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

Abstract

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.

N,N-Diethylurea-Catalyzed Amidation between Electron-Deficient Aryl Azides and Phenylacetaldehydes

“…This rearrangement is similar to the cycloaddition reaction of PFAA with enamines to yield amidines, where the electron-deficient aryl group promoted the transformation at room temperature. 13 In the presence of a stronger base, the triazoline instead underwent dehydration to form the 1,4-triazole ( 8 ), which was also reported recently by Ramachary et al 14 …”

1,3-Dipolar Cycloadditions of Diazo Compounds in the Presence of Azides

“…For example, electron-rich azides react more rapidly than do electron-deficient azides in a cycloaddition with DIBAC. 13,16 DIBAC also reacts faster than do other cyclooctynes with the diazoacetamide functionality. 6 …”

Design and synthesis of theranostic antibiotic nanodrugs that display enhanced antibacterial activity and luminescence

“…This unique reactivity of perfluoroaryl azides is due to their highly electron-deficient nature, which allows these electrophilically activated azides to undergo cycloaddition with enamines at room temperature without any catalysts (29,30), and also with other dipolarophiles and nucleophiles (31)(32)(33). Ciprofloxacin is sparingly soluble in common organic solvents.…”