Primary Amine Catalyzed Activation of Carbonyl Compounds: A Study on Reaction Pathways and Reactive Intermediates by Mass Spectrometry

Abstract

The field of organocatalysis is expanding at a fast pace. Its growth is sustained by major stimuli, such as the effort toward an understanding of the mechanisms of reaction and catalytic processes in general, the elucidation of basic properties leading to stereocontrol and the search for broad applicability and scalability of the synthetic methodology. This paper reports a thorough study based on ESI-MS spectrometry of aminoorganocatalyzed model reactions under different experimental conditions. Off-line reaction monitoring of mixtures containing different catalytic systems, by ESI-MS n showed the presence of several putative intermediate species, either in their protonated or sodiated forms. In addition, enantioselective chromatography of crude reactions provides the stereochemical outcome of asymmetric reactions. The bulk of the data collected offers a clue of the intricate pathways occurring in solution for the studied reactions.

Accelerated d-Fructose Acid-Catalyzed Reactions in Thin Films Formed by Charged Microdroplets Deposition

“…In addition to its use as an analytical tool, mass spectrometry (MS) has long been employed in reaction monitoring to intercept elusive intermediates and highlight the mechanistic details of a chemical transformation. − The introduction of electrospray ionization (ESI) by Fenn et al enables one to directly generate a plume of charged microdroplets from a diluted aliquot of a reaction mixture. Once desolvated, the microdroplets release isolated ionic species that provide an accurate picture of the reaction progress in solution.…”

Stereoselectivity in electrosprayed confined volumes: asymmetric synthesis of warfarin by diamine organocatalysts in microdroplets and thin films

“…In our previous studies, we found that the reaction between 1 and 2 (1 M in THF) by DACH 3 or DIPEDA 4 (10% mol) lead to the warfarin formation in 78(+)/22(−) or 86(+)/14(−) er (enantiomeric ratio) and yields >90% after 24 or 48 hours respectively. 16 Starting from this, in order to find the optimal conditions for the ESI experiments, we first test the reaction at lower concentrations 17 using DACH as catalyst in THF and in ACN at room temperature (r.t.) for 5 h, obtaining the results reported in Table 1 (entries 1–4). In addition to the room temperature, the effect of higher temperatures was also evaluated taking into account the availability to heat the ESI source.…”