Suzuki-type coupling

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

Nickel can also be used in place of Pd in Suzuki-type couplings of boronic acids. The main advantage of nickel in this application is that it reacts more readily with aryl chlorides275 and methanesulfonates276 than do the Pd systems. These reactants may be more economical than iodides or triflates in large-scale syntheses. 

A potentially interesting development is the microwave-assisted transition-metal-free Sonogashira-type coupling reaction (Eq. 4.10). The reactions were performed in water without the use of copper(I) or a transition metal-phosphine complex. A variety of different aryl and hetero-aryl halides were reactive in water.25a The amount of palladium or copper present in the reaction system was determined to be less than 1 ppm by AAS-MS technique. However, in view of the recent reassessment of a similarly claimed transition-metal-free Suzuki-type coupling reaction, the possibility of a sub-ppm level of palladium contaminants found in commercially available sodium carbonate needs to be ruled out by a more sensitive analytical method.25 ... 

Scheme 6.25 Suzuki-type couplings involving boroxarophenanthrenes.

Scheme 6.26 Suzuki-type couplings for the preparation of fluorescent dyes.

Scheme 6.27 Semiconducting polymers via Suzuki-type couplings.

Scheme 7.80 Fluorous phase Suzuki-type couplings.

Suzuki type coupling reactions (Figure 34) were performed by He et al. [62,63] in three different reactor types (Figure 32,33). Two consisted of plates and the third one was a U-type reactor prepacked with catalyst. 

Leadbeater, N.E. and Marco, M., Transition-metal-free Suzuki-type coupling reactions, Angew. Chem., Int. Ed. Engl, 2003,115, 1445-1447. 

Heck and Suzuki type couplings have been described by Fu [2] et al. The reaction of chlorobenzene and styrene in refluxing dioxane in the presence of [Pd2(dba)3 ] and the electron rich tri-tert.-butyl-phosphane [eq. (a)] gives rise to trans-stilbene in 83% yield. Besides the choice of the ligand - aryl phosphanes, tri-n-butyl-phosphane or tri-cyclo-hexyl-phosphane show no conversion - the base is also crucial for success. Cesium carbonate gives the best results, although the cheaper potassium phosphate gives comparable yields. 

Suzuki-type coupling protocols were also evaluated as a method to prepare some related tetrahedral stilbenoid molecules and the optimal yields were achieved when using Pd(dppf)Cl2 as the catalyst. The cruciform materials prepared using this strategy are shown in Scheme 3.3. Compounds 5a and b were obtained as a mixture of cis and trans isomers as identified by high-performance liquid chromatographic (HPLC) analysis. Nevertheless, the mixtures were readily converted into the all-trans isomers by irradiating the dissolved samples with a mercury lamp. 

Arylmethyl(homobenzyl)ethylsulfonium salts are appropriate substrates for Suzuki-type coupling reactions. In this reaction, performed on a polymer-bound sulfonium tetrafluoroborate, the benzyl fragment on the sulfur atom was transferred to the boronic acid residue. The sulfonium salt was prepared from an al-kylthiol resin by alkylation with a substituted benzyl halide to give thioether 98 and subsequent alkylation with triethyloxonium tetrafluoroborate. Reaction with a boronic acid derivative yielded diaryl methanes 99 [94] (Scheme 6.1.22). 

In a related reaction, Caddick et al. expanded this Suzuki-type coupling to other alkyl-alkyl couplings.21 Although the yields were still modest, the reaction seemed compatible with various functional groups and required only mild conditions (Table 10.1). 

Aryl diazonium salts can be used coupled with alkenes in a Heck-Uke reaction (12-15)7 Other reactive aryl species also couple with aryldiazonium salts in the presence of a palladium catalyst7 A Suzuki type coupling (13-9) has also been reported using arylboronic acids, aryldiazonium salts and a palladium catalyst/ ... 

Arvela RK, Leadbeater NE, Sangi MS, Williams VA, Granados P, Singer RD (2005) A reassessment of the transition-metal free Suzuki-type coupling methodology. J Org Chem 70 161... 

With the nickel catalysts the Suzuki-type couplings " are more convenient. 

Another germanium-based hnker has been developed for solid-phase synthesis of a pyrazole hbrary [79]. A new iterative synthesis of regioregular oligothiophenes has been developed in which double-couphng after each iteration minimizes deletion sequences. The method exploits the susceptibility of a-silyl- but not a-ger-myl-substituted thiophene derivatives towards nucleophilic ipso protodemetalation and features an unusual base-free Suzuki-type coupling product. The strategy... 

This methodology was extended very recently to the ligandless Suzuki type coupling of aryl bromide and substituted arylboronic acid in water [86]. 

A variation of the Suzuki-type coupling reaction provides another means for placing a functionalized carbon atom on to position 17. The sequence starts with conversion of estrone methyl ether to its hydrazide by reaction with hydrazine. Treatment of this intermediate with 1,1,3,3 tetramethylguanidine (TMG) and iodine leads to the 17-enol... 

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