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

ABSTRACT

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 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 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)3 (PF6 )2 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 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 range of AMS in on-line monitoring.