Single Heck-type reaction

A single alkyne relay is involved in the cascade oligocyclizations of 2-bromoalka-l,w-diene-//-ynes such as 90, 92, 94 and others. Three new rings are formed in these sequences of two intramolecular Heck-type reactions and a 67r-electrocyclization leading to various oligocyclic systems such as 91, 93, 95 in a rather elegant way (Scheme 25). - ... 

The catalytic system proved not only applicable to alkyl hahdes, but also allowed for the intramolecular conversion of aryl halides. Interestingly, the corresponding Mizoroki-Heck-type cyclization products were formed selectively, without traces of reduced side-products (Scheme 10.27) [55]. Therefore, a radical reaction via a single electron-transfer process was generally disregarded for cobalt-catalysed Mizoroki-Heck-type reactions of aromatic hahdes. Instead, a mechanism based on oxidative addition to yield an aryl-cobalt complex was suggested [51]. 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continnes to attract high level of research interest in simple couphng processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecirles in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

The Heck reaction, which initially appeared to be just an interesting new C - C-bond forming process to access alkenylarenes and conjugated dienes, has emerged as an extremely versatile tool for the synthesis of complex organic molecules. Heck reactions, especially when performed in a multifold manner and/or combined with pericyclic reactions in sequential or domino-type processes can lead to an impressive increase in molecular complexity in a single or just a few operations. Thus, starting from readily available... 

Simple open-chain 2-bromoheptadienes have frequently been used as substrates to generate 1,2-dimethylenecyclopentanes (Tables 2 and 3), which in turn have served as valuable starting materials in Diels-Alder cycloadditions. It has turned out to be even more favorable to carry out the intramolecular Heck reaction and subsequent Diels-Alder reaction as a domino-type sequence in a single operation (see Table 6). In the presence of secondary amines, aminoalkylcyclopentanes are produced (Sect. IV.3.2). 

Overman and coworkers have extensively developed the utility of asymmetric Mizoroki-Heck reactions for constructing quaternary carbon stereocentres through various alkaloid total synthesis endeavours. A particular focus of these studies has been the catalytic asymmetric synthesis of enantioenriched 3,3-disubstituted oxindoles, because oxindoles of this type are versatile precursors of many natural alkaloids, hi an early, unanticipated discovery, it was found that either enantiomer of spirocychc oxindole 103 could be formed with moderate selectivity using a single enantiomer of a chiral diphosphine ligand (Scheme 16.24) [13]. Specifically, the use of Ag3P04 as an HI scavenger in the cyclization of 102 produced (S)-103 in 71% ee, whereas use of the amine base PMP under otherwise identical reaction conditions yielded (7 )-103 in 66% ee. 

The preparation of the PPV skeleton can be generally classified into two main strategies (i) olefinations methods to prepare the vinylene double bond and (ii) transition-metal-catalyzed single bond formation between the arene and vinylene components. The former includes Wittig-, Wittig-Horner- and Knoevenagel-type condensations, whereas the latter approach was demonstrated via Heck, Stille, Suzuki Miyaura and McMurry coupling reactions (Scheme 7.5). 

Anions of the type 332 arc excellent models that provide strong support for the proposed intermediales in Heck reaction (also see 3.28). These anions have been made with diffaimt countercations and characterized by single-crystal X-ray diffiaction. Onreaction with styrene, they produce HiCH=CHF1i by a mechanism discussed in greater detail later (see Section 7.4.2). 

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