploring [9] the use of Re 2 O 7 -catalyzed allylic alcohol transposition reactions [10] in complex molecule synthesis.These processes,inwhich allylic alcohols react with Re 2 O 7 to form allylic perrhenate esters that rearrange and cleave to form isomeric allylic alcohols,e mploy appended electrophiles to dictate the regioselectivity of the transposi-tion reaction. However,w eo bserved [9c] that allylic alcohols can also serve as precursors to allylic cations (Scheme 1) during an investigation of epoxides as electrophilic traps.This result is consistent with calculations that show substantial charge separation in the transition states of perrhenate ester rearrangements [11] and with the generation of highly stabilized carbocations from allylic alcohols in bimolecular processes.…”