Synthesis of Benzo[c]phenanthridine Alkaloids by Pd(OAc)₂‐Induced Direct Aromatic Carbonylation

Abstract

The Pd(OAc)2‐induced carbonylation of alkoxy‐substituted 1‐amino‐2‐phenyltetralins and 1‐amino‐2‐phenylnaphthalenes was examined to provide the benzo[c]phenanthridine ring system. The carbonylation of substrates containing methylenedioxy groups gave oxysanguinarine and oxyavicine. The tetramethoxy derivatives gave O‐methyloxyfagaronine. The substrate with a benzyloxy group afforded a known synthetic precursor to the antileukemic alkaloid, fagaronine.

Biosynthetic Relationships and Total Syntheses of Naturally Occurring Benzo[c]Phenanthridine Alkaloids

“…In 2012, Orito and co‐workers have examined the Pd(OAc) 2 ‐induced carbonylation of alkoxy‐substituted 1‐( N ‐methylamino)‐2‐phenyltetralins 46 a and 1‐( N ‐methylamino)‐2‐phenylnaphthalenes 46 b to provide the benzo[ c ]phenanthridine ring system (Scheme ) . The carbonylation of tetralin 46 a with methylenedioxy groups by using a catalytic system of Pd(OAc) 2 /Cu(OAc) 2 /pyridine in refluxing toluene predominantly gave tetrahydro oxysanguinarine 46 c .…”

Synthesis of phenanthridine and phenanthridinone derivatives based on Pd‐catalyzed C–H activation

“…In 2012, Orito et al described the carbonylation of alkoxy‐substituted 1‐( N ‐methylamino)‐2‐phenyltetralins and 1‐( N ‐methylamino)‐2‐phenylnaphthalenes 148 to provide the alkoxy‐substituted 6‐oxobenzo[c]phenanthridines 149 using Pd(OAc) 2 and Cu(OAc) 2 under CO atmosphere and air as oxidant …”

Preparation of Amino-Substituted Indenes and 1,4-Dihydronaphthalenes Using a One-Pot Multireaction Approach: Total Synthesis of Oxybenzo[c]phenanthridine Alkaloids

“…As a result of these wide-ranging pharmacological activities, methods for the synthesis of oxybenzo­[ c ]­phenanthridines have received considerable attention. − For example, Clark and Jahangir reported the synthesis of oxynitidine ( 3 ) by forming the benzo­[ c ]­phenanthridine skeleton through cycloaddition of a lithiated toluamide with a benzaldimine . In an analogous approach, Cho and co-workers showed that cycloaddition between lithiated toluamides and benzonitriles could be used for the general synthesis of this class of natural product. − ,, The research group of Harayama prepared a number of oxybenzo­[ c ]­phenanthridines by initial formation of amide intermediates via coupling of aminonaphthalenes with o -halogenated benzoic acids .…”