Domino process optimized via ab initio study for an alternative access to bicyclic lactams

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Bicyclic lactams are important structural motifs in medicinal chemistry.
• Existing synthetic routes often require harsh conditions or lack efficiency.

Purpose of the Study:

• To develop a new, efficient, and acid-free method for synthesizing highly functionalized bicyclic γ- and δ-lactams.
• To optimize reaction conditions using mechanistic insights.

Main Methods:

• Development of a novel domino reaction sequence.
• Utilizing ethoxymethylene derivatives as starting materials.
• Employing computational chemistry to elucidate reaction mechanisms.

Main Results:

• Successful synthesis of highly functionalized bicyclic γ- and δ-lactams.
• Identification of key mechanistic steps through computational analysis.
• Optimization of reaction conditions leading to a 3.5-fold increase in yield.

Conclusions:

• The reported acid-free domino process offers a versatile and high-yielding route to valuable bicyclic lactam structures.
• Mechanistic understanding enabled significant yield improvements, highlighting the power of computational chemistry in synthetic route optimization.