Copper-Catalyzed Carbamoylation of Terminal Alkynes with Formamides via Cross-Dehydrogenative Coupling

Abstract

An efficient approach for direct carbamoylation of terminal alkynes with formamides affording propiolamides has been developed by copper-catalyzed oxidative cross coupling of C­(sp)-H and C­(sp2)-H bonds in the presence of a pincer ligand with two imidazolyl groups. The catalytic reaction is compatible with diverse functional groups but sensitive to the electronic effect of terminal alkyne and the steric effect of formamides. KIE study indicates the cleavage of the carbamoyl C–H bond affording formamide radical is the rate-determining step.

The Persistent Radical Effect in Organic Synthesis

“…It is known from the Sonogashira coupling that terminal alkynes can form copper acetylides. This reactivity was applied by the group of Ke and Ye for the synthesis of N , N ‐dialkyl propiolamides by cross‐dehydrogenative coupling using alkynes and formamides as substrates . With tert ‐butylhydroperoxide as the oxidant, a dialkylaminoacyl radical is generated from the formamide by intermolecular HAT to the tert ‐butoxyl radical generated upon SET reduction of t BuOOH with a Cu I species.…”

“…It is known from the Sonogashira coupling [323] that terminal alkynes can form copper acetylides.T his reactivity was applied by the group of Ke and Ye for the synthesis of N,N-dialkyl propiolamides by cross-dehydrogenative coupling using alkynes and formamides as substrates. [324] With tert-butylhydroperoxide as the oxidant, ad ialkylaminoacyl radical is generated from the formamide by intermolecular HATt ot he tert-butoxyl radical generated upon SET reduction of tBuOOH with aC u I species.I ti sl ikely that the dialkylaminoacyl radical is trapped by aCu II acetylide to give the corresponding Cu III adduct. Reductive elimination leads to the N,N-dialkyl propiolamide regenerating the starting Cu I complex.…”

Palladium(II)‐Catalysed Aminocarbonylation of Terminal Alkynes for the Synthesis of 2‐Ynamides: Addressing the Challenges of Solvents and Gas Mixtures

“…Lee and co‐workers reported the use of alkynyl carboxylic acids and amines with CO gas, using Ag 2 O as a base and oxidant (Scheme B) . Ye and co‐workers used a Cu catalyst for the cross dehydrogenative coupling of terminal alkynes with formamides (Scheme C) . In this case a large excess of the formamide reagent was required.…”

Der “Persistent Radical Effect” in der organischen Chemie

“…Es ist von Sonogashira‐Kupplungen bekannt, dass terminale Alkine Cu‐Acetylide ausbilden können. Diese Reaktivität wurde von der Gruppe von Ke und Ye für die Synthese von N , N ‐Dialkylpropiolamiden mittels dehydrierender Kreuzkupplung mit Alkinen und Formamiden als Substrate eingesetzt . Das tert ‐Butoxyl‐Radikal, welches durch SET‐Reduktion mit einer Cu I ‐Spezies aus tert ‐Butylhydroperoxid erzeugt wird, abstrahiert den aldehydischen Wasserstoff des Formamids.…”