John C. Walton

Name:

Organization: University of St. Andrews School of Chemistry St. Andrews , England

Department: University of St. Andrews School of Chemistry St. Andrews

Title: Professor(PhD)

Chemicals
References

Tethered 1,2-Si-Group Migrations in Radical-Mediated Ring Enlargements of Cyclic Alkoxysilanes: An EPR Spectroscopic and Computational Investigation

Co-reporter:John C. Walton, Ryutaro Kanada, Takeaki Iwamoto, Satoshi Shuto, and Hiroshi Abe

The Journal of Organic Chemistry July 7, 2017 Volume 82(Issue 13) pp:6886-6886

Publication Date(Web):June 5, 2017

DOI:10.1021/acs.joc.7b01011

5- to 6-member ring enlargements of 3-oxa-2-silacyclopentylmethyl to 4-oxa-3-silacyclohexyl radicals were investigated by EPR spectroscopy and QM computations of model indano-oxasilacyclopentane and oxasilinanyl compounds. Both experimental and computational evidence favored a mechanism via a concerted 1,2-migration of the “tethered” Si-group. Thus, the “forbidden” 1,2-Si-group migration from carbon to carbon becomes allowed when the Si-group is “tethered”. The EPR data from 3-oxa-2-silacyclopentylmethyl radicals disclosed ground state conformations having semioccupied p-orbitals close to antiperiplanar with respect to their β-Si–C bonds, but indicated Si-hyperconjugation (β-silicon effect) was insignificant in radicals. Kinetic data was obtained by the steady state EPR method for ring enlargement of indano-3-oxa-2-silacyclopentylmethyl radicals. The scope of the novel rearrangement in terms of other ring types and sizes, as well as the analogous 1,2-migration of “tethered” C-centered groups, was explored computationally.

Bicarbonate and Alkyl Carbonate Radicals: Structural Integrity and Reactions with Lipid Components

Co-reporter:Michael Bühl; Peter DaBell; David W. Manley; Rory P. McCaughan

Journal of the American Chemical Society 2015 Volume 137(Issue 51) pp:16153-16162

Publication Date(Web):December 1, 2015

DOI:10.1021/jacs.5b10693

The elusive neutral bicarbonate radical and the carbonate radical anion form an acid/conjugate base pair. We now report experimental studies for a model of bicarbonate radical, namely, methyl carbonate (methoxycarbonyloxyl) radical, complemented by DFT computations at the CAM-B3LYP level applied to the bicarbonate radical itself. Methyl carbonate radicals were generated by UV irradiation of oxime carbonate precursors. Kinetic EPR was employed to measure rate constants and Arrhenius parameters for their dissociation to CO2 and methoxyl radicals. With oleate and cholesterol lipid components, methyl carbonate radicals preferentially added to their double bonds; with linoleate and linolenate substrates, abstraction of the bis-allylic H atoms competed with addition. This contrasts with the behavior of ROS such as hydroxyl radicals that selectively abstract allylic and/or bis-allylic H atoms. The thermodynamic and activation parameters for bicarbonate radical dissociation, obtained from DFT computations, predicted it would indeed have substantial lifetime in gas and nonpolar solvents. The acidity of bicarbonate radicals was also examined by DFT methods. A noteworthy linear relationship was discovered between the known pKa’s of strong acids and the computed numbers of microsolvating water molecules needed to bring about their ionization. DFT computations with bicarbonate radicals, solvated with up to eight water molecules, predicted that only five water molecules were needed to bring about its complete ionization. On comparing with the correlation, this indicated a pKa of about −2 units. This marks the bicarbonate radical as the strongest known carboxylic acid.

Catalyst-Free Photoredox AdditionCyclisations: Exploitation of Natural Synergy between Aryl Acetic Acids and Maleimide

Co-reporter:David W. Manley; Andrew Mills;Christopher O'Rourke; Alexra M. Z. Slawin; John C. Walton

Chemistry - A European Journal 2014 Volume 20( Issue 18) pp:5492-5500

Publication Date(Web):

DOI:10.1002/chem.201304929

Abstract

Suitably functionalised carboxylic acids undergo a previously unknown photoredox reaction when irradiated with UVA in the presence of maleimide. Maleimide was found to synergistically act as a radical generating photoxidant and as a radical acceptor, negating the need for an extrinsic photoredox catalyst. Modest to excellent yields of the product chromenopyrroledione, thiochromenopyrroledione and pyrroloquinolinedione derivatives were obtained in thirteen preparative photolyses. In situ NMR spectroscopy was used to study each reaction. Reactant decay and product build-up were monitored, enabling reaction profiles to be plotted. A plausible mechanism, whereby photo-excited maleimide acts as an oxidant to generate a radical ion pair, has been postulated and is supported by UV/Vis. spectroscopy and DFT computations. The radical-cation reactive intermediates were also characterised in solution by EPR spectroscopy.

