Reactions domino

Domino reactions, in which a series of carefully planned reactions occurs in a single vessel, used to prepare complex biologically active organic compounds (Hall, 1994 Tietze, 1995). 

Tietze, L. F. (1995). Domino Reactions in Organic Synthesis. Chemistry dl Industry (19 June), 453-57. 

A domino reaction,in this case consisting of an inter- and an intramolecular Diels-Alder reaction, is a key step in the synthesis of the hydrocarbon pago-dane 30, reported by Prinzbach et al When the bis-diQnQ 27 is treated with maleic anhydride 4, an initial intermolecular reaction leads to the intermediate product 28, which cannot be isolated, but rather reacts intramolecularly to give the pagodane precursor 29 ... 

This reaction also represents an example of the intramolecular Heck reaction, a variant that has gained some importance in recent years. Another instructive example of the potential of this reaction for the construction of ring systems has been reported by de Meijere and coworkers, taking advantage of a sequence of four consecutive intramolecular Heck reactions. The bromodiene-yne 18 reacts in a sequence of domino reactions within 3 d at 80 °C under Heck conditions to give the tetracyclic product 19 in 74% yield ... 

A more recent application of the Knoevenagel reaction is its use in domino reactions. The term domino reaction is used for two or more subsequent transformations, where the next reaction step is based on the functionality generated in the preceding step. Such reactions are also called tandem reactions or cascade reactions. 

Scheme 8.50 Construction of the ABCD ring system of stachyflin by an acid-induced domino reaction.

Keywords Fischer carbenes Template synthesis Cocyclization Cycloaddition Cyclopentadienes Cyclopentenones Domino reactions... 

Tietze LF, Haunert F (2000) Domino reactions in organic synthesis. An approach to efficiency, elegance, ecological benefit, economic advantage and preservation of our resources in chemical transformations. In Vogtle F, Stoddart JF, Shibasaki M (eds) Stimulating concepts in chemistry. Wiley-VCH, Weinheim, p 39... 

An enzyme-initiated hydroxylation-oxidation carbo-Diels-Alder domino reaction [82]... 

Tietze L. F., Modi A. Multicomponent Domino Reactions for the Synthesis of Biologically Active Natural Products and Drugs Med. Res. Rev. 2000 20 304-322 Keywords Diels-Alder reactions... 

Tietze L. F. Domino-Reactions the Tandem-Knoevenagel-Hetero-Diels-Alder Reaction and Its Application in Natural Product Synthesis J. Heterocycl. Chem. 1990 27 47-69... 

The "one-pot domino reaction" of A/-benzylaniline with benzaldehyde in refluxing toluene results in a mixture of oxazolidines via a transient azomethine ylide (Scheme 14) <96S367>. The 2-benzoyloxazolidine 69 rearranges spontaneously to the oxazine 70 <96JHC1271>. The ring-closure of derivatives 71 (R = H or Me) of (f )-phenylglycinol to oxazolidin-2-ones... 

Cydoadditions Investigated in Micro Reactors [OS 56] Domino reactions... 

The domino reaction consists of a Knoevenagel condensation giving an intermediate which immediately undergoes an intramolecular hetero-Diels-Alder reaction with inverse electron demand [18]. 

Tietze, L.R Rackelmann, N. (2004) Domino Reactions in the Synthesis of Heterocyclic Natural Products and Analogs. Pure and Applied Chemistry, 76, 1967-1983. 

Tietze, L.F. Lieb, M.E. (1998) Domino Reactions for Library Synthesis of Small Molecules in Combinatorial Chemistry. Current Opinion in Chemical Biology, 2, 363-371. 

The hydroformylation reaction strategy has recently been extended, in a novel way, to the manufacture of primary amines by hydroaminomethylation of olefins with ammonia in a two-phase system. Thus, 1-pentene was reacted with ammonia here hydroformylation to an aldehyde, with CO and H2, with subsequent reductive amination occurs in a domino reaction. The catalyst was Rh/Ir/TPPS (Zimmermann et al., 1999). 

One notable result is the treatment of 2-hydroxy cyclic ether analog, 2-deoxy-D-ribose with aniline in water catalyzed by InCl3 to afford the novel tricyclic tetrahydroquinoline compounds (Eq. 12.60). The reaction can also be catalyzed by recoverable cation-exchange resin instead of indium chloride.132 By using a stoichiometric amount of indium metal, a domino reaction of nitroarenes with 2,3-dihydrofuran generates the same products. 133... 

Tietze, L.F., Brasche, G. and Gericke, K.M. (2006) Domino Reactions in Organic Synthesis, Wiley-VCH Verlag GmbH, Weinheim. 

Domino Reactions in Organic Synthesis. Lutz F. Tietze, Gordon Brasche, and Kersten M. Gericke Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527 29060-5... 

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. 

Domino reactions are not a new invention - indeed, Nature has been using this approach for billions of years However, in almost of Nature s processes different enzymes are used to catalyze the different steps, one of the most prominent examples being the synthesis of fatty acids using a multi-enzyme complex starting from acetic acid derivatives. 

The quality of a domino reaction can be correlated to the number of bond-forming steps, as well as to the increase of complexity and its suitability for a general application. The greater the number of steps - which usually goes hand-in-hand with an increase of complexity of the product, the more useful might be the process. 

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. 

Scheme 0.7. Enantioselective Pd-catalyzed domino reaction for the synthesis of Vitamin E (0-24).

One of the first enantioselective transition metal-catalyzed domino reactions in natural product synthesis leading to vitamin E (0-23) was developed by Tietze and coworkers (Scheme 0.7) [18]. This transformation is based on a Pdn-catalyzed addition of a phenolic hydroxyl group to a C-C-double bond in 0-20 in the presence of the chiral ligand 0-24, followed by an intermolecular addition of the formed Pd-spe-cies to another double bond. 

One very important aspect in modern drug discovery is the preparation of so-called substance libraries from which pharmaceutical lead structures might be selected for the treatment of different diseases. An efficient approach for the preparation of highly diversified libraries is the development of multicomponent reactions, which can be defined as a subclass of domino reactions. One of the most... 

As a requisite for all domino reactions, the substrates used must have more than two functionalities of comparable reactivity. They can be situated in one or two molecules or, as in the case of multicomponent domino reactions, in at least three different molecules. For the design and performance of domino reactions it is of paramount importance that the functionalities react in a fixed chronological order to allow the formation of defined molecules. 

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. 

In our opinion, this approach provides not only a clear overview of the existing domino reactions, but also helps to develop new domino reactions and to initiate ingenious independent research projects in this important field of synthetic organic chemistry. 

L. F. Tietze, F. Haunert, Domino Reactions in Organic Synthesis. An Approach to Efficiency, Elegance, Ecological Benefit, Economic Advantage and Preservation of our Resources in Chemical Transformations, in M. Shibasaki, J. F. Stoddart and F. Vogtle (Eds.), Stimulating Concepts in Chemistry, Wiley-VCH, Weinheim, 2000, pp. 39-64 (d) L. F. Tietze, A. Modi, Med. Res. Rev. 2000, 20, 304-322 (e) L. F. Tietze, M. E. Iieb, Curr. Opin. Chem. Biol. 

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