Presentation Title

Development of an Enantioselective Allenoate Claisen Rearrangement

Faculty Mentor

Anna Wenzel

Start Date

23-11-2019 10:45 AM

End Date

23-11-2019 11:30 AM

Location

210

Session

poster 4

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

The allenoate Claisen rearrangement is a thermodynamically-controlled reaction that works by utilizing an allene in a [3,3] sigmatropic rearrangement to create a more favorable carbonyl compound. Previous research has indicated that the reaction diastereoselectivity follows a Zimmerman-Traxler model via a chair-like transition state, which results in the highly diastereoselective formation of the syn product. However, despite the natural diastereoselectivity of the reaction, the development of an enantioselective version of this reaction has proven very challenging. Our laboratory is focused on achieving an asymmetric variant of this Claisen rearrangement as well as understanding its scope.

In 2016, researchers in the Wenzel laboratory developed a method to make this reaction enantioselective by placing a chiral auxiliary group on an allyl amine. The chiral auxiliary group sterically hinders attack on one side of the molecule, thereby forcing the preference of one enantiomer over another. Once the reaction is completed, the amine can be removed and recycled via hydrolysis, which forms the final Claisen product. Conditions of the reaction are optimal when utilizing a methoxymethyl chiral auxiliary substitution and 10 mol% silicated tosylic acid as the reaction catalyst in a 1:1 nitromethane:dichloromethane solvent mixture. The reaction is run at room temperature for 48 hours before being hydrolyzed and purified.

Our laboratory is currently expanding this discovery by understanding the scope of this reaction. In particular, by varying the substituents on both the allene and amine, we seek to understand which combinations will lead to high yield and enantioselective products in the Claisen rearrangement. Various combinations of allenes and amines have been reacted via our Claisen protocol, and the products analyzed via HPLC to determine their percent enantiomeric excess.

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Nov 23rd, 10:45 AM Nov 23rd, 11:30 AM

Development of an Enantioselective Allenoate Claisen Rearrangement

210

The allenoate Claisen rearrangement is a thermodynamically-controlled reaction that works by utilizing an allene in a [3,3] sigmatropic rearrangement to create a more favorable carbonyl compound. Previous research has indicated that the reaction diastereoselectivity follows a Zimmerman-Traxler model via a chair-like transition state, which results in the highly diastereoselective formation of the syn product. However, despite the natural diastereoselectivity of the reaction, the development of an enantioselective version of this reaction has proven very challenging. Our laboratory is focused on achieving an asymmetric variant of this Claisen rearrangement as well as understanding its scope.

In 2016, researchers in the Wenzel laboratory developed a method to make this reaction enantioselective by placing a chiral auxiliary group on an allyl amine. The chiral auxiliary group sterically hinders attack on one side of the molecule, thereby forcing the preference of one enantiomer over another. Once the reaction is completed, the amine can be removed and recycled via hydrolysis, which forms the final Claisen product. Conditions of the reaction are optimal when utilizing a methoxymethyl chiral auxiliary substitution and 10 mol% silicated tosylic acid as the reaction catalyst in a 1:1 nitromethane:dichloromethane solvent mixture. The reaction is run at room temperature for 48 hours before being hydrolyzed and purified.

Our laboratory is currently expanding this discovery by understanding the scope of this reaction. In particular, by varying the substituents on both the allene and amine, we seek to understand which combinations will lead to high yield and enantioselective products in the Claisen rearrangement. Various combinations of allenes and amines have been reacted via our Claisen protocol, and the products analyzed via HPLC to determine their percent enantiomeric excess.