Metal Suzuki-Miyaura cross-coupling

Chamoin S, Houldsworth S, Kruse CG, Bakker WI, Snieckus V. The Suzuki-Miyaura cross coupling reactions on solid support. Link to solution phase directed ortho metalation. The Leznoff acetal linker approach to biaryl and heterobiaryl aldehydes. Tetrahedron Lett 1998 39 4179-4182. 

No examples of such reactions have been disclosed. Displacement of halogens on the parent heterocycle through metal-catalyzed processes have surprisingly not been reported to our knowledge on the neutral heterocycle. Recently, Suzuki-Miyaura cross-coupling reactions of imidazolium bromide 113 with various boronic acids or esters were reported <2005T6207> to proceed in good yield, without deprotonation at the C-3 position (Scheme 35). 

Chamoin, S. Houldsworth, S. Kruse, C. G. Bakker, W. I. Snieckus, V. The Suzuki-Miyaura Cross Coupling Reactions on Solid Support. Link to Solution Phase Directed ortho Metalation. The Leznoff Acetal Linker Approach to Biaryl and Heterobiaryl Aldehydes, Tetrahedron Lett. 1998, 39, 4179-4182. 

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. 

The disclosure of a one-pot directed ortho metalation-boronation and Suzuki-Miyaura cross-coupling of derivatized pyridines 44 to give substituted azabiaryls 45 provided an excellent protocol for the in situ utilization of pyridyl boronic acids whose isolation is known to be difficult <07JOC1588>. The disclosed method relies on the in situ compatibility of LDA and B(Oz-Pr)3 and proceeds in good to excellent yields for the multi-step process. The report details a comprehensive survey of pyridyl boronates and is expected to be of considerable value in the synthesis of bioactive molecules. 

Acetylation, chlorination, reduction (aldehyde - alcohol), Benzoin condensation, Wittig-, (jrignard-, Aldol reaction, Suzuki-Miyaura cross-coupling, directed ortho-metalation [91]. 

The Suzuki-Miyaura cross-coupling reaction is a standard method for carbon-carbon bond formation between an aryl halide or triflate and a boronic acid derivative, catalyzed by a palladium-metal complex. As with the Mizoroki-Heck reaction, this cross-coupling reaction has been developed in ionic liquids in order to recycle and reuse the catalyst. In 2000, the first cross-coupling of a halide derivative with phenylboronic acid in [bmim] [BF4] was described. As expected, the reaction proceeded much faster with bromobenzene and iodobenzene, whereas almost no biphenyl 91 was obtained using the chloride derivative (Scheme 36). The ionic liquid allowed the reactivity to be increased, with a turnover number between 72 and 78. Furthermore, the catalyst could be reused repeatedly without loss of activity, even when the reaction was performed under air. Cross-coupling with chlorobenzene was later achieved - although with only a moderate yield (42%) - using ultrasound activation. 

Carboxylates Among various 0-substituted electrophiles, O-acylated phenols share a few distinct advantages over other pseudohahdes (i) they are readily available and affordable, (ii) they are relatively stable substrates to various reaction conditions, and (iii) they can serve as directing groups for aromatic substitution reactions such as directed ortho-metallations (DoMs) [58]. Moreover, these carboxylates are much more environmentally friendly, generating acetate salts as the only by-product in the Suzuki-Miyaura cross-coupling reaction [59,... 

I 14 The Directed Ortho Metallation (DoM) -Cross-Coupling Nexus Table 14.6 Selected DoM-Suzuki-Miyaura cross-coupling reactions forming Ar-6-HetAr systems. 

Quinn, R. M. (2002) Phosphorus-based directed metalation groups, DMGs Suzuki-Miyaura Cross coupling of di-t-butylphosphine oxide (P(0)t-Bu2) and development of di-t-butylphosphine sulfide (P(S)t-Bu2) for use as a DMG. M.Sc. Thesis. Queen s University, Canada. 

Green, A. L. (2001) The directed orhto metalation of pyridine derivatives with in situ boronation and links to the Suzuki-Miyaura cross coupling reaction. M.Sc. Thesis, Queen s University, Kingston, Canada. 

The DreM of 0-carbamates can be efficiently linked to transition metal-catalyzed cross-couplings like the Negishi and Suzuki-Miyaura couplings, eventually performed after DoM protocols [175]. For example, the synthesis of alkaloid schumanniophytine 79 has been accomplished involving DoM of 0-carbamate 78 followed by borylation, Suzuki-Miyaura cross-coupling, and an ort/jo-silicon-induced 0-carbamate remote anionic Snieckus-Fries rearrangement (Scheme 26.24). 

New highly bulky but flexible NHCs (14) have been synthesized and proved to be superior ff-donating ligand than more common IMes or IPr. These properties allowed metal complexes of these carbenes to perform efficient activations of aryl chlorides especially in the challenging Suzuki-Miyaura cross-coupling of bulky derivatives and in amination reactions. 

The nature of ligands, such as Boxs, phosphines, and N-heterocyclic carbenes (NHC), bound to a transition metal center usually afiects the selectivities and reaction rates in the organic reactions. Styring et al. described the preparation of a Pd (Il)-salen complex immobilized on Merrifield resin (42). The polymer catalyst facilitated the Suzuki-Miyaura cross-coupling reaction in a continuous-flow system (Scheme 7.32) [130]. The reactor continuously afforded biaryl adducts (43) from aryl... 

Given that trace Pd can mediate cross-coupling processes, it is important that in the development of base-metal catalysed cross-couplings the Pd concentration (down to ppb levels) is determined and appropriate controls conducted. Bedford showed that Pd contaminants were catalytically active in a supposedly Fe-catalyzed Suzuki-Miyaura cross-coupling methodology, employing common aryl bromide substrates. ... 

Catalytic hydroboration of alkenes and alkynes can be achieved by the reaction of dialkoxyboranes such as pinacolborane 55 and catecholborane 56 in the presence of transition metal catalysts such as CpjZrHCl, Rh(PPh3)3Cl, or Rh(PPh3)2COCl, (Scheme 28.14). This reaction is of particular significance because it readily provides alkyl/vinylboronates directly in one step for further utility in Suzuki-Miyaura cross-coupling reaction. 

Thus the proton abstraction mechanism seems to be the favored pathway in the metalation step of transition-metal-catalyzed arylations. This may seem surprising because a relatively weak base as carbonate is taking away an arylic proton, which has very low acidity. The presence of the metal is in this case key to stabilize the development of a negative charge in the carbon center, as proved by the structure of the transition states, where the metal-carbon bond is practically already formed. It is worth mentioning that external bases are key in both direct arylation and the Suzuki-Miyaura cross-coupling, but their roles are completely different. 

---