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

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. image