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2‐Bis (dimethylamino)phosphinoyl‐1‐lithio‐1, 2, 3, 4‐tetrahydroisoquinoline. A highly nucleophilic d 1 ‐reagent for the preparation of 1‐substituted tetrahydroisoquinolines
Author(s) -
Seebach Dieter,
Yoshifuji Masaaki
Publication year - 1981
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19810640305
Subject(s) - chemistry , electrophile , reagent , isoquinoline , tetrahydrofuran , alkylation , nucleophile , cleavage (geology) , medicinal chemistry , butyllithium , phosphoric acid , organic chemistry , solvent , geotechnical engineering , fracture (geology) , engineering , catalysis
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.