Enantioselective Synthesis of P‐Stereogenic Phosphinates and Phosphine Oxides by Molybdenum‐Catalyzed Asymmetric Ring‐Closing Metathesis

Abstract

Chiral phosphines have found widespread use in chemical synthesis as ligands for transition metal catalysis.[1] Along with phosphine oxides and other derivatives, they have also become popular choices as catalysts in organic synthesis.[2] Organophosphorus-based catalysis will undoubtedly benefit from a more diverse range of P-stereogenic phosphines. In response to this demand, metal-catalyzed asymmetric syntheses of P-stereogenic phosphines and their derivatives have recently emerged, with key contributions including alkyne hydrophosphorylation,[3] the alkylation and arylation of secondary phosphines,[4] enantioselective deprotonation,[5] and rhodium-catalyzed [2+2+2] cycloaddition.[6] To date, these catalytic enantioselective routes remain largely outnumbered by well-established methods based on resolutions[7] or on the use of chiral auxiliaries.[8] In spite of recent advances in the area of olefin metathesis, the utility of asymmetric ring-closing metathesis (ARCM)[9] has not been applied to the preparation of P-stereogenic phosphine derivatives.[10] In light of literature precedents, which demonstrate that various P-containing dienes, trienes, and tetraenes are suitable substrates for olefin metathesis,[11] we reasoned that the ARCM of P-templates would be a strategically unique and valuable reaction for the preparation of P-stereogenic compounds. We opted for a catalytic enantioselective desymmetrization process of prochiral P-templates, as this approach offers the opportunity to explore ARCM with the chirality arising from the formation of a stereogenic center other than a carbon atom (Scheme 1). Moreover, the resulting products are structurally novel P-stereogenic scaffolds amenable to rich chemistry further downstream. Herein, we report the first examples of catalytic enantioselective olefin metathesis reactions of phosphinates and phosphine oxides, which lead to the formation of five-, six-, and seven-membered P-heterocycles in up to 98% ee. We also report an unprecedented case of complementary asymmetric induction in reactions promoted by a pair of chiral molybdenum-based complexes differing structurally in their achiral imido ligand.