Domino Reactions Initiated by Oxidation or Reduction

Oxime 354 served as the starting material in the domino step, which, upon treatment with hypervalent iodine reagent PhI(OAc)2, led to an oxidative dearomatization. The quinone congener 356 was formed by intramolecular nucleophilic attack of the free hydroxyl group. Concomitantly, the oxime functionahty was oxidized to the nitrile oxide, which could then react with the a,fi-unsaturated ketone in a 1,3-dipolar cycloaddition to form the tetracyclic cortistatin carbon skeleton 355. 

The synthetic endeavor to the synthesis of racemic 359 via the advanced intermediate previously employed in Rawal s approach (i.e. 358) [149] commenced using Sml2 in a single electron transfer-induced domino sequence. After generation of 

oxidation of the allylic alcohol 363 to the corresponding aldehyde in the presence of a large excess of manganese dioxide initiated the domino oxidation/Diels-Alder/hetero-Diels-Alder sequence. After formation of 366 via an endo-E-syn transition state, the terminal aldehyde 367 then gave the tetracycle 364 in the concluding hetero-Diels-Alder step in 28% yield after 2 days. Intermediate 364 was then further transformed into the natural product 365 in an additional 14 steps, featuring an intramolecular Heck reaction and an iridium-catalyzed isomerization. 

The immense potency of domino reactions cannot be presented in a better way as in their apphcation to the total synthesis of complex natural products. Though nature has aheady shown that the domino concept is very useful in this field and several of the described natural product syntheses follow a biomimetic way, a multitude of other approaches have been developed over the last years, and we are convinced that in future most of the pubhshed total syntheses will be based on domino reactions. 

Pessoa, O.D.L, Silveira, E.R., Costa-Lotufo, L.V., Odorico de Moraes, 

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During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

Oxidation and reduction reactions play a vital role in the field of synthetic organic chemistry. Mild, selective, and economical catalytic oxidations as well as reduction reactions are recent developments in modern synthetic organic chemistry [1]. These transformations in combination with other reactions in a domino fashion give synthetically challenging organic products or intermediates in a very short and economical way [2]. After the first book by Tietze et al. [2a] in 2006 about domino reactions, where domino reactions initiated by oxidation or reduction reactions are reviewed as a separate chapter, enormous developments have taken place in the synthesis of a multitude of important organic compounds using oxidative or reductive domino reactions. 

Domino Reactions Initiated by Oxidation or Reduction Reaction... 

In this chapter, we presented the importance of oxidation and reduction reactions as part of a domino process in organic synthesis. Particularly, in the synthesis of complex organic molecules, this allows for short, simple, economical, as well as highly selective approaches in which several bonds are formed in one process. Domino reactions initiated by oxidation or reduction reactions have seen enormous growth in the last years. However, the protocols dealing with domino reactions having an oxidation or a reduction in the middle of a reaction sequence or as the terminating step are yet to be explored to their full potential. 

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