Iodine-Mediated α-C–H Amination of Carbonyl Compounds via Nitrogen-Directed Oxidative Umpolung

Abstract

A new synthetic strategy for direct C(sp 3 )−H amination of carbonyl compounds at their α-carbon has been established employing molecular iodine and nitrogen-directed oxidative umpolung. In this transformation, iodine acts not only as an iodinating reagent but also as a Lewis acid catalyst, and both the nitrogen-containing moiety and the carbonyl group in the substrate play important roles. This synthetic approach is applicable to a broad variety of carbonyl substrates, including esters, ketones, and amides. Its features also include no requirement for transition metals, mild reaction conditions, short reaction times, and gram-scale synthesis.

Copper‐Catalyzed α‐Indolmethylation of 2‐Pyridylacetates with 3‐Indoleacetic Acids via Alkylideneindolenine Intermediates

“…In 2020, Tan described palladium‐catalyzed α‐arylation of 2‐pyridylacetates with heteroaryl halides [7a] . In 2023, Chang and Yu reported iodine‐mediated α‐amination of 2‐pyridylacetates [7b] . The introduction of functional groups can significantly modify the properties and functions of these compounds.…”

Iodine-Mediated δ-Amination of sp3 C–H Bonds

“…To our knowledge, such remote sp 3 C–H amination transformations using I 2 as the sole oxidant have not been investigated. With our interest in I 2 -promoted C–H amination reactions, here, we report on a direct δ-amination reaction of sp 3 C–H bonds, employing iodine (I 2 ) as the sole oxidant.…”