Preparation of 1,3‐disubstituted isoquinoline derivatives from N ‐boc‐3‐substituted‐1,2‐dihydroisoquinolines

3‐Substituted N ‐Boc‐1,2‐dihydroisoquinolines 2 can be functionalized at the 1‐position via lithiation and subsequent electrophilic trapping. The resulting products 3 can be deprotected and oxidized to afford the corresponding 1,3‐disubstituted isoquinolines 5 . Deprotection of dihydroisoquinoline 3k followed by sodium borohydride reduction affords the cis ‐1,3‐disubstituted tetrahydroisoquinoline 11 . The 1,3‐disubstituted N ‐Boc‐1,2‐dihydroisoquinoline 3g is efficiently alkylated at the 1‐position to give 1,1,3‐trisubstituted analogs 12 .