Protecting‐Group‐Free Total Synthesis of Isoquinoline Alkaloids by Nickel‐Catalyzed Annulation of o‐Halobenzaldimine with an Alkyne as the Key Step |
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Authors: | Rajendra Prasad Korivi Dr Chien‐Hong Cheng Prof Dr |
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Institution: | Department of Chemistry, National Tsing Hua University, Hsinchu, 30013 (Taiwan), Fax: (+886)?3572‐4698 |
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Abstract: | An efficient short total synthesis of benzoc]phenanthridine alkaloids including oxyavicine, oxynitidine, and oxysanguinarine is described. Thus, N‐methyl‐o‐bromobenzaldimines 1 b – d undergo regioselective cyclization with 4‐(benzod]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 benzod]1,3]dioxol‐5‐yl substitution at the C3 atom and a (CH2)2OH group at the C4 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. |
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Keywords: | alkaloids isoquinolines nickel ring‐closing reactions total synthesis |
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