An all-purpose preparation of oxime carbonates and resultant insights into the chemistry of alkoxycarbonyloxyl radicals

Co-reporter:Roy T. McBurney, Andrew D. Harper, Alexandra M. Z. Slawin and John C. Walton

Chemical Science 2012 vol. 3(Issue 12) pp:3436-3444

Publication Date(Web):04 Sep 2012

DOI:10.1039/C2SC21298F

Oxime carbonates have been synthesised and their potential studied as a new class of radical precursor. A general synthetic route, avoiding laboratory use of phosgene, was developed. Alkyl or aryl 1H-imidazole-1-carboxylates were prepared from the corresponding alcohols and 1,1-carbonyldiimidazole, then reacted with oximes in the presence of base. UV photolyses of oxime carbonates released particular N- and O-centred radicals suitable for spectroscopic examination. Spiro-cyclisations of alkoxycarbonyloxyl radicals onto aromatic acceptors and 5-exo cyclisations onto alkene acceptors were studied by EPR spectroscopy. EPR data also provided insight to the loss of CO2 from alkoxycarbonyloxyl radicals. The conformational preferences of 2-oxo-1,3-dioxolan-4-yl-methyl and related radicals were established. Modest yields of cyclic carbonates were obtained from preparative scale photolyses.

Microwave assisted radical organic syntheses

Co-reporter:Roy T. McBurney, Fernando Portela-Cubillo and John C. Walton

RSC Advances 2012 vol. 2(Issue 4) pp:1264-1274

Publication Date(Web):20 Dec 2011

DOI:10.1039/C1RA00909E

Applications of microwave (MW)-assistance to radical-mediated organic preparations and procedures are reviewed. Radical additions and cyclisations onto a wide range of acceptors benefited from the technique, as did organic halide reductions by tin hydrides and numerous cascade and sequential processes. Reaction times of chain processes initiated by AIBN were, in several cases, reduced to a few minutes. Regioselectivity in radical additions and ring closures was normally maintained under MW conditions, although stereoselectivities were usually poorer. MW methods have been developed for generation of C-, N-, O-, S- and P-centred radicals. As a result of this a notable number and diversity of heterocycles have been accessed. MW-methods have opened up several new and innocuous alternatives to toxic organotin reagents. Alkoxyamines smoothly release C-centred radicals and oxime ethers provide a variety of iminyl radicals on MW heating. In addition, several types of organo-element and organometallic precursors have yielded novel C-centred and hetero-radicals. To date applications of MW-assistance to homolytic processes are comparatively limited, but it is clear the alliance of the two holds a lot of promise.

Electron Paramagnetic Resonance and Computational Studies of Radicals Derived from Boron-Substituted N-Heterocyclic Carbene Boranes

Co-reporter:John C. Walton ; Malika Makhlouf Brahmi ; Julien Monot ; Louis Fensterbank ; Max Malacria ; Dennis P. Curran ;Emmanuel Lacôte

Journal of the American Chemical Society 2011 Volume 133(Issue 26) pp:10312-10321

Publication Date(Web):May 28, 2011

DOI:10.1021/ja2038485

Fifteen second-generation NHC-ligated boranes with aryl and alkyl substituents on boron were prepared, and their radical chemistry was explored by electron paramagnetic resonance (EPR) spectroscopy and calculations. Hydrogen atom abstraction from NHC–BH2Ar groups produced boryl radicals akin to diphenylmethyl with spin extensively delocalized across the NHC, BH, and aryl units. All of the NHC–B·HAr radicals studied abstracted Br-atoms from alkyl bromides. Radicals with bulky N,N′-dipp substituents underwent dimerization about 2 orders of magnitude more slowly than first-generation NHC-ligated trihydroborates. The evidence favored head-to-head coupling yielding ligated diboranes. The first ligated diboranyl radical, with a structure intermediate between that of ligated diboranes and diborenes, was spectroscopically characterized during photolysis of di-t-butyl peroxide with N,N′-di-t-butyl-imidazol-2-ylidene phenylborane. The reactive site of B-alkyl-substituted NHC–boranes switched from the boron center to the alkyl substituent for both linear and branched alkyl groups. The β-borylalkyl radicals obtained from N,N′-dipp-substituted boranes underwent exothermic β-scissions with production of dipp-Imd–BH2· radicals and alkenes. The reverse additions of NHC–boryl radicals to alkenes are probably endothermic for alkyl-substituted alkenes, but exothermic for conjugated alkenes (addition of an NHC–boryl radical to 1,1-diphenylethene was observed). A cyclopropylboryl radical was observed, but, unlike other α-cyclopropyl-substituted radicals, this showed no propensity for ring-opening.

