Coupling biaryl

The very reactive phenyl radical reacts with the aromatic substrate 2, present in the reaction mixture. Subsequent loss of a hydrogen radical, which then combines with 7 to give 4, yields a biaryl coupling product e.g. the unsymmetrical biphenyl derivative 3 ... 

Bergman cycloaromatization 17, 523 f., 528 biaryl coupling -.intramolecular 516f., 519 bicyclic system -, concave face 59 -, convex face 59 bicyclo[3.3.0] system 221 f. bicyclo[4.2.0] system 221 f. bidentate ligands 680 f. 

This iron-ate complex 19 is also able to catalyze the reduction of 4-nitroanisole to 4-methoxyaniline or Ullmann-type biaryl couplings of bis(2-bromophenyl) methylamines 31 at room temperature. In contrast, the corresponding bis(2-chlor-ophenyl)methylamines proved to be unreactive under these conditions. A shift to the dianion-type electron transfer(ET)-reagent [Me4Fe]Li2 afforded the biaryl as well with the dichloro substrates at room temperature, while the dibromo substrates proved to be reactive even at —78°C under these reaction conditions. This effect is attributed to the more negative oxidation potential of dianion-type [Me4Fe]Li2. 

A diastereoselective imine alkylation and a palladium-catalysed biaryl coupling were important steps in the diastereoselective synthesis of 6,7-dihydro-5//-dibenz[c,e]azepines (Scheme 7) starting from (R)-l-(2-methoxyphenyl)ethylamine. Selection for the... 

Albisson DA,Bedford RB, Lawerence SE, Scully PN (1998) Orthopalladated triaryl phosphite complexes as highly active catalysts in biaryl coupling reactions. Chem Commun 2095-2096... 

Bedford RB, Limmert ME, Hazelwood SL, Albisson DA (2002b) Platinum-catalysts for Suzuki biaryl coupling reactions. Organometallics 21 2599-... 

In most cases, construction of axial nonracemic biaryls can be realized by metal-mediated intramolecular biaryl coupling in which the chirality is induced by ort/io-substituted auxiliaries in an aromatic system. 

This biocatalytic method is therefore quite promising for the synthesis of complex molecules. Very recently, it was reported 1121] that HRP catalyzes the oxidation of 2-naphthols to l,l -binaphthyl-2,2 -diols with moderate enantiomeric excess (ee 38-64%) (Eq. 5). However, in view of the analytical techniques used, these data have to be questioned [167]. As shown recently, atrop-selective biaryl coupling can only be achieved by means of dirigent protein as chiral auxiliary [122]. 

Lignans by Chiral Auxiliary-Based Biaryl Coupling. 187... 

Retrosynthetic analysis of 5 and 6 yielded ketone 7 as pivotal intermediate. A key reaction for the synthesis of 7 was the auxiliary-controlled, di-astereoselective biaryl coupling of a phenyl magnesium bromide (from 8 or 9) with aryloxazoline 10 (Scheme 1). This coupling strategy was developed in the Meyers laboratory [12] and previously applied to the enantioselective synthesis of other naturally occurring biaryl lignans, such as steganone [13]. 

Thieno benzazepine 109 was synthesized in moderate yield by oxidative biaryl-coupling using the hypervalent iodine reagent phenyliodine(lll)bis (trifluoroacetate) (FIFA) and BF3 OEt2 as the activating agent in methylene chloride (Equation (16) (2002X8581)). 

Murrayafoline A (7) required for this total synthesis was obtained starting from 3-formylindole (618) (577) (see Scheme 5.40). Lead tetraacetate-mediated oxidative non-phenolic biaryl coupling of 7 led to murrastifoline F (191) in 60% yield. The... 

Acid treatment of a 3 1 mixture of murrayafoline A (7) and koenoline (8) led to chrestifoline A (192) in 70% yield. Addition of murrayafoline A (7) to a mixture of 1057 and lithium aluminum hydride in ether and dichloromethane afforded bismurrayafoline-A (197) in 19% yield (662) (Scheme 5.166). In addition to the aforementioned methods, the same group also reported a stereoselective synthesis of axially chiral bis-carbazole alkaloids by application of their "lactone concept" (663) and a reductive biaryl coupling leading to 2,2 -bis-carbazoles (664). 

The Ullmann coupling is the classical example of Cu-catalyzed biaryl coupling, wherein (a) a phenol and arylhalide substrate are converted to a bis-arylether or (b) two arenes are coupled to form a bis-arene species. These coupling reactions are of great importance for general organic synthesis as well as pharmaceutical and fine chemicals. The copper-catalyzed phenol coupling to arrive at chiral biphenol derivatives is used extensively as a test reaction for the catalytic activity of new copper complexes [254,255]. 

The dihydrooxazol-mediated biaryl coupling of nonracemic 11 with the Grignard reagent derived from l-bromo-2,3,4-trimethoxy-6-methylbenzene yielded (via intermediates of type 12) the two diastereomeric coupling products 13 and 14 in a 6 1 ratio. In this case the relative configuration around the biphenyl axis had to be determined (see p 478)122. 

The low yields in the synthesis of electron-rich biaryls, which are the more frequently occurring natural biaryl targets, are clearly a limitation to this procedure. Further side reactions may arise from hydro-dehalogenation without biaryl coupling, and from intermolecular reactions, leading to dimers or oligomers34,35. 

Kita and Tohma found that exposure of p-substituted phenol ethers to [bis(tri-fluoroacetoxy)iodo]benzene 12 in the presence of some nucleophiles in polar, less nucleophilic solvents results in direct nucleophilic aromatic substitution [Eq. (84)] [156]. Involvement of a single-electron transfer (SET) from phenol ethers to A3-iodane 12 generating arene cation radicals was suggested by the detailed UV-vis and ESR studies. SET was involved in the oxidative biaryl coupling of phenol ethers by 12 in the presence of BF3-Et20 [157]. 

In the intermolecular mode, this reaction has been utilized for the preparation of products 28 from various nucleophiles, including C-nucleophiles (e. g. (3-dicarbonyl compounds). A similar reaction in the intramolecular mode provides a powerful synthetic tool for the preparation of various polycyclic compounds via oxidative biaryl coupling [21,27 - 30]. Several examples of these C-C bond forming reactions are shown in Schemes 13-15. Specifically, various dibenzoheterocyclic compounds 30 have been prepared by the oxidation of phenol ether derivatives 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of BF3-etherate in dichloromethane (Scheme 13) [27-29]. 

Similar types of nucleophilic substitutions have also been carried out when PIFA is activated by two equivalents of Lewis acids such as trimethylsilyl triflu-oromethanesulfonate (TMSOTf) and BF3 Et20 or heteropolyacid in standard solvents such as CH2C12 and MeCN. These reactions were applied to intramolecular reactions by the same authors leading to biaryls (49) [54-57], quinone imine derivatives (50) [58], and dihydrobenzothiophens (51) [59], which are important structures of bioactive natural products [Eqs. (7)-(9)]. Dominguez and co-workers have expanded the above biaryl coupling reaction to the syntheses of benzo[c]phenanthridine system (52) [60] and heterobiaryl compounds (53) [61] [Eqs. (10,11)]. 

An extension of the intramolecular biaryl coupling with PIFA-BF3 Et20 to a short and efficient access to benzo[c]phenanthridines (60) and phenanthri-... 

Concise total synthesis of a promising antiviral (anti-HIV) agent, michel-lamine A (58), was accomplished by Bringmann and Tasler via oxidative biaryl coupling reaction of korupensamine A (166) using PIFA (or Pb(OAc)4)-BF3 Et20 [128] (Scheme 35). 

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