Suzuki Miyaura biaryls

Other phenyl-pyrrole and phenyl-pyridine analogues of rhazinilam, having seven to nine-membered B-rings, have been synthesized using a Suzuki-Miyaura biaryl coupling to install the biaryl bond, Fig. (37). 

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

The transition metal catalyzed cross coupling of an organohalide with a boronic acid derivative, the Suzuki-Miyaura coupling, has become one of the most popular ways of preparing biaryls.3 The reaction is very robust and can easily be scaled to provide multigrams of material.4... 

The aforementioned PEPPSI-IPr pre-catalyst 16 has also been used in the Suzuki-Miyaura reaction. This pre-catalyst allowed the easy preparation of hindered biaryls and drug-like heteroaromatic compounds in good to excellent yields (Scheme 6.27). 

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... 

Chamoin S, Houldsworth S, Kruse CG, Bakker WI, Snieckus V. The Suzuki-Miyaura cross coupling reactions on solid support. Link to solution phase directed ortho metalation. The Leznoff acetal linker approach to biaryl and heterobiaryl aldehydes. Tetrahedron Lett 1998 39 4179-4182. 

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... 

Chamoin, S. Houldsworth, S. Kruse, C. G. Bakker, W. I. Snieckus, V. The Suzuki-Miyaura Cross Coupling Reactions on Solid Support. Link to Solution Phase Directed ortho Metalation. The Leznoff Acetal Linker Approach to Biaryl and Heterobiaryl Aldehydes, Tetrahedron Lett. 1998, 39, 4179-4182. 

An alternative to solid-supported catalysts are catalysts that are insoluble themselves [136]. A pyridine-aldoxime ligand was presented and evaluated in the Suzuki-Miyaura reaction using water as a solvent. Using an Irori kan to contain the polymeric catalyst, the reaction could be repeated 14 times without any noticeable reduction in efficiency. The optimized reaction conditions were then used to create a small library of approximately 30 biaryl compounds using aryl iodides, bromides, triflates as well as an activated chloride (Scheme 56) [136]. 

Directed remote metalation (DreM) of biaryl amides and O-carbamates, conceptually based on the complex-induced proximity effect (CIPE) [15] provides, especially in view of their link to transition metal-catalyzed cross coupling regimens [16], general and versatile routes to fluorenones (16 —> 15, Scheme 4) [5,17] and biaryl amides (16 —> 17) [18] whose features are overriding Friedel-Crafts reactivity and yield enhancement in comparison to Suzuki-Miyaura coupling routes for highly hindered biaryls, respectively. Additional features of the O-carbamate DreM result is potential further DoM of 17 with appropriate phenol protection and cyclization to dibenzopyranones [18]. 

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]. 

Scheme 39. Biaryl O-carbamate anionic remote Fries rearrangement. Conquering steric encumbrance in direct Suzuki-Miyaura crosscoupling.

When IBioxl2 HOTf was employed as the ligand precursor for the Suzuki-Miyaura coupling of sterically hindered aryl chlorides and aryl boronic acids, excellent to good yields were obtained in refluxing toluene for a variety of starting materials (Table 6). Notably, this work represents the first report of tetra-orf/zo-substitulcd biaryl compounds achieved from aryl chlorides [143]. 

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

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... 

The formation of unsymmetric biaryls via catalytic cross-coupling of aryl halides and organometallic compounds has been shown to proceed in ionic liquids with enhanced activity. The Suzuki-Miyaura cross coupling (cf. Section 2.11)... 

In this case, the approach involved the construction of two bibenzyl and one biaryl units using Homer-Wadsworth-Emmons and an intramolecular Suzuki-Miyaura reaction. The overall yield for the 11 steps was 10.6%. 

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