Metal-free synthesis of chlorinated <tex>$\beta$</tex>-amino ketones via an unexpected Reaction of imines with arylacetylenes in 1,1,1,3,3,3-hexafluoro-2-propanolMetal-free synthesis of chlorinated <tex>$\beta$</tex>-amino ketones via an unexpected Reaction of imines with arylacetylenes in 1,1,1,3,3,3-hexafluoro-2-propanol
Vande Velde, Christophe M.L.
Abbaspour Tehrani, Kourosch
Faculty of Sciences. Chemistry
Faculty of Applied Engineering Sciences
Advanced Reactor Technology (ART)
Advanced synthesis and catalysis. - Weinheim
358(2016):1, p. 41-49
University of Antwerp
The metal-free reaction of terminal arylacetylenes with α,α-dichloroaldimines in 1,1,1,3,3,3-hexafluoro-2-propanol as the sole solvent results in the rapid and selective formation of γ,γ-dichloro-β-amino ketones. In this solvent the expected dichlorinated propargylamines and/or allylic amines are not formed. The dichloromethylene moiety of the aldimine acts as an activating group and is essential to accomplish this transformation. Electron-rich acetylenes lead to the best results and work well with all imines (with or without α′-H at the nitrogen substituent), while electron-deficient acetylenes only reacted with N-tert-butylaldimines (no α′-H). The mechanistic pathway showed 1,1,1,3,3,3-hexafluoro-2-propanol to protonate the aldimine, which in the rate-determining step will react with the arylacetylene to form a resonance-stabilized allene cation, which is trapped by a HFIP molecule giving rise to an enol ether, which promptly hydrolyzes to furnish exclusively the β-amino ketones. Using DFT techniques we found that the first C[BOND]C bond forming step is the rate-determining step and is associated with a barrier of about 21 kcal mol−1.