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Breslow intermediates (BIs) are the crucial nucleophilic amino enol intermediates formed from electrophilic aldehydes in the course of N‐heterocyclic carbene (NHC)‐catalyzed umpolung reactions. Both in organocatalytic and enzymatic umpolung, the question whether the Breslow intermediate exists as the nucleophilic enol or in the form of its electrophilic keto tautomer is of utmost importance for its reactivity and function. Herein, the preparation of charge‐tagged Breslow intermediates/keto tautomers derived from three different types of NHCs (imidazolidin‐2‐ylidenes, 1,2,4‐triazolin‐5‐ylidenes, thiazolin‐2‐ylidenes) and aldehydes is reported. An ammonium charge tag is introduced through the aldehyde unit or the NHC. ESI‐MS IR ion spectroscopy allowed the unambiguous conclusion that in the gas phase, the imidazolidin‐2‐ylidene‐derived BI indeed exists as a diamino enol, while both 1,2,4‐triazolin‐5‐ylidenes and thiazolin‐2‐ylidenes give the keto tautomer. This result coincides with the tautomeric states observed for the BIs in solution (NMR) and in the crystalline state (XRD), and is in line with our earlier calculations on the energetics of BI keto–enol equilibria., Breslow intermediates in the gas phase: In N‐heterocyclic carbene (NHC)‐catalyzed Umpolung, the reaction of the substrate aldehyde with the NHC gives the Breslow intermediate (BI) as pivotal species. The combination of IR ion spectroscopy with quantum chemical computations can determine whether the BI exists as a nucleophilic amino enol or as its keto tautomer in the gas phase, which is decisive for its reactivity both in enzymatic catalysis and in organocatalysis.

While hydrogen tunneling at elevated temperatures has, for instance, often been postulated in biochemical processes, spectroscopic proof is thus far limited to cryogenic conditions, under which thermal reactivity is negligible. We report spectroscopic evidence for H-tunneling in the gas phase at temperatures around 320-350K observed in the isomerization reaction of a hydroxycarbene into an aldehyde. The charge-tagged carbene was generated in situ in a tandem mass spectrometer by decarboxylation of oxo[4-(trimethylammonio)phenyl]acetic acid upon collision induced dissociation. All ion structures involved are characterized by infrared ion spectroscopy and quantum chemical calcula-tions. The charge-tagged phenylhydroxycarbene undergoes 1,2-H-shift to the corresponding aldehyde with an half-life of about 10 s, evidenced by isomer-selective two-color (IR-IR) spectroscopy. In contrast, the deuterated (OD) carbene analogue showed much reduced 1,2-D-shift reactivity with an estimated half-life of at least 200 seconds under the experimental conditions, and provides clear evidence for hydrogen atom tunneling in the H-isotopologue. This is the first spectroscopic confirmation of hydrogen atom tunneling governing 1,2-H-shift reactions at non-cryogenic temperatures, which is of broad significance for a range of (bio)chemical processes, including enzymatic transformations and organocatalysis.