Atropodiastereoselectivity in solid state BINOL synthesis: leads from the estradiol platform

Area of Science:

• Organic Chemistry
• Stereochemistry
• Materials Science

Background:

• Steroidal scaffolds are crucial in medicinal chemistry.
• BINOL (1,1'-bi-2-naphthol) derivatives are important chiral ligands and building blocks.
• Developing efficient synthetic routes to functionalized steroidal BINOLs is challenging.

Purpose of the Study:

• To synthesize a novel functionalized steroidal BINOL scaffold.
• To develop a straightforward and efficient synthetic methodology.
• To explore solid-state synthesis for atroposelective coupling.

Main Methods:

• A sequence involving dehydrogenation, chlorination, and atroposelective phenolic coupling.
• One-step synthesis under solid-state conditions.
• Utilizing a functionalized steroidal precursor.

Main Results:

• Successful production of a novel functionalized steroidal BINOL scaffold.
• The synthesis is achieved in a single step under solid-state conditions.
• Chiral additives are not required for the atroposelective coupling.

Conclusions:

• A novel steroidal BINOL scaffold can be efficiently synthesized via a one-step solid-state reaction.
• This method offers a straightforward and potentially scalable approach to complex chiral molecules.
• The absence of chiral additives simplifies the synthetic process and reduces costs.