Showcase of Undergraduate Research and Creative Endeavors (SOURCE)

Reaction of Protected Cyanohydrins 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 β-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, especially those of Evans and related strategies, have allowed for significant enantio- and diastereoselectivity in the reaction. These methods, while extremely useful, have several drawbacks, including poor atom economy, use of expensive auxiliaries, and 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 approach for the stereoselective formation of aldols. The scope and limitations of the method have been investigated with respect to epoxide and cyanohydrin structure. The tert-butyldimethylsilyl (TBS) ethers of several aryl cyanohydrins were 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 tetrabutylammonium fluoride (TBAF) to form the desired aldol products. Yields up to 90 % for the two-step process (alkylation-desilylation) were achieved.