Related Experiment Video
Updated: Jul 2, 2026

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Conformation-driven C3-C(sp 3)-H arylation of saturated azacycles using Pd catalyst
Chia-Yu Chen1, Zhoulong Fan1, Daniel A Strassfeld1
1Department of Chemistry, The Scripps Research Institute, La Jolla, CA USA.
None:
Directed Pd-catalysed site-selective C(sp 3)-H activation offers an effective route to functionalized amines that are highly valued yet synthetically challenging in drug discovery. Despite the central importance of diverse saturated azacycles in biologically active molecules, a general strategy harnessing native endocyclic nitrogen that only works for specific types of conformation as the directing element for C-H activation of these scaffolds has remained unsolved due to conformational constraints imposed by transannular transition states. Here we report a Pd-catalysed, site- and diastereo-selective C3-C(sp 3)-H arylation of saturated azacycles, enabled by temporarily converting the endocyclic nitrogen into an N-oxide directing group and a bifunctional ligand. This one-bond extension strategy enables favourable five-membered cyclopalladation, with axial N-oxide orientation being crucial for overcoming transannular ring strain as to reach the syn-axial C3-C(sp 3)-H bond.
More Related Videos
11:45Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
09:35Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units
Published on: September 18, 2016
Related Concept Videos
Cycloaddition Reactions: Overview
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Thermal Electrocyclic Reactions: Stereochemistry
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement