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DOI: 10.1055/a-2714-8611
A Computational Study of C–H Bond Abstraction in β-Amino Alcohols: O-side Activation over N-side via Boronate Adduct Formation
Authors
Supported by: Agencia Estatal de Investigación PID2021-126075NB-I00,RYC2022-035776-I
Supported by: Fundación Banco Santander Contratos Predoctorales 2023
Funding Information I.F.-A. and N.S. thank the project PID2021-126075NB-I00 funded by MCIN/AEI/10.13039/501100011033 and the European Union “Next Generation EU”/PRTR. He also acknowledges MCIN/AEI/ 10.13039/501100011033 for the “Ramón y Cajal” scholarship (RYC2022-035776-I). N.S. thanks the Universidad de La Rioja for the Becas Santander/Contratos Predoctorales 2023.
Abstract
A density functional theory (DFT) study was performed to evaluate the reaction mechanism underlying the chemoselective C–H abstraction in β-amino alcohols under a photoredox-catalyzed platform. Our results support a three-step mechanism based on the formation of a highly activated tetracoordinated boronate adduct followed by a selective hydrogen atom transfer (HAT) and a Giese-type radical addition, which together generate the experimentally observed γ-oxo-δ-amino esters. We demonstrated that α-hydroxy C–H bonds are more readily activated toward the HAT step than the α-amino C–H bond. This enhanced chemoselectivity arises from the tetracoordinated boronate adduct, which increases the hydridic character of the α-hydroxy H atom and lowers the bond dissociation enthalpy (BDE) of the C–H bond.
Keywords
Density functional theory - β-Amino alcohols - Chemoselectivity - Boron activation - Reaction mechanism - HATPublication History
Received: 31 July 2025
Accepted after revision: 01 October 2025
Accepted Manuscript online:
01 October 2025
Article published online:
04 November 2025
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