Friedel‐Crafts dealkylation reaction mediated by a stereoselective proton transfer in the fragmentation of protonated cyclic indolyl α‐amino esters

Abstract

Using H/D exchange experiments combined with theoretical calculations, a Friedel-Crafts dealkylation reaction mediated by a stereoselective proton transfer in the [cyclic N-sulfonyl ketimino esters/protonated indoles] complex was proposed for the fragmentation of protonated cyclic indolyl α-amino esters in high-energy collisional dissociation tandem mass spectrometry for the first time. Copyright © 2016 John Wiley & Sons, Ltd.

Comparing the fragmentation reactions of protonated cyclic indolyl α‐amino esters in quadrupole/orbitrap and quadrupole time‐of‐flight mass spectrometers

“…In general, the spectral profiles of the protonated cyclic indolyl α‐amino esters in these two instruments are very similar, except that the relative abundance of the product ions varies as the substituent changes. Just as shown in our previous work, a pair of complementary ions of protonated indoles ( a ) and protonated cyclic N‐sulfonyl ketimino esters ( b ) (Table S1 and S2, supporting information) and two minor ions of protonated cyclic indolyl N‐sulfonyl ketiminos and protonated cyclic N‐sulfonyl ketimino acids were observed in both HCD‐MS/MS (Figure S1, supporting information) and CID‐MS/MS (Figure S2, supporting information) spectra of protonated cyclic indolyl α‐amino esters. The representative HCD‐MS/MS and CID‐MS/MS spectra of the protonated compound 1 are shown in Figures A and B, respectively, in which the same protonated indole at m/z 118.0653 and 118.0651, protonated cyclic N‐sulfonyl ketimino ester at m/z 240.0320 and 240.0321, protonated cyclic indolyl N‐sulfonyl ketimino at m/z 283.0530 and 283.0526, and protonated cyclic N‐sulfonyl ketimino acid at m/z 212.0009 and 212.0003 were present.…”

“…In our previous work, we speculated that the external proton added on the thermodynamically favored protonation site (the N 8 position) of the protonated compound 1 could directly migrate to the C 3 position via a 1,3‐H shift. However, in this study, another more reasonable path was put forward in view of energy.…”

“…Taking into consideration the HDX reaction between the deuterated product ion b‐d 1 and the residual water in the HCD cell, another fragmentation pathway (path A, Scheme ) may be possible, which was denied based on HDX experiment in our previous paper . In path A, when the added proton on the N 8 position of the protonated cyclic indolyl α‐amino esters stepwise migrated to the C 3 position via two sequential 1,4‐H‐shifts, a charge‐directed heterolytic cleavage of the C 3 –C 10 bond resulted in an ion‐neutral complex, INC 1 , of [protonated cyclic N‐sulfonyl ketimino ester/indole].…”

“…The fragmentations of protonated cyclic indolyl α-amine esters have been studied using Q/Orbitrap MS with the HCD activation mode in our previous work. 25 Their molecular structures were confirmed by NMR spectroscopy, mass spectrometry and X-ray single crystal diffraction. 5 Samples were dissolved in HPLC-grade methanol (Merck, Darmstadt, Germany) for mass spectrometry analysis.…”

“…Investigating ion behaviors using various tandem mass spectrometers is essential to establish a universal tandem mass spectrometry (MS/MS) library for organic compounds. The fragmentations of protonated cyclic indolyl α‐amine esters have been studied using Q/Orbitrap MS with the HCD activation mode in our previous work . In this paper, systematic comparison of the INC‐mediated fragmentation reactions of protonated cyclic indolyl α‐amine esters by Q/Orbitrap MS and QTOFMS was performed by high‐resolution MS/MS studies and hydrogen/deuterium exchange (HDX) experiments combined with regiospecific H/D‐labeling experiments and density functional theoretical (DFT) calculations.…”