Domino process

Brandi A., Cicchi S. Domino Processes Involving Pericyclic reactions in Seminars in Organic Synthesis. 23th Summer Sch A. Corhella 1998 3, Ed. Trombini, Pb. Soc. Chim. Ital. 

A number of new MCRs, that are either facilitated or accelerated by microwave irradiation, have been reported recently for the synthesis of simple N-, 0- and S-containing heterocycles. These one-pot domino processes offer... 

Scheme 12 Synthesis of tetrasubstituted pyrroles by coupled domino processes...

Tetrasubstituted pyrroles were also obtained in a coupled domino process carried out under solvent-free conditions on silica gel (Scheme 9). The process involved the transformation of the alkynoate 27 into the 1,3-oxazoUdine 28 that could be further rearranged (through loss of one molecule of water)... 

Tejedor, D., Gonzalez-Cruz, D., Santos-Exposito, A., Marrero-Tellado, J.J., de Armas, R, Garcid-TeUado, F. (2005) Multicomponent Domino Processes Based on the Organocatalytic Generation of Conjugated Acetylides Efficient Synthetic Manifolds for Diversity-Oriented Molecular Construction. Chemistry A European Journal, 11, 3502-3510. 

Selective transformations Selective styrene ring opening [103] One-pot domino process for regioselective synthesis of a-carbonyl furans [104] Tandem process for synthesis of quinoxalines [105] Atmospheric oxidation of toluene [106] Cyclohexane oxidation [107] Synthesis of imines from alcohols [108] Synthesis of 2-aminodiphenylamine [109] 9H-Fluorene oxidation [110] Dehydrogenation of ethane in the presence of C02 [111] Decomposition of methane [112] Carbon monoxide oxidation [113]... 

Thus, domino processes are time-resolved transformations, an excellent illustration being that of domino stones, where one stone tips over the next, which tips the... 

The time-resolved aspect of domino processes would, however, be in agreement with cascade reactions as a third expression used for the discussed transformations. Unfortunately, the term cascade is employed in so many dilferent connections - for example, photochemical cascades, biochemical cascades or electronic cascades - on each occasion aiming at a completely dilferent aspect, that it is not appropriate moreover, it also makes the database search much more difficult Moreover, if water molecules are examined as they cascade, they are simply moving and do not change. Several additional excellent reviews on domino reactions and related topics have been published [7], to which the reader is referred. 

For clarification, individual transformations of independent functionalities in one molecule - also forming several bonds under the same reaction conditions -are not classified as domino reactions. The enantioselective total synthesis of (-)-chlorothricolide 0-4, as performed by Roush and coworkers [8], is a good example of tandem and domino processes (Scheme 0.1). I n the reaction of the acyclic substrate 0-1 in the presence of the chiral dienophile 0-2, intra- and intermolecular Diels-Alder reactions take place to give 0-3 as the main product. Unfortunately, the two reaction sites are independent from each other and the transformation cannot therefore be classified as a domino process. Nonetheless, it is a beautiful tandem reaction that allows the establishment of seven asymmetric centers in a single operation. 

There are, however, also many examples where the domino process is triggered by only one enzyme and the following steps are induced by the first event of activation. 

The term domino process is correlated to substrates and products without taking into account that the different steps may be catalyzed by diverse catalysts or enzymes, as long as all steps can be performed under the same reaction conditions. 

The domino approach is also used by Nature for the synthesis of several alkaloids, the most prominent example being the biosynthesis of tropinone (0-16). In this case, a biomimetic synthesis was developed before the biosynthesis had been disclosed. Shortly after the publication of a more than 20-step synthesis of tropinone by Willstatter [14], Robinson [15] described a domino process (which was later improved by Schopf [16]) using succinaldehyde (0-13), methylamine (0-14) and acetonedicarboxylic acid (0-15) to give tropinone (0-16) in excellent yield without isolating any intermediates (Scheme 0.5). 

Tropinone is a structural component of several alkaloids, including atropine. The synthesis is based on a double Mannich process with iminium ions as intermediates. The Mannich reaction in itself is a three-component domino process, which is one of the first domino reactions developed by humankind. 

Another beautiful example of an early domino process is the formation of daphnilactone A (0-19), as described by Heathcock and coworkers [17]. In this process the precursor 0-17 containing two hydroxymethyl groups is oxidized to give the corresponding dialdehyde, which is condensed with methylamine leading to a 2-azabutadiene. There follow a cycloaddition and an ene reaction to give the hexacycle 0-18, which is transformed into daphnilactone A (0-19) (Scheme 0.6). 

