(±)-Polysiphenol and Other Analogues via Symmetrical Intermolecular Dimerizations: A Synthetic, Spectroscopic,...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Stereochemistry

Background:

• Polysiphenol and its analogues are complex natural products with potential biological activities.
• Efficient synthetic routes to substituted dihydrophenanthrenes are valuable for chemical research.

Purpose of the Study:

• To develop an improved total synthesis of 4,5-dibromo-9,10-dihydrophenanthrene-2,3,6,7-tetraol, (±)-polysiphenol.
• To explore the applicability of the synthetic route to various halogenated and alkylated analogues.
• To investigate the stereochemical properties, specifically atropisomerism, of the synthesized compounds.

Main Methods:

• Intermolecular McMurray dimerization of 5-bromovanillin.
• Intramolecular oxidative coupling.
• Nuclear Magnetic Resonance (NMR) spectroscopy (¹H NMR).
• X-ray crystallography.
• Density Functional Theory (DFT) computational studies.

Main Results:

• An improved total synthesis of (±)-polysiphenol and its dichloro- and difluoro-analogues was achieved.
• The dibromo and dichloro compounds were identified as stable room-temperature atropisomers, confirmed by ¹H NMR and X-ray crystallography.
• The largest observed atropisomeric twist angle (48°) in a 4,5-disubstituted-9,10-dihydrophenanthrene was reported for a synthetic precursor.
• DFT studies revealed distinct two-stage atropisomeric interconversion mechanisms for different halogenated analogues.

Conclusions:

• The developed synthetic route is versatile and applicable to a range of analogues.
• The study provides significant insights into the stable atropisomerism of substituted dihydrophenanthrenes.
• Understanding the stereochemical behavior and interconversion mechanisms is crucial for future applications of these compounds.