Direct synthesis of 1‐naphthylamines enabled by 6‐endo‐dig cyclization strategy using copper catalysis.

Here, we describe a facile approach for the synthesis of substituted 1‐naphthylamines via three‐component 6‐endo‐dig cyclization of terminal alkynes with 2‐bromoaryl ketones, primary or secondary amines in water under Pd‐free conditions. The Cu(I) catalytic system avoids a fundamental problem related to these substrates, which competitively evolve through 5‐endo‐dig cyclization pathways under metal catalysis. This unique performance unlocks a rapid access to a diverse 1‐naphthylamines library that previously required longer synthetic routes. The synthetic potential of this method was further demonstrated by the gram‐scale synthesis, and the mechanism study showed that the reaction experienced sequential halide exchange, imine‐enamine tautomerization and 6‐endo‐dig cyclization. [ABSTRACT FROM AUTHOR]