The Reaction of Protected Cyanohydrins with Epoxides as an Alternative for the Enantio- and Diastereoselective Preparation of Aldols: Studies with Lactonitrile
Poster Number
13
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
Aaron M. Hartel, Ph.D.
Abstract
The aldol addition is one of the most important carbon-carbon bond forming reactions in chemical synthesis. The traditional form of this reaction, between an aldehyde or ketone and a second enolized aldehyde or ketone, results in the formation of a b -hydroxycarbonyl (often referred to as an “aldol product”). The reaction can result in the formation of up to two new chiral centers, and the absolute and relative stereochemistry of the product can be challenging to control. Modern variations have allowed for significant enantio- and diastereoselectivity in the reaction. These useful methods are not without drawbacks, including poor atom economy, use of expensive auxiliaries, and the additional synthetic steps required to introduce and remove these auxiliaries. An alternative potential route for the enantio- and diastereoselective preparation of aldol products is the reaction of O-silylated cyanohydrin anions with epoxides. This method would take advantage of the wealth of excellent asymmetric epoxidation procedures available, providing an efficient method for the stereoselective formation of aldols. Experiments were performed to determine conditions that would allow for the successful reaction of cyanohydrins lacking an electron-stabilizing group adjacent to the developing carbanion. The tert-butyldimethylsilyl (TBS) ether of lactonitrile was prepared and reacted with a variety of bases in various solvents to attempt to form the cyanohydrin anion. Several forms of decomposition of the anion were observed, including evidence of Thorpe condensation and retro-Brook rearrangement. Deprotonation was also complicated by trace amounts of water and other impurities found in the substrate.
Start Date
24-4-2015 1:20 PM
End Date
24-4-2015 2:50 PM
The Reaction of Protected Cyanohydrins with Epoxides as an Alternative for the Enantio- and Diastereoselective Preparation of Aldols: Studies with Lactonitrile
Richardson Ballroom
The aldol addition is one of the most important carbon-carbon bond forming reactions in chemical synthesis. The traditional form of this reaction, between an aldehyde or ketone and a second enolized aldehyde or ketone, results in the formation of a b -hydroxycarbonyl (often referred to as an “aldol product”). The reaction can result in the formation of up to two new chiral centers, and the absolute and relative stereochemistry of the product can be challenging to control. Modern variations have allowed for significant enantio- and diastereoselectivity in the reaction. These useful methods are not without drawbacks, including poor atom economy, use of expensive auxiliaries, and the additional synthetic steps required to introduce and remove these auxiliaries. An alternative potential route for the enantio- and diastereoselective preparation of aldol products is the reaction of O-silylated cyanohydrin anions with epoxides. This method would take advantage of the wealth of excellent asymmetric epoxidation procedures available, providing an efficient method for the stereoselective formation of aldols. Experiments were performed to determine conditions that would allow for the successful reaction of cyanohydrins lacking an electron-stabilizing group adjacent to the developing carbanion. The tert-butyldimethylsilyl (TBS) ether of lactonitrile was prepared and reacted with a variety of bases in various solvents to attempt to form the cyanohydrin anion. Several forms of decomposition of the anion were observed, including evidence of Thorpe condensation and retro-Brook rearrangement. Deprotonation was also complicated by trace amounts of water and other impurities found in the substrate.
