Combined Catalytic System of Scandium Triflate and Boronic Ester for Amide Bond Cleavage

Abstract

We have found that the combination of scandium with boronic ester enables the cleavage of amide bonds. Primary amides were converted to the corresponding esters in the presence of catalytic amounts of scandium triflate and boronic ester under mild and neutral conditions. This unique catalytic system can be applied to the deprotection of acetylaniline derivatives. In addition, control NMR experiments were carried out to examine the effect of the boronic esters.Keywords: amides; boron; scandium; solvolysis The amide bond is a ubiquitous and thermodynamically stable entity due to amide resonance where the lone pair of electrons on the nitrogen is delocalized into the carbonyl. [1,2] Although amide-directed C À H bond functionalization is an attractive topic of interest, [3] cleavage of the amide bond is difficult owing to the inert nature of amides and thus its application is limited. Among amide transformations, amide alcoholysis has attracted widespread attention from synthetic chemists because the resulting esters can be subjected to further transformations. Amide alcoholysis under mild conditions can be classified into three categories: (i) transformation using activated acyl compounds, [4] (ii) directing group-assisted reactions, [5] and (iii) usage of twisted amides for minimizing the amide resonance [6] (Scheme 1). We recently reported the selective cleavage of b-hydroxyethylamides catalyzed by a simple zinc triflate, achieving a catalytic serine sequence-selective peptide bond cleavage. [7] In these reports, however, stoichiometric amounts of the activator or specific substituents were required and thus more atom-economical and general systems are in high demand.In the course of our continued research interest in the transformation of carboxylic acid derivatives, we previously developed oxo-bridged clusters with high catalytic activity and unique chemoselectivity for transesterification.[8] Herein, we have designed a new cooperative catalyst system by combining two different Lewis acidic atoms. Our findings indicate that the Scheme 1. Alcoholysis of amides.

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

“…Conventionally, enzyme‐ or strong‐acid/base‐mediated C−N bond cleavage reactions of amides with alcohols generate huge amounts of undesired byproducts . Recently, catalytic C−N bond cleavage reactions, specifically the alcoholysis of amides into the corresponding esters, have received much attention and several examples have been reported . In general, the structural diversity of esters is relatively wide and they have found numerous applications in the chemical and pharmaceutical industry .…”

Green alternative solvents for the copper-catalysed arylation of phenols and amides

“…60,61 Berreau and Rivas reported the use of group 12 metal complexes with polydentate ligands for this reaction, mimicking the active site of peptidase enzymes, 62,63 showing that coordination of the metal to the carbonyl oxygen facilitates the nucleophilic attack of the alkoxide, leading to the formation of the ester. The same activation may be at the basis of the amide alcoholysis catalysed by simple transition metal salts [64][65][66][67][68] or lantanides salts and oxides. 64,69,70 Some examples of Cu-mediated alcoholysis of coordinated amides (i.e.…”

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

“…4). [25] The boronic ester was recovered unreacted after the reaction, and the parent boronic acid was totally inactive in the present system. On the basis of controlled NMR experiments, we found that alcohol-coordinated borane species cooperatively worked with Sc(OTf) 3 , to enhance the alcohol nucleophilicity through the formation of borate species.…”