Quinone methides (QMs) are highly reactive compounds that have been defined as “elusive” intermediates, or even as a “synthetic enigma” in organic chemistry. Indeed, there were just a handful of examples of their utilization in catalytic asymmetric settings until some years ago. This review collects organocatalytic asymmetric reactions that employ QMs as substrates and intermediates, from the early examples, mostly based on stabilized QMs bearing specific substitution patterns, to more recent contributions, which have dramatically expanded the scope of QM chemistry. In fact, it was only very recently that the generation of QMs in situ through strategies compatible with organocatalytic methodologies has been realized. This tactic has finally opened the gate to the full exploitation of these unstable intermediates, leading to a series of remarkable disclosures. Several types of synthetically powerful asymmetric addition and cycloaddition reactions, applicable to a broad range of QMs, are now available.

The asymmetric Povarov reaction of N-arylimines with 2- and 3-vinylindoles has been developed using a chiral phosphoric acid ((S)-TRIP) as catalyst. The peculiar reactivity of vinylindoles allowed also the disclosure of a Povarov Friedel–Crafts sequence, and the trapping of the reaction intermediate with nucleophilic species, thus providing a versatile platform for the preparation of highly enantioenriched indole derivatives.

Sulfoxonium ylides, manageable compounds with an appealing safety profile, adapt to reaction partners like chameleons to their environment, resulting in a variety of useful, and sometimes surprising and unique, reactions.

The Povarov reaction provides a straightforward and modular entry to 1,2,3,4-tetrahydroquinolines (THQs). Despite its importance, it was only very recently that several highly efficient catalytic asymmetric protocols for this reaction have been developed, as summarized in this review which falls on the 50^th anniversary of Povarov’s pioneering disclosure. Furthermore, this review collects and critically discusses the interrupted versions of the reaction, often featuring intriguing and still unclear mechanicistic pathways. 1 Introduction 2 Catalytic Asymmetric Povarov Cycloaddition Reactions 2.1 Chiral Lewis Acid Catalysis 2.2 Chiral Brønsted Acid Catalysis 2.2.1 Chiral Phosphoric Acid Catalyzed Povarov Cycloaddition Reactions 2.2.2 Chiral Urea Catalyzed Povarov Cycloaddition Reactions 3 Catalytic Asymmetric Interrupted Povarov Reactions 3.1 Intermolecularly Interrupted Povarov Reactions 3.2 Intramolecularly Interrupted Povarov Reactions 3.2.1 Interrupted Povarov Reactions with Salicyaldehyde-Derived Imines 3.2.2 Interrupted Povarov Reactions with Glyoxylic Acid Derived Imines 4 Conclusion

Amongst nitrogen heterocycles of different ring sizes and oxidation statuses, dihydropyridines (DHP) occupy a prominent role due to their synthetic versatility and occurrence in medicinally relevant compounds. One of the most straightforward synthetic approaches to polysubstituted DHP derivatives is provided by nucleophilic dearomatization of readily assembled pyridines. In this article, we collect and summarize nucleophilic dearomatization reactions of pyridines reported in the literature between 2010 and mid-2018, complementing and updating previous reviews published in the early 2010s dedicated to various aspects of pyridine chemistry. Since functionalization of the pyridine nitrogen, rendering a (transient) pyridinium ion, is usually required to render the pyridine nucleus sufficiently electrophilic to suffer the attack of a nucleophile, the material is organized according to the type of N-functionalization. A variety of nucleophilic species (organometallic reagents, enolates, heteroaromatics, umpoled aldehydes) can be productively engaged in pyridine dearomatization reactions, including catalytic asymmetric implementations, providing useful and efficient synthetic platforms to (enantioenriched) DHPs. Conversely, pyridine nitrogen functionalization can also lead to pyridinium ylides. These dipolar species can undergo a variety of dipolar cycloaddition reactions with electron-poor dipolarophiles, affording polycyclic frameworks and embedding a DHP moiety in their structures.