Reductive Elimination from Palladacycle

As shown in stoichiometric experiments treated in Sect. 2.4, Eq. 13 hexahydromethanobiphenylenes are formed by reductive elimination from palladacycles. These compounds are often present as secondary products in the catalytic reactions shown. Path b of Scheme 1 is an example. In the absence of competitive reactants the palladacycle ehminates a hexahydromethanobiphenylene, forming palladium(O). A catalytic process was thus worked out starting with an aryl iodide or bromide, norbornene, Pd(OAc)2, and K2CO3 [23]. Yields were good to excellent with o-substituted iodo- or bromobenzene (94% with... 

In transition metal complexes of suitable geometry the metal may undergo intramolecular oxidative insertion into C-H bonds. Intermediates of Pd-catalyzed C-C bond formation can also undergo such cyclometalations to yield palladacycles . This can give rise to unexpected products or, if the palladacycles are too stable, the catalyst will be consumed and no further reaction will occur. At high temperatures reductive elimination from such complexes can occur to yield cyclic products. 

The stereochemistry of oxidative addition to the palladium(II) palladacycle was studied by Lautens using an enantioenriched secondary alkyl halide (Scheme 9) [32], From alkyl halide 23, product 24 was obtained, showing a net inversion of stereochemistry [33-35], Previous work by Stille showed that reductive elimination from palladium(IV) occurs with retention of stereochemistry [36], suggesting that oxidative addition occurs with an inversion of stereochemistry. This corresponds with the generally accepted SN2 mechanism for the reaction of palladium(O) with alkyl halides [37, 38],... 

For substrates that have a methyl group in the benzylic position, C-H activation of this methyl group can be chemoselectively achieved. In this event, P-hydride elimination is impossible, and the formation of benzocyclobutene products is observed instead (Table 7) [66], However, even if there is a choice between methyl C-H bonds and methylene C-H bonds (the latter allowing for p-hydride elimination), steric factors favor methyl C-H activation, leading to the formation of benzocy-clobutenes. That being said, this reaction may not mechanistically involve a complete migration of palladium. The product may simply be formed by reductive elimination from a five-membered palladacycle intermediate. 

The results of the crossover experiments argue against a mechanism initiated by hy-drosilylation. An alternative mechanistic possibility, which is consistent with all of the data and which adequately accounts for the stereoselective formation of only diastere-omers 148 and 149, is given in Scheme 51. Complexation of the silane to an initially formed palladacycle such as 155 would afford a complex such as 156. Sigma bond metathesis to a mixture of 7r-allylpalladium complexes 157 (presumed major) and 158 (presumed minor) followed by reductive elimination from each of these would generate the observed products 148 (major) and 149 (minor). 

Instead, Pd° P(o-Tol)3 2 (9) is formed upon fast protonation of 7 followed by reductive elimination from complex 8 (Scheme 1.38) [28], Therefore, in DMF, the palladacycle 5 is reduced to a Pd° complex at a rather high negative potential that could be reached by zinc powder (Scheme 1.38). Such a strong reducing agent is, however, never present in Mizoroki-Heck reactions. No oxidation peak was detected when the cyclic voltammetry of 5 was performed directly towards oxidation potentials, establishing that a Pd(0) complex is not generated spontaneously from the palladacycle 5 in DMF at 25 °C. 

Vinylogous amides react with arynes to yield 2+2-cycloadducts at ambient temperatures. These cycloadducts rmdergo ring opening to produce orffto-quinodimethide intermediates. A new method for the selective formation of Catellani-Heck isomers from arynes with norbomene has been described. The use of a bulky P(Bu03 ligand on the catalyst accelerates the C-C reductive elimination from the key intermediate palladacycle. ... 

The domino carbonylation and Diels-Alder reaction proceed only as an intramolecular version. Attempted carbonylation and intermolecular Diels-Alder reaction of conjugated 2-yne-4-enyl carbonates 101 in the presence of various alkenes as dienophiles give entirely different carbocyclization products without undergoing the intermolecular Diels-Alder reaction. The 5-alkylidene-2-cyclopenten-4-onecarboxy-lates 102 were obtained unexpectedly by the incorporation of two molecules of CO in 82% yield from 101 at 50 °C under 1 atm [25], The use of bidentate ligands such as DPPP or DPPE is important. The following mechanism of the carbocyclization of 103 has been proposed. The formation of palladacyclopentene 105 from 104 (oxidative cyclization) is proposed as an intermediate of 108. Then CO insertion to the palladacycle 105 generates acylpalladium 106. Subsequent reductive elimination affords the cyclopentenone 107, which isomerizes to the cyclopentenone 108 as the final product. 

Whereas 6-membered palladacycles readily undergo reductive elimination to give 5-membered rings as final products, the analogous process to give 4-mem-bered carbocycles from 5-membered palladacycles is less feasible, although not completely ruled out, and restricted to special cases (see, for instance, product 7 in... 

