Intramolecular hydroxycarbene C–H-insertion: The curious case of (o-methoxyphenyl)hydroxycarbene

Abstract

SummaryThe first C–H insertion of a hydroxycarbene species in the gas phase has been observed experimentally by means of high vacuum flash pyrolysis (HVFP) and subsequent matrix isolation: (o-Methoxyphenyl)glyoxylic acid gives non-isolable (o-methoxyphenyl)hydroxycarbene upon pyrolysis at 600 °C, which rapidly inserts into the methyl C–H bond. The insertion product, 2,3-dihydrobenzofuran-3-ol, was trapped in an excess of Ar at 11 K and characterized by infrared spectroscopy. The insertion process kinetically outruns the alternative [1,2]H-tunneling reaction to o-anisaldehyde, a type of reaction observed for other hydroxycarbenes. Traces of the dehydration product, benzo[b]furan, were also detected. The potential energy hypersurface including the insertion and hydrogen migration processes was computed at the all-electron coupled-cluster level of theory encompassing single and double substitutions and perturbatively included triple excitations [AE-CCSD(T)] in conjunction with a correlation-consistent double-ζ basis set (cc-pVDZ) by utilizing density functional theory (DFT) optimized geometries (M06-2X/cc-pVDZ) with zero-point vibrational energy (ZPVE) corrections. Exchange of the methoxy for a trifluoromethoxy group successfully prevents insertion and (o-trifluoromethoxy)benzaldehyde is produced instead; however, the carbene cannot be observed under these conditions. Thermal decomposition of (o-methoxyphenyl)glyoxylic acid in refluxing xylenes does not give the insertion product but yields o-anisaldehyde. This unanticipated outcome can be rationalized by protonation of the hydroxycarbene intermediate leading to the tautomeric formyl group. Thermochemical computations at M06-2X/cc-pVDZ in conjunction with a self-consistent solvent reaction field model support this suggested reaction pathway.

Silicon‐Derived Singlet Nucleophilic Carbene Reagents in Organic Synthesis

“…[20,58] Of interest, an analogous C-H insertion process was observed during pyrolysis of 2-(2-methoxyphenyl)-2-oxoacetic acid which proposedly proceeds via the hydroxy carbene generated following decarboxylation (Scheme 23). [59]…”

Gas‐Phase Structure Determination of Dihydroxycarbene, One of the Smallest Stable Singlet Carbenes

“…[3] The first experimental evidence for the existence of dihydroxycarbene was inferred by neutralization/reionization mass spectroscopy. [7,27,37,38] We present here the first direct gas-phase evidence for trans,cis-HOÀC ÀOH, and a precise determination of its rotational spectrum and geometric structure, using a combination of Fourier transform microwave spectroscopy (FTMW), microwave-millimeter-wave double resonance (DR) spectroscopy, and high-level theoretical calculations. [6,26] In contrast, HOÀC ÀOH displays no tunneling behavior and is stable under the low-temperature matrix conditions.…”

“…Subsequent work with several substituted oxycarbenes indicates that the propensity for tunneling is greatly influenced by the identity of the substituent. [7,27,37,38] We present here the first direct gas-phase evidence for trans,cis-HOÀC ÀOH, and a precise determination of its rotational spectrum and geometric structure, using a combination of Fourier transform microwave spectroscopy (FTMW), microwave-millimeter-wave double resonance (DR) spectroscopy, and high-level theoretical calculations. The 5-43 GHz Balle-Flygare-type FTMW spectrometer used in these experiments has been described elsewhere, [39][40][41][42] so only a brief description is provided here; a more extensive discussion can be found in the Supporting Information.…”

Computational methods for contemporary carbene chemistry

“…However, the barrier of insertion was found to be higher than the binding enthalpy of the initial complex, thereby rationalizing why no reaction can occur in the first place. In the following, the first CH insertion reaction of a hydroxycarbene was observed by Gerbig et al124 The authors examined the intramolecular CH insertion in ( o ‐methoxyphenyl)hydroxycarbene ( 29 ) by high vacuum flash pyrolysis (HVFP) of the corresponding glyoxylic acid and studied the insertion process computationally at the M06–2X/cc‐pVDZ level 124. The insertion product was found to be 2,3‐dihydrobenzofuran‐3‐ol, which was present in the matrix along with dehydration product benzo[ b ]furan.…”