Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

Abstract

The treatment of 2-(2-vinylphenyl)acetaldehydes or 3-(2-vinylphenyl)propanals with BF3·Et2O results in an intramolecular Prins reaction affording intermediary benzyl carbenium ions, which are then trapped by a variety of electron-rich aromatics via Friedel–Crafts alkylation. This cascade Prins/Friedel–Crafts cyclization protocol paves an expedient path to medicinally useful 4-aryltetralin-2-ol and 5-aryltetrahydro-5H-benzo[7]annulen-7-ol derivatives.

Synthesis of Antimicrobial Benzo[1,2,4]triazoloazepinium Salts and Tetrahydronaphtho[1,2-e][1,2,4]triazines by Polar [3+ + 2] and [4 + 2]-Cycloaddition Reactions

“…Quite recently, we have disclosed a Prins/Friedel–Crafts cyclization methodology for the synthesis of substituted β-tetralones . We envisioned that the β-tetralones could be used to generate novel 1-aza-2-azoniaallenium cation intermediates for reaction with nitriles to produce [1,2,4]­triazoloazepine scaffolds with a new annulation pattern.…”

“…19−21 Quite recently, we have disclosed a Prins/Friedel−Crafts cyclization methodology for the synthesis of substituted βtetralones. 22 We envisioned that the β-tetralones could be used to generate novel 1-aza-2-azoniaallenium cation intermediates for reaction with nitriles to produce [1,2,4] Azoacetate 4a was selected as a model substrate to probe the strategy of sequential [3 + + 2] cycloaddition and rearrangement using 4-methoxybenzonitrile (Scheme 3). A Lewis acid screen in CH 2 Cl 2 at 0 °C was first carried out.…”

Access to Hexahydroindeno[2,1-c]pyran-Based Propellanes by a Domino Prins/Friedel–Crafts Cyclization

“…Such a strategy combining both Prins reaction and Friedel-Crafts cyclization has been recently reviewed 23 and is still under investigation. [24][25][26][27][28][29] For example, Reddy et al described a concise and practical synthesis of indenopyran scaffolds from (E)-3,5-diphenylpent-4-en-1-ol 3, various aldehydes and through the activation of BF3.OEt2 at 70°C (Scheme 2). 30 Scheme 2.…”

“…It differs by possessing one additional methoxy group that considerably enhances the electron density of the aromatic ring, as already identified as a requirement for tandem Prins/intermolecular Friedel-Crafts reactions. 9,23,26 The reaction was initially carried out with p-nitrobenzaldehyde (11a) at 0 °C in the presence of BF 3 •OEt 2 as the catalyst (20 mol%) under stirring at room temperature for 21 hours (Scheme 7 and Table 1). After treatment, two new compounds, 12a and 13a, were isolated in 53% yield as a 3:1 mixture, which were separated by flash chromatography on silica gel.…”

“…It differs by possessing one additional methoxy group that considerably enhances the electron density of the aromatic ring, as already identified as a requirement for tandem Prins/intermolecular Friedel–Crafts reactions. 9 23 26…”