A Computational Study of C–H Bond Abstraction in β-Amino Alcohols: O-side Activation over N-side via Boronate Adduct Formation

Nil Sanosa; Adrián Gómez-Suárez; Ignacio Funes-Ardoiz

doi:10.1055/a-2714-8611

Synthesis 2026; 58(01): 62-66
DOI: 10.1055/a-2714-8611

Paper

Published as part of the Special Issue dedicated to Prof. Franziska Schoenebeck, recipient of the 2025 Dr. Margaret Faul Women in Chemistry Award

A Computational Study of C–H Bond Abstraction in β-Amino Alcohols: O-side Activation over N-side via Boronate Adduct Formation

Authors

Nil Sanosa

¹Departamento de Química, Instituto de Investigación en Química de la Universidad de La Rioja (IQUR), Complejo Científico Tecnológico, Universidad de La Rioja, Logroño, Spain
Adrián Gómez-Suárez

²Organic Chemistry, Bergische Universität Wuppertal, Wuppertal, Germany
Ignacio Funes-Ardoiz

¹Departamento de Química, Instituto de Investigación en Química de la Universidad de La Rioja (IQUR), Complejo Científico Tecnológico, Universidad de La Rioja, Logroño, Spain

Abstract

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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 - HAT

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References

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