Biaryl compounds synthesis

Another area of interest to the industrial sector is the development of a more efficient synthesis of biaryl compounds. This has been accompHshed using a Ni(II)-cataly2ed Grignard coupling reaction with an aryl haUde (86—89). 

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

Solid-phase Suzuki reaction was first used in the preparation of biaryls [248]. One recent example is given by Baudoin et al. for the synthesis of biologically active biaryl compounds (Scheme 3.13) [249]. 

It is especially noteworthy that this reaction sequence to ( + )-ancistrocladisine (8) offers the unique possibility of synthesizing a natural biaryl compound with two identical ortho-substituents, e.g, methoxy groups, next to the biaryl linkage (see also the nonstereoselective synthesis of ancistrocladisine as a mixture of all four possible stereoisomers13). 

The ferrocenylphosphine-nickel catalysts are also applied to asymmetric synthesis of axially chiral biaryl compounds through the cross-coupling reaction. Although initial attempts to this... 

Biaryl bisphosphines, atropisomeric, in hydrogenation, 10, 2 Biaryl-bridged bis(iminooxazolidine) complexes, with Zr(IV) and Hf(IV), 4, 811-812 Biaryl compounds, directed synthesis, 10, 145 Bicyclic arenes, in hexaruthenium carbido clusters,... 

Scheme 17 illustrates another fluorous sulfonate-based synthesis of library scaffolds. The tagged substrates were taken through aldol condensation and cycloaddition reactions to form the pyrimidine ring 18. The intermediates were then reacted with boronic acids for Suzuki reactions to form biaryl compounds 19 [31], reacted with HCO2H to give traceless detagged products 20 [34], or reacted with amine to form products 21 [33]. 

G. Bringmann, R. Walter, R. Weirich, The Directed Synthesis of Biaryl Compounds Modem Concepts and Strategies, Angew. Chem. Int. Ed. Engl. 1990, 29, 977-991. 

Table 6 Synthesis of tetra-orf/io-substituted biaryl compounds by Suzuki-Miyaura crosscoupling...

The possibility of coupling an aryl halide with an unreactive C - H bond opens a plethora of possibilities in the synthesis of biaryl compounds [171, 172]. A (NHC)Pd(II) complex has recently been used to promote the intramolecular direct arylation of aryl chlorides [173]. Whereas a number of complexes with different NHC were screened, (IPr)Pd(OAc)2 was found to be the pre-catalyst of choice (Scheme 22). The use of IPr HC1 as additive led to an enhancement of reactivity, probably due to the preventive effect on the catalyst decomposition at the high reaction temperature. These conditions... 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

Stereoselective Synthesis of Biaryl Compounds. The best known application of (1) to the asymmetric oxidative coupling of phenolic compounds is the copper(II)-catalyzed synthesis of l,r-binaphthyl-2,2 -diol in greater than 95% ee (eq 1). ... 

The Suzuki reaction provides a versatile, general method for the stereo- and regiospe-cific synthesis of conjugated dienes, enynes, aryl substituted alkenes, and biaryl compounds via Pd-catalyzed cross-coupling of vinyl halides or aryl halides with... 

Aryl cation chemistry was likewise successful in the synthesis of biaryls, a common structural component of many pharmaceutically and biologically active compounds. In this way, sterically crowded biphenyls were smoothly synthesized by a direct Ar-H substitution in alkyl benzenes. The desired coupling took place satisfactorily, forming various bulky biaryl compounds in yields greater than 50% (mostly >70%, see Scheme 2.12). ... 

In 2010, Organ and co-workers investigated the activity of Pd-PEPPSI-IPr (27) and Pd-PEPPSI-IPent (29) in the synthesis of di-, tri-, and tetra-ort/io-substituted biaryl and heterobiaryl products. With a few exceptions, 29 was found to be the optimal pre-catalyst system, generating various biaryl and heterobiaryl products possessing a variety of functional groups and/or orf/io-substituents (Scheme 29). In particular, a number of tetra-ort/jo-substituted biaryl compounds were synthesized in excellent... 

Over the past century, several methods have been developed for the synthesis of biaryl compounds [7]. Among these are the Ullmann-type coupling [8,9], the Scholl reaction [10], the Gomberg-Bachmann reaction [11], and recently transition-metal-catalyzed cross-coupling reactions [12], In particular, palladium-catalyzed crosscoupling reactions have been successfully applied to the synthesis of biaryls due to their generally high yields and excellent selectivities. 

Bringmann G, Price Mortimer AJ, Keller PA, Gresser MJ, Gamer J, Breuning M (2005) Atroposelective synthesis of axially chiral biaryl compounds. Angew Chem Int Ed 44 5384-5427... 

Synthesis of biaryl compounds is not the only use for oxidative dimerization it can lead to formation of new carbon-carbon bonds also in the aliphatic series. These reactions have been carried out with peroxides, especially diacetyl peroxide, for example, the formation of 2,3-dichlorosuccinic acid from chloro-acetic acid and of 2,3-dimethyl-2,3-diphenylbutane from isopropylbenzene 291 and hydrogen peroxide292 and a mixture of ammonium persulfate and sodium... 

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