On the other hand, many reactions are known where in a first intermolecular step a functionality is introduced which than can undergo an intramolecular reaction. A nice example is the reaction of dienone 0-34 with methyl acrylate in the presence of diethylaluminum chloride to give the bridged compound 0-35 (Scheme 0-11). The first step is an intermolecular Michael addition, which is followed by an intramolecular Michael addition. This domino process is the key step of the total synthesis of valeriananoid A, as described by Hagiwara and coworkers [21]. 

A different situation exists if the single steps in a domino process follow different mechanisms. Here, it is not normally adjustment of the reaction conditions that is difficult to differentiate between similar transformations rather, it is to identify conditions that are suitable for both transformations in a time-resolved mode. Thus, when designing new domino reactions a careful adjustment of all factors is very important. 

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... 

The overwhelming number of examples dealing with domino processes are those where the different steps are from the same category, such as cationic/ cationic or transition metal/transition metal-catalyzed domino processes, which we term homo domino processes . An example of the former reaction is the synthesis of progesterone (see Scheme 0.3), and for the latter the synthesis of vitamin E (Scheme 0.7). 

There are, however, also many examples of mixed domino processes , such as the synthesis of daphnilactone (see Scheme 0.6), where two anionic processes are followed by two pericydic reactions. As can be seen from the information in Table 0.1, by counting only two steps we have 64 categories, yet by including a further step the number increases to 512. However, many of these categories are not - or only scarcely - occupied. Therefore, only the first number of the different chapter correlates with our mechanistic classification. The second number only corresponds to a consecutive numbering to avoid empty chapters. Thus, for example in Chapters 4 and 6, which describe pericydic and transition metal-catalyzed reactions, respectively, the second number corresponds to the frequency of the different processes. 

In most of the hitherto known cationic domino processes another cationic process follows, representing the category of the so-called homo-domino reactions. In the last step, the final carbocation is stabilized either by the elimination of a proton or by the addition of another nucleophile, furnishing the desired product. Nonetheless, a few intriguing examples have been revealed in which a succession... 

Scheme 1.1. General scheme of a cationic-cationic domino process.

In the following sections, we detail another functionality which is of major value in the area of carbocationic domino processes, namely the epoxides. On the basis of their high tendency to be opened in the presence of Lewis or Bronsted acids, thereby furnishing carbocationic species, several challenging domino procedures have been elaborated relatively recently. 

Scheme 1.13. Cationic domino process in the synthesis of pseudomonic acid C analogue.

Another interesting cationic domino process is the acid-induced ring opening of a-cyclopropyl ketones and subsequent endocyclic trapping of the formed carboca-... 

Scheme 1.21. Epoxidation/ring contraction domino process.

Recently, a novel domino process for the synthesis of benzazepines with the concomitant formation of a C-N and a C-C bond has been published by the Basavaiah group [38]. These authors have shown that, under acidic conditions in the presence... 

One of the most fascinating aspects of domino reactions is the fact that the number of steps being included in one sequence is not really limited therefore, the complexity of a domino process is simply a question of imagination and skill. 

As an alternative mechanistic assumption the initiation of the domino process by one molecule of water could be considered. However, this would lead to the corresponding enantiomer mt-1-146, which was excluded by crystallographic structure determination. 

An impressive number of eight steps within one cationic domino process was observed by Mulzer and coworkers, when treating the entriol derivative 1-161 with... 

Scheme 1.40. Eight-step cationic domino process.

As discussed earlier, Ila, Junjappa and coworkers used cyclopropyl units as cation-provider in cationic domino processes. Within their interesting approach, the indole derivatives 1-170 could be converted into the unexpected carbazoles 1-171 with 54-69% yield in a five-step transformation using SnCl4 as reagent (Scheme 1.41) [48],... 

Another carbocationic domino process by the same group resulted in the formation of indane derivatives using cyclopropyl carbinol compounds as starting mate-... 

As discussed previously, West and coworkers developed a two-step domino process, which is initiated by a Nazarov reaction. This can be extended by an electrophilic substitution. Thus, reaction of 1-179 with TiCl4 led to 1-182 via the intermediate cations 1-180 and 1-181. The final product 1-183 is obtained after aqueous workup in 99% yield (Scheme 1.43) [23]. It is important to mention here that all six stereocenters were built up in a single process with complete diastereoselectivity hence, the procedure was highly efficient. 

Cationic/reductive domino processes were first described in 2003, and are consequently among the youngest domino procedures described in this book. To date, only two (albeit very useful) examples typifying a combination of a cationic reaction with a reduction procedure have been identified. 

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

---