Section 1.1 Palladium Chemistry

While palladium, ruthenium, and rhodium are the most common metal catalysts used to facilitate Alder-ene cyclization, a few successful examples of catalysis using different metals have been published. Both of the references reviewed in this section demonstrate chemistry that is novel and complimentary to the patterns of reactivity exhibited by late transition metals in the Alder-ene cyclization. 

Palladium chemistry involving heterocycles has its unique characteristics stemming from the heterocycles inherently different structural and electronic properties in comparison to the corresponding carbocyclic aryl compounds. One example illustrating the striking difference in reactivity between a heteroarene and a carbocyclic arene is the heteroaryl Heck reaction (vide infra, see Section 1.4). We define a heteroaryl Heck reaction as an intermolecular or an intramolecular Heck reaction occurring onto a heteroaryl recipient. Intermolecular Heck reactions of carbocyclic arenes as the recipients are rare [12a-d], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles, pyrroles and indoles, etc. are excellent substrates. For instance, the heteroaryl Heck reaction of 2-chloro-3,6-diethylpyrazine (1) and benzoxazole occurred at the C(2) position of benzoxazole to elaborate pyrazinylbenzoxazole 2 [12e]. 

Most of the palladium chemistry mentioned was found in Heck s classic work Palladium Reagents in Organic Synthesis . Industrial perspectives came from interviews with industrial chemists and the Encyclopedia of Chemical Processing and Design , specifically the sections on Oxo Process Alcohols and Butyraldehydes and Butyl Alcohols . If a reaction or result in this review is not referenced it came from one of the books mentioned here. ... 

Palladium chemistry has been utilised to introduce aryl groups to a furan a-position by substitution of hydrogen, and via boronic acids, and in Heck-type alkenylations, again at C-2, via oxidative type palladation (cf. section 2.7.2.1). 

C.iii.c. Preparation of Small Molecules for Materials Science. Pd-catalyzed amination has also been used to prepare small molecules that are useful as hole-transport materials, selective metal-cation detection systems, and dyestuffs. As mentioned briefly in the section on reacting diarylamines with aryl halides, Marder and co-workers used palladium chemistry to form triarylamines, which are useful as hole-transport layers. Reactions of primary arylamines with aryl halides using DPPF-hgated palladium as catalyst allows for the selective addition of one aryl halide, followed by the addition of a second aryl halide to form mixed triarylamines, as shown in Eq. 42. This procedure has been used to generate unsymmetrical triarylamines that are analogs of TPD, as shown in Eq. 43. hi addition, they have used aminoferrocene as a substrate to conduct diarylations to form N, A-diarylaminoferrocenes. ... 

Two hypothetical mechanisms have been proposed to explain the Heck reaction on the basis of Pd(II)/Pd(IV) cycles (Scheme 2.12). As discussed in Section 2.2.1, oxidative addition of aryl halides to Pd(II) precursors is both kinetically and thermodynamically difficult. The Pd(II)/Pd(IV) mechanism proposed by Shaw for the Heck reaction (Scheme 2.1) tried to elude this problem by postulating the intermediacy of anionic Pd(II) complexes with increased nucleophilicity, but it is not evident how this mechanism could be adapted to complexes containing PCP or related pincer ligands. With this problem in mind, Jensen [93] made an alternative proposal (Scheme 2.12a), which starts with the oxidative addition ofa C-H bond of the olefin to the Pd(II) pincer complex to afford a Pd(IV) vinyl-hydride intermediate. This idea was inspired by a similar reaction observed with an isostructural Ir(I) PCP complex, but such C-H bond activations are unusual in palladium chemistry. A theoretical analysis by Freeh [63] raled out such possibility, leading instead to the alternative Pd(II)/Pd(IV) cycle depicted in Scheme 2.12b. A key element... 

The Alder-ene cyclization of allylic silyl ethers represents a clever use of cycloisomerization chemistry, as the enol ether products can be easily unmasked to yield aldehydes. Palladium-catalyzed cycloisomerization of 1,6- and 1,7-enynes containing an allylic oxygen most often gives rise to 1,3-dienes (see Section 10.12.4.1). However, enynes of type 63 underwent facile Alder-ene cyclization to the corresponding five- or six-membered rings (Equation (40)) using both [CpRu(MeCN)3]PF6 41 and the Cp analog ([Cp Ru(MeCN)3]PF6, 64).53... 

Much of the chemistry of palladium and platinum sulfoxide complexes has been discussed in previous sections and so only additional salient points will be mentioned here. A complete listing of all palladium and platinum sulfoxide complexes prepared would require a review article in itself. 

Common protectors of hydroxyls are benzyl and 2-bromobenzyl for Boc chemistry and tert-butyl for Fmoc chemistry. Trityl provides a third level of selectivity for both chemistries because it can be removed by mild acid (1% CF3C02H in CH2C12), which does not affect tert-butyl based protectors. O-Allyl is not removable by palladium-catalyzed allyl transfer, so it is not appropriate. Protection by acyl such as benzyloxycarbonyl is possible, but 0 -acyl protectors can be problematic because of their tendency to shift to adjacent amino groups (see Section 6.6) and... 

Palladium(0)-catalyzed cross-coupling of aryl halides and alkenes (i.e., the Heck reaction) is widely used in organic chemistry. Oxidative Heck reactions can be achieved by forming the Pd -aryl intermediate via direct palladation of an arene C - H bond. Intramolecular reactions of this type were described in Sect. 4.1.2, but considerable effort has also been directed toward the development of intermolecular reactions. Early examples by Fu-jiwara and others used organic peroxides and related oxidants to promote catalytic turnover [182-184]. This section will highlight several recent examples that use BQ or dioxygen as the stoichiometric oxidant. 

Palladium-mediated cross-coupling reactions in pteridine chemistry provide for variation at position 6 using halogenated pyrazines or pteridines as substrates (see Section 10.18.7.4). The 6-bromopyrazine 168 is a versatile intermediate leading to pteridine 169 both compounds have been shown to be substrates for palladium-mediated cross-coupling reactions <2000J(P1)89> (Scheme 32). 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

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