# Halide Abstraction-Mediated Synthesis of a Highly Twisted Amide

## TL;DR

Scientists synthesized a highly twisted amide using a new method involving silver and rhodium catalysts.

## Contribution

A novel Ag(I)-mediated halide abstraction strategy was developed to synthesize a strained bicyclic amide.

## Key findings

- A second-generation strategy enabled the synthesis of amidium 10 via intramolecular alkylation.
- X-ray crystallography confirmed the [3.2.1] bicyclic framework of amidium 10.
- The twisted amide 2 was fully characterized in solution.

## 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.