Bioinspired Synthesis of (-)-PF-1018

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Pericyclic Reactions

Background:

• Electrocyclizations and cycloadditions are key reactions in forming complex natural products.
• Common cascades involve 8π electrocyclizations followed by 6π electrocyclizations and cycloadditions.

Purpose of the Study:

• To report the synthesis of the tetramic acid PF-1018.
• To investigate a novel pericyclic cascade involving an 8π electrocyclization and Diels-Alder cycloaddition.

Main Methods:

• Synthesis of tetramic acid PF-1018.
• Utilizing an 8π electrocyclization immediately followed by a Diels-Alder cycloaddition.
• Employing DFT calculations to rationalize the cascade's success.

Main Results:

• Successful synthesis of tetramic acid PF-1018 via an 8π electrocyclization and Diels-Alder cycloaddition cascade.
• Demonstrated critical dependence of the cascade on the starting polyene's substitution pattern.
• Completed the synthesis by installing a trisubstituted double bond via radical deoxygenation.
• Recycled an unexpected 4-exo-trig radical cyclization side product through triflation/fragmentation.

Conclusions:

• The reported pericyclic cascade provides an efficient route to tetramic acid PF-1018.
• Substitution patterns significantly influence the success of such pericyclic cascades.
• Developed an unprecedented method for recycling a radical cyclization side product.