Synthesis of push-pull-activated ynol ethers and their evaluation in the bioorthogonal hydroamination reaction.
Org Biomol Chem
; 20(46): 9217-9221, 2022 11 30.
Article
in En
| MEDLINE
| ID: mdl-36367436
ABSTRACT
A new class of push-pull-activated alkynes featuring di- and trifluorinated ynol ethers was synthesized. The difluorinated ynol ether exhibited an optimal balance of stability and reactivity, displaying a substantially improved half-life in the presence of aqueous thiols over the previously reported 1-haloalkyne analogs while reacting just as fast in the hydroamination reaction with N,N-diethylhydroxylamine. The trifluorinated ynol ether reacted significantly faster, exhibiting a second order rate constant of 0.56 M-1 s-1 in methanol, but it proved too unstable toward thiols. These fluorinated ynol ethers further demonstrate the importance of the hyperconjugation-rehybridization effect in activating alkynes and demonstrate how substituent effects can both activate and stabilize alkynes for bioorthogonal reactivity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ethers
/
Ether
Language:
En
Journal:
Org Biomol Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2022
Type:
Article
Affiliation country:
United States