Biphenyl derivatives, synthesis

An elegant application of the Vilsmeier reaction is the synthesis of substituted biphenyls as reported by Rao and RaoJ Starting with homoallylic alcohol 8, the biphenyl derivative 9 was obtained from a one-pot reaction in 80% yield ... 

General procedure for the reaction of an o-substituted aryl iodide in the presence of benzyl alcohol. Synthesis of biphenyl derivatives. 

Andrus also reported the synthesis and use of biphenyl-derived bis(oxazoline) (154) as a ligand for Cu(I) (110). In the presence of this catalyst, cyclohexene is oxidized in comparable yield and selectivity as 55c CuOTf complexes. The ni-trobenzoate perester was found to be a more reactive oxidant than perbenzoate, although the reaction still requires 5 days to proceed to completion, Eq. 93. 

A second example from the same group is the synthesis of an elaborate diethynyltriphenylene derivative (Scheme 7 Table 8,entries 12,13) [58].Zn/Pd-promoted homocoupling of a 4-iodo-l,2-dialkoxybenzene furnishes the desired tetraalkoxybiphenyl, an electron-rich aromatic system. Iron trichloride-catalyzed Friedel-Crafts arylation of the biphenyl derivative with dimethoxy-benzene furnishes an unsymmetrical triphenylene derivative. Deprotection, oxidation, and subsequent Diels-Alder reaction with cyclohexadiene is followed by catalytic hydrogenation and reoxidation. TMS-CC-Li attack on the quinone delivers the alkyne modules, treatment with SnCl2 aromatizes the six-mem-bered ring, while KOH in MeOH removes the TMS groups cleanly to give the elaborate monomer. 

Another way to produce biphenyl derivates using flow was described by Leeke et al. [34] where they performed a Pd catalyzed Suzuki-Miyaura synthesis in the presence of a base. First experiments were carried out in toluene/methanol solvent. A reaction mixture was passed through the encapsulated Pd filled column bed length 14.5 cm (some cases 10 cm) x 25.4 mm id. 45 g of PdEnCat. Base concentration, temperature and flow rate were optimized and at optimum parameters (0.05 M base concentration, 100°C and 9.9 mL/min) the conversion was 74%. Then the reaction was performed under supercritical conditions using supercritical CO2 at high pressure and temperature. After optimizing the concentration of base, flow rate, pressure and temperature, the highest conversion rate (81%) was observed at 166 bar and 100°C where the reactant mixture was monophasic in the supercritical state. This system is able to produce 0.06 g/min of the desired product. 

The synthesis of 2,7-dinitrodibenzothiophene via cyclization of the biphenyl derivative (38) with bromine, at 200°, could be usefully extended to the synthesis of other deactivated dibenzothiophenes. The 2,7-disubstitution pattern is rare, the only other reference to it being the... 

The arylamine 709 required for the total synthesis of hyellazole (245) was synthesized by Diels-Alder reaction of l-methoxycyclohexa-l,3-diene (710) and ethyl phenylpropynoate 711. The biphenyl derivative 719 thus obtained was transformed to the arylamine 709 by excecuting a similar reaction sequence as shown in Scheme 5.66. The arylamine 709 was obtained in six steps and 7% overall yield based on 1-methoxycyclohexa-l,3-diene (710) (599,600) (Scheme 5.68). 

The intramolecular cyclization of a nitro group with a triple bond has been extended to the synthesis of six- and seven-membered ring compounds analogous to isatogens. Thus, the reaction of the acetylene group with the nitro group in 39 yields 2-phenyl-3-oxobenzo[prepared from the corresponding biphenyl derivative.19... 

A recent publication described the synthesis of a series of dipeptide nitriles and the evaluation of their interaction with various papain-like cysteine proteases. Different P2 side chains were explored within the series of 44 compounds and microwave-assisted Suzuki couplings were used in a limited part of the synthetic efforts. Two different biphenyl derivatives were synthesized from the corresponding aryl bromides, as shown in Scheme 25, using 30 min of microwave heating at 70 °C [87]. Especially the meta-biphenyl derivative 52 was shown to be a potent inhibitor of papain and the cathepsins L, S, and K. 

The same group reported on the synthesis and characterization of all-hydrocarbon MCLCPs, poly-(XXXX), and their hydrogenated derivatives poly-(XXXXI), based on 4,4 -bis(a-co-alkenyl)-l,r-biphenyl derivatives, see Fig. 23. Monomers with different a-co-alkenyl chain lengths were used to prepare not only the corresponding homopolymers but also statistical copolymers. Crystallinity, thermal transition properties and LC properties were studied. 

