Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

Abstract

ConspectusThe cores of many types of polymers, ligands, natural products, and pharmaceuticals contain biaryl or substituted aromatic structures, and efficient methods of synthesizing these structures are crucial to the work of a broad spectrum of organic chemists. Recently, Pd-catalyzed carbon-carbon bondforming processes, particularly the Suzuki-Miyaura cross-coupling reaction (SMC), have risen in popularity for this purpose. The SMC has many advantages over other methods for constructing these moieties, including mild conditions, high tolerance toward functional groups, the commercial availability and stability of its reagents, and the ease of handling and separating byproducts from its reaction mixtures.Until 1998, most catalysts for the SMC employed triarylphosphine ligands. More recently, new bulky and electron-rich phosphine ligands, which can dramatically improve the efficiency and selectivity of such cross-coupling reactions, have been introduced. In the course of our studies on carbonnitrogen bond-forming reactions, we found that the use of electron-rich and bulky phosphines enhanced the rate of both the oxidative addition and reductive elimination processes; this was the beginning of our development of a new family of ligands, the dialkylbiarylphosphines L1-L12. These ligands can be used for a wide variety of palladium-catalyzed carbon-carbon, carbon-nitrogen, and carbon-oxygen bond-forming processes as well as serving as supporting ligands for a number of other reactions.The enhanced reactivity of these catalysts has expanded the scope of cross-coupling partners that can be employed in the SMC. Using such dialkylbiarylphosphine ligands, the coupling of unactivated aryl chlorides, aryl tosylates, heteroaryl systems, and very hindered substrate combinations have become routine. The utility of these ligands has been successfully demonstrated in a wide number of synthetic applications, including industrially relevant processes.In this account, we provide an overview of the use and impact of dialkylbiarylphosphine ligands in the SMC. We discuss our studies on the mechanistic framework of the reaction, which have allowed us to rationally modify the ligand structures in order to tune their properties. We also describe selected applications in the synthesis of natural products and new materials to illustrate the utility of these dialkylbiarylphosphine ligands in various "real-world" synthetic applications. IntroductionThe impact of the Suzuki-Miyaura reaction (SMC) on academic and industrial research as well as on production has been immense. 1 Over the past two decades, it has become arguably one of the most efficient methods for the construction of biaryl or substituted aromatic moieties; compounds that contain these substructures constitute important building blocks of polymers, sbuchwal@mit.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 2 ligands, 3 a wide range of natural products such as alkaloids, as well as in numerous biologically active pharmaceutic...

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

“…The use of [(allyl)PdCl] 2 , a Pd(II) complex precursor of Pd(0), and potassium phosphate in acetonitrile were shown to be essential (entries 1-6). In conjunction with XPhos as the ligand 4 , a high yield of 2-substituted coupling product 6 was obtained with exclusive g-regioselectivity (entry 6).…”

“…Thus, in these conditions, both XPhos and (4-CF 3 -C 6 H 4 ) 3 P are expected to first provide s-bonded allylic Pd(II) complex B via a syn-S E 0 pathway made favourable through coordination of the electron-deficient Pd(II) to the electron-rich alkene. From complex B, the bulky strong s-donor phosphine ligand XPhos provides the steric effect to encourage a prompt reductive elimination that yields the g regioisomer product 4,28,43 . Being smaller and less conducive of reductive elimination, it is possible that the weaker, more labile s-donor phosphine (4-CF 3 -C 6 H 4 ) 3 P encourages slippage of the Z 1 s-bonded complex B to the Z 3 p-allyl intermediate C (that is, K s-p 4K RE ).…”

“…For example, in the highly popular Suzuki Miyaura crosscoupling reaction, the sp 2 -hybridized C-B bond of alkenyl or aryl boron compounds can be coupled selectively with the sp 2 -hybridized C-X bond of alkenyl or aryl halides (Fig. 1a) [2][3][4][5] . Coupling of sp 3 -hybridized partners such as alkylboron compounds is more challenging as it is rendered difficult by a slower transmetallation and possible side reactions such as bhydride elimination 6 .…”

Cellulose Oxidation and the Use of Carboxyl Cellulose Metal Complexes in Heterogeneous Catalytic Systems to Promote Suzuki-Miyaura Coupling and C−O Bond Formation Reaction

“…Again, these are very challenging substrates for the Suzuki cross-coupling, where only the addition of a very specific ligand can effectively promote the coupling reaction. 45 Nickel carboxyl cellulose (NiCC) was also evaluated for the Suzuki coupling reactions. 46 First, a test was performed for 6 h in the absence of ligands; however, no coupling product was formed.…”

Synthesis of Terphenyls and Quaterphenyls via the Nickel N-Heterocyclic Carbene-Catalyzed Cross-Coupling of Neopentyl Arenesulfonates with Aryl Grignard Reagents

“…1 A variety of organic halides and pseudohalides, usually containing sp-and sp 2 -hybridized C-X bonds (X = halogen, OTf, etc. ), have been adopted as electrophilic substrates in these reactions.…”