Examination of Electronically Mismatched Diels–Alder Reaction by Online Mass Spectrometry

Rationale

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

Methods

A syringe-based photocatalytic reactor and in-situ AMS evaluation system was constructed for mechanism studies. The role of oxygen was confirmed via control reaction employed in the N₂-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 identifiedand the cycloaddition process is 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)₃(PF₆)₂ and radical cations.

Conclusions

The mechanism of 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 O₂ 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 of AMS in on-line monitoring.