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

Dennis Gerbig,Peter R Schreiner,David Ley,Hans Peter Reisenauer

doi:10.3762/bjoc.6.121

Abstract

The 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.

Highlights

Hydroxycarbenes have been the subject of many theoretical and experimental studies since the early years of last century, these proved to be elusive for a long time [1]
The 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
Ring insertions characteristic for other singlet phenylcarbenes, i. e., phenylmethylcarbene [16] and phenylchlorocarbene [17], were not experimentally observed for 3, and we report the first C–H-bond insertion reaction of a hydroxycarbene that is akin to other heterocarbenes [18,19,20] (Scheme 2). (o-Methoxyphenyl)hydroxycarbene (5) serves as the model compound for studying the intramolecular carbene C–H-bond

Summary

Introduction

Hydroxycarbenes have been the subject of many theoretical and experimental studies since the early years of last century, these proved to be elusive for a long time [1]. Several hydroxycarbenes exhibit remarkable [1,2]H-tunneling under cryogenic conditions in solid noble gas matrices, even at temperatures as low as 11 K: Hydroxymethylene (1) [13] and phenylhydroxycarbene (3) [14] yield formaldehyde (2) and benzaldehyde (4), respectively, as a result of facile [1,2]hydrogen tunneling from the hydroxy group to the carbene center. Dihydroxycarbene (a) [15] and methoxyhydroxycarbene (c) [15], do not undergo [1,2]H-tunneling under the same conditions: Their respective products, formic acid (b) and methyl formate (d) were not detected in matrix isolation experiments (Scheme 1). Insertion both under matrix isolation and solution conditions (Scheme 3) The generation of such carbenes in solution in high-boiling solvents would provide convenient preparative access to dihydrobenzofuranols from readily accessible α-keto acids as the starting materials.

Methods

Results

Conclusion