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Data-Driven Approach to Understanding Tetrabutylammonium Decatungstate-Catalyzed C(sp3)-H Functionalization
Mimi Lavin1, Makeda A Tekle-Smith1
1Department of Chemistry, Columbia University, New York, USA.
Angewandte Chemie (International Ed. in English)
|May 22, 2026
Summary
Photocatalytic hydrogen atom transfer (HAT) using tetrabutylammonium decatungstate (TBADT) enables selective C-C bond formation. Regioselectivity in complex molecules is governed by both hydrogen atom abstraction accessibility and radical addition kinetics.
Area of Science:
- Organic Chemistry
- Photocatalysis
- Synthetic Methodology
Background:
- Photocatalytic hydrogen atom transfer (HAT) is a key strategy for C(sp³)-C bond formation.
- Tetrabutylammonium decatungstate (TBADT) is effective for functionalizing electron-rich C-H bonds with high regioselectivity.
- Predicting regioselectivity in complex molecules remains a challenge.
Purpose of the Study:
- To elucidate the factors governing regioselectivity in TBADT-mediated C-H functionalization.
- To integrate electronic and steric descriptors for predicting site selectivity.
- To understand the interplay between catalyst-controlled hydrogen atom abstraction (HAA) and radical-controlled addition (RA).
Main Methods:
- Mechanistic investigations using deuterium labeling studies.
- Kinetic analyses to determine radical addition rates.
- Logistic regression analysis with electronic and steric descriptors.
Main Results:
- TBADT exhibits broad hydrogen atom abstraction (HAA) accessibility across electronically similar C-H bonds.
- SOMO energy directly correlates with radical addition (RA) rates, indicating frontier orbital control.
- Mechanistically rich features effectively predict site selectivity in complex scaffolds.
Conclusions:
- Regioselective outcomes in TBADT-mediated functionalization are determined by a combination of broad HAA accessibility and kinetically controlled RA.
- Frontier orbital interactions play a crucial role in directing product distributions.
- This work provides a kinetic framework for understanding radical sampling in complex C-H functionalization.
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