Suzuki-Miyaura reaction methodology

The cross-coupling of organoboron reagents with organic electrophiles in the presence of a base and a Pd catalyst is commonly referred to as the Suzuki-Miyaura reaction and has proved to be one of the most popular cross-coupling methodologies... 

This type of retrosynthetic analysis has been utihzed by Yoshida and Imamoto to prepare an impressive range of substituted phenols [14]. For example, as shown in Scheme 17.2, triene 4 afforded phenol 5 in 92% yield on exposure to 2-Ru. In another example, exposure of triene 6, with a different arrangement of the three double bonds, to the same catalyst resulted in the formation of phenol 7 via the presumed ketone intermediate 8. It is also evident from these two examples that a biaryl system is formed during the RCM-aromatization process. This approach has thus added a new synthetic tool to the chemist s repertoire, in addition to traditional methodologies such as the Suzuki-Miyaura reaction. 

Some key developments in the methodology or conditions of the Suzuki-Miyaura reaction have been reported in recent years. In 2006, Liu et al. [137] reported a ligand-free Suzuki-Miyaura reaction. What was remarkable about this reaction was that without added ligand, the reaction could be carried out with 0.5 mol% Pd(OAc)2 and sodium carbonate as the base, at 35 °C in air, with water as cosolvent over 0.5-1 h, and give a plethora of compounds all in excellent yields. This methodology was also applied in consecutive multicoupling reactions to afford di- and tri-haloaromatics. 

The double alkenylation approach (Scheme 1.1) has only been exploited relatively recently, most probably because of the rise to prominence of cross-coupling methodologies in recent times. The first double cross-couplings between 1,1-dihaloalkenes and metalloalkenes were isolated examples appearing in 1998 [9] and 2000 [10]. In 2002, Oh and Lim [11] reported a series of double Suzuki-Miyaura reactions between a 1,1-dibromoalkene 6 and alkenyl boronic acids 7 (Scheme 1.2). In 2007 and 2008, the Sherburn research group reported syntheses of substituted [3] dendralenes [12] and the state-of-the-art synthesis of [5]dendralene [13] respectively, transforming a 1,1-dihaloalkene via double... 

The Suzuki-Miyaura reaction suffers from a few key drawbacks, the first of which is the requirement for basic conditions. A number of monomers may be unstable in basic conditions, thus rendering this methodology impractical for these applications, or require more complex protection-deprotection strategies. Also, the Suzuki-Miyaura reaction requires a two-phase system thus, polymers that rapidly decrease in solubility as molecular weight increases may form precipitate in poor yields or display very low molecular weights and high polydispersities under Suzuki-Miyaura conditions, which is disadvantageous for photovoltaic application. 

Iron-catalyzed Suzuki-Miyaura coupling reactions were also reported by Nakamura and colleagues (entry 27) [67]. Alkyl halides 1 and mixed pinacol aryl(butyl)borates, generated in situ from arylboronates and butyllithium, were used as the reagents and 10 mol% of the iron complexes 16a or 16b as the catalysts. The addition of 20 mol% of MgBr2 was essential for the success of the reaction. Products 3 were isolated in 65-99% yield. The methodology tolerates ester and nitrile functions. The reaction starts probably by initial boron-iron transmetalation to generate a diaryliron(II) complex. 

In the strategy described in Fig. 16b, the linear precursor is not built on the polymer, but the final cyclization reaction using the Suzuki-Miyaura coupling takes place on a polymer. The aryl boronic acid is captured on a Dowex ammonium hydroxide resin, leading to the polymer ionically bonded borate, which is subsequently treated in the appropriate conditions to give the final macrocyle. This methodology is called resin capture-release.. ... 

Synthetic Methodology Derived from the DoM-Cross-Coupling Nexus 1081 Table 14.8 One-pot DoM-Suzuki-Miyaura cross-coupling reaction to Pyr-Ar systems [25a],... 

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