Directing group-free site-selective and stereoretentive C-H amination of alkanes with phenyl triazolinedione (PTAD) as a σ-acid
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7222219279