Pyrazoleamides in Catalytic Asymmetric Reactions: Recent Advances

Abstract

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.

Enantioselective α-Fluorination and α-Chlorination of N-Acyl Pyrazoles Catalyzed by a Non-C2-Symmetric Chiral-at-Rhodium Catalyst

“…Finally, we like to corroborate the usefulness of N -acyl pyrazoles as precursors for carboxylic acids and its derivatives . In contrast to the related 2-acyl imidazoles, the pyrazole moiety can typically be removed under mild reaction conditions.…”

“…Finally, we like to corroborate the usefulness of N-acyl pyrazoles as precursors for carboxylic acids and its derivatives. 25 In contrast to the related 2-acyl imidazoles, the pyrazole moiety can typically be removed under mild reaction conditions. We therefore next sought out to establish conditions appropriate for removal of the auxiliary pyrazole moiety without leading to epimerization of the products.…”

Nitroxide‐Catalyzed Oxidative Amidation of Aldehydes to Yield N‐Acyl Azoles Using Sodium Persulfate

“…The desired N ‐acyl pyrazole product ( 6 ad ) was obtained when employing cinnamaldehyde as the aldehyde component. This shows the applicability of our methodology for the synthesis of pyrazole amides that are used for asymmetric transformations [14] …”

“…Azoles themselves are privileged heterocyclic structures known for their antifungal properties, [8,9] and when incorporated into an amide bond, they show interesting structural features and can be used by synthetic organic chemists as valuable synthons [10–13] . Furthermore, the heterocyclic functionality in N ‐acyl pyrazoles provides a nitrogen site useful for metal and hydrogen‐bonding interactions, making them useful for asymmetric catalysis [14,15] …”

Continuous Flow Synthesis of α-Trifluoromethylthiolated Esters and Amides from Carboxylic Acids: a Telescoped Approach

“…We recently reported the α-trifluoromethylthiolation of N -acyl pyrazoles using N , N , N’ , N’ -tetramethyl-1,8-naphthalenediamine (proton sponge) as a catalytic base and N -(trifluoromethylthio)phthalimide as the electrophilic source. 6 N -Acylpyrazoles are readily available carboxylic acid surrogates, 7 which were suitable for undergoing α-functionalization via enolate formation under mild basic conditions ( Scheme 1 ). In the same pot, the pyrazole group has been easily replaced by different nucleophiles, such as alcohols, amines, and water, to give the formal α-trifluoromethylthiolation of carboxylic acid derivatives.…”