Alkynyl Halo-Aza-Prins Annulative Couplings

Area of Science:

• Organic Chemistry
• Heterocyclic Chemistry
• Synthetic Chemistry

Background:

• The Prins reaction is a valuable tool for carbon-carbon bond formation.
• Developing efficient methods for synthesizing nitrogen-containing heterocycles is crucial in medicinal chemistry.
• Aza-Prins reactions offer a pathway to functionalized nitrogen heterocycles.

Purpose of the Study:

• To comprehensively report studies in aza-alkynyl Prins chemistry.
• To compare and contrast reaction partners and reactivities in method development.
• To establish synthetic strategies for preparing diverse nitrogen-containing heterocycles.

Main Methods:

• Alkynyl aza-Prins coupling combined with annulation.
• Exploration of various iminium ions as electrophiles.
• Cyclization followed by capture with a halogen nucleophile.
• Suzuki cross-coupling reactions for library synthesis.

Main Results:

• Successful preparation of various nitrogen-containing heterocycles.
• Identification of selective Prins couplings yielding vinyl halides with E geometry.
• Demonstration of synthetic utility via Suzuki cross-couplings.
• Formation of vinyl halides through anti-addition across the alkyne.

Conclusions:

• The developed synthetic strategy efficiently produces nitrogen-containing heterocycles.
• The aza-alkynyl Prins cyclization is a versatile method for accessing functionalized heterocycles.
• The vinyl halide intermediate serves as a valuable handle for further diversification through cross-coupling reactions.