Suzuki-Miyaura coupling boronate species

An interesting polymer-assisted variant of the Suzuki-reaction was recently disclosed by Vaultier and coworkers (Scheme 17) [43]. Aryl boronic acids can be immobilized on an ion exchange resin. Under Suzuki-Miyaura coupling conditions bisaryl species are released into solution and isolated with minimum purification. The authors also demonstrated that this strategy can be employed for the synthesis of macroheterocycles. 

Anticipating a B-alkyl Suzuki-Miyaura cross-coupling reaction between the Cl-Cl 4 and C15-C24 subunits, alcohol 57 was smoothly converted to vinyl iodide 60 in seven steps, including a Pt02 reduction of the crowded triple bond of intermediate 59, without overreduction. The coupling of the vinyl iodide 60 and C15-C24 subunit was performed by using trialkyl boronate species 61, prepared from alkyl iodide 46, under [Pd(dppf)Cl2] and AsPhs conditions to afford the DDM backbone 62 in 60% yield (Scheme 14). Finally, after carbamate formation and total deprotection, DDM 1 was obtained in 70% yield. The spectroscopic and analytical data of the synthetic samples of as well as their in vitro cytotoxicity levels were in full accord with those of the natural product reported in the literature. 

Boronic acids and boronate esters serve a myriad of purposes, and the discovery of the Suzuki-Miyaura reaction facilitated the widespread interest and application of organoboron compounds. This palladium-catalyzed C-C bond forming reaction initiated renewed interest in the preparation of diversely functionalized boronic acids that would lead to valuable products. From this synthetic standpoint, Suzuki coupling reactions have been employed in the production of natural products and the preparation of materials of interest. " The search for interesting starting materials for the Suzuki reaction produced a series of methods to prepare boronic acids so these species could be exploited in further applications. These compounds... 

The key challenge for computational chemistry with respect to the transmeta-lation step of the Suzuki-Miyaura cross-coupling was to understand the role of the external base. It is certainly well known from experiment that the presence of a base in solution is required for the reaction to take place. Several proposals have been put forward for the role of this base from experimental studies. Most of this information was summarized by Miyaura in a very clarilying paper [43], Two main pathways are proposed (Fig. 11.5) either the base binds the boronic acid to from the organoboronate species (path A), or the base substitutes the halide ligand in the coordination sphere of the catalyst (path B). These two proposed pathways were theoretically evaluated by us on a model system, using trans-PdBr(CH2 = CH)(PH3)2, CH2 = CH-B(OH)2 and OH species as reactants [44]. 

Alkynyl boronic acid derivatives were not used earlier in Suzuki couplings. An effective Suzuki-Miyaura reaction between alkynyl ate complexes (alkynyltrialk-oxy borate complexes) has been reported by Colobert [112] Oh [113]. 1-Alkynyl(trii-sopropoxy) borates (137) were prepared by borylation of the corresponding alkynyl lithium species. These stable borate complexes were subsequently used in Suzuki coupling leading to products of type 138 (Scheme 3.74). 

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