Titanium-Catalyzed Selective N‑Alkylation of Amines with Alcohols via Borrowing Hydrogen Methodology

The N-alkylation of amines with alcohols using earth-abundant and nonprecious metal catalysts has gained considerable attention in the pharmaceutical industry. We described titanium-catalyzed synthetic protocol for N-alkylation of amines with alcohols via borrowing hydrogen or hydrogen autotransfer reactions. The methodology enables the selective monoalkylation of various substituted (hetero)­aromatic amines in good to excellent yields (up to 97% yield). The importance of the protocol was further demonstrated by the applicability of earth-abundant metal catalysis and the synthesis of 32 N-alkylated amines. The work allows the utilization of titanium-based catalysts for various reactions to expand the nature blueprint in catalysis.