Suzuki-Miyaura coupling reaction conditions

Suzuki-Miyaura Coupling. The Suzuki-Miyaura coupling reaction is very useful for construction of carbon-carbon bonds under mild conditions. Because it is tolerant of many functional groups, it has been employed widely in the synthesis of many natural products and related compounds. The stereochemistry of such coupling reactions proceeds with retention of configuration at both the C-X and C-(9-BBN) centers, confirmed recently hy independent studies from the groups of Woerpel and Soderquist. ... 

To finalize this section, we mention a report by Christakakou etal. [162] in 2013 on the application of a simple Suzuki-Miyaura coupling reaction under continuous flow conditions with PdfPPhj) as the catalyst. Note the reactor was of a simple, homemade construction, and the designs are given in the supporting information section of their paper. 

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. 

Transition metal mediated cross couplings of epoxides have remained relatively unexplored, with only a few examples of this potentially useful reaction reported in the literature. A recent report details the Suzuki-Miyaura cross-coupling of epoxides <07JOC3253>. The reaction of aryl epoxides with arylboronic acids under Suzuki-Miyaura coupling conditions provides the coupled product in good yields. Careful monitoring of the reaction is essential to avoid Pd-catalyzed rearrangement of the epoxides. 

Our group recently reported the development of a coumarin library with diversity at the 6-position via Suzuki-Miyaura coupling.21 The reaction conditions were optimized for the reaction of the 6-bromocoumarin scaffold 9 with the unsubstituted phenyl boronic acid pinacol ester 10a (Figs. 18.6 and 18.7). 

Our plan was to connect the two 7-methyljuglone units D and I by Suzuki-Miyaura coupling. Diospyrin (58) is reported to be optically inactive, and there is no restricted rotation around the connecting bond between C-2 and C-6. It therefore seemed possible to connect D and I at the positions C-2 and C-6 under conventional conditions. Diels-Alder reactions were employed to prepare D and I. Accordingly, Diels-Alder cycloaddition between A and B gave C, which was methylated to furnish D. Similarly, the adduct G was prepared from E and F. The naphthoquinone G was converted to boronic acid I via bromonaphthalene H. 

Under the reaction conditions, phenylacetylene was found to be a much more reactive coupling partner than arylboronic acids in the analogous Suzuki-Miyaura coupling, as in addition to the desired product (38), alkynylation and further addition reactions occurred with a variety of transient palladium(II) species (Scheme 27). Despite these undesired side reactions, Catellani was able to fine-tune the reaction conditions to form predominantly product 38 or 39. The formation of the desired product 38 (and suppression of product 39) is promoted by acceleration of norbomene carbopalladation by KOAc [47] and by using an excess of alkyl halide affording several structurally similar unsymmetrical alkyne products in good yields (Scheme 28). 

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