|
Title
|
|
|
|
Metal-free synthesis of chlorinated -amino ketones via an unexpected Reaction of imines with arylacetylenes in 1,1,1,3,3,3-hexafluoro-2-propanol
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| 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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Advanced synthesis and catalysis. - Weinheim, 2001, currens
| |
|
Publication
|
|
|
|
Weinheim
:
2016
| |
|
ISSN
|
|
|
|
1615-4150
[print]
1615-4169
[online]
| |
|
DOI
|
|
|
|
10.1002/ADSC.201500519
| |
|
Volume/pages
|
|
|
|
358
:1
(2016)
, p. 41-49
| |
|
ISI
|
|
|
|
000370256000006
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|