The
aim of this study was to demonstrate the absolute necessity
of control experiments for a correct interpretation of mercury drop
test results when applied to mechanistic studies of palladacycle-catalyzed
reactions. It was shown that the interaction of diverse azapalladacycles
with metallic mercury leads to the formation of organomercuric chlorides
during the redox-transmetalation process. The structure of these organomercurials
was confirmed by elemental analysis, 1H, 13C{1H}, and 199Hg{1H} NMR spectra, X-ray
diffraction analysis, and DFT calculations. The behavior and properties
of C,N-mercuracycles bearing the
weak and labile N···Hg bond are discussed on the basis
of the temperature dependence of the NMR spectra and calculated thermodynamic
parameters of the dechelation process.
Machine
learning (ML) profoundly improves the accuracy of the fast
DU8+ hybrid density functional theory/parametric computations of nuclear
magnetic resonance spectra, allowing for high throughput in silico
validation and revision of complex alkaloids and other natural products.
Of nearly 170 alkaloids surveyed, 35 structures are revised with the
next-generation ML-augmented DU8 method, termed DU8ML.
DU8ML, a fast and accurate machine
learning-augmented density functional
theory (DFT) method for computing nuclear magnetic resonance (NMR)
spectra, proved effective for high-throughput revision of misassigned
natural products. In this paper, we disclose another important aspect
of its application: correction of unusual reaction mechanisms originally
proposed because of incorrect product structures.
Natural products continue to be reported at an astonishing rate from a wide range of multidisciplinary research activities in the pursuit of understanding the chemistry of biodiversity. However, the elucidation of chemical structure in the modern era is heavily reliant on the analysis and interpretation of multiple spectroscopic outputs, and in most cases this activity is by no means trivial. Structural errors continue to be described given the inherent complexity of natural products. Computer‐Assisted Structure Elucidation (CASE) continues to provide improved resolving power in this regard, but for enhanced accuracy quantum chemical spectrum prediction methodology is paramount. Reported herein are a range of counterfactual natural products, identified through chemical principal screening, which have been reassigned using a combination of chemical intuition, chemical synthesis, CASE and DU8+ spectrum prediction.
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