Palladium Kumada coupling

Of all the palladium-catalyzed coupling reactions, the Kumada coupling has been applied least often in indole chemistry. However, this Grignard-Pd cross-coupling methodology has been used to couple l-methyl-2-indolylmagnesium bromide with iodobenzene and a-bromovinyltrimethylsilane to form l-methyl-2-phenylindole and l-methyl-2-(l-trimethyl-... 

Palladium-catalyzed cross-coupling reaction of organostannanes with organic halides, triflates, etc. For the catalytic cycle, see Kumada coupling on page 345. 

One of the first indications that higher valent silanes could be useful donors in palladium-catalyzed cross-coupling reactions was reported by Kumada and Tamao, when they observed that the dipotassium salt of pentafluorosilicate 70 could transfer its vinylphenyl group for the palladium-catalyzed coupling with iodobenzene at high temperature (Scheme 6). ... 

Advantage has been taken of the aforementioned observations in the synthesis of a terthiophene natural product, arctic acid (250) [168]. Palladium-catalyzed carbonylation of bromobisthiophene 37, obtained from the Kumada coupling of 2-thienylmagnesium bromide and 2,5-dibromothiophene, gave bithiophene ester 247, which was converted to iodide 248 by reaction with iodine and yellow mercuric oxide. Subsequent propynylation of 248 was then realized using the Sonogashira reaction with prop-l-yne to give bisthienyl alkyne 249, which was subsequently hydrolyzed to 250, a natural product isolated from the root of Arctium lappa. 

The Kumada coupling of aryl halides with phenylmagnesium bromide, in the presence of palladium or nickel, showed high catalyst activity. TON up to 800 was observed for the conversion of chlorobenzene into biphenyl (Table 14.5) [182]. 

Kumada coupling. A report of biaryl synthesis from ArMgBr and Ar Cl highlights the use of a Ni carbenoid (1). Both bis(Ti -allyl)nickel and palladium complexes are also useful catalysts for the cross-coupling." ... 

Palladium-catalysed reactions involving organometallic partners based on B, Mg, Sn, and Zn are particularly important and are often referred to by the names of their discoverers Suzuki coupling for B, Kumada coupling for Mg, Stille coupling for Sn, and Negishi coupling for Zn. 

Zambon uses the palladium-catalysed Kumada coupling for the production of Difitmisal (135), a non-steroidal anti-inflammatory drug (Scheme 30) [86, 87]. 

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