Stereocontrol in Conformationally Stable C(sp²)─C(sp³) Atropisomers

Area of Science:

• Organic Chemistry
• Stereochemistry
• Asymmetric Synthesis

Background:

• Atropisomers are molecules with axial chirality due to restricted rotation around a single bond.
• Stable C(sp2)-C(sp3) atropisomers are rare and challenging to synthesize enantioselectively.
• Controlling stereochemistry in complex molecular architectures is crucial for drug discovery and materials science.

Purpose of the Study:

• To develop a novel two-step sequence for the enantioselective synthesis of stable C(sp2)-C(sp3) atropisomers.
• To introduce two additional stereogenic centers during the synthesis.
• To enhance the barrier to diastereomerization, thereby stabilizing the atropisomeric configuration.

Main Methods:

• Organocatalyzed dihydrobenzofurannulation to establish initial stereochemistry.
• Diastereoselective functionalization to stabilize the C(sp2)-C(sp3) bond.
• Utilizing stereochemical control throughout the reaction sequence.

Main Results:

• Successful enantioselective construction of a rare family of stable C(sp2)-C(sp3) atropisomers.
• Control over the stereochemistry of two carbon centers via dihydrobenzofurannulation.
• Significant enhancement of the diastereomerization barrier, leading to locked configurations.

Conclusions:

• The reported two-step sequence provides an effective route to enantiomerically pure C(sp2)-C(sp3) atropisomers.
• The method allows for the simultaneous introduction and control of multiple stereocenters.
• This work expands the accessibility of complex, stable atropisomeric scaffolds for further chemical exploration.