Oxidations and Reductions in Domino Processes

Covindasamy Sekar, iyyamr Kaiihikeyan, and Dhandapani Canapathy 

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. 

Since oxidation and reduction reactions can provide many organic compounds with reactive functional groups such as aldehydes, ketones, enones, amines, alcohol, allylic alcohols, and so on, further transformations can easily be added to give a domino process. Depending upon the position of the oxidation or reduction reaction in the domino process, this chapter is divided into three classes first, the domino reaction is initiated by an oxidation or reduction reaction second, the domino reaction has the oxidation or reduction step in the middle and third, the domino reaction is terminated by an oxidation or reduction reaction. Most of the oxidation and reduction reactions come under the category of anionic domino process, as they provide nucleophilic or electrophihc functionalities and only very few oxidation and reduction reactions proceed with cationic domino process. 

Domino Reactions Concepts for Efficient Organic Synthesis, First Edition. Edited by Lutz F. Tietze. 

Domino Reactions Initiated by Oxidation or Reduction Reaction 

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Besides the numerous examples of anionic/anionic processes, anionic/pericydic domino reactions have become increasingly important and present the second largest group of anionically induced sequences. In contrast, there are only a few examples of anionic/radical, anionic/transition metal-mediated, as well as anionic/re-ductive or anionic/oxidative domino reactions. Anionic/photochemically induced and anionic/enzyme-mediated domino sequences have not been found in the literature during the past few decades. It should be noted that, as a consequence of our definition, anionic/cationic domino processes are not listed, as already stated for cationic/anionic domino processes. Thus, these reactions would require an oxidative and reductive step, respectively, which would be discussed under oxidative or reductive processes. 

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. 

For the reason of comparison and the development of new domino processes, we have created a classification of these transformations. As an obvious characteristic, we used the mechanism of the different bond-forming steps. In this classification, we differentiate between cationic, anionic, radical, pericyclic, photochemical, transition metal-catalyzed, oxidative or reductive, and enzymatic reactions. For this type... 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

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. 

In an alternative two-step transformation of 5-spirocyclopropane isoxazolidines to tetrahydropyridones, for example, 7-amino cyclopropanol 214, prepared by chemoselective N-O reduction of isoxazolidine 213, was converted into 215 by treatment with Cu(OAc)2 and LiOAc in the presence of catalytic amounts of Pd(OAc)2. Interestingly, 7-amino cyclopropanols can also undergo a Pd-catalyzed domino ring-opening/cyclization/oxidation process to afford dihy-dropyridones such as 216 when the reaction is carried out in the presence of air or O2 (Scheme 49) <2005JOC5636>. 

As was the case in our earlier publications, the total syntheses described herein were classified according to the first step of the domino process they feature. Hence, the distinction has been made between cationic, anionic, radical, pericyclic, transition-metal-catalyzed, and reductive or oxidative domino processes. 

Anionic/oxidative reaction sequences have been developed in addition to the domino anionic/reductive processes. For example, with regard to the synthesis of novel diaryl heterocycles as COX-2 inhibitors [500], including rofecoxib (Vioxx) 2-972 [501] (which has recently been withdrawn from the market) or the pyrrolin-2-one derivative 2-973 [494], Pal and coworkers reported on a so-far unique domino aldol condensation/oxidation sequence (Scheme 2.218) [503]. 

In 2010, Jaegli et al. reported a novel palladium-catalyzed intramolecular domino spirocyclization process for the preparation of biologically relevant spiropyrroUdine-3,3 -oxindoles 86 [32] (Scheme 6.19). Oxidative addition of the aryl halide to Pd(0) aminopalladation via the coordinated intermediate 84 leads to palladacycle 85 reductive elimination of complex 85 generates the final product. Both Heck reaction and aminopalladation processes were viable pathways from amide 83, and the route that occurs is dependent on the ligand chosen. The use of tBuMePhos as the ligand is required for the successful formation of spirooxindoles. 

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