2‐Bis (dimethylamino)phosphinoyl‐1‐lithio‐1, 2, 3, 4‐tetrahydroisoquinoline. A highly nucleophilic d1‐reagent for the preparation of 1‐substituted tetrahydroisoquinolines

The title compound 4 is generated from the phosphoric amide 5 in tetrahydrofuran with butyllithium. The lithium reagent 4 is stable at room temperature; its reactions with electrophiles furnish the products 6–22, 26, 27, see Table 1 and the Scheme. A second alkylation is also possible, see 23–25. The cleavage to tetrahydroisoquinolines is accomplished in refluxing aqueous‐methanolic hydrochloric acid, see Table 2. Phosphinoylation, lithiation, reaction with electrophiles and cleavage constitute an efficient sequence for 1‐alkylation of the isoquinoline nucleus.