N2Phos – an easily made,highly effective ligand designed for ppm level Pd-catalyzed Suzuki–Miyaura cross couplings in water |
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| Authors: | Nnamdi Akporji Ruchita R Thakore Margery Cortes-Clerget Joel Andersen Evan Landstrom Donald H Aue Fabrice Gallou Bruce H Lipshutz |
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| Institution: | Department of Chemistry & Biochemistry, University of California Santa Barbara, Santa Barbara CA 93106 USA.; Novartis Pharma AG, Basel Switzerland ; Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221 USA |
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| Abstract: | A new biaryl phosphine-containing ligand from an active palladium catalyst for ppm level Suzuki–Miyaura couplings, enabled by an aqueous micellar reaction medium. A wide array of functionalized substrates including aryl/heteroaryl bromides are amenable, as are, notably, chlorides. The catalytic system is both general and highly effective at low palladium loadings (1000–2500 ppm or 0.10–0.25 mol%). Density functional theory calculations suggest that greater steric congestion in N2Phos induces increased steric crowding around the Pd center, helping to destabilize the 2 : 1 ligand–Pd(0) complex more for N2Phos than for EvanPhos (and less bulky ligands), and thereby favoring formation of the 1 : 1 ligand–Pdo complex that is more reactive in oxidative addition to aryl chlorides.A new, biaryl phosphine-containing ligand, N2Phos, forms a 1 : 1 complex with Pd resulting in an active catalyst at the ppm level for Suzuki–Miyaura couplings in water, enabled by an aqueous micellar medium. Notably, aryl chlorides are shown to be amenable substrates. |
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