Phosphines biaryl

In a Kumada-Corriu reaction, an aryl halide is oxidatively coupled with a homogeneous nickel(ll)-phosphine catalyst [2], This species reacts with a Grignard reagent to give biaryl or alkylaryl compounds. Later, palladium-phosphine complexes were also successfully applied. By this means, stereospecific transformations were achieved. 

Fagnou and co-workers reported on the use of a palladium source in the presence of different phosphine ligands for the intramolecular direct arylation reaction of arenes with bromides [56]. Later, they discovered that new conditions employing palladium complex 27 promoted the direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls including different functionalities as ether, amine, amide and alkyl (Scheme 7.11) [57]. 

In terms of methodologies for the preparation of A-arylindoles 140, Buchwald reported improved conditions for the palladium-catalyzed coupling of aryl chlorides, bromides, iodides and triflates 138 with a variety of 2-, 7- and polysubstituted indoles 139 utilizing novel electron-rich biaryl(dialkyl)phosphine ligands in combination with Pd2(dba)3 <00OL1403>. Alternatively, Watanabe reports similar A-arylations of pyrrole, indole and carbazoles with aryl bromides and chlorides using Pd(OAc)2/P(f-Bu)3 in xylene at 120°C <00TL481>. 

Biaryl synthesis from aryl halides is a more interesting reaction due to the value of these molecules and their difficult access by chemical methods. The first electrosyntheses were simultaneously done in 1979-80 by three groups [21-23] who used NiCljPPha (1-20%) as catalyst precursor in the presence of excess PPhs. Later, several groups investigated the use of bidentate phosphines like dppe associated with nickel in the synthesis of various biaryls, and notably 2,2 -bipyridine and of 2,2 -biquinoline from respectively 2-chloropyridine and 2-chloroquinoline [24], More recently new nickel complexes with l,2-bis(di-2-alkyl-phosphino)benzene have been studied from both fundamental and synthetic points of view [25]. They have been applied to the coupling of aryl halides. 

Milne and Buchwald used phosphine ligand 91 (Figure 19) in combination with Pd2(dba)3 to prepare tri- and tetra-6 r/i -substituted biaryls.Excellent yields were obtained even at low catalyst loadings (0.1-1 mol% Pd), with a good tolerance for group functionalities. 

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. 

Reactions of cycloaurated complexes with phosphine ligands that lead to reductive coupling and the formation of biaryls are discussed separately in Section IV.K. 

Nishimura, M. Ueda, M. Miyaura, N. Palladium-catalyzed biaryl-coupling reaction of arylboronic adds in water using hydrophilic phosphine ligands. Tetrahedron 2002, 58, 5779-5787. 

Because each generation learns from the last, this generation of ligands has focused on use of highly electron-rich phosphines to increase catalyst activity, increased backbone rigidity or the minute detail of the biaryl backbones to enhance enantioselectivities, or the development of a new class of asymmetric hydrogenation catalysts. 

The binaphthyl backbone of BINAP has inspired many variations of atropisomeric biaryl bisphosphines. One approach by Roche was to substitute the binaphthyl backbone with a 6,6 -dimethox-ybiphenyl backbone. MeO-Biphep (96a) was synthesized in approximately 26% yield in 6 steps from 3-bromoanisole (97a) (Scheme 12.30). MeO-Biphep can also be synthesized in 5 steps from 2-iodo-3-nitroanisole in approximately 18% yield. Several phosphine analogues can be prepared by the addition of R2PC1 to the lithio intermediate.117... 

Optically active Cr-complexed arylphosphines 57 can be prepared in three steps from achiral arene-Cr(CO)3 precursors 56. A successful addition of PPh2Li to the complex 56a with concomitant carbamate displacement has been suggested, giving rise to the desired phosphine complex 57a as an air-stable crystalline solid in 96 % yield (R = H) (Scheme 26). Therefore, efficient C-P bond construction can be achieved by reacting, for example, the biaryl complex 56b with PPh2Li, providing the optically active monophosphine ligand 57b in 87 % yield, which has been used in Pd-catalyzed allylic alkylation reactions (Scheme 26) [42]. 

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