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Updated: Aug 13, 2025

Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Steric Shielding Effects Induced by Intramolecular C-H⋯O Hydrogen Bonding: Remote Borylation Directed by Bpin Groups
Jose R Montero Bastidas1, Arzoo Chhabra1, Yilong Feng1
1Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
Abstract:
Regioselectivities in catalytic C-H borylations (CHBs) have been rationalized using simplistic steric models and correlations with nuclear magnetic resonance (NMR) chemical shifts. However, regioselectivity can be significant for important substrate classes where none would be expected from these arguments. In this study, intramolecular hydrogen bonding (IMHB) can lead to steric shielding effects that can direct Ir-catalyzed CHB regiochemistry. Bpin (Bpin = pinacol boronic ester)/arene IMHB can promote remote borylations of N-borylated anilines, 2-amino-N-alkylpyridine, tetrahydroquinolines, indoles, and 1-borylated naphthalenes. Experimental and computational studies support molecular geometries with the Bpin orientation controlled by a C-H⋯O IMHB. IMHB-directed remote CHB appeared operative in the C6 borylation of 3-aminoindazole (seven-membered IMHB) and C6 borylation of an osimertinib analogue where a pyrimidine IMHB creates the steric shield. This study informs researchers to evaluate not only inter- but also intramolecular noncovalent interactions as potential drivers of remote CHB regioselectivity.
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