The other primary application of asymmetric Grignard coupling reactions has been in the synthesis of axially chiral binaphthyl and biphenyl derivatives. Hayashi performed a binaphthyl synthesis (equation 6) in 95% ee using a nickel catalyst and ligand (7), a P-O chelating analog to (3). For a similar synthesis of chiral biaryls (equation 7) ligand, (8) was found to yield the most successful results (93% ee). ... 

Quinone ketals, fonnation of 1170, 1171 /j-Quinone methide radical 1158 Quinone methides 1217, 1282 dimerization of 1255, 1256 enzymatic formation of 1223 from biphenyl derivatives 1035-1038 from fluorenols 1038 intramolecular cyclization of 1220 reactions of 1308 synthesis of 1253, 1255 m-Quinone methides 1024... 

Oxidation phenol - biphenyl derivatives with VOCl.i [218], synthesis of oligonucleotide [219], Mitsunobu reaction [220]. 

Stepanova A. R. Liguid-crystalline polyethers synthesis on the basis of biphenyl derivatives. // Abstract of Chemistry Masters. Thesis. St. Peterburg 1992. 

The synthesis proceeds in 22% yield from the biphenyl derivative (36), a key step being preferred formation of the axial alcohol (38) using iridium tetrachloride. 

Biphenyl synthesis. Monoarylation of 1,4-dibromobenzene makes further functionalization of biphenyl derivatives possible. 

A study of the palladium-catalysed reaction of benzene with iodoarenes has included a synthesis of a phosphine-ligated aryl palladium pivalate complex. However, this species fails to form the biaryl product and it is suggested that a ligandless arylpalladium(II) carboxylate complex is involved in the carbon-hydrogen cleavage step. In the palladium-catalysed reaction of cyanobenzene with iodoarenes in trifluoroacetic acid, biphenyl derivatives are formed by substitution of hydrogen ortho to the cyano group. The first step in the process is likely to involve co-ordination of... 

The intramolecular hydroarylation of alkynes is a useful method for the synthesis of fused arenes. For example, biphenyl derivatives, bearing an alkyne unit at the ortho position, were converted into substituted phenanthrene derivatives in the presence of various jc-electrophihc transition metal catalysts such as platinum, palladium, gold, gaUium, indium, iron, and so on (Scheme 21.48) [54]. 

Bis(l,5-cyclooctadiene)nickel(0) [Ni(COD)2] reacts with a variety of aryl halides in dirnethylformamide to produce biaryls in good yield. An arylnickel species has been suggested as an intermediate (Semmelhack et al., 1971). By this method 1, -bis(iodoaryl)alkanes are readily converted into the corresponding biphenyl derivatives. The total synthesis of alnusone dimethyl ether (CXLI) shows the usefulness of this procedure (Semmelhack and Ryono, 1975). Tris(triphenylphosphine)nickel is a superior coupling reagent in some instances (Kende et al., 1975). 

An elegant reaction to underline this conceptual approach is the synthesis of carb-azole from 2-amino biphenyl derivatives. For example, during the screening of metal catalyses for this transformation, Chang observed that the transformation from 1 to 2 proceeded readily in the presence of hypervalent iodine reagent itself (Scheme 1) [5]. 

Guo, M., Jian, F., and He, R. (2006). Efficient synthesis of fluorinated biphenyl derivatives via Pd-catalyzed Suzuki coupling reactions in aqueous solvents at room temperature. 7. Fluorine Chem., 127, 177 181. 

The first report of the synthesis and activity of these compounds as PPAR agonists concerned the biphenyl derivative 6 (Fig. 3.6) and its congeners [9, 10]. The crystal structure and activity of the two enantiomeric forms of 6, complexed with the ligandbinding domain (LED) of PPARy, provided a molecular explanation for their different potency and efficacy. Docking of the S-6 enantiomer in the PPARy-LBD was... 

The cobalt-catalyzed Diels-Alder reaction of alkynylboron units could also be applied to the synthesis of boron-functionalized biphenyl derivatives such as 46. In... 

Syntheses via Biphenyl Derivatives. The main content of this group of syntheses is Johnson s so-called second synthesis of estrone (Scheme 46) and the production of intermediates for it (Schemes 47). 

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