Transition-Metal-Catalyzed Domino Reactions

In transition metal-catalyzed domino reactions, more than one catalyst is often employed. In Tietze s definition and the classification of domino reactions, no distinction has been made between transfonnations where only one or more transition metal catalyst is used for the different steps, provided that they take place in a chronologically distinct order. Poli and coworkers [13] differentiated between these processes by calling them pure-domino reactions (which consisted of a single catalytic cycle driven by a single catalytic system) or pseudo-domino reactions . The latter type was subdivided into  

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 

Such an inter-type difference will not be utilized in this book, mainly because it complicates the classification and is not necessary as the focus is placed on the substrates and the products. The argument is also valid for enzymatic transformations [12d, 14], where one enzymatic system with one enzyme or different independent enzymatic systems with one or more enzymes may be used. In Nature, as well as in several artificial enzymatic domino reactions, a mixture of different enzymes catalyzing independent cycles is employed. 

Transition-metal-catalyzed reactions have become very popular in the total synthesis of natural products since they usually allow a late-stage assembly of functionalized structural fragments and, especially when used in a domino process, a rapid increase of complexity. 

Key step was a copper-catalyzed domino Buchwald-Hartwig amidation/ Diels-Alder reaction of amide 247 with 2-bromofuran 248 to give 249. In the first 

Palladium-catalyzed cross coupling of pyrone 252 with stannane 253 resulted in the intermediate 257, which underwent a Diels-Alder reaction to give cycloadducts 254 and 255 in a combined yield of 45%, favoring the endo product 255 (endo/exo = 2.5 1). In this reaction, the addition of Cul was cracial, as without Cul only traces of the cycloadducts were obtained. Further transformations of 255 resulted in racemic galanthamine (256). In 2000, the group of Trost [103] reported an enantioselective synthesis of this alkaloid applying a Pd-catalyzed asymmetric aUyUc alkylation and an intramolecular Heck reaction to assemble the 

The shimalactones, isolated from the cultured marine fungus Emericdla vane-color, are neuritogenic natural products which contain a bicyclo[4.2.0]octa-2,4-diene core structure in combination with an oxabicyclo[2.2.1]heptane moiety [105]. The complex structure of the shimalactones represents quite a synthetic challenge, which was overcome in 2008 by Trauner and coworkers [106] in a convergent synthetic approach using a domino Stille reaction/electrocyclization. 

87t/67t-electrocydization process might also be present in the biosynthesis of these 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

In a similar manner, cross-coupling reactions have been used as the first step, followed by a second Pd-catalyzed transformation or other reactions. 

Several Pd-catalyzed domino processes start with a Tsuji-Trost reaction, a pal-ladation of alkynes or allenes [5], a carbonylation [6], an amination [7] or a Pd(II)-cat-alyzed Wacker-type reaction [8]. A novel illustrious example of this procedure is the efficient enantioselective synthesis of vitamin E [9]. 

Within this chapter, two sections are devoted to rhodium and ruthenium. The two main procedures using rhodium are first, the formation of 1,3-dipoles from diazocompounds followed by a 1,3-dipolar cycloaddition [10] and second, hy-droformylation [11], The ruthenium-catalyzed domino reactions are mostly based on metathesis [12], with the overwhelming use of Grubbs I and Grubbs 11 catalysts. 

Inthe final section of the chapter, the use ofthe remaining transition metals indom-ino processes, including cobalt, nickel, copper, titanium, and iron, will be discussed. 

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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. 

Transition Metal-Catalyzed Domino Reactions 6.1.1.3 Heck/Tsuji-Trost Reactions... 

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