Biaryls, reductive elimination

The possible mechanism for the reactions involving stoichiometric amount of preformed Ni(0) complexes is shown in Fig. 9.8. The first step of the mechanism involves the oxidative addition of aryl halides to Ni(0) to form aryl Ni(II) halides. Disproportion of two aryl Ni(II) species leads to a diaryl Ni(II) species and a Ni(II) halide. This diaryl Ni(II) species undergoes rapid reductive elimination to form the biaryl product. The generated Ni(0) species can reenter the catalytic cycle. 

The reaction involves a key transesterification of the phenol with the phosphinite ligand. Orthometallation of the resulting phosphinite leads to a metallacycle. After reductive elimination, the biaryl product is formed and undergoes a transesterification to afford the phenol product (Scheme 27).123... 

The bromo-aryl groups are first linked by (5,5 )-stilbene diol to form the dibromide 33. Compound 33 is then dilithiated with t-BuLi at —78°C, followed by addition of CuCN. Intermediate 34 is presumably formed during the reaction. Reductive elimination promoted by molecular oxygen provides compound 35 at 77% yield with 93 7 diasteroselectivity. The final biaryl compound ellagi-... 

The Pd-PPh3 system (Scheme 3) is characterized by a two-electron reduction step of the cr-aryl-palladium intermediate [37], as also proposed previously for aryl-nickel complexes ligated to PPha [23, 38]. The formation of the biaryl proceeds by reductive elimination from the diarylpalladium and regeneration of Pd°. 

C)C12] complexes [302], which has been used with azobenzene, N,N -dimethylben-zylamine, and so on. Sequential arylations enable the synthesis of complexes with two different ligands of the type [Au(C,N)ArCl], Upon treatment with phosphine or chloride, some of the N,C quelated diarylgold(III) chloride complexes undergo reductive elimination of the aryl ligands to give biaryls [303]. Figure 1.60 presents some examples of these complexes. 

Biaryls are available through coupling of the aryl halide with an excess of copper at elevated temperatures (200 °C). The active species is a copper(I)-compound which undergoes oxidative addition with the second equivalent of halide, followed by reductive elimination and the formation of the aryl-aryl carbon bond. 

Another example of transient formation of a palladacycle is the Pd-mediated ortho-alkylation and ipso-vinylation of aryl iodides depicted in Scheme 8.23. In this multicomponent reaction the ability of norbomene to undergo reversible arylation and palladacycle formation is exploited. This reaction also illustrates that aryl halides undergo oxidative addition to Pd faster than do alkyl halides, and that aryl-alkyl bond-formation by reductive elimination also proceeds faster than alkyl-alkyl bond-formation. The large excess of alkyl iodide used in these reactions prevents the formation of biaryls. Benzocyclobutenes can also be formed in this reaction, in particular when the alkyl group on the aryl iodide is sterically demanding or when a secondary alkyl iodide is used [161]. 

Since the reactivity correlates with the amount of Au111 on the surface, it is assumed that the reaction is initiated by a twofold transmetallation from boron to Aum followed by reductive elimination of the biaryl compound. The catalytic cycle is completed when Au1 is re-oxidized to Au111. The reaction takes place in the absence of oxygen, and hydrogen can be detected by Raman spectroscopy. It also takes place in the absence of potassium carbonate but the catalyst is less stable. The TOF was at least 20 (calculated as the moles of boronic acid converted divided by two and by the moles of gold in the catalyst per hour). 

Reductive elimination of biaryls is a common decomposition route Benzyne ligands might also be (Figure 4.9a), as illustrated by the osmium example (Figure 4.9b) in which described as phenyiene-1,2-diyls the biaryl remains hexahapto coordinated. Alternatively, benzyne com-J plexes may result from p-C-H or P-C-Br abstraction processes (see below). 

The synthesis of unsymmetrical biaryls 8 from two monoaryl species involves the coupling of a metallated aromatic molecule 6 with an aryl halide or triflate 4 under the action of palladium(O) catalysis. The reaction involves a catalytic cycle in which palladium(O) inserts into the C-halogen bond via an oxidative addition to generate an arylpalladium(II) species 5 (Scheme 10.18). This undergoes a trans-metallation with the metallated component, producing a biarylpalladi-um(II) complex 7. The biaryl product is formed by reductive elimination. In the process, Pd(0) is regenerated and this can then react with a second molecule of aryl halide. Pd(0) is therefore a catalyst for the reaction. 

In the first step, it was proposed that the highly electrophilic Pdn(TFA)2 catalyst affected selective electrophilic C-H bond activation exclusively on the electron rich indole. This generated an indole-Pd(II) complex I, which was able to selectively activate the benzene via a transfer-palladation pathway, which is controlled by C-H acidity. Reductive elimination afforded biaryl C-C bond formation and released Pd(0) which required oxidation to regenerate the active Pd(II) catalyst. 

Conditions first described by Fagnou were used to affect the C-H to C-H bond cyclization, which proceeded in 47% yield. Mechanistically the direct coupling reaction is thought to proceed via intramolecular nucleophilic attack of the pyrrole moiety onto the Pd(II) centre. It was postulated that the electron rich DavePhos ligand facilitates both oxidative addition and forms a more reactive cationic Pd(II) species by dissociation of the halide. Following a deprotonation step, reductive elimination of Pd(0) then resulted in formation of the biaryl bond, completing the core framework. Application of this direct palladium-catalyzed biaryl coupling facilitates a very efficient and concise synthesis of rhazinilam as a racemate. 

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). 

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