Sterically hindered biaryls

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. 

Yin, J. Rainka, M. P. Zhang, X.-X. Buchwald, S. L. A highly active Suzuki catalyst for the synthesis of sterically hindered biaryls novel ligand coordination. J. Am. Chem. Soc. 2002, 124, 1162-1163. 

The sequence starts with the synthesis of the sterically hindered biaryl entity, formed by the Grignard reaction, followed by further conversions... 

Leadbeater and Griffiths developed palladium catalysts for the Suzuki cross-coupling of aryl halides bearing two ortho substituents with phenylboronic acid, and used them in the synthesis of sterically hindered biaryls [83]. 

A general method for biaryl coupling has been limitedly used for tri-ort o-substituted biaryls. A phenanthrene-based ligand exceptionally allowed the synthesis of sterically hindered biaryls where each reactant possesses two ortfo-substituents (Equation (205)).879... 

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

The first total synthesis of three naturally occurring cyclophane derivatives belonging to the turriane family of natural products was also described by A. Furstner et al These natural products have a sterically hindered biaryl moiety and saturated as well as unsaturated macrocyclic tethers. Stereoselective entry to this class of compounds is possible using RCAM followed by Lindlar reduction of the resulting cycloalkynes. 

Proazaphosphatrane bases were used for palladium catalysed Stille reactions of aryl chlorides. These bases efficiently catalyse the coupling of electronically diverse aryl chlorides with an array of organotin reagents. The catalyst system based on benzyl (Bn)-proazaphosphatrane is active for the synthesis of sterically hindered biaryls. The use of the proazaphosphatrane allows room temperature coupling of aryl bromides and it also permits aryl triflates and vinyl chlorides to participate in Stille coupling [69] (Scheme 5.47). 

Sulfur-containing palladacycle XVIII-13 is a precursor of an effective catalyst in the presence of Bu4NBr [36]. Palladacycle XVIII-1 is an efficient catalyst, and high TON (74 000) was obtained in the coupling of electron-deficient aryl bromide 27 [37]. Preparation of sterically hindered biaryl 28 was carried out with bulky phenanthrene-based phosphine V-5 [38]. 

The two-phase, e.g. toluene / water, protocol has been described (Table 1), while here a non-aqueous procedure is illustrated. Sterically hindered biaryl 261 was prepared in absence of water in 75% yield from sterically hindered boronic acid 262 and bromide 263, respectively [14], Scheme 12. 

The lactone concept also allowed easy access to monodentate phosphine ligands with sterically hindered biaryl axes, which catalysed the asymmetric hydrosilylation of styrenes in the presence of palladium (Scheme 5.49). ... 

Alternatively, biaryls (including sterically hindered biaryls) can be synthesized by the reaction of arene carboxylic acids with diaryhodonium salts by means of a PdCl /DEPhos catalytic system at 150°C in the presence of Ag COj [58]. 

Genet et al. have reported recently that Suzuki cross-coupling reactions between a range of aryl bromides and boronic acids using a water-soluble Pd/TPPTS (sodium triphenylphosphinometatrisulfonate) catalyst occur under mild conditions with high efficiency. The process tolerates both electron-rich and electron-poor substituents and provides an efficient access to sterically hindered biaryls. Good turnovers are observed and the catalyst can be recycled three times without loss of activity (Equation 48) [57]. 

Buchwald et al. have reported a number of bulky phosphine ligand PR 2R which give high activity in Suzuki— Miyaura catalysis for the synthesis of sterically hindered biaryls.The conditions used in the catalysis involved the in situ preparation of the Pd(0) catalyst from Pd2(dba)3 and the phosphine. Two ligands which proved superior to the others had in common the same polyaromatic R (R = Cy, Ph) as a difference from the rest. A Pd(0) complex could be prepared by mixing Pd2(dba)s and PR 2R in toluene, which has the X-ray structure 40 sketched in the upper reaction of Scheme 25. The key structural feature of the complex is the short distance of Pd to one double bond of the phenanthrene moiety (distances to the two carbons are 2.298 and 2.323 A) supporting an 77 -phenanthrene... 

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