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.

In den letzten Jahrzehnten hat wohl keine andere Reaktion das Forschungsgebiet der Totalsynthese mehr gepragt als die Diels-Alder-Reaktion. Mit einer Vielzahl von Anwendungen dieser grosartigen pericyclischen Reaktion, oftmals als entscheidendes Element einer eleganten Kaskadenreaktion zur Herstellung komplexer Molekulstrukturen, ermoglichte die Diels-Alder-Cycloaddition die Losung einer Reihe unterschiedlicher, von der Natur in Form von Naturstoffen gestellter Syntheseprobleme. Zur Feier des hundertjahrigen Jubilaums von Alders Geburtstag soll dieser Aufsatz die ungemeine Leistungsfahigkeit der von ihm entdeckten Reaktion anhand ausgewahlter Beispiele im Kontext der Totalsynthese verdeutlichen und ihre Vielseitigkeit sowie ihr gewaltiges, noch immer nicht vollstandig erfasstes Potential unterstreichen.

Die Diels‐Alder‐Reaktion in der Totalsynthese

In the canon of reactions available to the organic chemist engaged in total synthesis, the Diels–Alder reaction is among the most powerful and well understood. Its ability to rapidly generate molecular complexity through the simultaneous formation of two carboncarbon bonds is almost unrivalled, and this is reflected in the great number of reported applications of this reaction. Historically, the use of quinones as dienophiles is highly significant, being the very first example investigated by Diels and Alder. Herein, we review the application of the Diels–Alder reaction of quinones in the total synthesis of natural products. The highlighted examples span some 60 years from the landmark syntheses of morphine (1952) and reserpine (1956) by Gates and Woodward, respectively, through to the present day examples, such as the tetracyclines.

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Quinones as Dienophiles in the Diels–Alder Reaction: History and Applications in Total Synthesis

Protecting‐Group‐Free Total Synthesis of (−)‐Rhazinilam and (−)‐Rhazinicine using a Gold‐Catalyzed Cascade Cyclization

Asymmetric induction in 19-norsteroid total synthesis is discussed. It should be noted that the (S)-(+)-enedione can be made available by cyclization of the triketone with (S)-proline and its derivatives (asymmetric synthesis). Also mention must be made of the elegant approaches to progesterone and 11-substituted progesterones using biomimetic polyolefin cyclizations in which substantial asymmetric induction at several chiral centers is observed (diastereoselective synthesis). It is concluded that the successful utilization of asymmetric transformations demonstrated in the steroid field defines the potential of such processes and bodes well for their equally successful application in other areas of natural product synthesis.

Asymmetric induction in 19-norsteroid total synthesis.

A total synthesis of ring A aromatic D-homosteroids and the conversion of one of them to estrone and its derivatives are described. The key reaction is a catalysed addition of 6-methoxy-1-vinyl-3,4...

Total synthesis of steroids. Part 1. Ring A aromatic compounds. Regiocontrol in diene additions with 6-methoxy-1-vinyl-3,4-dihydronaphthalene

A diene synthesis using 2,6-xyloquinone as dienophile and boron trifluoride as catalyst does not follow the normal orientation rules and leads to a facile synthesis of ring A-aromatic steroids. A tetracyclic adduct prepared by a similar reaction and containing the steroidal C19-methyl group is also reported.

A Stereospecific Synthesis of Ring A-aromatic Steroids

Thermolyses in polar solvents, of Δ3-1,3,4-oxadiazolin-2-ones or 2-phenylimino-Δ3-1,3,4-oxadiazolines derived from α,β-epoxyketones, yields acetylenic carbonyl compounds. Good yields of acetylenic ...

Thermolysis of Δ3-1,3,4-oxadiazolin-2-ones and 2-phenylimino-Δ3-1,3,4-oxadazolines derived from α,β-epoxyketones. An alternative method for the convers of α,β-epoxyketones to alkynones and alkynals

Gerald A. MacAlpine

Papers

Total synthesis of steroids. Part 1. Ring A aromatic compounds. Regiocontrol in diene additions with 6-methoxy-1-vinyl-3,4-dihydronaphthalene

A Stereospecific Synthesis of Ring A-aromatic Steroids

Thermolysis of Δ3-1,3,4-oxadiazolin-2-ones and 2-phenylimino-Δ3-1,3,4-oxadazolines derived from α,β-epoxyketones. An alternative method for the convers of α,β-epoxyketones to alkynones and alkynals

Thermolysis of 2-acetoxy-.DELTA.3-1,3,4-oxadiazolines. Evidence for stepwise homolysis of cyclic diazenes

Stereospezifische synth. von steroiden mit aromatischem ring a