Highly Diastereoselective Hydroxy-Aza-Prins Cyclization: Rapid Access to 4'-Hydroxy Six-Membered Spiro Azacyclic...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Developing stereoselective synthetic methods is crucial for creating complex molecules.
• Spiro azacyclic oxindoles are important scaffolds in medicinal chemistry.

Purpose of the Study:

• To develop a novel, highly diastereoselective method for synthesizing 4'-hydroxy six-membered spiro azacyclic oxindoles.
• To control the stereochemistry at the C4' position through nucleophilic addition and cyclization.

Main Methods:

• Utilized palladium-catalyzed Tsuji-Trost umpolung allylation.
• Employed aza-Prins cyclization with N-2,2,2-trifluoroethylisatin ketimines.
• Investigated the role of hydrogen bonding interactions in stereochemical outcomes.

Main Results:

• Achieved highly diastereoselective synthesis of axial-4'-hydroxy six-membered spiro azacyclic oxindoles in excellent yields using a one-pot protocol.
• Demonstrated selective synthesis of equatorial-4'-acetoxy six-membered spiro azacyclic oxindoles by employing acetoxy-aza-Prins cyclization.

Conclusions:

• Established a versatile and efficient synthetic strategy for stereocontrolled synthesis of spiro azacyclic oxindoles.
• Highlighted the influence of nucleophile choice on the stereochemical outcome of the aza-Prins cyclization.