Catalytic Atroposelective Synthesis of C−N Axially Chiral Aminophosphines via Dynamic Kinetic Resolution

• Published in: Angewandte Chemie International Edition Vol. 63; no. 37; pp. e202409524 - n/a
• Main Authors: Rodríguez‐Franco, Carlos, Roldán‐Molina, Esther, Aguirre‐Medina, Alberto, Fernández, Rosario, Hornillos, Valentín, Lassaletta, José M.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 09-09-2024
• Edition: International ed. in English
• Subjects: Aliphatic amines; Amination; Amines; Aromatic compounds; asymmetric catalysis; axial chirality; Carbonyl compounds; Carbonyls; Chemical synthesis; dynamic kinetic resolution; Lewis acid; Phosphine; Phosphines; Pyrroles; Ruthenium; ruthenium catalysis; Substrates; transfer hydrogenation; axial chirality; transfer hydrogenation; asymmetric catalysis; ruthenium catalysis; dynamic kinetic resolution
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202409524

A ruthenium‐catalyzed reductive amination via asymmetric transfer hydrogenation (ATH) has been used to perform an efficient dynamic kinetic resolution (DKR) of N‐aryl 2‐formyl pyrroles decorated with a phosphine moiety positioned at the ortho’ position. The strategy relies on the labilization of the stereogenic axis in the substrate facilitated by a transient Lewis acid‐base interaction (LABI) between the carbonyl carbon and the phosphorus center. The reaction features broad substrate scope of aliphatic amines and N‐aryl pyrrole scaffolds, and proceeds under very mild conditions to afford P,N atropisomers in good to high yields and excellent enantioselectivities (up to 99 % ee) for both diphenyl and dicyclohexylphosphino derivatives.
Axially chiral P,N ligands were synthesized through ruthenium‐catalyzed ATH of in situ generated iminophosphines. The transient interaction between iminium and phosphine groups as a Lewis acid‐base pair causes the labilization of the stereogenic axis, enabling the scenario for a DKR. The reaction proceeds with good to high yields and reaching up to 99 % ee across a range of substrates, including both dicyclohexyl‐ and diphenylphosphino derivatives.