Directing group-free site-selective and stereoretentive C-H amination of alkanes with phenyl triazolinedione (PTAD) as a σ-acid
Abstract
4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) is known as the most reactive commercially available dienophile, as it rapidly reacts with dienes at low temperatures and high dilution. In general terms, PTAD is a very soft Lewis acid, with a strong affinity towards electron rich alkenes. In this work, we report that the potent π-acid PTAD also shows a very useful and general σ-acid reactivity towards electron rich C(sp3)-H bonds, opening up its use in alkane amination reactions, as well as in late stage functionalization applications. The experimental observations over a wide range of alkanes, as well as in more functionalized substrates, indicate a carbocationic mechanism involving a hydride ion transfer of the alkane substrate to PTAD. The carbocation is very transient, as C-N bond formation proceeds generally with retention of the original configuration of a stereogenic carbon. The reaction can be run at high conversion of the alkane substrate using a catalytic amount of a gold(I)-catalyst combined with a mild proton donor such as hexafluoroisopropanol (HFIP). The reaction can often fully discriminate between very similar C-H bonds, such as cyclic alkanes over linear ones, equatorial C-H bonds over axial ones and tertiary over secondary ones. These observed reactivity orders closely follow expected trends in carbocation stability, offering a conveniently predictability. This novel C-H functionalization method does not require extensive catalyst or reagent design and offers good complementary to more conventional C-H activation or amination methodologies.
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BibTeX
@misc{uherek2026directing,
title = {{Directing group-free site-selective and stereoretentive C-H amination of alkanes with phenyl triazolinedione (PTAD) as a σ-acid}},
author = {Daniel Uherek and Marios Kidonakis and Kevin Bevernaege and Kristof Van Hecke and Johan Maurits Winne},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010490/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010490/v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Directing group-free site-selective and stereoretentive C-H amination of alkanes with phenyl triazolinedione (PTAD) as a σ-acid
AU - Daniel Uherek
AU - Marios Kidonakis
AU - Kevin Bevernaege
AU - Kristof Van Hecke
AU - Johan Maurits Winne
PY - 2026
DA - 2026/10/15
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010490/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010490/v1
AB - 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) is known as the most reactive commercially available dienophile, as it rapidly reacts with dienes at low temperatures and high dilution. In general terms, PTAD is a very soft Lewis acid, with a strong affinity towards electron rich alkenes. In this work, we report that the potent π-acid PTAD also shows a very useful and general σ-acid reactivity towards electron rich C(sp3)-H bonds, opening up its use in alkane amination reactions, as well as in late stage functionalization applications. The experimental observations over a wide range of alkanes, as well as in more functionalized substrates, indicate a carbocationic mechanism involving a hydride ion transfer of the alkane substrate to PTAD. The carbocation is very transient, as C-N bond formation proceeds generally with retention of the original configuration of a stereogenic carbon. The reaction can be run at high conversion of the alkane substrate using a catalytic amount of a gold(I)-catalyst combined with a mild proton donor such as hexafluoroisopropanol (HFIP). The reaction can often fully discriminate between very similar C-H bonds, such as cyclic alkanes over linear ones, equatorial C-H bonds over axial ones and tertiary over secondary ones. These observed reactivity orders closely follow expected trends in carbocation stability, offering a conveniently predictability. This novel C-H functionalization method does not require extensive catalyst or reagent design and offers good complementary to more conventional C-H activation or amination methodologies.
ER -