Directed ortho metalation strategies. Effective regioselective routes to 1,2-, 2,3-, and 1,2,3-substituted naphthalenes.

The regioselective synthesis of 2,3-di- and 1,2,3-trisubstituted naphthalenes via Directed ortho Metalation (DoM) strategies of N,N-diethyl-O-naphthyl-2-carbamate (1) is presented. Sequential LiTMP metalation-electrophile quench and s-BuLi/TMEDA (or t-BuLi)-electrophile quench of naphthyl-2-carbamate 1 provides a general route to contiguously substituted naphthalenes (6) with full regioselectivity. Further derivatization via ipso-halodesilylation and Suzuki-Miyaura cross-coupling leads ultimately to substituted halonaphthalenes and benzonaphthopyranones (9).