Phosphino‐amine (PN) Ligands for Rapid Catalyst Discovery in Ruthenium‐Catalyzed Hydrogen‐Borrowing Alkylation of Anilines: A Proof of Principle

Abstract

AbstractA general synthetic protocol for the synthesis of simple phosphino‐amine (PN) ligands is described with 19 ligands being isolated in good yields. High‐throughput ligand screening uncovered the success of two of these ligands for aromatic amine alkylations via ruthenium‐catalyzed hydrogen borrowing reactions. The combination of N,N′‐bis(diphenylphosphino)‐N,N′‐dimethylpropylenediamine with a ruthenium(II) source and potassium hydroxide (15 mol%) is the optimal system for selective monobenzylations of aromatic amines (method A). Over 70% isolated yields have been achieved for the formation of 14 secondary aromatic amines under mild reaction conditions (120 °C and 1.05 equivalents of benzyl alcohol). On the other hand, N,N‐bis(diphenylphosphino)‐isopropylamine was the ligand utilized for both selective monomethylation and monoethylation reactions of aromatic amines (method B). Here the alcohol is charged as both the reaction medium and substrate and 9 examples are disclosed with all isolated yields exceeding 70%. These methods have been applied to the synthesis of important synthetic building blocks based on aminoferrocene.magnified image