Taming hypervalent bonds and strained rings for catalysis and synthesis

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Medicinal Chemistry

Background:

• Complex organic molecule synthesis is crucial for medicine, agrochemicals, and materials science.
• Non-classical bond disconnections offer innovative synthetic strategies.
• Hypervalent iodine reagents and strained rings are key energy-loaded organic molecules.

Purpose of the Study:

• To review recent progress (since 2011) in developing non-classical bond disconnections.
• To highlight advancements using hypervalent iodine reagents and strained rings.
• To showcase novel synthetic routes to complex organic molecules and nitrogen-rich building blocks.

Main Methods:

• Utilized cyclic hypervalent iodine reagents for various functionalization reactions.
• Employed amino-substituted aminocyclopropanes and aminocyclobutanes in annulation reactions.
• Developed domino cyclization and dynamic kinetic annulation strategies.

Main Results:

• Extended hypervalent iodine chemistry to C2-selective alkynylation of indoles, domino cyclization-alkynylation of allenes, thiol alkynylation, and carbonyl azidation.
• Synthesized nitrogen-rich building blocks, including nucleoside analogues, via [3+2] and [4+2] annulations of strained rings.
• Achieved the first dynamic kinetic [3+2] annulation of aminocyclopropanes with enol ethers and aldehydes.

Conclusions:

• Significant progress has been made in leveraging hypervalent iodine reagents and strained rings for efficient organic synthesis.
• These methods provide powerful tools for constructing complex molecular architectures and valuable nitrogen-containing compounds.
• The reported advancements offer new possibilities for drug discovery, agrochemical development, and materials innovation.