Biaryl haloarene

The protocol offers a direct and efficient method for the synthesis of the boronic ester in the solid phase, which hitherto met with little success using classical methodology (Scheme 1-42). A solid-phase boronate (113 [155], 114 [156]) is quantitatively obtained by treating a polymer-bound iodoarene with the diboron (82). The subsequent coupling with haloarenes furnishes various biaryls. The robot synthesis or the parallel synthesis on the surface of resin is the topic of further accounts of the research. 

As an alternative to the Ullmann reaction, haloarenes are coupled to form the biaryls using palladium acetate in the presence of abase and tetra-n-butylammonium bromide [24], Yields are generally high (>70%) but dehalogenation of the haloarene may also occur as a side reaction. 

The arylborane, or heteroarylborane (8 mmol), TBA-Br (1.28 g, 4 mmol), powdered KOH (11.8 g), the haloarene (12 mmol) and Pd(Ph3P)4 (0.46 g, 0.4 mmol) are refluxed in THF under N2 for 8 h. EtOAc (100 ml) is added to the cooled mixture and the organic mixture is washed with brine (40 ml) and dried (MgS04). Evaporation under reduced pressure and chromatography from silica gives the biaryl system [e.g. 3-(2-pyridyl)pyri-dine, 85% 3-(3-pyridyl)pyridine, 82% 3-(5-methoxycarbonyl-2-pyridyl)pyridine, 63% 3-(6-methoxy-2-pyridyl)pyridine, 77% 3-(2-thienyl)pyridine, 75%]. 

In 2005, the group of Alcaide has reported the regiocontrolled preparation of biaryl-2-azetidinones (I and II, Fig. 17), via aryl-aryl radical cyclization and/or rearrangement of (3-lactam-tethered haloarenes [286]. 

Watanabe, T. Miyaura, N. Suzuki, A. Synthesis of sterically hindered biaryls via the Pd-cat-alyzed cross-coupling reaction of arylboronic acids or their esters with haloarenes. Synlett 1992, 207-210. 

Fused tetracyclic biaryl-2-azetidinones have been prepared by the radical cyclization of aryl /3-lactam-tethered haloarenes. Azetidin-2-one 504, having an extra radical acceptor on C-3, underwent radical cyclization with tributyltin hydride to give the biaryl-2-azetidinone 505 in a low yield, with debrominated 3-phcnoxyA-phcnyl-l -(/ -methoxy-phenyl)-2-azetidinone as the main product (60% yield) (Equation 82). But when the azetidinones 506 (Rz = R6 = H) bearing an extra link (O) on the radical precursor at C-3 or N-l of the /3-lactam ring were treated with tributyltin hydride, the expected cyclization products 507 were obtained. If azetidinones 506 (Rz = OMe, or Me R6 = H, OMe, or Me) were treated in the same way then the tetracyclic azetidinones 508 were produced (Equation 83) <2005T7894>. 

A new synthetic approach to fluorescent 4-amino-4 -boryl biaryls by a boronate selective Suzuki-coupling of / -(dimesitylboryl)phenylboronates with haloarenes under the employed reaction conditions has been reported. The triarylboryl unity is not attacked whereas non-sterically hindered triarylboranes like tri-l-naphthylborane gave coupling products in good yields 207.120... 

The first observation concerning the preparation of biaryls was reported in 1981 [4]. Thus, the palladium-catalyzed cross-coupling reaction of phenylboronic acid with a number of haloarenes was found to proceed smoothly in the presence of base to selectively afford the corresponding biaryls in high yields (Eq. (1) and Table 1). 

The mixed Ullman reaction in which two haloarenes couple in the presence of copper powder is still commonplace in industrial process, but the catalyzed cross-coupling reactions appear to be more productive and provide reliable results in synthesis of unsymmetrical biaryls (Scheme 30). The isomeric michel-... 

Previously Davidson and Triggs have reported that arylboronic acids react with sodium palladate to give the dimeric biaryls. The synthetic utility of this dimerization reaction is, however, limited owing to stoichiometric requirement of the palladium compound. On the other hand, the palladium-catalyzed crosscoupling reaction between arylboronic acids and haloarenes in the presence of bases provides a clean synthesis of biaryls (Eq. 106) In this case, sodium carbonate has been proven to be most effective base. 

Reaction of Arylboronic Acids with Haloarenes Synthesis of Sterically Hindered Biaryls [110] (Scheme 2-66)... 

The nickel-catalyzed reductive homocoupling of haloarenes is an excellent method for the synthesis of symmetrical biaryls (Eq. 22). The remarkable ability of [Ni(cod)2] to promote the stoichiometric formation of biaryls from aryl iodides and bromides was originally reported by Semmelhack, Helquist, and Jones [25a]. Unlike the Ullmann reaction [3], the Ni-promoted homocoupling of... 

In 1901, Fritz Ulknann (Figure 1.6) showed that stoichiometric amounts of copper enabled the reductive coupling of haloarenes for the synthesis of symmetrically substituted biaryls (Scheme 1.3) [27]. 

The cross-coupling protocol provides a valuable method for homologation of arylboronic acids or direct borylation of haloarenes. The coupling takes place at the Sn-C bond in preference to the boronic ester because the B-C bond is inert to biaryl coupling in the absence of a base (Eq. 11). Bulky 1,3-diphenylpropandiol protects boronic acid during... 

Xriethylamine induces biaryl coupling at 100 °C in DMF or EtOH, though it is limitedly used for electron-deficient haloarenes having a withdrawing group (Eq. 39). ... 

Table 3. Effects of substituents on the Selectivity of Biaryl Coupling between p-Tolylboronic Acid [Ar BCOHlj] and Haloarenes (ArX) ...

Campi, E.M. Jackson, W.R. Marcuccio, S.M. Naeslund, C.G.M. (1994) High yields of unsymmetrical biaryls via cross-coupling of arylboronic acids with haloarenes using a modified Suzuki-Beletskaya procedure, Chem. Commun., 2395. 

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