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

Abstract

The anodic treatment of 2,4‐dimethylphenol offers a powerful and direct method for the construction of a dehydrotetramer with four contiguous stereocentres on a multigram scale. The installation of propellanes on this scaffold using enantiomerically pure carbonyl compounds leads to a mixture of diastereomers. This mixture is easily separable using standard chromatography and gives rise to optically pure cyclopenta[b]benzofurans which are important scaffolds in a variety of natural products. The synthesis is easy to perform and allows a reliable access to chiral compounds with very high enantiomeric excess. It was possible to determine the absolute configuration of these compounds by comparison of experimentally recorded and calculated VCD spectra of all enantiomers.

Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations

“…On the other hand, in 69 % of the cases the DP4 probabilities were based on both 1 H and 13 C NMR data (as recommended by the DP4 developers) –,,–,,,,–,,,–,,,–. In the remaining cases, the 13 C NMR data was strongly preferred to compute the DP4 probability (27 %), finding only 2 examples (4 %) that were built using 1 H NMR data ,…”

“…In fact, 71 % of papers published that reported the use of DP4 have been carried out following this approach ,–,–. Another interesting fact is that in 28 % of the cases the predictions made by DP4 were actually validated experimentally (mainly by total synthesis of the most likely candidate),,,,,,,,,,, indicating a clear trend for the scientific community to accept stereochemical assignments based on theoretical calculations.…”

Electrochemical strategies for C–H functionalization and C–N bond formation

“…558,559 In addition to generating the desired biphenol product, several additional coupling motifs can also be produced. [560][561][562][563][564][565] To circumvent the lack of selectivity, Waldvogel and coworkers realized that boron-doped diamond (BDD) electrodes 22 gave almost exclusive selectivity for the ortho-coupling product (Scheme 67). 566,567 It was rationalized that the observed selectivity originated from the high chemical and electrochemical stability of the BDD electrodes in combination with the high overpotential for oxygen evolution in aqueous media and efficient formation of reactive alkoxy or hydroxyl radicals at the anode that can serve as mediators.…”

Organic Electrosynthesis: Applications in Complex Molecule Synthesis

“…The electron‐rich properties associated with phenolic compounds make them particularly amenable to oxidation, a feature that makes them especially attractive in natural product synthesis . Early studies by the Waldvogel laboratory have demonstrated that phenols can be electro‐oxidatively coupled to produce biphenols as well as polycyclic scaffolds . A related strategy was recently employed by the Opatz and Waldvogel groups in the syntheses of (−)‐thebaine and (−)‐oxycodone .…”