Suzuki-Miyaura coupling partners

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). 

How might you use a Suzuki-Miyaura coupling to prepare the following biaryl compound Show the two potential reaction partners. 

Regioselectivity can usually be reliably obtained when two of the alkyne partners are tethered. A Cp RuCl(cod)-catalyzed intermolecular cyclotrimerization of three different monoalkynes could be performed by an in situ-tethering approach with the formation of a temporal C-B-O linkage from alkynylboronates and propargyl alcohols [13-15] [Eq. (9)]. The resultant arylboronates could not be isolated and were further converted to substituted biaryls via the Suzuki-Miyaura coupling or into a sequential one-pot process [14], or to phtalides via a palladium-catalyzed carbonylation [15]. 

Recently, Caddick and Cloke have developed an extension of this procedure that allows the use of alkyl bromides as coupling partners. The basic changes consist of a stoichiometric amount of the bulkier KO Bu instead of KOMe to activate the borane, and the addition of AgOTf to the reaction mixture [119]. These results, although poor in terms of yield, clearly confirm that sp -sp Suzuki-Miyaura cross-couplings are possible and should be further developed (Scheme 6.35). 

The palladium-catalyzed coupling of boronic acids (as well as other boron derivatives) with aryl and vinyl halides and psendohalides is known as the Suzuki or Suzuki-Miyaura reaction. Because boron is nontoxic, this reaction has been used in pharmaceutical syntheses. In addition, hydroboration or borate substitution allows for the synthesis of virtually any desired coupling partner. For these reasons, as well as the high yields and functional group compatibility, the Suzuki reaction is the first reaction to consider for carrying out a cross coupling. Representative substrates and catalysts are shown in Scheme 17. The various bases are used to generate four-coordinate boron ate complexes that are more reactive in transmetalation. 

The first total synthesis of the potent antibiotic marine natural product ( )-spiroxin C was completed by T. Imanishi et al., who employed a TBAF-activated Suzuki cross-coupling as the key step to form the biaryl linkage. The coupling partner naphthylborate ester was prepared using the Miyaura boration. 

A quite obvious solution to this problem is to replace both partners of the crosscoupling reaction with simple arenes by the cleavage of C-H bond during the coupling reaction. To assess this possibility, the catalytic cycle of the Suzuki-Miyaura reaction is depicted in Scheme 2. Palladium-catalyzed Suzuki-Miyaura reaction follows a similar catalytic cycle to those of many other cross-coupling... 

The first example of a Suzuki-Miyaura reaction on a pyridopyrimidine skeleton was used for decoration of a 4-diloro[2,3-d]pyrimidin-7(8H)one scaffold. Phe-nylboronic acid was used as a coupling partner with a good isolated yield (Scheme 15.18) [51]. 

Recent innovations have involved the use of trifluoroborate [29], tetraarylborate [30], and trihydroxyborate [31] salts, some originating from DoM reactions, as coupling partners in the Suzuki-Miyaura cross-couplings. 

The Suzuki-Miyaura reaction is perhaps one of the most well-known coupling protocols developed to date. A seareh of the literature reveals over 15000 citations to work employing this eoupling protocol that was first developed in 1979 and for whieh Akira Suzuki shared the Nobel Prize in Chemistry in 2010. The two seminal papers in 1979 co-authored by Suzuki and Miyaura deseribe the eross-eoupling of vinyl boronic acids with vinyl bromides (Scheme 13.1) or aryl halides (Scheme 13.2), employing 1 mol.% tetrakis(triphenylphosphene)palladium and a base such as sodium ethoxide. The stereoselectivity of the reactions was excellent with >99% retention of double bond geometry. The evolution of the various Suzuki coupling partners is shown in Scheme 13.3. 

The original cross-coupling reactions of aryl and vinyl halides with boronic acid coupling partners have been extensively developed since their inception. Over the past few years several interesting adaptions have expanded the scope of the original coupling protocol, below are just a few recent examples of systems that have harnessed the Suzuki-Miyaura protocol to access enantio-enriched coupling products. 

Buckley s chapter makes an impressive overview of the use of boron as a cross-coupling partner. The Suzuki-Miyaura reaction is one of the most versatile and important reactions in modern day organic synthesis and this... 

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