Electrophiles cascade reactions

Our interest in this chapter is in silver-catalyzed cycloisomerization reactions. Therefore, we shall present different silver-catalyzed cycloisomerization reactions as a function of the nucleophilic and electrophilic moiety. Cycloisomerization reactions including the classical ene-yne cycloisomerization (with X = CHR, Scheme 5.1), and the related heterocyclization reactions with heteroatoms embedded in unsaturated systems (X = NR, O Scheme 5.1) belong to the same reaction family. In addition, the alkynyl part can be exchanged for an allene unit. Internal or external nucleophiles (Nu) can then stabilize, through cascade reactions, the positive charge created.24... 

It is very well known that jr-allyl palladium complex 1, which is a key intermediate for the Tsuji-Trost type allylation, has an electrophilic character and reacts with nucleophiles to afford the corresponding allylation products. We discovered that bis 7r-allyl palladium complex 2 is nucleophilic and reacts with electophiles such as aldehydes [27] and imines [28-32] (Scheme 2, Structure 2). We have also shown that bis 7r-allyl palladium complex 2 can act as an amphiphilic catalytic allylating agent it reacts with both nucleophilic and electrophilic carbons at once to produce double allylation products [33]. These complexes incorporate two allyl moieties that can bind with different hapticity to palladium (Scheme 3). The different complexes may interconvert by ligand coordination. The complexes 2a, 2b and 2c are called as r]3,r]3-bisallypalladium complex (also called bis-jr-allylpalladium complex), r)l,r)3-bis(allyl)palladium complex, -bis(allyl)palladium complex, respectively. Bis zr-allyl palladium complex 2 can easily be generated by reaction of mono-allylpalladium complex 1 and allylmetal species 3 (Scheme 4) [33-36]. Because of the unique catalytic activities of the bis zr-allyl palladium complex 2, a number of interesting cascade reactions appeared in the literature. The subject of the present chapter is to review some recent synthetic and mechanistic aspects of the interesting palladium catalyzed cascade reactions which in-... 

Abstract Cascade reactions involving a transition metal-promoted step and a Michael-type addition process have emerged as a powerful tool to construct cyclic and polycyclic structures. In this review, recent advances in this field are presented. The first part is related to cycloaddition reactions based on zwitterionic jr-allylPd complexes. The second part deals with Michael initiated metal-catalyzed cyclofunctionalization reactions of unactivated C C jt-bonds. Parts three and four feature reactions where an initial Michael addition reaction is followed by either a coupling reaction or an electrophilic trapping. Part five is devoted to Michael terminated reactions. 

Kristensen and coworkers179a reported the design and execution of new anionic cascade reactions based on the cyano group functioning as an electrophile giving access to condensed aromatic heterocycles. They reported the intramolecular trapping of metalated... 

Some mechanistic aspects of the above cascade reaction deserve comment. Thus, after the intermolecular addition of the nucleophilic acyl radical to the alkene, the electrophilic radical adduct A, instead of undergoing reduction, reacts intramolecularly at the indole 3-position (formally a 5-endo cyclization) to give a new stabilized captodative radical B, which is oxidized to the fully aromatic system. (For a discussion of this oxidative step, see Section 1.5.)... 

The addition of organometals to non-activated carbon-carbon double or triple bonds, although a breakthrough in polymer chemistry about 70 years ago, has now become an efficient way of creating linear or cyclic substituted structures. The new organometallic thus formed can be quenched by various electrophiles, or can be used, in the case of polyunsaturated systems, to create polycycles via cascade reactions. 

Cascade reactions can be designed that depend on the relative electrophilicities of the intermediate organic radicals, and carbon monoxide can provide one of the components (equation 9-28).60... 

Cascade reaction. With 2-oxiranylethyl tosylate and related bifunctional electrophiles that enable regeneration of a carbanionoid species by Si-C bond scission, ring formation is essentially accomplished in one step. For example, the preparation of 3,3-bismethylthiocyclopentanol in 80% yield has been reported. 

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

Mechanistic insights as proposed by Kumar and coworkers supported the very design of the branching cascade strategy because the successful nucleophiles have utilized the dispersed electrophilic sites over the surface of common precursors 27 beautifully to provide different products via different cascade reactions (Scheme 27.4). In many cases, the reaction sequence apparently begins with the addition of nucleophiles to aldehyde or ketoester moiety and followed by further cyclization on to the chromones moiety (cascades I, III, IV, VI) before the second nucleophilic addition or rearrangement leading to diverse scaffolds. 

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