Coumarins by Direct Annulation: β-Borylacrylates as Ambiphilic C₃ -Synthons

Area of Science:

• Organic Synthesis
• Catalysis
• Medicinal Chemistry

Background:

• Coumarins are a vital class of heterocyclic compounds with broad applications.
• Existing synthetic methods for coumarins often lack efficiency or versatility.

Purpose of the Study:

• To develop a novel, programmable synthetic strategy for diverse coumarins.
• To utilize modular β-borylacrylates as C3-synthons in cascade annulation reactions.

Main Methods:

• Employing modular β-borylacrylates as ambiphilic C3-synthons.
• Utilizing a [3+3] disconnection strategy involving 2-halo-phenol derivatives.
• Leveraging the BPin unit for C(sp2)-C(sp2) coupling and alkene geometry control via energy transfer catalysis.
• Implementing mild isomerization for accessing 3-substituted coumarins.

Main Results:

• Successful synthesis of structurally and electronically diverse coumarins.
• Demonstrated dual role of the BPin unit as a linker and chromophore.
• Achieved inversion of alkene geometry through selective energy transfer catalysis.
• Showcased the method's utility in synthesizing natural products and π-expanded estrone derivatives.

Conclusions:

• The developed method offers a versatile and efficient route to complex coumarin derivatives.
• The strategy facilitates the synthesis of natural products and analogs for drug discovery and repurposing.
• This work expands the synthetic toolkit for accessing valuable coumarin scaffolds.