Related Experiment Video
Updated: Jun 16, 2025

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Halide Abstraction-Mediated Synthesis of a Highly Twisted Amide
Mizhi Xu, Krista K Bullard, John Bacsa1
1X-ray Crystallography Center, Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States.
Abstract:
Highly strained [3.2.1] bicyclic twisted amide 2 and corresponding amidium 10 were synthesized for the first time through Ag(I)-mediated halide abstraction. After initial lactamization attempts failed, a second-generation strategy was devised to target amidium 10 via intramolecular alkylation. The 3,4-dihydroisoquinolone cyclization precursor was regioselectively prepared via a Rh(III)-catalyzed C-H activation/annulation reaction. After Ag(I)-assisted cyclization, the [3.2.1] bicyclic framework of amidium 10 was confirmed by X-ray crystallography and enabled full solution characterization of twisted amide 2.
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...
Nucleophilic Aromatic Substitution: Elimination–Addition
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

![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)