Metal-Catalyzed Multicomponent Reactions

As part of our efforts to develop new efficient one-pot methodologies to access novel heterocyclic structures, we also reported an efficient synthesis of spiro[4,61-lactones and lactames by sequential multicomponent reaction/metal-catalyzed carbo-cyclizations from simple five-membered cyclic (3-ketoesters and (3-ketoamides,... 

Habib-Zahmani H, Viala J, Hacini S, Rodriguez J (2007) Synthesis of functionalized spiroheterocycles by sequential multicomponent reaction/metal-catalyzed carbocylizations from simple beta-ketoesters and amides. Synlett 1037-1042... 

Isocyanide-based multicomponent reaction Metal-catalyzed multicomponent reaction... 

Chart 1 Transition metal cocatalysts used in multicomponent aerobic palladium-catalyzed oxidation reactions... 

In line with the tremendous renewed activity witnessed in recent years in the field of multicomponent reactions, remarkable new strategies have been developed based on metal-catalyzed coupling processes. Advances in this area take advantage of the myriad of bond-forming processes that can be achieved with metal catalysts. 

Metal-catalyzed Multicomponent Reactions 8.8.2.2 Alkylmetal Reagents... 

The chemistry illustrated above demonstrates the outstanding potential of metal-catalyzed processes for the discovery of new multicomponent one-pot reactions. 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

Very common Cl fragments bound to a polymeric support are carbenoids. The simplest carbenoid is CO itself, which can be used in transition metal-catalyzed insertions between benzofuran-3yl palladium and a nucleophile such as trifluoroethanol [161]. One of the most common carbenoids is isonitrile, which is used in a large number of multicomponent reactions. Diazoalkanes have often been used as carbene precursors, since they can be readily obtained from support-bound anions and sulfonyl azides [252]. Commonly, diazoalkanes are converted transi-... 

Few examples of stereoselective transition metal catalyzed carbonylative multicomponent cycloadditions leading to other than five-membered rings have been reported1 72. Typical is the reaction of 3,3-dimethylcyclopropene with carbon monoxide, catalyzed by a palladium(O) complex, to stereoselectively form hexamcthyltrishomotropone as a tetracyclic adduct l73. 

Approaches to the synthesis and medicinal importance of pyrroles have been reviewed. The synthesis of pyrroles using multicomponent reactions was reviewed and advances in this area from mid-2009 to the end of 2013 are covered (14CSR4633). Another review covered the synthesis of pyrroles using the Paal-Knorr reaction (14AHC95).The synthetic approaches and biosynthetic hypotheses of pyrrole—imidazole alkaloids were discussed in another report (14CC8628). Synthesis of pyrrole-based heterocyclic molecules through metal triflate-catalyzed addition reactions of pyrrole to C—C and C-N bonds was reviewed (14PAC925). 

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