Switching Chemoselectivity: Using Mechanochemistry to Alter Reaction Kinetics

• Published in: Angewandte Chemie International Edition Vol. 57; no. 49; pp. 16104 - 16108
• Main Authors: Howard, Joseph L., Brand, Michael C., Browne, Duncan L.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 03.12.2018; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Additives; ball milling; chemoselectivity; Comminution; Communication; Communications; Grinding mills; Kinetics; mechanochemistry; Reaction kinetics; Reaction mechanisms; solventless reactions; Switching; chemoselectivity; solventless reactions; mechanochemistry; reaction kinetics; ball milling
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201810141

A reaction manifold has been discovered in which the chemoselectivity can be altered by switching between neat milling and liquid assisted grinding (LAG) with polar additives. After investigation of the reaction mechanism, it has been established that this switching in reaction pathway is due to the neat mechanochemical conditions exhibiting different kinetics for a key step in the transformation. This proof of concept study demonstrates that mechanochemistry can be used to trap the kinetic product of a reaction. It is envisaged that, if this concept can be successfully applied to other transformations, novel synthetic processes could be discovered and known reaction pathways perturbed or diverted. Shaking things up: A reaction manifold has been discovered in which the covalent structure of the obtained product is dependent on whether the reaction is conducted under neat milling or in solution. Further investigation has highlighted that the kinetic product is produced by milling and the thermodynamic by solution‐phase reaction.