The Azide-Allene Dipolar Cycloaddition: Is DFT Able to Predict Site- and Regio-Selectivity?

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Reaction Mechanism

Background:

• 1,3-Dipolar cycloadditions are fundamental reactions in organic synthesis.
• Understanding the selectivity of these reactions is crucial for controlling product formation.
• Arylazides and allenes are key reaction partners with diverse electronic properties.

Purpose of the Study:

• To investigate the site- and regio-selectivity of thermal, uncatalyzed 1,3-dipolar cycloadditions.
• To compare conceptual reactivity indices and computational Density Functional Theory (DFT) approaches.
• To validate computational predictions against experimental data for arylazide-allene reactions.

Main Methods:

• Utilized conceptual DFT reactivity indices.
• Employed computational DFT methods (M08-HX, ωB97X-D, B3LYP).
• Performed DFT transition state calculations for experimental selectivity prediction.
• Analyzed 1H-NMR data for mechanistic insights.

Main Results:

• Both conceptual and computational DFT approaches indicate a nonpolar, one-step reaction mechanism.
• DFT transition state calculations achieved semiquantitative agreement with experimental site- and regio-selectivity.
• Investigated selectivity for various substituted allenes, including methoxycarbonyl-, sulfonyl-, tetramethyl-, and tetrafluoro-allenes.
• 1H-NMR provided evidence for a methylene-1,2,3-triazoline intermediate.

Conclusions:

• The study confirms a nonpolar, one-step mechanism for arylazide-allene cycloadditions.
• Computational DFT methods reliably predict experimental selectivity, validating their utility.
• The identified intermediate reinforces the accuracy of the computational scheme for mechanistic studies.