Presentation Title

Synthesis of Chiral Tetrahydropyrans by a Tandem Sakurai Allylation/Intramolecular 6-Exo-Tet Cyclization

Start Date

November 2016

End Date

November 2016

Location

Surge 173

Type of Presentation

Oral Talk

Abstract

Heterocycles are ubiquitous in a variety of bioactive natural products, many of which have found use as potential drug targets. The potency of these molecules with regards to treating disease is often dependent upon their chirality. While several methods have been developed to synthesize a variety of chiral heterocycles, we propose a new method that utilizes chiral allyl silane substrates and proceeds through a stereospecific cascade reaction. The synthesis of a variety of chiral allyl silanes containing pendant electrophiles was achieved via a nickel-catalyzed cross-coupling method recently developed in our laboratory. We have since shown that these allyl silanes can provide the desired tetrahydropyran heterocyclic product under Lewis acid-catalyzed conditions. This mechanism proceeds through an intermolecular Sakurai allylation followed by an intramolecular 6-exo-tet cyclization. We report on the development and optimization of this cascade reaction and envision using this method to access a variety of other chiral heterocycles, including tetrahydrofurans, piperidines, pyrrolidines, and butyrolactones.

This document is currently not available here.

Share

COinS
 
Nov 12th, 11:00 AM Nov 12th, 11:15 AM

Synthesis of Chiral Tetrahydropyrans by a Tandem Sakurai Allylation/Intramolecular 6-Exo-Tet Cyclization

Surge 173

Heterocycles are ubiquitous in a variety of bioactive natural products, many of which have found use as potential drug targets. The potency of these molecules with regards to treating disease is often dependent upon their chirality. While several methods have been developed to synthesize a variety of chiral heterocycles, we propose a new method that utilizes chiral allyl silane substrates and proceeds through a stereospecific cascade reaction. The synthesis of a variety of chiral allyl silanes containing pendant electrophiles was achieved via a nickel-catalyzed cross-coupling method recently developed in our laboratory. We have since shown that these allyl silanes can provide the desired tetrahydropyran heterocyclic product under Lewis acid-catalyzed conditions. This mechanism proceeds through an intermolecular Sakurai allylation followed by an intramolecular 6-exo-tet cyclization. We report on the development and optimization of this cascade reaction and envision using this method to access a variety of other chiral heterocycles, including tetrahydrofurans, piperidines, pyrrolidines, and butyrolactones.