Reactions of [2‐(2‐Naphthyl)phenyl]acetylenes and 2‐(2‐Naphthyl)benzaldehyde O‐Phenyloximes: Synthesis of the Angucycline Tetrangulol and 1,10,12‐Trimethoxy‐8‐methylbenzo[c]phenanthridine

Abstract

The Suzuki–Miyaura coupling reaction between (1,4,5‐trimethoxynaphthalen‐2‐yl)boronic acid and 2‐iodo‐3‐methoxy‐5‐methylbenzaldehyde gave the intermediate 3‐methoxy‐5‐methyl‐2‐(1,4,5‐trimethoxynaphthalen‐2‐yl)benzaldehyde. Conversion of this benzaldehyde into the alkyne 2‐(2‐ethynyl‐6‐methoxy‐4‐methylphenyl)‐1,4,5‐trimethoxynaphthalene was accomplished through a Corey–Fuchs reaction. Exposure of the derived acetylene to a catalytic platinum(II)‐mediated ring closure gave the required tetracyclic aromatic product, 1,7,8,12‐tetramethoxy‐3‐methyltetraphene, which was then converted into tetrangulol. Exposure of the related 3‐methoxy‐5‐methyl‐2‐(1,4,5‐trimethoxynaphthalen‐2‐yl)benzaldehyde O‐phenyloxime to microwave irradiation in an ionic liquid yielded 1,10,12‐trimethoxy‐8‐methylbenzo[c]phenanthridine, instead of the desired natural product phenanthroviridone.

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

“…Based on the results reported by Rodrıguez and Walton we envisaged that under these photochemcial conditions, intermediate 8 would be formed. Contrary to the expected results, in our labs exposure of oxime 7 to UV irradiation yielded phenanthridine 9 as the main product alongside the nitrile 10 in lower yields [ 13 ]. We hypothesized that oxime 7 undergoes a homolytic cleavage of the N–O bond giving the iminyl radical 11 [ 14 ] followed by an intramolecular cyclization with concomitant expulsion of the ortho -methoxy group, liberating phenanthridine 9 .…”

“…Contrary to the expected results, in our labs exposure of Scheme 1: Previous unexpected synthesis of the phenanthridine framework. oxime 7 to UV irradiation yielded phenanthridine 9 as the main product alongside the nitrile 10 in lower yields [13]. We hypothesized that oxime 7 undergoes a homolytic cleavage of the N-O bond giving the iminyl radical 11 [14] followed by an intramolecular cyclization with concomitant expulsion of the ortho-methoxy group, liberating phenanthridine 9.…”

Synthesis of Angucycline/Tetrangulol Derivatives Using Suzuki‐Miyaura Cross‐Coupling and Ring‐Closing Carbonyl‐Olefin Metathesis Reactions

“…2-Iodo-3-methoxy-5-methylbenzaldehyde 21 [5] A pestle and mortar were used to grind together KMnO 4 (142 mg, 0.90 mmol, 2.5 eq), CuSO 4 • 5H 2 O (225 mg, 0.90 mmol, 2.5 eq), and iodo-alcohol 26 (100 mg, 0.36 mmol, 1.0 eq) until a completely homogenous mixture was formed. This homogenous mixture was then transferred to a round bottom flask and heated to 120 °C for 3 h. After cooling, the reaction mixture was diluted with EtOAc (20 ml) and water (10 ml).…”

“…[3] As part of our programme on the synthesis of aromatic and heteroaromatic compounds, [4] we have reported on the synthesis of the simplest angucycline, tetrangulol 1. [5] One of the key steps was an aromatic ring forming reaction by exposure of the 2-naphthylphenylacetylene 7 to platinum(II) chloride or gold(III) chloride to afford the desired oxygenated skeleton 8 that could easily be converted into tetrangulol 1. However, in utilizing either the platinum or gold catalyst, significant amounts of the unwanted aromatic product 9 were also produced (Scheme 1).…”

“…However, in utilizing either the platinum or gold catalyst, significant amounts of the unwanted aromatic product 9 were also produced (Scheme 1). [5] …”