Metathesis multicomponent reactions

A multicomponent reaction involving 84, 85, and 86 has been realized in the high yielding synthesis of the imidazole 87, which could be converted in turn into the novel imidazo azepine 88 via a ring closing metathesis process <05TL9049>. 

As the intermolecular multicomponent reactions, three-component cycloaddition reactions (21.2 [2+2-1-2] cycloaddition and 21.3 [3+2+1] cycloaddition) and two-component cycloaddition reactions (21.4 [4+2] cycloaddition) are described. As the intramolecnlar single-component reactions, cycloaromatization reactions (21.5 intramolecular hydroarylation of alkynes and cychzation via transition metal vinybdenes) are described. Aromatic ring constrnction reactions involving aryne reactions (Chapter 12), rearrangement reactions (Chapters 16 and 18), metathesis reactions (Chapter 17), and coupling reactions (Chapters 19 and 20) are described in these different chapters. 

SCHEME 3.78 Ru-catalyzed cross-enyne metathesis/Diels-Alder multicomponent reactions. 

C. S. Junker, M. E. Welker, Tetrahedron 2012, 68, 5341-5345. Ruthenium carbenes as catalysts in stereoselective ene-yne metathesis/Diels-Alder and ene-yne metathesis/ Diels-Alder/cross coupling multicomponent reactions. 

SCHEME 5.59 Mechanism of ene-yne metathesis/Diels-Alder multicomponent reaction. 

Starling with the development of new multicomponent reactions (MCRs) in water, hydrojgr thiazolidinethiones and oxazolidinones were prepared efficiently in a one-pot procedure [1] (Scheme 8.1). The reaction was carried out under mild conditions, consistent with the principles of green chemistiy. These precursors were converted into different dienes containing terminal C-C double bonds by modify ing the hydroxy group in one- or two-step sequences. A final ring- closing metathesis (RCM) reaction led to various classes of unsaturated bicycles. 

Stalling T, Saak W, Martens J (2013) Synthesis of bicyclic thiazolidinethiones and oxazolid-inones by water- mediated multicomponent reactions (MCR) and ring-closing metathesis (RCM). Eur J Org Chem 2013(35) 8022-8032... 

Copper(I) chloride can be an effective catalyst in multicomponent reactions, such as in the synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydrop3nimidine-2-(l//)-ones, the synthesis of quinoline derivatives (eq 69), and the synthesis of fully substituted triazoles. The use of CuCl as an additive is also reported in cross-metathesis reactions leading to significant turnover enhancement. ... 

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. 

This review focuses on the cross-metathesis reactions of functionalised alkenes catalysed by well-defined metal carbene complexes. The cross- and self-metath-esis reactions of unfunctionalised alkenes are of limited use to the synthetic organic chemist and therefore outside the scope of this review. Similarly, ill-defined multicomponent catalyst systems, which generally have very limited functional group tolerance, will only be included as a brief introduction to the subject area. 

Although the bulk of this review is concerned with well-defined metal carbene catalysts, it is important to note the contributions made to cross-metathesis chemistry by ill-defined or multicomponent catalysts. A brief discussion of the cross-metathesis reactions of functionalised alkenes using catalysts of this type will therefore be included here [1]. 

Previously acrylonitrile had proved to be inert towards transition metal catalysed cross- and self-metathesis using ill-defined multicomponent catalysts [lib]. Using the molybdenum catalyst, however, acrylonitrile was successfully cross-metathesised with a range of alkyl-substituted alkenes in yields of40-90% (with the exception of 4-bromobut-l-ene, which gave a yield of 17.5%). A dinitrile product formed from self-metathesis of the acrylonitrile was not observed in any of the reactions and significant formation (>10%) of self-metathesis products of the second alkene was only observed in a couple of reactions. 

Banfi L, Basso A, Guanti G, Riva R (2003) Application of tandem Ugi reaction/ring-closing metathesis in multicomponent synthesis of unsaturated nine-memhered lactams. Tetrahedron Lett 44 7655-7658... 

As seen in the preceding sections, many multicomponent procedures are based on the production of conjugated dienes that are in situ involved in Diels-Alder reactions to obtain polycyclic compounds. In recent years, intramolecular enyne metathesis has become a very popular method by which to access cyclic conjugated dienes [172]. In line with this, Lee [173] has developed a new three-component re-... 

For the cross-metathesis reactions we used two different homogeneous ruthenium catalysts one multicomponent catalyst prepared in situ, and the other catalyst consisting of one single component. Both are based on ruthenium(II) and the latter can be isolated in pure form. Figure 1 shows the ruthenium catalysts that were used in cross-metathesis reactions to synthesize silicon-containing ot,(o-dienes. 

S. Fustero, P. Bello, J. Mird, A. Sim6n, C. del Pozo, Chem.-Eur. J. 2012, 18, 10991-10997. 1,7-Octadiene-assisted tandem multicomponent cross-enyne metathesis (CEYM)-Diels-Alder reactions a useful alternative to Mori s condition. 

From the point of view of organic synthesis, the multicomponent, multisite, catalytic systems for metathesis reactions are of limited use. The conditions used with these catalysts are harsh, and the catalysts require long induction periods. Much research over the last two decades... 

In metathesis reactions where alkylidene complexes are not used as the precatalysts, e.g., in the old multicomponent systems, they are formed under the reaction conditions. Basically, this happens through the formation of metal alkyls followed by a-elimination. It may be recalled that the formation of one of the first fully characterized alkylidene complexes involves reaction (7.3.2.8) (see Section 2.1.5). 

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