Two-Dimensional (2D) Correlation Analysis and the Search for Intermediates: A Strictly Mathematical Approach to an Important Mechanistic Question

Abstract

In situ spectroscopic studies of metal-mediated syntheses of new and previously unstudied systems are being increasingly used to better understand speciation and mechanistic aspects. These types of experiments give rise to an interesting question: namely, can one deduce from in situ data alone, and with no a priori chemical knowledge (i.e. chemical assignments), which pure component spectral estimates correspond to intermediates? In the present contribution, a statistical 2D correlation analysis is introduced to solve this problem for unicyclic catalytic systems. Such a methodological development achieves two goals: (1) it allows the experimentalist to concentrate on the most meaningful information at the outset of a new exploratory study (focus on the species directly associated with the catalysis), and (2) it helps to free the experimentalist from chemical bias and prejudice, i.e. believing that a specific organometallic species has to be an intermediate due to one or more chemical arguments, when in fact it may be just a side product or spectator species in the metal-mediated synthesis. The 2D correlation analysis is first tested with a numerically simulated data set and then with a real in situ FTIR data set from an unmodified rhodium-catalyzed hydroformylation. The resulting statistical 2D correlation analysis provides a clear and correct answer.

The Burden of Disproof

“…For example, formate ions are abundant spectators rather than reactive intermediates in methanol synthesis by CO 2 hydrogenation over supported Cu catalysts . Identifying spectator species may be possible using methods such as nonsteady-state kinetics, including temporal analysis of products, steady-state isotopic transient kinetic analysis, modulation excitation spectroscopy, correlation analysis of in situ spectra, and catalysis informatics, but the results cannot prove that a particular species is a reaction intermediate.…”

“…For example, formate ions are abundant spectators rather than reactive intermediates in methanol synthesis by CO 2 hydrogenation over supported Cu catalysts. 13 Identifying spectator species may be possible using methods such as nonsteady-state kinetics, including temporal analysis of products, 14 steady-state isotopic transient kinetic analysis, 15 modulation excitation spectroscopy, 16 correlation analysis of in situ spectra, 17 and catalysis informatics, 18 but the results cannot prove that a particular species is a reaction intermediate. qualitative identification of reaction intermediates should be based not only on plausibility but also on the informed application of rigorous physical chemistry principles, 19 and intensities should be consistent with the expected abundance of reaction intermediates.…”

Disulfonated xantphos for mass spectrometric mechanistic analysis

“…[1][2][3][4][5] Catalytically relevant species are typically much less abundant than the aforementioned and partitioned between precatalyst, resting state(s), decomposition products, and intermediates, and only a fraction may be on-cycle at any point in time. [6][7][8][9][10][11][12][13][14][15] Direct methods of investigation need to be sufficiently sensitive to delve down to very low concentration levels, and in electrospray ionization mass spectrometry (ESI-MS), chemists have a tool to do exactly that. However, the technique has an Achilles heel: it operates solely on ions, transferring them to the gas phase for analysis, and ignoring neutral compounds, which are unaffected by the electric fields used to manipulate charged species.…”

Disulfonated Xantphos for Mass Spectrometric Mechanistic Analysis

“…[1][2][3][4][5] Catalytically relevant species are typically much less abundant than the aforementioned and partitioned between precatalyst, resting state(s), decomposition products, and intermediates, and only a fraction may be on-cycle at any point in time. [6][7][8][9][10][11][12][13][14][15] Direct methods of investigation need to be sufficiently sensitive to delve down to very low concentration levels, and in electrospray ionization mass spectrometry (ESI-MS), chemists have a tool to do exactly that. However, the technique has an Achilles heel: it operates solely on ions, transferring them to the gas phase for analysis, and ignoring neutral compounds, which are unaffected by the electric fields used to manipulate charged species.…”