Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation
Alexandru Grozavu1, Hamish B Hepburn1, Elliot P Bailey1
1Chemistry Research Laboratory, University of Oxford Oxford OX1 3TA UK timothy.donohoe@chem.ox.ac.uk.
Abstract:
Pyridines are ubiquitous aromatic rings used in organic chemistry and are crucial elements of the drug discovery process. Herein we describe a new catalytic method that directly introduces a methyl group onto the aromatic ring; this new reaction is related to hydrogen borrowing, and is notable for its use of the feedstock chemicals methanol and formaldehyde as the key reagents. Conceptually, the C-3/5 methylation of pyridines was accomplished by exploiting the interface between aromatic and non-aromatic compounds, and this allows an oscillating reactivity pattern to emerge whereby normally electrophilic aromatic compounds become nucleophilic in the reaction after activation by reduction. Thus, a set of C-4 functionalised pyridines can be mono or doubly methylated at the C-3/5 positions.
More Related Videos
11:44Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions
Published on: March 20, 2014
09:45Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene
Published on: March 20, 2017
Related Concept Videos
Carboxylic Acids to Methylesters: Alkylation using Diazomethane
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Olefin Metathesis Polymerization: Overview
Ruthenium-based Grubbs catalyst is the most commonly used catalyst for olefin metathesis polymerization. Grubbs catalyst consists of a...
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Diazonium Group Substitution: –OH and –H
