Temperature dependence of turnover in a Sc(OTf) 3 -catalyzed intramolecular Schmidt reaction

Abstract

The intramolecular Schmidt reaction of ketones and tethered azides is an efficient method for the generation of amides and lactams. This reaction is catalyzed by Lewis acids, which tightly bind the strongly basic amide product and result in product inhibition. We report herein conditions to achieve a catalytic Schmidt reaction using substoichiometric amounts of the heat-stable Lewis acid Sc(OTf)3. This species was shown to effectively release products of the Schmidt reaction in a temperature-dependent fashion. Thus, heat was able to promote catalyst turnover. A brief substrate scope was conducted using these conditions.

Recent Advances in Reactions of Azides

“…Lately, Sc(OTf) 3 promotion of the intramolecular Schmidt reaction of ketones with alkyl azides has been investigated by the same group . A high temperature can promote catalyst turnover.…”

Chemical Synthesis and Biological Applications of O‐GlcNAcylated Peptides and Proteins

“…[13] Comparatively stronger Lewis acids such as TMSOTf (Figure 4B) and BF 3 •Et 2 O (Figure 4C) will form Bronsted acids following coordination with the leaving group, thereby hindering the ability to perform Lewis acid activation as a result of product inhibition. [14] As with other minimally competent Lewis acids, InBr 3 can dissociate from the leaving group and maintain is ability to act as an activator at elevated temperatures, [15] allowing substoichiometric use and improved yields (Figure 4C). [13,16] An alternative amino acid glycosylation strategy utilized is thioglycoside activation.…”

A Short and Versatile Approach for the Synthesis of Pyrrolizidinones

“…For recent methods to access pyrrolizidinone derivatives, see references[31][32][33][34][35][36]. For recent syntheses of pyrrolizidinone containing natural products, see references[37 - 43].…”