Catalytic Asymmetric Synthesis of P-Stereogenic Phosphines: Beyond Precious Metals

Abstract

AbstractMetal-catalyzed asymmetric synthesis of P-stereogenic phosphines is a potentially useful approach to a class of chiral ligands with valuable applications in asymmetric catalysis. We introduced this idea with chiral platinum and palladium catalysts, exploiting rapid pyramidal inversion in diastereomeric metal–phosphido complexes (ML*(PRR′)) to control phosphorus stereochemistry. This Account summarizes our attempts to develop related synthetic methods using earth-abundant metals, especially copper, in which weaker metal–ligand bonds and faster substitution processes were expected to result in more active catalysts. Indeed, precious metals were not required. Without any transition metals at all, we exploited related P-epimerization processes to prepare enantiomerically pure phosphiranes and secondary phosphine oxides (SPOs) from commercially available chiral epoxides.1 Introduction2 Copper-Catalyzed Phosphine Alkylation3 Copper-Catalyzed Tandem Phosphine Alkylation/Arylation4 Nickel-Catalyzed Phosphine Alkylation5 Proton-Mediated P-Epimerization in Synthesis of Chiral Phosphiranes6 Diastereoselective Synthesis of P-Stereogenic Secondary Phosphine Oxides (SPOs) from (+)-Limonene Oxide7 Conclusions