Heterocycle Synthesis Based on Allylic Alcohol Transposition Using Traceless Trapping Groups

Abstract

Allylic alcohols undergo transposition reactions in the presence of Re2 O7 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.

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

“…In this case, the reduction of the carbonyl group in the open chain hydroxyketone is preferred (Scheme , pathway b) to give diols 13 as a mixture of epimers. Although bulkier silyl hydrides such as Ph 3 SiH had been shown to provide a better diastereoselection in the formation of 2,6‐ cis disubstituted tetrahydropyran derivatives, in our case, the mentioned 1,3‐interaction as well as entropic factors, must be difficulting the evolution through the cyclic intermediate and favouring the direct reduction of the acyclic precursor.…”

“…The mechanistic studies carried out allowed to establish the electronic effects of ring substituents in the cyclic oxocarbenium ion intermediate as the main factors that control the stability of the reactive conformations and, as a consequence, the stereoselectivity of the nucleophilic additions. The size of the nucleophilic hydride also influences the diastereoselectivity . When dealing with seven or eight‐membered cyclic oxocarbenium ions, studies on C3, C4 and C5 alkyl or alkoxy substituted systems, corroborated these conclusions .…”

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

“…128 However, only the formation of tetrahydropyranes leads to good diastereoselectivity using this approach.…”

Diarylmethane synthesis through Re2O7-catalyzed bimolecular dehydrative Friedel–Crafts reactions

“…Our studies in the applications of Re 2 O 7 to allylic alcohol transposition reactions5,6 resulted in a new dehydrative cyclization protocol in which allylic cations react with pendent hydroxy groups 7,8. Re 2 O 7 proved to be superior to Brønsted acids for promoting these processes, leading us to speculate that it could be an effective catalyst for enabling bimolecular dehydrative coupling reactions.…”