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Updated: May 10, 2025
Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Ligand non-innocence and an unusual σ-bond metathesis step enables catalytic borylation using
Milan Kumar Bisai1, Justyna Łosiewicz1, Gary S Nichol1
1EaStCHEM School of Chemistry, University of Edinburgh Edinburgh EH9 3FJ UK mingleso@ed.ac.uk.
Abstract:
The metal-catalyzed intermolecular C-H borylation of arenes is an extremely powerful C-H functionalization methodology. However, to date it is effectively restricted to forming organo-boronate esters (Aryl-B(OR)2) with its application to form other organoboranes rarely explored. Herein, we report a catalytic intermolecular heteroarene C-H borylation method using the commercial hydroborane 9-borabicyclo-[3.3.1]-nonane, (H-BBN)2. This process is effective for mono- and di-borylation to form a range of heteroaryl-BBN compounds using either NacNacAl or NacNacZn (NacNac = {(2,6-iPr2C6H3)N(CH3)C}2CH) based catalysts. Notably, mechanistic studies indicated a highly unusual σ-bond metathesis process between NacNacZn-Aryl and the dimeric hydroborane, with first order kinetics in the hydroborane dimer ((H-BBN)2). Our calculated metathesis pathway involves ligand non-innocence and addition of both H-BBN units in (H-BBN)2 to the NacNacZn-heteroaryl complex. This is in contrast to the conventional σ-bond metathesis mechanism using other hydroboranes which invariably proceeds by reaction of one equivalent of a monomeric hydroborane (e.g., H-B(OR)2) with a M-C unit. Overall, this work demonstrates the potential of extending catalytic arene C-H borylation beyond boronate esters, while highlighting that the σ-bond metathesis reaction can be mechanistically more complex when utilizing dimeric hydroboranes such as (H-BBN)2.
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