ABSTRACT
Symmetric secondary amines were synthesized by the self-condensation of primary amines over a palladium-loaded titanium dioxide (Pd/TiO2) photocatalyst. The reactions afforded a series of secondary amines in moderate to excellent isolated yields at ambient temperature (30 °C, in cyclopentyl methyl ether). Applicability for one-pot pharmaceutical synthesis was demonstrated by a photocatalytic reaction sequence of self-condensation of an amine followed by N-alkylation of the resulting secondary amine with an alcohol.
ABSTRACT
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ABSTRACT
Direct functionalization of amino groups in complex organic molecules is one of the most important key technologies in modern organic synthesis, especially in the synthesis of bio-active chemicals and pharmaceuticals. Whereas numerous chemical reactions of amines have been developed to date, a selective, practical method for functionalizing complex amines is still highly demanded. Here we report the first late-stage N-alkylation of pharmaceutically relevant amines with alcohols at ambient temperature. This reaction was achieved by devising a mixed heterogeneous photocatalyst in situ prepared from Cu/TiO2 and Au/TiO2. The mixed photocatalytic system enabled the rapid N-alkylation of pharmaceutically relevant molecules, the selective mono- and di-alkylation of primary amines, and the non-symmetrical dialkylation of primary amines to hetero-substituted tertiary amines.