Dimerization of Allylbenzenes into Cyclolignans by a Metathesis-Oxidation Sequence

Area of Science:

• Organic Chemistry
• Catalysis
• Natural Product Synthesis

Background:

• Allylbenzenes are precursors to valuable cyclolignan natural products.
• Existing synthetic routes for cyclolignans can be complex and lack scalability.
• Ruthenium-catalyzed olefin metathesis offers a powerful tool for C-C bond formation.

Purpose of the Study:

• To develop a streamlined, one-pot synthesis for dimeric cyclolignans from allylbenzenes.
• To explore the influence of oxidation conditions on product distribution.
• To investigate the reaction mechanism of the metathesis-oxidation sequence.

Main Methods:

• A two-step, one-pot sequence involving ruthenium-catalyzed olefin metathesis.
• Subsequent oxidation using iron or acid catalysis with DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone).
• Exploration of wet oxidation conditions for alternative product formation.

Main Results:

• Successful synthesis of dimeric cyclolignans, including arylnaphthalene and aryltetralin scaffolds.
• Oleralignan B and its derivatives were prepared efficiently.
• Benzyl styryl ketones were identified as major products under wet oxidation conditions.
• Mechanistic studies indicated a process involving single electron transfer, hydrogen atom transfer, and proton transfer.

Conclusions:

• The developed Ru-catalyzed metathesis and DDQ oxidation sequence provides a scalable and straightforward route to cyclolignans.
• The reaction conditions can be tuned to selectively produce either cyclolignans or benzyl styryl ketones.
• This methodology advances the synthesis of complex natural products and their analogs.