Diversity‐Oriented Synthesis of Polycyclic Scaffolds by Modification of an Anodic Product Derived from 2,4‐Dimethylphenol

Abstract

Like a Swiss army knife: The pentacycle shown, which results from the anodic oxidation of 2,4‐dimethylphenol, displays a wealth of potential reactivity. Depending on the applied reaction conditions a variey of polycyclic architectures are obtained with impressive stereo‐, regio‐, and chemoselectivity.

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

“…[23] In avery innovative and interesting approach that leads to structurally rich and diverse NP scaffolds,W aldvogel and coworkers employed an electrochemical transformation to build an intermediate (176)t hat was utilized to generate various complex molecular scaffolds (Scheme 15). [64] Anodic oxidation of 2,4-dimethylphenol (175)onplatinum electrodes with Ba(OH) 2 ·8 H 2 Oi nm ethanol as the electrolyte afforded oxygen-rich compound 176.F urther simple transformations (one to two steps) of 176 led to fourteen compounds based on four distinct scaffolds with almost exclusive selectivity and in reasonable yields.…”

Synthesis and Isolation of Enantiomerically Enriched Cyclopenta[b]benzofurans Based on Products from Anodic Oxidation of 2,4‐Dimethylphenol

“…In addition it was possible to verify the connection between the structures of 3a [13] and 3d [14] determined by Xray crystallography and the observed NMR spectroscopic data of both diastereomers [13,14] by calculating the 1 H and 13 C chemical shifts in silico which also ensured that the crystals picked for X-ray analysis corresponded to the bulk material in every case. To achieve this, the geometries of all four possible diastereomers (Scheme 5) were optimized at the B3LYP/6-311G(d,p) level of theory.…”

“…[14] As an extension of our chiroptical study, their absolute configuration was also determined after chiral HPLC separation in the same way as described for (-)-3a and (+)-3a. The VCD spectra (Figure 6) again show an excellent agreement of experiment and prediction.…”

“…[13] This reaction is the key step of a powerful methodology in a diversity-oriented synthetic approach to create multiple stereogenic centres on a multi-gram scale in a single synthetic step. [14] Furthermore, it offers access to numerous scaffolds of natural products in a highly chemo-, stereo-, regioselective and easy to perform manner. [14] The unique selectivities of the latter substitution reactions are based on a combination of strong hydrogen-bonding interactions and steric repulsions.…”

“…[14] Furthermore, it offers access to numerous scaffolds of natural products in a highly chemo-, stereo-, regioselective and easy to perform manner. [14] The unique selectivities of the latter substitution reactions are based on a combination of strong hydrogen-bonding interactions and steric repulsions. [15] Scheme 1.…”