Synthesis of the Carbon Framework of the Stephaoxocanes Employing a Sequential RCM/Pomeranz–Fritsch Approach

Abstract

The syntheses of two cyclodeca[ij]isoquinoline derivatives, which embody the carbon framework of stephaoxocanidine, excentricine and the recently isolated stephalonganines A, B and C, are reported. The target tricyclic compounds were prepared from isovanillin, employing a ring‐closing metathesis approach towards the synthesis of a benzocyclodecane‐type common intermediate; different modifications of thePomeranz–Fritsch protocol allowed the installation of the heterocyclic ring.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Bright, Color-Tunable Fluorescent Dyes Based on π-Expanded Diketopyrrolopyrroles

“…A retrosynthetic analysis allowed us to envision that such compounds could, in principle, be synthesized via alkylation of a given DPP with bromoacetaldehyde diethyl acetal followed by an intramolecular Friedel–Crafts-type reaction. In the preparation of simple isoquinolines, if an aromatic substituent is electron rich, the cyclization step can be effectively performed using aqueous hydrochloric acid as a catalyst. , Electron-poor aromatic substituents require an anhydrous system and a much stronger acid such as TfOH . The above-described, three-step synthetic strategy is presented in Scheme .…”

Exploitation of a Tuned Oxidation with N-Haloimides in the Synthesis of Caulibugulones A–D

“…The residue obtained was purified by column chromatography in silica gel using hexane/AcOEt (70:30, R f = 0.50) as eluent to yield 7 (>99%) as a yellowish oil. 1 5,8-Dimethoxy-3-methyl-2-tosyl-1,2-dihydroisoquinoline (10). A stirred suspension of 9 (409.5 mg; 1.0 mmol) in 10 mL of dioxane/HCl 6 M (4:1), in the dark and under argon atmosphere, was kept under reflux in a round-bottom flask for 7 h. After completion of the reaction as indicated by TLC, the pH of the reaction mixture was adjusted to 8 with Na 2 CO 3 and extracted with 3 × 50 mL of dichloromethane.…”

“…The combined extracts were dried over MgSO 4 , filtered, and evaporated to yield brownish oil. Purification of this oil by column chromatography in silica gel with hexane/AcOEt (60:40, R f = 0.50) as eluent furnished 5,8-dimethoxy-3-methyl-2-tosyl-1,2-dihydroisoquinoline (10) in 62% yield as a yellow solid. Mp: 128−130 °C dec; (lit.…”

“…12 It was only possible to generate isoquinoline 8 from 10 after treatment with t-BuOK/t-BuOH at 80 °C for 30 min. 10 5,8-Dimethoxyisoquinoline (8) was then converted to isoquinoline-5,8-diones (11−13) by reaction with N-haloimides (Scheme 3). Thereafter, caulibugulones A−D were promptly prepared from 11−13 after subsequent reaction with the corresponding amines.…”

Unexpected PF6 Anion Metathesis during the Bischler–Napieralski Reaction: Synthesis of 3,4-Dihydroisoquinoline Hexafluorophosphates and Their Tetrahydroisoquinoline Related Alkaloids

“…Phosphoryl chloride (POCl 3 ) has been traditionally used as a dehydrating agent in the synthesis of nitriles from amides, 1 but when N-phenethylacylamides are employed as the substrate, the formed nitrilium intermediate can easily undergo an intramolecular cyclization to afford 3,4-dihydroisoquinolines in what is well known as a Bischler-Napieralski reaction (BNR). 2 Despite its harsh reaction conditions, the BNR is still preferred over other methodologies, such as the intramolecular cyclization of N-(2-acetylphenethyl)acetamides promoted by HCl, 3 the Pictet-Spengler, 4 and Pomeranz-Fritsch reaction, 5 for the construction of the isoquinoline ring system, since it is not a stereospecific reaction it does not require chiral catalysts, it is more versatile, and allows the synthesis of functionalized isoquinoline compounds, including numerous relevant alkaloids like protoberberines 1, benzylisoquinolines 2, phenanthridones 3, pyrrolo[2,1a]isoquinolines 4, aporphines 5, and β-carbolines 6 ( Figure 1). 6,7…”