A novel copper-catalyzed [5 þ 1] annulation of 2-ethynylanilines with an N,O-acetal, which functioned as a C1 part, leading to the preparation of quinoline derivatives with an ester substituent on the 2-position is described. A combination of CuBr 2 and trifluoroacetic acid (TFA) promoting [5 þ 1] annulation of the 2-ethynylaniline with ethyl glyoxylate is also demonstrated.

Under Lewis acidic conditions using Hf(OTf)(4), the aminomethylation of an indole derivative with a typical N,O-acetal preferentially produced kinetically favored N-aminomethylated indole derivatives instead of thermodynamically favored 3-aminomethylated indoles.

Under relatively strong Lewis acidic conditions (a softer counter ion) using TMSOTf and TMSI, the aminomethylation of indole or pyrrole with a typical N,O-acetal preferentially produced the kinetically favored N-aminomethylated indole or pyrrole derivative. Use of a relatively weak Lewis acid (a harder counter ion), such as TMSCl and TMSBr, preferentially produced the thermodynamically favored C-aminomethylated indole and pyrrole derivative.

Treatment of various N‐heterocycles with N,O‐acetals like (II) results in unusual, regioselective formation of N‐aminomethylated products.

Conditions A) or B) are found to be suitable for the construction of quinoline or naphthyridine skeletons as basic structures of natural products.