1,3-Dipolar Cycloaddition Reactivities of Perfluorinated Aryl Azides with Enamines and Strained Dipolarophiles

• Published in: Journal of the American Chemical Society 2015-03, Vol.137 (8), p.2958-2966
• Main Authors: Xie, Sheng, Lopez, Steven A, Ramström, Olof, Yan, Mingdi, Houk, K. N
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja511457g

The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA–enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine–azide cycloadditions.