The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

A bis(oxazoline) (box) copper(II) complex and its hydrated counterpart (1 and 2) function as enantioselective Lewis acid catalysts for carbocyclic and hetero Diels−Alder, aldol, Michael, ene, and amination reactions with substrates capable of chelation through six- and five-membered rings. X-ray crystallography of the chiral complexes reveals a propensity for the formation of distorted square planar or square pyramidal geometries. The sense of asymmetric induction is identical for all the processes catalyzed by [Cu((S,S)-t-Bu-box)](X)2 complexes 1 and 2 (X = OTf and SbF) resulting from the intervention of a distorted square planar catalyst-substrate binary complex. These catalyzed processes exhibit excellent temperature−selectivity profiles. Reactions catalyzed by [Cu(S,S-Ph-pybox)](SbF6)2 and their derived chelation complexes are also discussed.

Chiral bis(oxazoline) copper(II) complexes: versatile catalysts for enantioselective cycloaddition, Aldol, Michael, and carbonyl ene reactions.

Supramolecular catalysis is a rapidly expanding discipline which has benefited from the development of both homogeneous catalysis and supramolecular chemistry. The properties of classical metal and organic catalysts can now be carefully tailored by means of several suitable approaches and the choice of reversible interactions such as hydrogen bond, metal–ligand, electrostatic and hydrophobic interactions. The first part of these two subsequent reviews will be dedicated to catalytic systems for which non-covalent interactions between the partners of the reaction have been designed although mimicking enzyme properties has not been intended. Ligand, metal, organocatalyst, substrate, additive, and metal counterion are reaction partners that can be held together by non-covalent interactions. The resulting catalysts possess unique properties compared to analogues lacking the assembling properties. Depending on the nature of the reaction partners involved in the interactions, distinct applications have been accomplished, mainly (i) the building of bidentate ligand libraries (intra ligand–ligand), (ii) the building of di- or oligonuclear complexes (inter ligand–ligand), (iii) the alteration of the coordination spheres of a metal catalyst (ligand–ligand additive), and (iv) the control of the substrate reactivity (catalyst–substrate). More complex systems that involve the cooperative action of three reaction partners have also been disclosed. In this review, special attention will be given to supramolecular catalysts for which the observed catalytic activity and/or selectivity have been imputed to non-covalent interaction between the reaction partners. Additional features of these catalysts are the easy modulation of the catalytic performance by modifying one of their building blocks and the development of new catalytic pathways/reactions not achievable with classical covalent catalysts.

/pdf/supramolecular-catalysis-part-1-non-covalent-interactions-as-4sw3itqtq6.pdf

Supramolecular catalysis. Part 1: non-covalent interactions as a tool for building and modifying homogeneous catalysts.

Multicomponent reactions have gained significant importance as a tool for the synthesis of a wide variety of useful compounds, including pharmaceuticals. In this context, the multiple component approach is especially appealing in view of the fact that products are formed in a single step, and the diversity can be readily achieved simply by varying the reacting components. The eco-friendly, solvent-free multicomponent approach opens up numerous possibilities for conducting rapid organic synthesis and functional group transformations more efficiently. Additionally, there are distinct advantages of these solvent-free protocols since they provide reduction or elimination of solvents thereby preventing pollution in organic synthesis “at source”. The chemo-, regio- or stereoselective synthesis of high-value chemical entities and parallel synthesis to generate a library of small molecules will add to the growth of multicomponent solvent-free reactions in the near future. In this review we summarized the results reported mainly within the last 10 years. It is quite clear from the growing number of emerging publications in this field that the possibility to utilize multicomponent technology allows reaction conditions to be accessed that are very valuable for organic synthesis. Therefore, diversity oriented synthesis (DOS) is rapidly becoming one of the paradigms in the process of modern drug discovery. This has spurred research in those fields of chemical investigation that lead to the rapid assembly of not only molecular diversity, but also molecular complexity. As a consequence multi-component as well as domino or related reactions are witnessing a new spring.

/pdf/recent-developments-in-solvent-free-multicomponent-reactions-4ugdax2te0.pdf

Kevin T. Chapman

Papers

Asymmetric Diels-Alder cycloaddition reactions with chiral .alpha.,.beta.-unsaturated N-acyloxazolidinones

The directed reduction of β-hydroxy ketones employing Me4NHB(OAc)3

Transition State π‐Solvation by Aromatic Rings: An Electronic Contribution to Diels–Alder Reaction Diastereoselectivity

Diastereofacial selectivity in intramolecular diels‐alder reactions of chiral triene‐n‐acyloxazolidones

π‐Solvatation von aromatischen Ringen im Übergangszustand — ein elektronischer Beitrag zur Diastereoselektivität von Diels‐Alder‐Reaktionen