Reactive halide coupling

A variety of organometallic compoundshave been used to couple with alkyl halides. " Organosodium and organopotassium compounds are more reactive than Grignard reagents and couple even with less reactive halides. Organolithium... 

In the more prolific aspect of the Stille couplings involving a pyrimidine fragment, pyrimidinyl halides or triflates have been coupled with a variety of stannanes. When there is only one reactive halide on the pyrimidine ring, the reaction outcome is straightforward with no regiochemical concern. The simpler stannanes are vinyl stannanes [35-37]. More complicated variants include stannylquinones [38] and l-(trialkylsilyloxy)vinyltin [39] as illustrated by the synthesis of 66. 

Aryl iodides and bromides are more reactive than the corresponding chlorides but the latter may be used when activating substituents (e.g. the nitro group) are present, as for example in the synthesis of 2,2 -dinitrobiphenyl (Expt 6.8). The coupling reaction can be effectively carried out in the absence of a solvent, but the use of dimethylformamide as a solvent and diluent often results in an increase of yield, particularly in the case of reactive halides, when the vigour of the exothermic reaction is moderated. 

Electrochemical activation of zinc use for the formation of zinc reagents and for coupling reactions involving reactive halides... 

Reactive halide (5) bearing electron-withdrawing groups, such as ester, cyano, or sulfonyl groups, at the a-position react with Fe/CuBr to form a, 3-diester (6) in good yield, through the coupling of the a-ester radical formed via SET as shown in eq. 2.3 [7]. 

Baizer and Chruma reported electrolytic reductive coupling, in a broad study in which reduction of organic halides was conducted in the presence of electrophiles as seen in equation 1034. Controlled potential electroreduction of reactive halides at a mercury cathode in the presence of olefinic substrates with electron-withdrawing groups (Michael receptors) gave moderate yields (50-75% in many cases) of carbanion addition products35. Current yields in excess of 100% in the case where chloroform was used as a cosolvent with carbon tetrachloride indicated the intervention of electrocatalytic reactions (equations 10 and 11). 

Allylic zinc reagents undergo cross-coupling reactions with reactive halides leading to 1,5-dienes. Usually the new carbon-carbon bond is formed from the more-substituted end of the allylic system (Scheme 9-11) [30]. 

Cross-coupling Reactions with Allylic Halides and Related Reactive Halides... 

Denmark et al. have found that in the presence of excess TBAF the Pd-catalyzed coupling of vinylsilacyclobutanes with aryl iodides and vinyl halides proceeds efficiently and highly stereospecifically at room temperature (Scheme 10.209) [543]. Although aryl(methyl)silacyclobutanes are insensitive to aryl and vinyl hahdes under a variety of conditions, aryl(chloro)silacyclobutanes have enough reactivity for coupling with aryl iodides [544]. In this biaryl couphng the use of t-BusP serves to suppress the formation of homo-couphng products. 

For Suzuki reactions using haloboronic acids and another halide, the obviously best course is to have a more reactive halide in the substrate than in the boronate, so there are quite a few examples of chloro-heteroaryl-boronic acids coupling efficiently with aryl bromides. This difference is clearly shown by the coupling reactions of 2-chloro- and 2-bromopyridine-5-boronic acids with bromo-heterocycles. ... 

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