Asymmetric Cascade Michael-Cyclopropanation-Rearrangement to Spiro[Furo[2,3-d]Pyrimidines].

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Medicinal Chemistry

Background:

• Oxindole derivatives are important scaffolds in medicinal chemistry.
• Developing efficient synthetic routes to complex heterocyclic compounds is crucial.
• Spirocyclic compounds containing fused pyrimidine rings are of significant interest.

Purpose of the Study:

• To develop a novel organocatalytic enantioselective methodology.
• To synthesize oxindole-fused spiro[furo[2,3-d]pyrimidines] with high efficiency and stereocontrol.
• To explore a cascade reaction involving Michael-Cyclopropanation-Rearrangement.

Main Methods:

• Organocatalysis
• Enantioselective synthesis
• Cascade reaction (Michael-Cyclopropanation-Rearrangement)
• Synthesis from 3-chlorooxindoles and 5-alkylidene barbituric acids

Main Results:

• Achieved high bond efficiency by forming two C-C bonds and one C-O bond.
• Synthesized spiro[furo[2,3-d]pyrimidines] in excellent yields (up to 90%).
• Obtained high stereoselectivity (dr up to 99:1, er up to 97:3) with two contiguous stereocenters.
• Reaction proceeds at room temperature.

Conclusions:

• An unprecedented organocatalytic enantioselective methodology has been established.
• The developed method provides efficient access to valuable oxindole-fused spiro[furo[2,3-d]pyrimidines].
• The reaction pathway was elucidated using 1H NMR and HRMS studies.