The results imply that the conjugated enallene ester system (l,2,4-alkatriene-3-carboxylate) 127 is required for incoiporation of the second molecule of carbon monoxide, and the following mechanism (Scheme 11-39) has been proposed. The formation of the palladacyclopentene 137 from 136 is suggested as an intermediate of 140. Then carbon monoxide insertion into the palladacycle 137 generates the acylpalladium 138. Subsequent reductive elimination affords the cyclopentenone 139, which isomerizes to give the cyclopentenone 140 as a final product. 

Once palladacycle formation has occurred, a number of possibilities exist for its reaction. A side product often seen in Catellani reactions is cyclobutane (21) formation resulting from a reductive elimination of the palladacycle (Scheme 7). In fact, under optimized conditions it is possible to achieve good yields of the cyclobutane products [26], However, the focus of this section will be to examine the reaction of the palladacycle with alkyl and aryl halides. 

In the cross-coupling reaction, starting from the simple arene (with directing group), palladation by a Pd(II) salt would lead to the formation of the palladacyclic complex (Ar1Pd(II)L) (Scheme 3). After the transmetallation and reductive elimination processes, the biaryl product is obtained together with Pd(0). If the Pd(0) can be further oxidized to Pd(II) catalyst, a catalytic cycle will be formed. By accomplishing this, arenes (C-H) are used to replace the aryl halides (C-X). Similarly, arenes (C-H) can be used to replace the aryl metals (C-M). 

Domino coupling reactions of aryl halides with norbornene and its derivatives provide a simple route to PAHs. In a four component sequence, norbornene (73) is arylated with an excess of iodobenzene to the terphenyl 74, that can be converted to the benz[e]pyrenes 75 and 76 by classical aromatic conversion reactions [131]. The domino sequence is a consequence of the fact that the five-membered intermediate palladacycle 77 a is able to add a second molecule of iodobenzene (77a —> 77b), and the intermediate arylpalladium halide resulting from reductive elimination in 77 b can even add a third molecule of iodobenzene before the final elimination of the Pd(0) complex PdL2 occurs (see Scheme 38). 

Internal alkynes will also readily undergo palladium-catalyzed annulation by functionally substituted aromatic or vinylic halides to afford a wide range of heterocycles and carbocycles. However, the mechanism here appears to be quite different from the mechanism for the annulation of terminal alkynes. In this case, it appears that the reaction usually involves (1) oxidative addition of the organic halide to Pd(0) to produce an organopalladium(II) intermediate, (2) subsequent insertion of the alkyne to produce a vinylic palladium intermediate, (3) cyclization to afford a palladacycle, and (4) reductive elimination to produce the cyclic product and regenerate the Pd(0) catalyst (Eq. 28). 

Bulky tri(o-tolyl)phosphine was used first by Heck [11]. A palladacycle obtained from it is known as the Herrmann complex (XVIII-1) and is used extensively in HR [12]. Also, palladacycles XVIII-7 [13] and XVIII-2 [14] are high performance catalysts. Turnover numbers as high as 630-8900 were achieved by tetraphosphine Tedicyp (X-1) [15]. Recently, the remarkable effect of electron-rich and bulky phosphines, typically P(t-Bu)3 and other phosphines shown in Tables 1.4, 1.5 and 1.6, have been vmveiled. Smooth reactions of aryl chlorides using these ligands are treated later. Electron-rich ligands accelerate oxidative addition of aryl chlorides, and reductive elimination is accelerated by bulky ligands. HR can be carried out in an aqueous solution by use of a water-soluble sulfonated phosphine (TPPMS, II-2) [16]. 

Formation of 2(biphenyl-2-yl)phenol (51) from 50 is explained by electrophilic attack of 57 to form 59 and its reductive elimination. As another explanation, oxidative addition of aromatic ortho C—H bond to 57 generates the palladacycle 58 and its reductive elimination affords 59. Domino arylations by a similar sequence of the reactions via 60 finally give rise to the pentaphenylated product 49 in 58 % yield. Certainly the reaction occurs by strong participation of OH group. It is surprising that efficient polyarylation of phenol with bromobenzene proceeds smoothly in the presence of CS2CO3 which is sparingly soluble in xylene and since it is difficult to abstract protons from phenol. 

Larock and Reddy obtained the 2-alkylidenecyclopentanone 72 by the reaction of l-(l-alkynyl)cyclobutanol 71 with iodobenzene. The bicyclononanone 74 was obtained from 73. Selective formation of 74 demonstrates that the more substituted bond a in the eyelobutanol 73 undergoes exclusive cleavage (or migration) [8,13]. Larock proposed the mechanism of the reaction of 75 involving ring expansion of 76 to form palladacycle 77 and reductive elimination to give 78. 

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]. 

The formation of phenanthridinones 98 from o-bromoamides 97 most Ukely involves a reaction between two metaUacycles (Scheme 11.33) [116, 117]. Accordingly, palladacycles 99 would react by a transmetaUation type-process to form 100 [116a], the elimination of which forms a seven-membered ring paUadacycle 101, followed by a reductive elimination to give phenanthridinones 98. Bimolecular transmetallation-type processes have also been proposed for the formation of other biaryls [69, 118]. 

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