Investigations of Remote C-H Insertion of Vinyl Cations Leading to Cyclopentenones
Conference Year
January 2019
Abstract
As the demand for pharmaceutical agents grow, efficient and cost effective syntheses of these target molecules becomes necessary. The discovery of synthetic strategies that improve on known reactions or provide a streamlined approach to previously inaccessible structures are important objectives of organic methodology development. Previously, the Brewer group developed a reaction that utilized a Lewis acid mediated ring fragmentation of γ-silyloxy-β-hydroxy-α-diazoesters that took advantage of a vinyl diazonium cation intermediate to produce aldehyde tethered ynone and ynoate products. With this chemistry, the group developed syntheses to several naturally occurring compounds: demissidine, (±)-cycloclavine, and the C,D,E ring system of aspidospermine. More recently, we have discovered that β-hydroxy-α-diazo ketones react with Lewis acids to give cyclopentenone bicyclic products. This reaction proceeds through a vinyl cation intermediate that undergoes a C-H insertion. The structural motif generated is ubiquitous in naturally occurring and pharmaceutical organic compounds, and it is important to develop methods to access these types of products. This chemistry could then be applied to syntheses of small molecules that may be difficult or arduous to achieve in other manners so their biological and pharmacological activity can be explored.
Primary Faculty Mentor Name
Matthias Brewer
Status
Graduate
Student College
College of Arts and Sciences
Program/Major
Chemistry
Primary Research Category
Engineering & Physical Sciences
Investigations of Remote C-H Insertion of Vinyl Cations Leading to Cyclopentenones
As the demand for pharmaceutical agents grow, efficient and cost effective syntheses of these target molecules becomes necessary. The discovery of synthetic strategies that improve on known reactions or provide a streamlined approach to previously inaccessible structures are important objectives of organic methodology development. Previously, the Brewer group developed a reaction that utilized a Lewis acid mediated ring fragmentation of γ-silyloxy-β-hydroxy-α-diazoesters that took advantage of a vinyl diazonium cation intermediate to produce aldehyde tethered ynone and ynoate products. With this chemistry, the group developed syntheses to several naturally occurring compounds: demissidine, (±)-cycloclavine, and the C,D,E ring system of aspidospermine. More recently, we have discovered that β-hydroxy-α-diazo ketones react with Lewis acids to give cyclopentenone bicyclic products. This reaction proceeds through a vinyl cation intermediate that undergoes a C-H insertion. The structural motif generated is ubiquitous in naturally occurring and pharmaceutical organic compounds, and it is important to develop methods to access these types of products. This chemistry could then be applied to syntheses of small molecules that may be difficult or arduous to achieve in other manners so their biological and pharmacological activity can be explored.