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.

S inglet oxygen is a powerful tool in the armament of the synthetic organic chemist and possibly in that of nature itself. In this Account, we illustrate a small selection of the many ways singlet oxygen can be harnessed in the laboratory to aid in the construction of the complex molecular motifs found in natural products. A more philosophical question is also addressed: namely, how much do singlet oxygen oxidations influence the biogenesis of these natural products?All the synthetic examples surveyed in this Account can be characterized as belonging to the same class because they all involve the oxidation of a substituted furan nucleus by singlet oxygen. Readily accessible and relatively simple furans can be transformed into a host of complex motifs present in a diverse range of natural products by the action of singlet-oxygen-mediated reaction sequences.These reactions are highly advantageous because they frequently deliver a rapid and dramatic increase in molecular complexity in high yield. Furthermore, an unusually wide structural diversity is exhibited by the molecular motifs obtained from these reaction sequences. For example, relatively minor modifications to the starting substrate and to the reaction conditions may lead to products as variable as spiroketal lactones, 3-keto-tetrahydrofurans, various types of bis-spiroketals, 4-hydroxy cyclopentenones, or spiroperoxylactones. In addition, two more specialized examples are discussed in this Account. The core of the prunolide molecules and the chinensine family of natural products were rapidly synthesized using effective and short singlet oxygen mediated strategies; this adds weight to the assertion that singlet oxygen is a very effective moderator of complex cascade reaction sequences.We also show how our synthetic investigations have provided evidence that these same strategies might be used in the biogenesis of these molecules. In the cases of the chinensines and the litseaverticillols, an entire and diverse family of natural products was synthesized beginning from known naturally occurring furan-bearing terpenes. Additionally, in several cases, intermediates in our syntheses have been isolated from natural sources, which suggests that we have followed the same synthetic paths as nature.Certainly, the limit of the synthetic potential of singlet oxygen has not yet been reached, and we can look forward to seeing the boundaries expand in the future in a slew of new and interesting ways.

Members of the coleophomone family of natural products all possess several intriguing and challenging architectural features, as well as exhibit unusual biological activity. They, therefore, constitute attractive targets for synthesis. In this Article, we describe the total synthesis of coleophomones B (2), C (3), and D (4). The highly strained and congested 11-membered macrocycle of coleophomones B (2) and C (3) was constructed using an impressive olefin metathesis reaction. Furthermore, both of the requisite geometric isomers of the Delta(16,17) within the macrocycle could be accessed from a common precursor, facilitating a divergence that lent the coleophomone B (2)/C (3) synthesis an unusually high degree of efficiency. The synthesis of coleophomone D (4) confirmed that it exists as a dynamic mixture of isomeric forms with a different aromatic substitution pattern from the other family members.

The cover picture shows portraits of Otto Diels (top left) and Kurt Alder together with the original Diels–Alder reaction between cyclopentadiene and p‐quinone. Also illustrated are the key Diels–Alder reactions that enabled the total synthesis of prostaglandins and taxol as they were carried out by the research groups of Corey and Nicolaou, respectively. This year marks the centennial anniversary of Alder's birth—and this date will be celebrated at Alder's University, the Universität Köln, by a symposium on the 27th May—while last year was the 125th anniversary of the birth of Diels and next year will signify the 75th anniversary of the first publication of Diels and Alder on the reaction of 1,3‐dienes with olefins. The Diels–Alder reaction, as it has become known, is without doubt one of the most important reaction of organic syntheses, and thus it is a bonanza that Corey and Nicolaou et al. have written appropriate reviews, which can be found on pp. 1650–1667 and 1668–1698, respectively.

The purpose of this article is to give a taste of just how powerful the union between furans and photochemically-generated singlet oxygen is proving to be as a synthetic tool and to suggest that this chemistry is only now really coming of age. In attempting to achieve this goal, its progress from mechanistic curiosity to rapidly maturing applied science will be followed. It will be shown how the field has reached a point where the diversity of product structures attainable is expanding all the time at a tremendous pace and how this expansion allows for a wide variety of important developments from the discovery of new materials and methods for DNA-crosslinking, to the delineation of more sustainable synthetic technologies. To begin with, however, we look briefly at the investigations of the pioneers who laid all the necessary foundations by unravelling the reactions' key characteristics and then we will move on to show how their crucial work has been exploited and applied in increasingly creative ways over the years that have followed.