By Suzuki-Miyaura biaryl

Fig. (37). Rhazinilam analogues obtained by Suzuki-Miyaura biaryl coupling [164-166]...

This anionic remote Fries rearrangement provides a general route to highly substituted biaryls 146 which, due to steric effects, may be difficult to prepare directly by Suzuki-Miyaura cross-coupling, as evidenced in the comparison with the synthesis of dibenzopyr-anones 147 (Scheme 39) [66]. The efficient acid-catalyzed cyclization to dibenzopyranones shows broad scope both for unusually substituted (148-150, Scheme 40) and various heterocyclic analogues (151-153, Scheme 40) [65, 67]. 

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

The Stille reaction has developed as a popular protocol for the formation of C-C bonds due to the air- and moisture-stability as well as functional group compatibility of organotin compounds. Together with the Suzuki-Miyaura coupling it is one of the most powerful methods for the synthesis of molecules containing unsymmetrical biaryl moieties. However, despite its efficiency, this versatile reaction has slowly been displaced by other procedures that avoid the use of highly toxic organostannanes. 

The Leznoff acetal linker 69 was used to anchor an aldehyde to the solid support and following a series of reactions, the aldehyde was released by acidic cleavage [78]. An application of this resin was demonstrated for a biaryl aldehyde library synthesis which incorporated a Suzuki-Miyaura reaction (Scheme 37) [79]. Cleavage was effected by a solution of 3 M HC1... 

If the stannane bears substituents at the position geminal to tin, the reaction requires activation by Cu1 (Section 9.6.3.2.1). The cross-coupling of aryl (or heteroaryl) stannanes with aryl (or heteroaryl) halides or triflates is a general route to various biaryls and their analogues, particularly useful in those cases when the Suzuki-Miyaura reaction is less effective for... 

A rapid and efficient Suzuki-Miyaura coupling protocol utilising fibrous PS-based palladium catalysts (FibreCaF ) and microwave irradiation has been reported by Wang and Sauer (Scheme 8). The biaryl motif 26, formed in this reaction, is an important pharmacophore in many biologically active compounds. Each reaction... 

In most cases microwave reactions have been conducted in a batch system, but very recently the use of a microflow system for microwave reactions has been reported. For example, Suzuki-Miyaura coupling of aryl halides with phenylboronic acid to form biaryls is promoted by microwave irradiation of the supported Pd catalyst (Table 5.1). A thin, gold film patch located on the outside surface of the base of a glass microreactor is quite effective for absorbing microwaves. 

Unprotected 4-heteroaryl phenylalanines have been prepared by microwave-assisted Suzuki-Miyaura reactions. Amino adds containing the biaryl motif have several interesting applications in medicinal chemistry and this method enabled their synthesis without protection of the amino acid. Optically pure boronic acids could be used without racemization (Scheme 15.16) [49]. 

Suzuki-Miyaura coupling, involving the reaction of aryl boronic derivatives with aryl halides in the presence of a palladium catalyst, is a very powerful method for the preparation of biaryls. Solutions of aryl bromides or iodides supported on onium salts via an ester link in an RTIL lead to BTSILs that can be engaged in the Suzuki-Miyaura coupling reaction with aryl boronic derivatives. like the Heck reaction, this coupling is also sensitive to the variations in different parameters. The possibility to synthesize libraries of biarylic derivatives by parallel synthesis is illustrated by (Scheme 5.5-39) [51]. 

During the course of an investigation into the Suzuki-Miyaura cross-coupling of l-bromo-2,4,6-tri-tert-butylbenzene with phenylboronic acid, a, a -dimethyl-)8-phenyl dihydrostyrene by-product was isolated in excellent yield, while the desired biaryl product was not observed. This unexpected transformation likely proceeded via a pathway involving a tandem C-H activation/ Suzuki-Miyaura cross-coupling sequence (eq 40). ... 

Although the SM reactions of haloferrocenes proceed rather slow, they are clean and chemoselective, providing the production of arylferrocenes which would be hardly accessible by other strategies. Several papers regarding improved and alternative technics for performing the Suzuki-Miyaura reactions have been published. A useful procedure involves transmetallation of (half amount) simple aryl halides with only 0.5 eq. of -BuLi, followed by quenching the resulted aryllithium reagent with trimethyl borate [88], Thus obtained arylboronic ester is coupled under the standard SM conditions method A) with an excess of parent aryl halide to furnish the symmetrical biaryl in fair yields. For example, 2-bromoanisole (218) was coupled by this way to afford 2,2 -dimethoxybiphenyl (92) in 56% yield [88], Scheme 36. 

Enantioselective synthesis of axially chiral biaryls include all approaches where the starting material is achiral and the chirality is induced by an influence of chiral catalyst or reagent. Among enantioselective reactions that have been successfully used in the synthesis of axially chiral biaryls are the Kharasch reaction [34-36], Suzuki-Miyaura reaction [37,38], oxidative phenolic coupling mediated by copper complexes... 

The enantioselective Suzuki-Miyaura reaction (SM) can be accomplished by using the chiral ligands 213 [37] or 631 [38], whose palladium complexes catalysed the crosscoupling reaction of sterically hindered iodides and bromides with also quite encumbered arylboronic acids furnishing the axially chiral, sterically demanded biaryls in moderate to good yields with low to moderate enantioselectivity. 

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