Electrospray mass spectrometry for detailed mechanistic studies of a complex organocatalyzed triple cascade reaction

Abstract

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.

Brønsted Acid Catalyzed Enantioselective α-Amidoalkylation in the Synthesis of Isoindoloisoquinolines

“…The course of reaction was investigated using 1 H NMR and ESI-MS . The reaction of 2 with 1 equiv of phosphoric acid 3d in CDCl 3 and in THF- d 6 was monitored by 1 H NMR.…”

Catalytic C–C Bond-Forming Multi-Component Cascade or Domino Reactions: Pushing the Boundaries of Complexity in Asymmetric Organocatalysis

“…Details about the mechanism of this complex triple cascade reaction were probed by means of electronspray ionization mass spectrometry (ESI-MS) studies. Important information about the short-lived intermediates was obtained using these techniques to support the proposed mechanism …”

Organocatalytic Asymmetric Conjugate Addition of Aldehydes to Nitroolefins: Identification of Catalytic Intermediates and the Stereoselectivity‐Determining Step by ESI‐MS

“…[12] In contrast to ESI-MS-based mechanistic investigations that solely rely on the detection of reaction intermediates, [5,13] this methodology also provides information on the enantioselectivity-determining step and the intermediates involved therein. [12] In contrast to ESI-MS-based mechanistic investigations that solely rely on the detection of reaction intermediates, [5,13] this methodology also provides information on the enantioselectivity-determining step and the intermediates involved therein.…”

“…ESI-MS back-reaction screening using equimolar mixtures of mass-labeled quasienantiomeric substrates is a valuable tool for the rapid determination of the enantioselectivity of chiral catalysts and catalyst mixtures. [12] In contrast to ESI-MS-based mechanistic investigations that solely rely on the detection of reaction intermediates, [5,13] this methodology also provides information on the enantioselectivity-determining step and the intermediates involved therein. It has been successfully used for screening a variety of reactions including palladium-catalyzed allylic substitutions, [12a-e] metal-and organocatalyzed Diels-Alder reactions, [12e,f] and Michael additions.…”