Origin of the Conformational Modulation of the ¹³C NMR Chemical Shift of Methoxy Groups in Aromatic Natural Compounds

Abstract

The interpretation of nuclear magnetic resonance (NMR) parameters is essential to understanding experimental observations at the molecular and supramolecular levels and to designing new and more efficient molecular probes. In many aromatic natural compounds, unusual (13)C NMR chemical shifts have been reported for out-of-plane methoxy groups bonded to the aromatic ring (~62 ppm as compared to the typical value of ~56 ppm for an aromatic methoxy group). Here, we analyzed this phenomenon for a series of aromatic natural compounds using Density Functional Theory (DFT) calculations. First, we checked the methodology used to optimize the structure and calculate the NMR chemical shifts in aromatic compounds. The conformational effects of the methoxy group on the (13)C NMR chemical shift then were interpreted by the Natural Bond Orbital (NBO) and Natural Chemical Shift (NCS) approaches, and by excitation analysis of the chemical shifts, breaking down the total nuclear shielding tensor into the contributions from the different occupied orbitals and their magnetic interactions with virtual orbitals. We discovered that the atypical (13)C NMR chemical shifts observed are not directly related to a different conjugation of the lone pair of electrons of the methoxy oxygen with the aromatic ring, as has been suggested. Our analysis indicates that rotation of the methoxy group induces changes in the virtual molecular orbital space, which, in turn, correlate with the predominant part of the contribution of the paramagnetic deshielding connected with the magnetic interactions of the BD(CMet-H)→BD*(CMet-OMet) orbitals, resulting in the experimentally observed deshielding of the (13)C NMR resonance of the out-of-plane methoxy group.

Counterintuitive deshielding on the 13C NMR chemical shift for the trifluoromethyl anion

“…Interpretation of σ para is more complex than σ dia because the paramagnetic mechanism involves magnetic coupling of occupied and unoccupied orbitals. As several articles deeply describe the theory of σ para , we omitted a detailed description in the present work. However, it is important to mention that the magnitude of σ para (sign is usually negative) depends on the strength of the magnetic coupling and the energy gap between coupled orbitals.…”

“…For a complete understanding about the description of shielding tensor and the “orbital rotation model,” applied in this work to explain the paramagnetic shielding, we suggest to the reader some references …”

Structure and NMR properties of 6‐substituted‐5,6‐dihydrobenzo[c]phenanthridine alkaloids

“…S1 in Supporting Information) show the out‐of‐plane orientation of the methoxy groups in position 7 characterized by somewhat deshielded 13 C NMR resonance of the methyl carbon (δ ~ 61 ppm, see Table ). This deshielding for out‐of‐plane conformation was reported several times and has been rationalized very recently by the paramagnetic deshielding effect of BD C‐H → BD* C‐O transition . The NMR chemical shift of C8 was found in the range typical for the methoxy groups bonded to the aromatic system (δ ~ 56 ppm, see Table ).…”

“…This deshielding for out-of-plane conformation was reported several times [25][26][27][28] and has been rationalized very recently by the paramagnetic deshielding effect of BD C-H → BD* (2) transition. [29] The NMR chemical shift of C8 was found in the range typical for the methoxy groups bonded to the aromatic system (δ~56 ppm, see Table 2). …”

Molecular and Silica-Supported Molybdenum Alkyne Metathesis Catalysts: Influence of Electronics and Dynamics on Activity Revealed by Kinetics, Solid-State NMR, and Chemical Shift Analysis

“…[78][79] An orbital analysis, closely related to the original Natural Chemical Shift (NCS) analysis, [80][81][82] of the computed shielding provides detailed insight into the nature of the frontier orbitals, helping to relate the electronic structure of reaction intermediates with activity. [83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] Applying this approach to alkyne metathesis catalysts, the chemical shift tensor components ( 11 >  22 > model compound with three tris(tert-butoxy)siloxy ligands, at low spinning rates (Table 4) (Table 4) with a maximum deviation of less than 20 ppm, while the calculated and experimental principal components differ more, possibly due to the presence, at least in part, of dynamics (vide infra).…”