Related Experiment Video
Updated: Jun 3, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Asymmetric Deoxy-Fluoroalkylation of Amides Enabled by Transimination
Jason A Wilt1, Samirah Muhammad1, R Yasoda H Rajapaksha1
1Department of Chemistry, Clemson University, Clemson, South Carolina 29634, United States.
None:
Asymmetric deoxy-fluoroalkylation of amides remains a highly challenging goal, especially for accessing chiral α-fluoroalkyl amines, prevalent motifs in pharmaceuticals. Herein, we report a new sequential strategy for an asymmetric deoxy-fluoroalkylation of amides, enabling synthesis of diverse chiral α-fluoroalkyl amines bearing CF3, CF2H, and C6F5 substituents in good yields and diastereoselectivities (up to >20:1 dr). This transformation involves Ti-catalyzed amide partial reduction, in situ transimination with Ellman's sulfinamide to form chiral sulfinimines, and diastereoselective fluoroalkylation.
Related Concept Videos
Preparation of Amides
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

