Domino cascade process

Another application of the domino cascade process toward the construction of alkaloids involved the synthesis of ( )-lycopodine 48 (Scheme 12) (1997JOC78). The isomtinchnone cycloadduct 45 was formed from the Rh(II)-catalyzed reaction of diazoimide 44 and was found to be the precursor of the key Stork intermediate 47 (via 46). 

Tandem/Domino/Cascade Processes on Zeolites and Zeolite-Like Materials... 

There is certain confusion in the Hterature with respect to terminology of one-pot/ tandem or domino/cascade-type processes. We understand under true domino/cascade processes, those where the intermediate cannot be isolated and the individual steps cannot be performed separately. Contrary conventional reactions performed sequentially are referred as tandem reactions, and they can provide significant process improvements when performed in a one-pot fashion. 

The one-pot multistep process has been named in various ways domino, cascade, tandem, timed, consecutive, transmissive, etc. Sometimes the word used does not describe the real meaning of the procedure in that there is no conformity between the customary use of the term and the chemical transformation. These terms were recently defined more pertinently [59]. 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continnes to attract high level of research interest in simple couphng processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecirles in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

Padwa et al. (187,188) concisely summarized his domino cycloaddition/ A -acyliminium ion cyclization cascade process, which involves sequentially the generation of an isomiinchnone 1,3-dipole, intramolecular 1,3-dipolar cycloaddition reaction, 77-acyliminium ion formation, and, hnally, Mannich cyclization. Kappe and co-workers (189) utilized Padwa s cyclization-cycloaddition cascade methodology to construct several rigid compounds that mimic the putative receptor-bound conformation of dihydropyridine-type calcium channel modulators. 

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

In a narrower sense, this review covers intramolecular Mizoroki-Heck [1] reactions forming carbocycles [2] that is, the palladium-catalyzed intramolecular coupling of vinyl/aryl (pseudo-)halides with an alkene tethered by a hydrocarbon chain. Ring closures furnishing heterocycles are covered in Chapter 6 also beyond the scope of this chapter are the domino/cascade or tandem (Chapter 8) and asymmetric processes (Chapters 12 and 16) dealing with formation of a carbocycle. 

In this section, only examples of Mizoroki-Heck reactions where a proper addition of the cr -aryl- or a -alkeny Ipalladium(II) complex to a double bond of an alkene or alkyne occurs are considered. As a consequence, an often-met deviation from the classic Mizoroki-Heck mechanism, the so-called cyclopalladation, will not be treated in further detail [12, 18]. However, as it is of some importance, especially in heterocycle formation and mainly because it will be encountered later during polycyclization cases, it shall be mentioned briefly below. Palladacycles are assumed to be intermediates in intramolecular Mizoroki-Heck reactions when j3-elimination of the formed intermediate cannot occur. These are frequently postulated as intermediates during intramolecular aryl-aryl Mizoroki-Heck reactions under dehydrohalogenation (Scheme 6.1). The reactivity of these palladacycles is strongly correlated to their size. Six-membered and larger palladacycles quickly undergo reductive elimination, whereas the five-membered species can, for example, lead to Mizoroki-Heck-type domino or cascade processes [18,19]. 

The living nature of acylpalladium and other organopalladium species permits a series of their interconversions under one set of conditions, one representative example being the Pd-catalyzed copolymerization of alkenes and CO (Sect. VL4.2). A series of such processes can also occur in cyclic manners, and they are the subject of this subsection. Some chemists call combinations of two same or different successive processes tandem processes. These chemists have tended to call successively occurring multiple processes cascade processes, which may include tandem processes. Other chemists, on the other hand, would call them domino processes. Since these are rather loosely defined terms involving fundamentally nonchemical words, selection among them is a subjective matter, and all are used here and throughout this Handbook. 

Supercritical Fluids, Cascade Processes, Domino Reactions... 

More complex cascade processes involving this type of three-component couphng include the Cu(I)-catalyzed cascade coupling/cyclization reaction for the synthesis of 2-(aminomethyl) indoles 104 (Scheme 5.69) [72] and 105 (Scheme 5.70) [73], and the Cu(I)-catalyzed domino three-component coupling/cyclization/N-arylation reaction, which provided a concise synthesis of indole-fused 1,4-diazepines 106 (Scheme 5.71) [74]. 

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