Challenges and Breakthroughs in Selective Amide Activation

Abstract

In contrast to ketones and carboxylic esters, amides are classically seen as comparatively unreactive members of the carbonyl family, owing to their unique structural and electronic features. However, recent decades have seen the emergence of research programmes focused on the selective activation of amides under mild conditions. In the past four years, this area has continued to rapidly develop, with new advances coming in at a fast pace. Several novel activation strategies have been demonstrated as effective tools for selective amide activation, enabling transformations that are at once synthetically useful and mechanistically intriguing. This Minireview comprises recent advances in the field, highlighting new trends and breakthroughs in what could be called a new age of amide activation.

Recent Applications of Trifluoromethanesulfonic Anhydride in Organic Synthesis

“…[3] Additionally, electrophilic activation of tertiary and secondary amides with triflic anhydride under mild conditions gives rise to iminium and imino triflates, respectively, which could be utilized as versatile reagents to react with various C-, N-, O-and S-nucleophiles for the transformation of an amide function into different products. [4][5][6][7][8][9] Other oxygen-containing nucleophiles, such as sulfoxides and phosphorus oxides could also undergo nucleophilic attack with Tf 2 O to generate thionium triflate, electrophilic P-species and phosphonium triflate. [10][11][12] These highly active transient species could readily undergo nucleophilic substitution reactions for further diverse transformations.…”

“…In recent years, there have been some review articles that generally summarize the electrophilic activation of amides, sulfoxides, and phosphorus oxides with Tf 2 O, [4][5][6][7][8][9][10][11][12] so these aspects would not been discussed here. In this review, we particularly focus on the recent advances in new applications of Tf 2 O in organic synthesis, which are devideded into three parts: a) activation of nitrogen-containing heterocycles and nitriles for further transformation; b) used as trifluoromethylation and trifluoromethylthiolation reagents for the synthesis of trifluoromethylated and trifluoromethylthiolated compounds; c) electrophilic activation of nitro group and nitrone for new reactions development.…”

Recent Applications of Trifluoromethanesulfonic Anhydride in Organic Synthesis

“…The Hammett σ p value for the triflate group has been determined by titration of the appropriate benzoic acids and found to be +0.47, indicating its strong electron‐withdrawing characteristic [3] . Additionally, electrophilic activation of tertiary and secondary amides with triflic anhydride under mild conditions gives rise to iminium and imino triflates, respectively, which could be utilized as versatile reagents to react with various C ‐, N ‐, O ‐ and S ‐nucleophiles for the transformation of an amide function into different products [4–9] . Other oxygen‐containing nucleophiles, such as sulfoxides and phosphorus oxides could also undergo nucleophilic attack with Tf 2 O to generate thionium triflate, electrophilic P ‐species and phosphonium triflate [10–12] .…”

“…[3] Additionally, electrophilic activation of tertiary and secondary amides with triflic anhydride under mild conditions gives rise to iminium and imino triflates, respectively, which could be utilized as versatile reagents to react with various C-, N-, O-and S-nucleophiles for the transformation of an amide function into different products. [4][5][6][7][8][9] Other oxygen-containing nucleophiles, such as sulfoxides and phosphorus oxides could also undergo nucleophilic attack with Tf 2 O to generate thionium triflate, electrophilic P-species and phosphonium triflate. [10][11][12] These highly active transient species could readily undergo nucleophilic substitution reactions for further diverse transformations.…”

“…In recent years, there have been some review articles that generally summarize the electrophilic activation of amides, sulfoxides, and phosphorus oxides with Tf 2 O, [4][5][6][7][8][9][10][11][12] so these aspects would not been discussed here. In this review, we particularly focus on the recent advances in new applications of Tf 2 O in organic synthesis, which are devideded into three parts: a) activation of nitrogen-containing heterocycles and nitriles for further transformation; b) used as trifluoromethylation and trifluoromethylthiolation reagents for the synthesis of trifluoromethylated and trifluoromethylthiolated compounds; c) electrophilic activation of nitro group and nitrone for new reactions development.…”