Examination of electronically mismatched Diels-Alder reaction by on-line mass spectrometry.

RATIONALE

Electronically mismatched Diels-Alder reactions have gained much attention as an alternative pathway for C-C bond formation. To facilitate the development of facile organic transformations, mechanistic investigations are required. Spectroscopic methods (NMR, electron paramagnetic resonance and UV-visible) are normally adopted for mechanistic examinations, but further improvements in directly obtaining structural information of short-lived intermediates are encouraged. Herein, an electronically mismatched Diels-Alder reaction between indole and 1,3-cyclohexadiene was studied using in situ electrospray ionization mass spectrometry (in situ ESI-MS). Based on direct sampling and detection of the in situ ESI-MS without sample pretreatment, the structures and dynamics of important intermediates were examined on-line.

METHODS

A syringe-based photocatalytic reactor and in situ ambient MS (AMS) evaluation system was constructed for mechanism studies. The role of oxygen was confirmed via control reaction employed in the N-bubbled system. The stepwise cation radical-based pathway and the [2 + 2] cycloaddition process were determined through a series of experiments, including solvent evaluation, MS/MS experiments and dynamic monitoring.

RESULTS

The dependence of the reaction on solvent polarity demonstrated that the reaction occurs via the formation of cation radicals, which were captured, identified and dynamically monitored via in situ ESI-MS. Without pre-separation, the intermediate of [2 + 2] cycloaddition was identified and the cycloaddition process was thereby determined to be the combination of [4 + 2] cycloaddition and [2 + 2] cycloaddition. In addition, oxygen was proved to act as an electron mediator for both catalyst Ru(bpz)(PF) and radical cations.

CONCLUSIONS

The mechanism of an electronically mismatched Diels-Alder reaction was successfully deduced by in situ MS associated with a syringe-based photocatalytic reactor. The structures and dynamics of cation radicals, the effect of O for the reaction and the detailed process of [2 + 2] cycloaddition have been well demonstrated. This work could not only promote the understanding and development of facile photocatalytic transformations, but also enlarge the application range of AMS in on-line monitoring.