Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates

This review highlights a number of additives that can be used to make asymmetric reactions perfect. Without changing other reaction conditions, simply adding additives can lead to improved asymmetric catalysis, such as reduced reaction time, improved yield, or/and increased selectivity.

Additive Effects on Asymmetric Catalysis

Recent efforts directed to the development of more sustainable asymmetric organocatalysis

Organocatalytic enantioselective desymmetrisation of achiral or meso compounds is a powerful strategy for the construction of enantiomerically enriched complex molecules, often with multiple stereocentres and in high selectivities. Recent years have seen increasing use of organocatalysts in desymmetrisation methodology, in contrast to traditional metal- or enzyme-catalysed reactions, with many impressive advances made in the current decade. This review will provide an overview of the field since 2010, with the aim of highlighting both the practical applications and elegance of enantioselective desymmetrisation to the wider synthetic community.

Organocatalytic enantioselective desymmetrisation

ConspectusThe Passerini three-component (P-3CR) and the Ugi four-component (U-4CR) are two of the most prominent isocyanide-based multicomponent reactions (IMCRs). The P-3CR transforms isocyanides, aldehydes (ketones), and carboxylic acids to α-acyloxy carboxamides, while the U-4CR converts isocyanides, aldehydes (ketones), amines, and carboxylic acids to α-acetamido carboxamides. Conversion of the high energy formal divalent isocyano carbon into a tetravalent amide carbonyl carbon provides the driving force for these reactions. While the prototypical P-3CR and U-4CR provide linear adducts, many heterocycles and macrocycles are now readily synthesized by modifying these truly versatile reactions. As one stereocenter is generated by the nucleophilic addition of the isocyanide to the carbonyl and imine functions, the search for enantioselective versions of these reactions has become a much sought after goal among synthetic chemists. This seemingly trivial endeavor turns out to be extremely difficult to achi...

Still Unconquered: Enantioselective Passerini and Ugi Multicomponent Reactions

Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis. Its success relies to a large extent upon the introduction of novel and generic activation modes. Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition-metal catalysis, a general and well-defined activation mode for this useful and abundant substance class is still lacking. Herein we propose the heterodimeric association of carboxylic acids with chiral phosphoric acid catalysts as a new activation principle for organocatalysis. This self-assembly increases both the acidity of the phosphoric acid catalyst and the reactivity of the carboxylic acid. To illustrate this principle, we apply our concept in a general and highly enantioselective catalytic aziridine-opening reaction with carboxylic acids as nucleophiles.

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Papers

Activation of Carboxylic Acids in Asymmetric Organocatalysis

Direct aldol reactions catalyzed by a heterogeneous guanidinium salt/proline system under solvent-free conditions.

General Metal-Free Baeyer–Villiger-Type Synthesis of Vinyl Acetates

Highly enantioselective proline-catalysed direct aldol reaction of chloroacetone and aromatic aldehydes.

TBD-catalyzed α-sulfenylation of cyclic ketones: desymmetrization of 4-substituted cyclohexanones