Coupling reactions Butyllithium

Diphenylbutadiene has been obtained from phenylacetic acid and cinnamaldehyde with lead oxide, by the dehydrogenation of l,4-diphenyl-2-butene with butyllithium, and by the coupling reaction of benzenediazonium chloride and cinnamyl-ideneacetic acid." The present method gives better yields than those previously reported, is adaptable to the preparation of a variety of substituted bistyryls, and is relatively easy to carry out. 

Various intermolecular coupling reactions involving acetylene hydrocarbons have been reported to lead to vinylallenes. For example, 1-phenylpropyne (93), after activation with Hg(II) chloride, is first metalated by butyllithium treatment, then trans-metalated with zinc bromide and finally coupled with 1-iodo-l-phenylethene (94) in the presence of tetrakis(triphenylphosphine)palladium to provide the diphenylvinyl-allene 95 in moderate yield (Scheme 5.12) [31]. 

A complementary approach for cross-couplings with allenes was applied by using metallated allene species instead of allenyl halides, which have already been discussed in Sect. 14.2.1. Since allenyllithium compounds are readily available by deprotonation of allenes with n-butyllithium, successful cross-coupling reactions between lithiated allenes such as 54 or 57 and aryl or vinylic halides allowed convenient routes to aryl- and vinyl-substituted allenes, e.g. 55, 58 and 60 (Scheme 14.15) [30],... 

Coupling reactions (Continued) Cross-coupling of two alkyl groups Butyllithium, 56... 

Iron-catalyzed Suzuki-Miyaura coupling reactions were also reported by Nakamura and colleagues (entry 27) [67]. Alkyl halides 1 and mixed pinacol aryl(butyl)borates, generated in situ from arylboronates and butyllithium, were used as the reagents and 10 mol% of the iron complexes 16a or 16b as the catalysts. The addition of 20 mol% of MgBr2 was essential for the success of the reaction. Products 3 were isolated in 65-99% yield. The methodology tolerates ester and nitrile functions. The reaction starts probably by initial boron-iron transmetalation to generate a diaryliron(II) complex. 

For example, ( )-l-octenylzinc chloride (5.50), generated in situ from ( )-l-octenyliodide, terf-butyllithium and dry ZnCb, on cross-coupling reaction with ( )-l-hexenyliodide (5.51) in the presence of Pd catalyst Pd(PPh3)4 gave (5 ,7 )-5,7-tetradecadiene 5.52 in 95% yield (Scheme 5.23). 

The compound prepared in this way is the symmetric isomer obtainable also by the active metal coupling reaction or by the reaction of butyllithium with the product obtained from treatment of B2[N(CH3)2]2(C4H,)2 with HCl (79). Formation of a compound formulated as 9,10-dibora-9,10-bis(dimethylamino)phenanthrene has been reported from the reaction of l,2-bis(dimethylamino)-l,2-dichlorodiborane(4) with magnesium and 2,2 -dibromobiphenyl (5J). 

Fused pyrazole compounds have been prepared from A -alkyl-substituted pyrazoles. For example, a palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp C-H functionalization as the key step has been described, in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one pot. A variety of highly substituted six-membered annulated pyrazoles 433 were synthesized in a one-step process in moderate yields from iV-bromoalkyl pyrazoles 431 and aryl iodides 432 (Equation 87) <20060L2043>. An intramolecular cyclization version has also been reported. Exposure of 2equiv of -butyllithium to l//-pyrazole-l-alkanoic acids 434 afforded the cyclic ketones 435 via a Parham-type cyclization process (Equation 88) <1997SL1013>. 

Sestelo and Sarandeses generated tris(indol-2-yl)indium 49 for use in palladium-catalyzed cross-coupling reactions (Scheme 9) [227]. Lithiation of 4 with n-butyllithium followed by treatment with indium trichloride gave 49 which was used directly in palladium-catalyzed cross-coupling reactions leading to 2-arylin-doles 50. These same authors exploited this chemistry to prepare indole-substituted maleimides [228]. 

The coupling reaction of 1,1-dihaloalkenes at the trans position is much faster than that at the cis position because of steric reasons, and therefore, the cis trisubstituted alkenes can be obtained in good yields. In contrast, when a good leaving group is placed at the cis position, the corresponding trisubstimted alkenes having trans stereochemistry can be produced. One typical example is use of (Z)-l-chloro-l-iodoalkenes, which are synthesized by treattnent of ( )-l-chloroalkenes with butyllithium at-100 °C followed... 

In 1993, Corriu et al. studied the synthesis of nitrogen-containing heterocycles from (Z)-3-(tribulylstannyl)allylamine, which was prepared by the reaction of Af-(trimethylsilyl)allylamine with 2 mol of ra-butyllithium followed by treatment with chlorotributyltin and subsequent hydrolysis. The unprotected (Z)-3-(tributylstannyl)allylamine underwent a palladium-catalyzed cross-coupling reaction with aromatic bromides affording a stereospecific preparation of substituted allylic amines with Z configuration of the carbon-carbon double bond. The reactions of o/t/zo-functionalized aryl bromides offer a one-step preparation of 7-membered nitrogen heterocycles in high yields (Scheme 4.18). 

The nonsteroidal anti-inflammatory flurbiprofen 100 has been prepared via deprotonation of 3-fluorotoluene 98 with Schlosser-Lochmann superbase (Scheme 26.29) [182]. The selectivity improves significantly when a combination of ieri-butyllithium and potassium ferf-butoxide is used as the mixed-metal reagent. The deprotonation occurs at the least-hindered position adjacent to fluorine. Trapping of the organometallic intermediate with fluorodimethoxyborane-diethyletherate and hydrolysis affords the boronic acid, which is then employed in a Suzuki-Miyaura coupling reaction. Another superbase metalation of 99, now with a combination of LDA and potassium tert-butoxide, allows the deprotonation of the benzylic position, followed by carboxylation and a second metalation, and trapping with Mel to afford flurbiprofen 100. 

A series of tri- and tetrasubstituted alkenyldimethylsilanols were prepared to study the substituent effects on the stereochemical outcome of a subsequent cross-coupling reaction. The products were obtained in high geometrical purity by the combination of D3 and the geometrically defined alkenyllithium reagents generated by bromine-lithium exchange with f-butyllithium (Scheme 3). 

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