Ynamide Protonation-Initiated N-Heteropolyene Cyclization.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Stereoselective Synthesis

Background:

• N-containing polycyclic frameworks with chiral centers are crucial in natural products and bioactive molecules.
• Stereoselective construction of these complex frameworks is a significant synthetic challenge.

Purpose of the Study:

• To develop an efficient and stereoselective method for synthesizing complex N-containing polycyclic skeletons.
• To overcome limitations of existing multi-step strategies for accessing these structures.

Main Methods:

• Utilized ynamide-initiated polyene cyclization triggered by protonation.
• Employed Density Functional Theory (DFT) calculations to elucidate the reaction mechanism.

Main Results:

• Successfully constructed complex N-containing polycyclic frameworks with excellent stereoselectivity from linear precursors.
• Identified a nonclassical carbocation intermediate with a cyclopropane ring as key to diastereoselectivity.

Conclusions:

• Protonation of ynamide-initiated polyene cyclization offers a powerful strategy for stereoselective synthesis.
• The mechanistic insights from DFT calculations aid in understanding and controlling the stereochemical outcome.