Hydrogen Bonding Shuts Down Tunneling in Hydroxycarbenes: A Gas-Phase Study by Tandem-Mass Spectrometry, Infrared Ion Spectroscopy, and Theory.
Mathias PaulThomas ThomulkaWacharee HarnyingJörg-Martin NeudörflCharlie R AdamsJonathan MartensGiel BerdenJos OomensAnthony J H M MeijerAlbrecht BerkesselMathias SchäferPublished in: Journal of the American Chemical Society (2023)
Hydroxycarbenes can be generated and structurally characterized in the gas phase by collision-induced decarboxylation of α-keto carboxylic acids, followed by infrared ion spectroscopy. Using this approach, we have shown earlier that quantum-mechanical hydrogen tunneling (QMHT) accounts for the isomerization of a charge-tagged phenylhydroxycarbene to the corresponding aldehyde in the gas phase and above room temperature. Herein, we report the results of our current study on aliphatic trialkylammonio-tagged systems. Quite unexpectedly, the flexible 3-(trimethylammonio)propylhydroxycarbene turned out to be stable─no H-shift to either aldehyde or enol occurred. As supported by density functional theory calculations, this novel QMHT inhibition is due to intramolecular H-bonding of a mildly acidic α-ammonio C-H bonds to the hydroxyl carbene's C-atom (C:···H-C). To further support this hypothesis, (4-quinuclidinyl)hydroxycarbenes were synthesized, whose rigid structure prevents this intramolecular H-bonding. The latter hydroxycarbenes underwent "regular" QMHT to the aldehyde at rates comparable to, e.g., methylhydroxycarbene studied by Schreiner et al. While QMHT has been shown for a number of biological H-shift processes, its inhibition by H-bonding disclosed here may serve for the stabilization of highly reactive intermediates such as carbenes, even as a mechanism for biasing intrinsic selectivity patterns.
Keyphrases
- density functional theory
- room temperature
- molecular dynamics
- tandem mass spectrometry
- high resolution
- ionic liquid
- ultra high performance liquid chromatography
- high performance liquid chromatography
- liquid chromatography
- simultaneous determination
- energy transfer
- single molecule
- gas chromatography
- solid state
- mass spectrometry
- diabetic rats
- high glucose
- open label
- randomized controlled trial
- drug induced
- molecular dynamics simulations
- ms ms
- monte carlo
- visible light