Domino multicomponent synthesis

Our own group is also involved in the development of domino multicomponent reactions for the synthesis of heterocycles of both pharmacologic and synthetic interest [156]. In particular, we recently reported a totally regioselective and metal-free Michael addition-initiated three-component substrate directed route to polysubstituted pyridines from 1,3-dicarbonyls. Thus, the direct condensation of 1,3-diketones, (3-ketoesters, or p-ketoamides with a,p-unsaturated aldehydes or ketones with a synthetic equivalent of ammonia, under heterogeneous catalysis by 4 A molecular sieves, provided the desired heterocycles after in situ oxidation (Scheme 56) [157]. A mechanistic study demonstrated that the first step of the sequence was a molecular sieves-promoted Michael addition between the 1,3-dicarbonyl and the cx,p-unsaturated carbonyl compound. The corresponding 1,5-dicarbonyl adduct then reacts with the ammonia source leading to a DHP derivative, which is spontaneously converted to the aromatized product. 

Coquerel Y, Eilippini MH, Bensa D, Rodriguez J (2008) The MARDi cascade a Michael-initiated domino-multicomponent approach for the stereoselective synthesis of seven-membered rings. Chem Eur J 14 3078-3092... 

For other example of catalyst free multicomponent synthesis of pyrroles, see X. Wang, X.-P. Xu, S.-Y. Wang, W. Zhou, S.-J. Ji, Org. Lett. 2013, 15, 4246- 249. Highly efficient chemoselective synthesis of polysubstituted pyrroles via isocyanide-based multicomponent domino reaction. 

A year later, after Maikd s first article about SMS reaction, Tietze et al. published a stereoselective version of the same reaction using trimethylsilyl ether of (lR,2R)-Af-trifluoro-acetylnorpseudoephedrin, which acts as chiral auxiliary [77]. Since then, Tietze s group has been working extensibly in the domino multicomponent allylation reaction (MCAR) for the stereoselective synthesis of homoallylic ethers... 

SCHEME 12.16 Domino multicomponent allylation reaction (MCAR) for the stereoselective synthesis of homoallylic ethers and alcohols, a proposed mechanism. 

L. F. Tietze, T. Kinzel, C. C. Brazel, Acc. Chem. Res. 2009,42, 367-378. The domino multicomponent aUylation reaction for the stereoselective synthesis of homoallylic alcohols. 

On the basis of these considerations, this book will focus on modem tools for efficient stereoselective synthesis proceeding exclusively with MBFTs including selected examples of domino, multicomponent, or consecutive sequences that have been described in the last 10 years. In this book, we highlight the best of these... 

Grigg et al. reported a successful four-component domino reaction for the synthesis of functionalized dienes 316 from aryl iodides, allyl amine derivative, allene, and carbon monoxide [110] (Scheme 6.83). Carbon monoxide could insert into the C—Pd bond of arylpalladium(II) iodides to generate a carbonylpalladium species, which is followed by allenylation to form n-allylpalladium species. Finally, the attack of the nitrogen nucleophile produces the product observed. The products of this domino multicomponent reaction could be subjected efficiently to ring-closing metathesis in the presence of Grubbs second-generation catalyst. 

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... 

An interesting multicomponent domino free radical reaction in which five new bonds are formed in one operation has recently been applied in the total synthesis ofyingzhaosu A by Bachi and coworkers. Thus, a 2,3-dioxabicyclo[3.3.1]nonane system reacts with phenylthiol and 2 equiv. of molecular oxygen in the presence of AIBN, which under irradiation with UV light led to a diastereomeric mixture of en-doperoxide-hydroperoxides [127]. 

Jean Rodriguez was born in Gieza, Spain, on 25 June 1958, and in 1959 his family emigrated to France. After studying chemistry at the University Paul Cezanne in Marseille, France, he completed his PhD as a CNRS student with Prof. B. Waegell and Prof. P. Brun in 1987. He completed his Habilitation in 1992, also at Marseille, where he is currently Professor and Director of the UMR-CNRS-6178-SYMBIO. His research interests include the development of domino and multicomponent reactions, and their applications in stereoselective synthesis. In 1998, he was awarded the Acros prize in Organic Chemistry from the French Chemical Society. 

Without doubt, multicomponent reactions have become an attractive tool for the synthesis of biologically active molecules. In this regard, Jeong et al. reported an interesting domino synthesis of bicyclopentenones [50]. They employed a bimetallic system consisting of [Pd2(dba)3(CHCl3)] and... 

Lieby-Muller E, Simon C, Imhof K, Constantieux T, Rodriguez J (2006) A multicomponent domino reaction and in situ aerobic oxidation sequence for the first one-pot synthesis of polycyclic benzimidazoles from 1,3-dicarbonyl derivatives. Synlett 1671-1674... 

Table 5 lndolo[2,3-a]carbazole synthesis by multicomponent domino reactions... 

Abstract Sequentially palladium-catalyzed reactions consist of combinations of identical, related, or significantly different palladium-catalyzed processes that occur in a sequential or consecutive fashion in the same reaction vessel without addition of further amounts of catalyst to the reaction media. This novel type of cascade reaction can be elaborated into both domino and multicomponent processes and represents a significant contribution to the highly topical field of diversity-oriented synthesis. 

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. 

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