A5063312579- Molecular spectroscopy and chirality
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Analytical Chemistry and Chromatography
- Metabolomics and Mass Spectrometry Studies
- Catalytic C–H Functionalization Methods
- Computational Drug Discovery Methods
- Radical Photochemical Reactions
- Marine Sponges and Natural Products
- Catalytic Alkyne Reactions
- Axial and Atropisomeric Chirality Synthesis
- Cyclopropane Reaction Mechanisms
- Synthesis and Biological Activity
- Machine Learning in Materials Science
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Inorganic and Organometallic Chemistry
- Mass Spectrometry Techniques and Applications
- Advanced Chemical Physics Studies
- Asymmetric Hydrogenation and Catalysis
- Crystallization and Solubility Studies
- Advanced Data Processing Techniques
- Crystal structures of chemical compounds
- Organoboron and organosilicon chemistry
- Marine Toxins and Detection Methods
University of Nottingham
2022-2025
University of Cambridge
2016-2022
University College London
2017
University of York
2012-2016
A robust system for automatic processing and assignment of raw <sup>13</sup>C <sup>1</sup>H NMR data DP4-AI has been developed integrated into our computational organic molecule structure elucidation workflow.
Abstract Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α‐amino radical coupling partners. We report a substantial evolution of the reaction that enables α‐hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through direct oxidative two C−H bonds on simple and pyridine partners hydrogen atom transfer (HAT)‐driven approach: challenging process achieve due numerous side can...
Improvements to the DP4 computational structure elucidation method have led a 2-fold reduction in structural uncertainty and 7-fold improvement of statistical confidence.
What computational methods should be used to achieve the most reliable result in structure elucidation? A study on effect of quality and quantity geometries NMR elucidation performance is reported.
The Minisci reaction is one of the most valuable methods for directly functionalizing basic heteroarenes to form carbon–carbon bonds. Use prochiral, heteroatom-substituted radicals results in stereocenters being formed adjacent heteroaromatic system, generating motifs which are medicinal chemistry and chiral ligand design. Recently a highly enantioselective regioselective protocol was developed, using phosphoric acid catalysis. However, precise mechanism by this process operated origin...
The DP4 parameter, which provides a confidence level for NMR assignment, has been widely used to help assign the structures of many stereochemically-rich molecules.
The nucleophilic propargylation of azinium ions with a propargylboronate proceeds efficiently under gold(I) catalysis. A range N‐alkylated pyridinium, quinolinium, and pyrazinium undergo good yields high regioselectivities to give various functionalized 1,4‐dihydropyridines, 1,2‐dihydropyridines, 1,4‐dihydroquinolines, 1,2‐dihydroquinolines, 4,5‐dihydropyrazines. No allenylation side‐products are observed. Density functional theory (DFT) calculations provided insight into the mechanisms...
Rendering a common ligand scaffold anionic and then pairing it with chiral cation represents an alternative strategy for developing enantioselective versions of challenging transformations, as has been recently demonstrated in the borylation arenes using quinine-derived cation. A significant barrier to further generalization this approach is lack understanding specific interactions involved between cation, ligand, substrate, given complexity system. We have embarked on detailed computational...
Novel atropisomeric N -chloroamides were prepared by efficient halogenation reactions and shown to racemize via a pathway involving geared bond rotation.
Four-component reactions at room temperature delivered C–N atropisomeric peptide analogues possessing both central and axial chirality with complete diastereocontrol. Reactions elevated selectively afforded the other diastereoisomer.
A combined computational and anisotropic NMR investigation defined likely configuration of phormidolide.
Gold(I)-catalyzed nucleophilic allylations of pyridinium and quinolinium ions with various allyl pinacolboronates are reported. The reactions completely selective respect to the site azinium ion that is attacked, give functionalized 1,4-dihydropyridines 1,4-dihydroquinolines. Evidence suggests proceed through allylgold(I) intermediates formed by transmetalation from allylboronates. Density functional theory (DFT) calculations provided mechanistic insight.
The development of an asymmetric "clip-cycle" synthesis 2,2- and 3,3-disubstituted pyrrolidines spiropyrrolidines, which are increasingly important scaffolds in drug discovery programs, is reported. Cbz-protected bis-homoallylic amines were activated by "clipping" them to thioacrylate via alkene metathesis reaction. Enantioselective intramolecular aza-Michael cyclization onto the alkene, catalyzed a chiral phosphoric acid, formed pyrrolidine. reaction accommodated range substitutions form...
An account of our development the Pot, Atom and Step Economic (PASE) synthesis tetrahydropyrans, dihydropyrans piperidines, based on Maitland-Japp reaction is given. The value these reactions as a strategy in natural product highlighted recent further developments PASE syntheses literature reported.
Computational and synthetic studies have elucidated the origins of stereodivergence in an oxy-Michael synthesis 2,6-disubstituted tetrahydropyrans.
A catalyst selection program, BINOPtimal, has been developed.
A stereoselective synthesis of the C20–C32 tetrahydropyran core phorboxazoles has been achieved in only seven steps and a 31% overall yield. The C22 epimer was also synthesized. key step silyl ether deprotection/oxy-Michael cyclization. When this conducted under Brønsted acid conditions, formed with desired 2,6-cis-stereochemistry. However, when cyclization fluoride conditions buffered acetic acid, sole product.
We report a method for the direct and rapid conversion of primary secondary alcohols to corresponding phosphorothiolates in yields ranging from 64% 97%, using as coupling agent iminium salt prepared N,N-dimethylthioformamide Meerwein's salt. Selective reaction presence is possible. The proceeds stereospecifically with inversion configuration.
ω-Unsaturated alcohols were "clipped" via alkene metathesis to a thioester activating group, which was followed by chiral phosphoric acid catalyzed intramolecular oxa-Michael cyclization yield tetrahydropyrans and spiro-tetrahydropyrans with excellent enantioselectivity. The mechanism origin of the enantioselectivity probed DFT calculations kinetic isotope studies, where there correlation between computational synthetic investigations.
New representations and machine learning calculate DFT minima from force field geometries.
<div> <p>A robust system for automatic processing and assignment of raw 13C 1H NMR data DP4-AI has been developed integrated into our computational organic molecule structure elucidation workflow. Starting from a molecular with undefined stereochemistry or other structural uncertainty, this allows completely automated elucidation. Methods peak picking using objective model selection algorithms matching the calculated shifts to peaks in noisy experimental were developed. achieved...
Abstract Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α‐amino radical coupling partners. We report a substantial evolution of the reaction that enables α‐hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through direct oxidative two C−H bonds on simple and pyridine partners hydrogen atom transfer (HAT)‐driven approach: challenging process achieve due numerous side can...