Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

Abstract

Readily synthesized biphenyl-2-carbaldehyde O-acetyl oximes were exposed to UV radiation affording phenanthridines. The scope and limitations of this novel reaction were explored. For example, exposure of 2',3'-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde O-acetyl oxime to UV radiation afforded 4-methoxyphenanthridine in 54% yield. This methodology was applied to the synthesis of trisphaeridine to afford the product in four linear steps in an overall yield of 6.5% from 1-bromo-2,4,5-trimethoxybenzene.

Efficient synthesis of new 6-arylphenanthridines based on microwave-assisted Suzuki–Miyaura cross-coupling and Pictet–Spengler dehydrogenative cyclization in a zinc chloride/[Bmim]BF4 mixture

“…According to the reported methods, the construction of a phenanthridine core is achieved through the following synthetic models (Fig. 2): (1) C Ar -C Ar bond formation via intramolecular cyclization of functionalized imines or anilines or by transitionmetal-catalysed coupling of ortho-halogenated amines/imines with aryl halides or triflates 12,13 (model 1); (2) C Ar -N bond formation of the respective ortho-biaryl keto and aldoximes [14][15][16][17] (model 2); and (3) C-C bond formation through intramolecular cyclization of ortho-aryl isocyanides [18][19][20] or C Ar -C ymine bond formation through intramolecular cyclization of ortho-arylimines (amines, imines or amides) [21][22][23][24][25][26] (model 3). The latter disconnection type includes the well-known Bischler-Napieralski and Pictet-Hubert type cyclization reactions, which are primary methods for phenanthridine preparation using N-acylbiphenyl-2-amine derivatives.…”