Metal‐Free, Regioselective, Dehydrogenative Cross‐Coupling between Formamides/Aldehydes and Coumarins by C–H Functionalization

Abstract

A highly efficient, single‐step, metal‐free synthetic approach to the synthesis of coumarin‐3‐carboxamides has been developed. The protocol employs tert‐butyl peroxybenzoate as a radical initiator to achieve the regioselective carboxamidation of coumarins at C‐3 in good‐to‐moderate yields. The established reaction protocol offers a wide substrate scope as it allows the use of both formamides as well as aldehydes as coupling partners with excellent regioselectivity. Furthermore, mechanistic investigations illustrate that the reaction proceeds by a free‐radical pathway.

The Chemistry of Peresters

“…Aryl‐substituted coumarins may be coupled with hydrogen‐atom donors: cycloalkanes and formamides and aldehydes, upon thermolysis in the presence of TBPB (see Figure ). Presumably, abstraction of hydrogen by tert ‐butoxyl generates a reactive carbon radical able to add to the coumarin; loss of hydrogen atom from the resulting intermediate regenerates the alkene.…”

Piperidine-Iodine as Efficient Dual Catalyst for the One-Pot, Three-Component Synthesis of Coumarin-3-Carboxamides

“…Alternatively, MCRs using magnetic nanoparticles (NPs) such as Ni–NiO and Fe 3 O 4 have also been applied in the synthesis of a variety of coumarin-3-carboxamides ( Figure 1 b) [ 24 , 25 ]. Other reported approaches to the synthesis of coumarin-3-carboxamide involve regioselective carboxamidation of coumarins at C-3 with formamides by using the radical initiator tert -butyl peroxybenzoate (TBPB) ( Figure 1 c) [ 26 ], and amidation reactions of coumarin-3-carboxylic acids using tetraalkylthiuram disulfides as amine sources ( Figure 1 d) [ 27 ].…”

Aldehydes: magnificent acyl equivalents for direct acylation

“…have been explored extensively. [11][12][13][14] Amongst these acylating surrogates, aldehydes (aliphatic and aromatic) have received profound…”