Direct Phenolysis Reactions of Unactivated Amides into Phenolic Esters Promoted by a Heterogeneous CeO₂ Catalyst

Abstract

The direct catalytic esterification of amides that leads to the construction of C−O bonds through the cleavage of amide C−N bonds is a highly attractive strategy in organic synthesis. While aliphatic and aromatic alcohols can be readily used for the alcoholysis of activated and unactivated amides, the introduction of phenols is more challenging due to their lower nucleophilicity in the phenolysis of unactivated amides. Herein, we demonstrate that phenols can be used for the phenolysis of unactivated amides into the corresponding phenolic esters using a simple heterogenous catalytic system based on CeO2 under additive‐free reaction conditions. The method tolerates a broad variety of functional groups (>50 examples) in the substrates. Results of kinetic studies afforded mechanistic insights into the principles governing this reaction, suggesting that the cooperative effects of the acid–base functions of catalysts would be of paramount importance for the efficient progression of the C−N bond breaking process, and consequently, CeO2 showed the best catalytic performance among the catalysts explored.

Catalytic Cleavage of Amide C−N Bond: Scandium, Manganese, and Zinc Catalysts for Esterification of Amides

“…The bimetallic associative mechanism might be related to heterogeneous CeO 2 system exhibited catalytic activity toward alcoholysis of N,N-dialkylamides using alcohols and phenols (eq. 15), [36,37] though it only worked at very higher temperature (175-180°C) for long reaction time (36-100 h).…”

Esterification of Tertiary Amides: Remarkable Additive Effects of Potassium Alkoxides for Generating Hetero Manganese–Potassium Dinuclear Active Species

“…[16] With respect to the catalytic transformation of tertiary amides, which are more stable than primary and secondary amides, [17] three mechanisms have been reported including oxidative addition, N,O-acyl rearrangement, and Lewis acid-assisted mechanisms. [18][19][20][21][22][23][24][25][26][27] Oxidative addition-esterification was first reported by Garg and co-workers who used nickel(0) catalysts to activate the CÀN bond of tertiary arylamides bearing functional groups such as Ph, Boc, and Ts by oxidative addition as a key step to afford the corresponding aryl esters. [18,19] Danoun and Gosmini used a low-valent cobalt catalyst system supported by 2,2'-bipyridine with metallic manganese as a reductant to catalytically activate the CÀN bond of activated arylamides bearing a Boc, Ts, or methoxycarbonyl group to give the corresponding aryl esters.…”

“…For Lewis acid-assisted esterification, FeCl 3 required stoichiometric amounts of HCl for the catalytic esterification of tertiary amides, [24] and heterogeneous cerium dioxide required a high temperature (175 8C) for the catalytic esterification of tertiary amides (Scheme 1 c). [25,26] In this context, we focused our attention on developing effective catalysts for the esterification of simple tertiary N,N-dialkyl amides. We previously found that an alkoxide-bridged manganese dinuclear complex, [(acac)(Me 2 N-Phen)Mn(m-OnBu)] 2 (2 a) (Me 2 N-Phen = 4,7-bis(dimethylamino)-1,10-phenanthroline), derived by treating an alkoxide-bridged manganese tetranuclear cubic complex [Mn(acac)(OEt)(EtOH)] 4 (1) with Me 2 N-Phen in nBuOH, was an excellent catalyst for the esterification of various N,N-dialkyl arylamides via a cooperative mechanism in which one manganese center functioned as a Lewis acid for coordinating to the amide carbonyl moiety and the second manganese center activated an alcohol to provide more nucleophilic alkoxide species (Scheme 1 d).…”

“…With respect to the catalytic transformation of tertiary amides, which are more stable than primary and secondary amides, three mechanisms have been reported including oxidative addition, N , O ‐acyl rearrangement, and Lewis acid‐assisted mechanisms . Oxidative addition‐esterification was first reported by Garg and co‐workers who used nickel(0) catalysts to activate the C−N bond of tertiary arylamides bearing functional groups such as Ph, Boc, and Ts by oxidative addition as a key step to afford the corresponding aryl esters .…”

“…For N , O ‐acyl rearrangement esterification, we reported two catalyst systems, Mn(acac) 2 combined with 2,2′‐bipyridine and zinc triflate, that catalyzed the esterification of N ‐alkyl‐ N ‐β‐hydroxyethylamides, although these catalysts required substrates with a β‐hydroxyethyl group on the nitrogen atom (Scheme b). For Lewis acid‐assisted esterification, FeCl 3 required stoichiometric amounts of HCl for the catalytic esterification of tertiary amides, and heterogeneous cerium dioxide required a high temperature (175 °C) for the catalytic esterification of tertiary amides (Scheme c) …”