Zinc‐Catalyzed Esterification of N‐β‐Hydroxyethylamides: Removal of Directing Groups under Mild Conditions

Abstract

Amide transformations involving C–N bond cleavage are recognized as difficult reactions owing to the inert nature of amides resulting from resonance. Accordingly, a strong inductive effect and geometrical distortion reasonably decrease the resonance stabilization to attenuate the C–N linkage. Although the conversion of such activated amides has been studied intensively, reaction systems for “unactivated” amides are underdeveloped. We herein report that a zinc(II) trifluoromethanesulfonate [Zn(OTf)2] catalyst achieves the esterification of a wide range of unactivated tertiary amides with the assistance of intramolecular acyl rearrangement. The reaction was applied to the one‐pot removal of various amide‐based directing groups under mild reaction conditions to afford the corresponding esters in high yields.

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

“…Amides represent one of the most abundant functional moieties in natural and synthetic compounds . They are an indispensable structural motif in proteins, peptides, resins, fibers, polymers, enzymes, drugs, and define most biological functionalities in plants . The direct functionalization of amides is thus a highly attractive strategy in organic syntheses, where the major challenge lies in the cleavage of the amide C−N bond, which is due to the functional group interconversion arising from amidic resonance (Figure A) that renders amides poor electrophiles and unreactive toward nucleophiles.…”

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

“…10). [31] As a representative substrate, 8-aminoquinolyl amide 24 was deprotonated with NaH and then treated with propylene oxide in the presence of a catalytic amount of Zn (OTf) 2 to yield the corresponding N-β-hydroxyethyl amide, which was subsequently reacted with methanol to give the corresponding ester 25 (Scheme 15).…”

Dinuclear manganese alkoxide complexes as catalysts for C–N bond cleavage of simple tertiary N,N-dialkylamides to give esters

“…On the other hand, we reported a catalytic C–N bond cleavage of N -alkyl- N -β-hydroxyethylamides via N , O -acyl rearrangement by manganese complexes supported by an N ^ N -bidentate ligand27 and zinc complexes (Fig. 1C),28 though these catalysts required substrates with functional groups, such as a β-hydroxyethyl group on the nitrogen atom. Very recently, Shimizu and Siddiki reported the first example of the esterification of N , N -dialkylamides using CeO 2 as a reusable heterogeneous catalyst, though the catalyst system requires a high reaction temperature and large amount of catalyst.…”