The development of a highly enantioselective catalytic oxa-Pictet-Spengler reaction has proven a great challenge for chemical synthesis. We now report the first example of such a process, which was realized by utilizing a nitrated confined imidodiphosphoric acid catalyst. Our approach provides substituted isochroman derivatives from both aliphatic and aromatic aldehydes with high yields and excellent enantioselectivities. DFT calculations provide insight into the reaction mechanism.

A highly enantioselective Brønsted acid catalyzed intramolecular carbonyl-ene reaction of olefinic aldehydes has been developed. Using a confined imidodiphosphate catalyst, the reaction delivers diverse trans-3,4-disubstituted carbo- and heterocyclic five-membered rings in high yields and with good to excellent diastereo- and enantioselectivities. ESI-MS, NMR, and DFT mechanistic studies reveal that the reaction proceeds via a stepwise pathway involving a novel covalent intermediate.

By defining the fragmentation mechanism in complex oil samples it was possible to structurally characterize individual compounds present in a chromatographically simplified VGO. The compounds consist of an aromatic core with aliphatic side chains. Cleavage of all side chains can be achieved by MS measurements, allowing characterization of the remaining core structure.

A multicatalytic three-step reaction consisting of epoxidation, hydrolysis, and enantioselective monoacylation of cyclohexene was studied by using mass spectrometry (MS). The reaction sequence was carried out in a one-pot reaction using a multicatalyst. All reaction steps were thoroughly analyzed by electrospray ionization (ESI) MS (and MS/MS), as well as high-resolution MS for structure elucidation. These studies allow us to shed light on the individual mode of action of each catalytic moiety. Thus, we find that under the epoxidation conditions, the catalytically active N-methyl imidazole for the terminal acylation step is partially deactivated through oxidation. This observation helps to explain the lower efficiency of the catalyst in the last step compared to the monoacylation performed separately. All reactive intermediates and products of the reaction sequence, as well as of the side-reactions, were monitored, and we present a working mechanism of the reaction.

The development of modular combinations of organocatalytic reactions into cascades has been shown to be an effective tool despite the fact that the mechanism of such a complex organocatalytic multistep cascade reaction still remains poorly understood. Here the detailed mechanistic studies of a complex organocatalytic triple cascade reaction for the synthesis of tetra-substituted cyclohexene carbaldehydes are reported. The investigation has been carried out using a triple quadrupole mass spectrometer with electrospray ionization. Important intermediates were detected and characterized through MS/MS studies. A detailed formation pathway is presented based on these characterized intermediates, and supporting the proposed mechanism of the formation of the substituted cyclohexene carbaldehydes.