Kumada-coupling

Ketones, coupling reactions of aryl halides with, 487-489 k-factor, 244 Kinetic studies, 73 Kumada coupling, 467, 489, 491... 

A more general procedure for high-speed microwave-assisted Negishi and Kumada couplings of unactivated aryl chlorides has recently been reported by Walla and Kappe (Scheme 6.40) [82]. This procedure uses 0.015-2.5 mol% oftris(dibenzyl-... 

Coupling reactions with organometallic reagents 3.3.1 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-... 

Kondo employed the Kumada coupling using the Grignard reagents derived from 2- and 3-iodo-l-(phenylsulfonyl)indole to prepare the corresponding phenyl derivatives in 50% yield [92], Widdowson expanded the scope of the Kumada coupling and provided some insight into the mechanism [93],... 

Organomagnesium reagents, which can serve as the nucleophiles in the Kumada coupling, are easy to make and many of them are commercially available. Even though some Kumada reactions can be run at room or lower temperature, many functional groups are not tolerant of Grignard reagents. Nonetheless, in the synthesis of thienylbenzoic acid 24, the carboxylic acid moiety did survive the reaction conditions [25],... 

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl halides with ethynylmetals, formation of diarylethynes is one of the potential side reactions. Indeed, the Kumada coupling of 2-iodo-5-methylthiophene (29) with ethynylmagnesium chloride gave the desired 2-ethynyl-5-methylthiophene (30) in only 35% yield, along with 24% of bis(5-methyl-2-thienyl)ethyne (31) [29], The high propensity for H-Mg exchange reaction to occur was blamed for the diarylethyne formation. 

Advantage has been taken of the aforementioned observations in the synthesis of a terthiophene natural product, arctic acid (147) [123]. Pd-catalyzed carbonylation of bromobisthiophene 25, obtained from the Kumada coupling of 2-thienylmagnesium bromide and 2,5-dibromothiophene, gave bithiophene ester 144, which was converted to iodide 145 by reaction with iodine and yellow mercuric oxide. Subsequent propynylation of 145 was then realized using the Sonogashira reaction with prop-l-yne to give bisthienyl alkyne 146, which was subsequently hydrolyzed to 5 -(l-propynyl)-2,2 -bithienyl-5-carboxylic acid (147), a natural product isolated from the root of Arctium lappa. 

Rossi and associates described a Kumada coupling of 2-bromofuran with 2-thienylmagnesium bromide to assemble thienylfuran 11 [19], The reaction proceeded readily at room temperature. 

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

An alternative Stille approach was not considered due to concerns about the toxicity of tin, and an attempted Kumada coupling between 2-pyridylmagnesium bromide and 5-iodo-2-chloropyrimidine 991 in the presence of Ni(Cl2)DPPF failed to give the desired product. An attempted Suzuki coupling with 2-bromopyridine 992 also failed, due to the deboronation of 2-chlotopyrimidine-5-boronic acid 993, which gave 2-chloropyrimidine 994 as the... 

Low reactive aryl chlorides are converted to the respective organomagnesium species in excellent yields through transition metal catalysis using 2 mol% FeCU (4-6, equation 3). Alternatively, a safe and reproducible method for activation of aryl chlorides or bromides 7 uses microwave irradiation (equation 4). In a synthesis of a novel HIV-1 protease inhibitor, microwave irradiation was essential to generate the starting arylmagnesium halide as well as to promote the subsequent Kumada coupling reaction. ... 

Interestingly, the analogous double Kumada coupling of 2,3-dibromothiophene and 2 equivalents of a thienylmagnesium bromide... 

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