Reductive Mizoroki-Heck-Type Arylations

In conventional Mizoroki-Heck chemistry, catalytic turnover is ensured by a generally accepted sequence of fundamental steps (cf Section 7.2.1). Within this catalytic process, both migratory insertion-and importantly 3-hydride elimination-are diastereospecific, the latter usually necessitating a synperiplanar arrangement of a Cp—H bond and the Pd bond. The absence of conformationally accessible 

P-hydrogens in the o-alkyl palladium] 11) intermediate will therefore not only thwart P-hydride elimination but also intercept the catalytic cycle. In order to provoke this situation, particular structural features of the substrate are required, which are satisfied by alkenes having rigid bicyclo[2.2.1]heptane or bicyclo[2.2.2]octane skeletons. Instead of suffering P-hydride elimination, the C— Pd bond in these systems might then enter different reaction channels. 

These findings clearly foreshadowed that the C(sp )—Pd bond might enable synthetically usefijl C—C, as well as C—H bond-forming reactions, yet almost a decade passed until the latter process was systematically investigated (cf Section 

Apart from standard subsequent transformations, it was later discovered by Catellani et al. that the C(sp )—Pd bond in norbornene-derived paUadium(II) alkyls activates proximal C(sp )—H bonds, thereby rendering this chemistry a general methodology [87]. 

The present section summarizes reductive Mizoroki-Heck-type arylations-that is, palladium-catalyzed hydroarylation reactions of alkenes-which are essentially limited to (hetero-)norbomenes (Section 7.3.2). It should be noted however, that only a handful of remarkable examples are known that are not based on the bicyclo[2.2.1]heptane framework (see Section 7.3.3). 

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Scheme 7.35 Simplified catalytic cycle of reductive Mizoroki-Heck-type arylations.

Extension of the asymmetric hydroarylation to oxanorbornenes, as well as aza-norbornenes, was the obvious step forward. Fiaud et al. made several remarkable observations while examining the reductive Mizoroki-Heck-type arylation of the annulated 7-oxanorbornene 160 (Scheme 7.37) [100]. First, intermediate o-aUcyl... 

Reductive Mizoroki-Heck-Type Arylation in Action... 

In this section, only examples of Mizoroki-Heck reactions where a proper addition of the cr -aryl- or a -alkeny Ipalladium(II) complex to a double bond of an alkene or alkyne occurs are considered. As a consequence, an often-met deviation from the classic Mizoroki-Heck mechanism, the so-called cyclopalladation, will not be treated in further detail [12, 18]. However, as it is of some importance, especially in heterocycle formation and mainly because it will be encountered later during polycyclization cases, it shall be mentioned briefly below. Palladacycles are assumed to be intermediates in intramolecular Mizoroki-Heck reactions when j3-elimination of the formed intermediate cannot occur. These are frequently postulated as intermediates during intramolecular aryl-aryl Mizoroki-Heck reactions under dehydrohalogenation (Scheme 6.1). The reactivity of these palladacycles is strongly correlated to their size. Six-membered and larger palladacycles quickly undergo reductive elimination, whereas the five-membered species can, for example, lead to Mizoroki-Heck-type domino or cascade processes [18,19]. 

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