Zinc‐Catalyzed Amide Cleavage and Esterification of β‐Hydroxyethylamides

Abstract

Snipping tool: Zn(OTf)2 is an efficient catalyst for selective cleavage of amides bearing a β‐hydroxyethyl group on the nitrogen atom. The mechanism involves an N,O‐acyl rearrangement and transesterification. This new catalytic system can be applied to sequence‐specific peptide bond scission at the amine side of a serine residue. Tf=trifluoromethanesulfonyl.

Proton Shuttle Mechanism in the Transition State of Lipase‐Catalyzed N‐Acylation of Amino Alcohols

“…The apparent k cat value for N‐acylation of methoxy‐2‐propylamine was found to be tenfold higher than for ( R )‐2‐butylamine ( 5 ) and only twofold lower than the corresponding value for alaninol ( 1 b ). This is in sharp contrast to chemical N‐acylation as well as to metal catalysis, in which it has been found that methylation of the oxygen atom in the amino alcohol molecule leads to a decrease in the reaction rate of two orders of magnitude 6–8. Furthermore, 1,2‐diaminopropane ( 7 ) afforded the highest rate acceleration, which cannot be explained by the acyl migration hypothesis.…”

“…Transacylation reactions involving amino alcohols have recently gained attention 6. In acylation reactions of amino alcohols, the alcohol and amino groups have different reactivities.…”

“…Recently, the focus has been on using enzymes as catalysts for the chemoselective acylation of amino alcohols 12. However, the selectivity in enzyme‐catalyzed acylation of amino alcohols is different from the selectivity obtained by using metal catalysis, for which N‐ to O‐acyl migration occurs in the reaction mechanism and which facilitates alcoholysis of amides 6. It has been suggested that the lipase‐catalyzed chemoselective N‐acylation of 1,2‐amino alcohols proceeds through initial O‐acylation followed by spontaneous O‐ to N‐acyl migration 13.…”

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.…”

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

“…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.…”