Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Asymmetric enamine catalysis.

Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of CC bonds by directly connecting two different CH bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both CH bonds. This strategy was introduced by the group of Li as cross-dehydrogenative coupling (CDC) and discloses waste-minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross-dehydrogenative C sp 3C formations and provides a comprehensive overview on existing procedures and employed methodologies.

The Cross-Dehydrogenative Coupling of C sp 3H Bonds: A Versatile Strategy for CC Bond Formations

Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously. This kind of addition and reaction has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects. All these advantages, together with the high level of stereoselectivity attained in some of these reactions, will force chemists in industry as in academia to adopt this new strategy of synthesis, or at least to consider it as a viable option. The positive aspects as well as the drawbacks of this strategy are discussed in this Review.

Asymmetric multicomponent reactions (amcrs): the new frontier

Stereoselective organic reactions in water.

Important building blocks for the synthesis of drugs or natural products are found in Mannich bases and their derivatives Modern variants of the Mannich reaction that expand the potential of the classical intermolecular reaction significantly and enable efficient control of the regioselectivity and stereoselectivity are therefore the topic of intensive research Intramolecular reactions, in particular as part of domino reaction sequences, often afford astoundingly simple and elegant approaches to complex target compounds

Modern Variants of the Mannich Reaction

Begehrte Bausteine fur die Synthese von Wirk- oder Naturstoffen sind Mannich-Basen und deren Derivate. Moderne Varianten der Mannich-Reaktion, die die Bandbreite der klassischen intermolekularen Reaktion deutlich erweitern und eine effektive Kontrolle der Regio- und Stereoselektivitat ermoglichen, sind daher Gegenstand intensiver Forschung. Intramolekulare Reaktionen, insbesondere als Teil von Dominoreaktionssequenzen, fuhren haufig verbluffend einfach und elegant zu komplexen Zielverbindungen.

Moderne Varianten der Mannich‐Reaktion

A Convenient and Highly Regioselective One-Pot Synthesis of Quinolines by Addition of a Vilsmeier-Type Reagent to N-Arylimines

Modern methodologies such as the design of chiral catalysts using combinatorial techniques play a key role in the development of asymmetric aminoalkylations. Thus, powerful enantioselective syntheses for many attractive target compounds using chiral Lewis acid or base catalysts like 1 or 2 were created.

Asymmetric Catalytic Aminoalkylations: New Powerful Methods for the Enantioselective Synthesis of Amino Acid Derivatives, Mannich Bases, and Homoallylic Amines

Michael Arend

Papers

Modern Variants of the Mannich Reaction

Moderne Varianten der Mannich‐Reaktion

A Convenient and Highly Regioselective One-Pot Synthesis of Quinolines by Addition of a Vilsmeier-Type Reagent to N-Arylimines

Asymmetric Catalytic Aminoalkylations: New Powerful Methods for the Enantioselective Synthesis of Amino Acid Derivatives, Mannich Bases, and Homoallylic Amines

Aminoalkylation of Electron-Rich Aromatic Compounds Using Performed Iminium Salts Derived from Aldehydes other than Formaldehyde