The Reaction of O-Silylated Cyanohydrin Anions with Epoxides as an Alternative for the Enantio- and Diastereoselective Preparation of Aldols
Poster Number
31
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 beta-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. The scope and limitations of the method have been investigated with respect to the epoxide structure. The tert-butyldimethylsilyl (TBS) ether of mandelonitrile was prepared and reacted with a variety of differentially substituted epoxides. The reactions were carried out using LiHMDS as the base in either toluene or ether solvent. The newly formed adducts were then desilylated with tetrabutyl-ammonium fluoride (TBAF) to form the desired aldol product. Yields up to 90 % for the two-step process could be achieved.
Start Date
24-4-2015 1:20 PM
End Date
24-4-2015 2:50 PM
The Reaction of O-Silylated Cyanohydrin Anions with Epoxides as an Alternative for the Enantio- and Diastereoselective Preparation of Aldols
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 beta-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. The scope and limitations of the method have been investigated with respect to the epoxide structure. The tert-butyldimethylsilyl (TBS) ether of mandelonitrile was prepared and reacted with a variety of differentially substituted epoxides. The reactions were carried out using LiHMDS as the base in either toluene or ether solvent. The newly formed adducts were then desilylated with tetrabutyl-ammonium fluoride (TBAF) to form the desired aldol product. Yields up to 90 % for the two-step process could be achieved.
