Doubling the Power of DP4 for Computational Structure Elucidation

A large-scale optimisation of density functional theory (DFT) conditions for computational NMR structure elucidation has been conducted by systematically screening the DFT functionals and statistical models. The extended PyDP4 workflow was tested on a diverse and challenging set of 42 biologically-active and stereochemically rich compounds, including highly flexible molecules. MMFF/mPW1PW91/M06-2X in combination with 2 Gaussian, 1 region statistical model was capable of identifying the correct diastereomer among up to 32 potential diastereomer upper limit. Overall a 2-fold reduction in structural uncertainty and 7-fold reduction in model overconfidence has been achieved. Tools for rapid set-up and analysis of computational and experimental results, as well as for the statistical model generation have been developed and are provided. All of this should facilitate rapid and reliable computational NMR structure elucidation, which has become a valuable tool to natural product chemists and synthetic chemists alike.Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council.

Conversion of Alcohols to Phosphorothiolates Using a Thioiminium Salt as Coupling Agent

We report a method for the direct and rapid conversion of primary and secondary alcohols to the corresponding phosphorothiolates in yields ranging from 64% to 97%, using as a coupling agent the iminium salt prepared from N,N-dimethylthioformamide and Meerwein’s salt. Selective reaction of primary alcohols in the presence of secondary alcohols is possible. The reaction of secondary alcohols proceeds stereospecifically with inversion of configuration

Synthesis, Structure and Stereodynamics of Atropisomeric <em>N</em>‑Chloroamides

Atropisomeric N-chloroamides were efficiently accessed by electrophilic halogenation of ortho-substituted secondary anilides. The stereodynamics of atropisomerism in these novel scaffolds was interrogated by detailed experimental and computational studies, revealing that racemization is correlated with amide isomerization. The stereoelectronic nature of the amide was shown to significantly influence racemization rates, with potentially important implications for other C-N atropisomeric scaffolds

The computational input and output files for the paper "Doubling the Power of DP4 for Computational Structure Elucidation"

Macromodel conformational search input and output files, Gaussian DFT and GIAO calculation input and output files, as well as NMR description files for DP4 analysis.Medivi