A direct and general one-pot approach to α-trifluoromethylthiolated amides, esters and carboxylic acids has been successfully developed under mild, catalytic and metal-free conditions.

Pyrazoleamides are a class of compounds which have received significant attention in the last years in asymmetric catalysis as more reactive and practical surrogates of esters or amides. These readily available reagents have served in a variety of diastereo-and enantioselective metal-and organocatalytic transformations, spanning from simple carbon-carbon or carbon-heteroatom bond formation to cascade and rearrangement reactions, to produce valuable classes of heterocyclic compounds. More recently, pyrazoleamides have proved to be pertinent reagents in asymmetric catalysis merged with photoredox catalysis, and in more challenging stereoselective bond-forming reactions, occurring directly from a visible-light activated substrate/catalyst complex without any charge separation. Both strategies enable new activation concepts useful for the production of difficult-to-access intermediates and pharmaceuticals. In this review, an overview of the progress achieved in asymmetric catalytic reactions of pyrazoleamides from 2015 up to middle 2020, is illustrated. Rearrangements of α-Diazo Pyrazoleamides 7. Combined Metal-and Organocatalysis 8. Pyrazoleamides in Visible-Light-Activated Photochemical Reactions 8.1. Merging Visible Light Photoredox Activation with Asymmetric Catalysis 8.2. Stereocontrolled Direct Photoreactions from Electronically Excited State 8.3. Merging HAT Photocatalysis with Chiral Lewis Acid Catalysis 9.

A continuous flow approach to access α-trifluoromethylthiolated esters and amides using commercially available arylacetic acids and N -(trifluoromethylthio)phthalimide as the electrophilic reagent is described. The experimental protocol involves the in-flow conversion of the carboxylic acid into N- acylpyrazole followed by the α-trifluoromethylthiolation in a PTFE coil reactor and final reaction with primary or secondary amines, or alcohols, to afford in a telescoped process α-substituted SCF 3 amides and esters, respectively, in good overall yield and short reaction times.

A highly enantioselective one-pot synthesis of functionalized triflones, bearing a quaternary stereocenter, has been developed, exploiting the Michael reaction of α-(trifluoromethylsulfonyl) aryl acetic acid esters with N-acryloyl-1Hpyrazole catalyzed by commercially available Takemoto's catalyst, followed by nucleophilic acyl substitution with alcohols. Preliminary investigations highlighted the attractive potential of the triflinate anion as the leaving group for stereocontrolled postfunctionalizations.

The front cover picture, designed by Sara and Luca Meninno, illustrates poorly reactive carboxylic acids and their ester and amide derivatives transformed into pyrazoleamides super‐molecules with superpowers. Where carboxylic acids, esters and amides fail pyrazoleamides succeed, allowing the transition from a world with limited possibilities to a rich and futuristic world, meeting the increasing needs of the society. The super‐powers consist in: i) easy one‐step synthesis from readily available carboxylic acids; ii) easy metal and H‐bonding coordination with catalysts, unlocking otherwise inaccessible reactions on carboxylic acid derivatives; iii) exceptional leaving group ability which enables several post‐functionalizations with different nucleophiles. Pyrazoleamides, unlike carboxylic acid derivatives have proven increasingly useful starting materials in a variety of diastereo‐ and enantioselective metal‐, organocatalytic and photoinduced transformations, giving access to valuable intermediates, heterocycles and pharmaceuticals. Details can be found in the Review by Meninno, Franco, Benaglia, and Lattanzi. (S. Meninno, F. Franco, M. Benaglia, A. Lattanzi, Adv. Synth. Catal. 2021, 363, 3380–3410; DOI: 10.1002/adsc.202100006)