Premium
Protecting‐Group‐Free Total Synthesis of Isoquinoline Alkaloids by Nickel‐Catalyzed Annulation of o ‐Halobenzaldimine with an Alkyne as the Key Step
Author(s) -
Korivi Rajendra Prasad,
Cheng ChienHong
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200902275
Subject(s) - isoquinoline , chemistry , total synthesis , moiety , alkyne , aldehyde , annulation , medicinal chemistry , catalysis , stereochemistry , organic chemistry
Abstract An efficient short total synthesis of benzo[ c ]phenanthridine alkaloids including oxyavicine, oxynitidine, and oxysanguinarine is described. Thus, N ‐methyl‐ o ‐bromobenzaldimines 1 b – d undergo regioselective cyclization with 4‐(benzo[ d ][1,3]dioxol‐5‐yl)but‐3‐yn‐1‐ol ( 2 b ) in the presence of [Ni(cod) 2 ] (cod=1,5‐cyclooctadiene). In situ oxidation of the resultant isoquinolinium salts gives isoquinolinone derivatives 5 b – d with benzo[ d ][1,3]dioxol‐5‐yl substitution at the C 3 atom and a (CH 2 ) 2 OH group at the C 4 atom. Later, oxidation of the alcohol group in 5 b – d to the aldehyde moiety followed by acid‐catalyzed cyclization and dehydration completes the total syntheses to give oxyavicine, oxynitidine, and oxysanguinarine in 67, 65, and 60 % yields, respectively. The synthesis requires four steps from o ‐bromobenzaldehyde derivatives. Transformations of these alkaloids to the other alkaloids in this family are also discussed herein.