Event Title

The Reaction of Protected Cyanohydrins with Epoxides as an Alternative for the Enantio- and Diastereoselective Preparation of Aldols: Studies with Lactonitrile

Poster Number

13

Presenter Information

James R. Dean, Winthrop University

Faculty Mentor

Aaron M. Hartel, Ph.D.

College

College of Arts and Sciences

Department

Chemistry, Physics and Geology

Location

Richardson Ballroom

Start Date

24-4-2015 1:20 PM

End Date

24-4-2015 2:50 PM

Description

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.

Comments

Supported by a grant from the Winthrop University Research Council

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Apr 24th, 1:20 PM Apr 24th, 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.