Bioinspired Functionalization of Carbonyl Compounds Enabled by Metal Chelated Bifunctional Ligands.

In Nature, enzymatic reactions proceed through exceptionally ordered transition states giving rise to extraordinary levels of stereoselection. In those reactions, the active site of the enzyme plays crucial roles - through one position, it holds the substrate in the proximity to the reaction epicentre that facilitates both the reactivity and stereoselectivity of the chemical process. Inspired by this natural phenomenon, synthetic chemists have designed bifunctional ligands that not only coordinate to a metal centre but also preassociate with an organic substrate, for example aldehyde and ketone, and exerts stereodirecting influence to accelerate the attack of the incoming reacting partner from a particular enantiotopic face. The chief goal of the current review is to give an overview of the recently developed approaches enabled by privileged bio-inspired bifunctional ligands that not only bind to the metal catalyst but also activates carbonyl substrates via organocatalysis, thereby easing in the new bond forming step. As carbonyl α-functionalizations are dominated by enamine and enolate chemistry, the current review primarily focusses on enamine- and enolate-metal catalysis by bifunctional ligands. Thus, developments based on traditional cooperative catalysis occurring through two directly coupled but independent catalytic cycles of an organocatalyst and a metal catalyst are not covered.

Exploring amine-rich supramolecular silver(I) metallogels for autonomous self-healing and as catalysts for a three component coupling reaction.

A series of Ag(I) supramolecular organo-aqueous gels have been synthesized in the presence of an amine-rich triazole ligand as a gelator. Judicious choice of the triazole derivative and counter anion allows a desired spatial orientation of the pendant amine functionality to accentuate the gelation ability and autonomous self-healability via hydrogen bonding. In addition, the hydrogen bond donors, i.e. pendant -NH2 groups, offer a critical proximity of counter anions to the Lewis acidic Ag(I) and the reactants for promoting a three component coupling reaction of an aldehyde, a terminal alkyne and an amine, giving expedient access to propargyl amines, with remarkable functional group tolerance for both aromatic and aliphatic aldehydes, and aryl acetylenes. Experiments substantiate the pivotal role of counter anions and H-bonding interactions in the observed preference for propargylamines over the diacetylene by-product. Our catalyst is robust, bench-stable, and recyclable, and demonstrates a catalytic efficiency comparable to or better than those of reported systems. The catalyst was found equally effective for the gram-scale synthesis of propargylamines. Our approach lies at the intersection of metal-based, H-bond-mediated counter anion-tuned catalysis, evincing a potential for the development of purpose-built supramolecular gels for desired catalytic applications in the future.

Recent advances in catalytic decarboxylative transformations of carboxylic acid groups attached to a non-aromatic sp2 or sp carbon.

Chemists learn the most important transformations of the carboxylic acid functionality (COOH) from as early as the first semester of their studies. Carboxylic acids are not only safe to store and handle, but also broadly accessible with great structural diversity either from commercial sources or by means of a large variety of well-known synthesis routes. Consequently, carboxylic acids have long been recognized as a highly adaptable starting material in organic synthesis. A large body of reactions of carboxylic acids are based on catalytic decarboxylative conversions, in which the COOH group of carboxylic acids is catalytically replaced without trace by extrusion of CO2 chemo- and regioselectively. Within the last two decades, the area of catalytic decarboxylative transformations has expanded significantly by utilizing various classes of carboxylic acids as the substrate, including (hetero)aromatic acids, alkyl acids, α-keto acids, α,ß-unsaturated acids and alkynoic acids. A literature survey reveals that compared to aromatic acids, the number of original research papers on decarboxylative reactions of α-keto acids, α,ß-unsaturated acids and alkynoic acids has been rising every year lately, particularly within past five to six years. The prime aim of the current review is to give an overview of the decarboxylative transformations of α-keto acids, α,ß-unsaturated acids and alkynoic acids that have been developed since 2017. The article focuses on the decarboxylative functionalizations that occur in the presence or absence of transition metal catalysts and/or under photoredox catalysis.

Catalytic Methylene Insertion between Amines and Terminal Alkynes via C-N Bond Cleavage of N,N-Dimethylacetamide: A Unique Route to Propargylic Amines.

A copper-based system allows for the methylene insertion between an amine and a milder nucleophile, including a terminal alkyne counterpart, via C-N bond cleavage of N,N-dimethylacetamide. The method gives an expedient access to propargylic amines in good to excellent yields. A wide-ranging substrate scope and late-stage functionalization of complex molecules make the protocol practically valuable.

Cooperativity between the Substrate and Ligand in Palladium-Catalyzed Allylic Alkylation Using 1-Aryl-1-propynes.

A monoprotected amino acid Bz-Gly-OH assists in the allylic alkylation of a variety of ketones, ß-keto esters, aldehydes, etc., during enamine-palladium catalysis. Density functional theory calculations reveal that Bz-Gly-OH assists in the formation of an enamine that attacks the π-allylpalladium complex via an outer sphere mechanism. The preliminary result points to an asymmetric allylic alkylation under a new mode of bifunctional catalysis.

Catalytic Approaches for the Direct Heterofunctionalization of Aliphatic Carboxylic Acids and Their Equivalents with Group 16 Elements.

In contrast to traditional multistep synthesis, modern organic synthesis extensively depends on the direct functionalization of unactivated C-H bonds for the construction of various C-C and C-heteroatom bonds in atom- and step-economic manner. Common aliphatic substrates, e. g. carboxylic acids and their synthetic equivalents, are regiospecifically functionalized based on either a directed approach, in which the polar directing group assists to functionalize a specific C-H bond positioned at ß- and γ-carbon centers, or a non-directed approach typically leading to α-functionalization. While numerous reviews on catalytic C-H functionalization have appeared, a concise review on the direct C(sp3 )-H heterofunctionalization of carboxylic acid synthons with Group 16 elements has been awaited. The recent advances on the direct oxy-functionalization and chalcogenation of aliphatic carboxylic acid synthons enabled by transition metal, organo- and photocatalysts are described herein.

Direct α-Chalcogenation of Aliphatic Carboxylic Acid Equivalents.

A novel approach to α-chalcogenation of aliphatic carboxylic acids has been developed by means of transforming them as the corresponding benzazoles. The catalyst system, consisting of CuI, DMSO, and a base, operates through a unique mechanism to access a range of practically significant thio- and selenoethers that are otherwise challenging to achieve. The applicative potentials have been exemplified by utilizing the resultant chalcogenated compounds as the precursor for the synthesis of biologically pertinent molecules and synthetic intermediates.