UV promoted phenanthridine syntheses from oxime carbonate derived iminyl radicals

Co-reporter:Roy T. McBurney, Alexandra M. Z. Slawin, Laura A. Smart, Yanping Yu and John C. Walton

Chemical Communications 2011 vol. 47(Issue 28) pp:7974-7976

Publication Date(Web):16 Jun 2011

DOI:10.1039/C1CC12720A

Oxime carbonates were found to be excellent precursors for the clean and direct generation of iminyl radicals under UV irradiation. Suitably functionalised iminyls underwent cyclisations yielding various phenanthridines and also substituted quinolines and isoquinolines. EPR and X-ray analyses of oxime carbonates provided insight into the mechanism.

EPR Studies of the Generation, Structure, and Reactivity of N-Heterocyclic Carbene Borane Radicals

Co-reporter:John C. Walton ; Malika Makhlouf Brahmi ; Louis Fensterbank ; Emmanuel Lacôte ; Max Malacria ; Qianli Chu ; Shau-Hua Ueng ; Andrey Solovyev ;Dennis P. Curran

Journal of the American Chemical Society 2010 Volume 132(Issue 7) pp:2350-2358

Publication Date(Web):January 27, 2010

DOI:10.1021/ja909502q

N-Heterocyclic carbene boranes (NHC−boranes) are a new “clean” class of reagents suitable for reductive radical chain transformations. Their structures are well suited for their reactivity to be tuned by inclusion of different NHC ring units and by appropriate placement of diverse substituents. EPR spectra were obtained for the boron-centered radicals generated on removal of one of the BH3 hydrogen atoms. This spectroscopic data, coupled with DFT computations, demonstrated that the NHC−BH2• radicals are planar π-delocalized species. tert-Butoxyl radicals abstracted hydrogen atoms from NHC−boranes more than 3 orders of magnitude faster than did C-centered radicals, although the rate decreased markedly for sterically shielded NHC−BH3 centers. Combinations of two NHC−boryl radicals afforded 1,2-bis-NHC−diboranes at rates which also depended strongly on steric shielding. The termination rate increased to the diffusion-controlled limit for sterically unhindered NHC−boryls. Bromine atoms were rapidly transferred to imidazole-based NHC−boryl radicals from alkyl, allyl, and benzyl bromides. Chlorine-atom abstraction was, however, much less efficient and only observed for sterically unhindered NHC−boryls reacting with allylic and benzylic chlorides. For an NHC−borane containing a bulky thexyl substituent at boron, the tertiary H atom of the thexyl group was selectively removed. The resulting β-boron-containing alkyl radical rapidly underwent β scission of the B−C bond with production of an NHC−boryl radical and an alkene.

N-Heterocyclic Carbene Boryl Radicals: A New Class of Boron-Centered Radical

Co-reporter:Shau-Hua Ueng ; Andrey Solovyev ; Xinting Yuan ; Steven J. Geib ; Louis Fensterbank ; Emmanuel Lacôte ; Max Malacria ; Martin Newcomb ; John C. Walton ;Dennis P. Curran

Journal of the American Chemical Society 2009 Volume 131(Issue 31) pp:11256-11262

Publication Date(Web):July 16, 2009

DOI:10.1021/ja904103x

Reduction of xanthates by N-heterocyclic carbene boranes (NHC-boranes) has been suggested to occur by a radical chain mechanism involving heretofore unknown NHC-boryl radicals. In support of this suggestion, both the expected borane dithiocarbonate product and an unexpected borane xanthate product have now been isolated. These are the first NHC-boranes with boron−sulfur bonds, and their structures have been secured by spectroscopic and crystallographic means. The first rate constants for H-atom transfer from an NHC borane complex were determined by using the ring opening of a substituted cyclobutylcarbinyl radical as a clock reaction. The rate constant for reaction of the NHC-borane with a secondary alkyl radical at ambient temperature is 4 × 104 M−1 s−1, and the Arrhenius function displayed an entropic term (log A term) that was typical for a bimolecular reaction. The B−H bond dissociation energy of an NHC-borane complex has been estimated at 88 kcal/mol. The putative NHC-boryl radical in these transformations has been detected by EPR spectroscopy. Spectral analysis suggests that it is a π-radical, analogous to the benzyl radical.

Programmierung organischer Moleküle: Design und Management organischer Synthesen über radikalische Kaskaden

Co-reporter:Andrew J. McCarroll Dr.

Angewandte Chemie 2001 Volume 113(Issue 12) pp:

Publication Date(Web):13 JUN 2001

DOI:10.1002/1521-3757(20010618)113:12<2282::AID-ANGE2282>3.0.CO;2-F

Kaskaden-, Domino- und Tandemreaktionen, bei denen zwei oder mehr chemische Umwandlungen als Eintopfreaktionen ablaufen, werden immer populärer, da sie die Effizienz von Synthesen verbessern und die Umwelt weniger belasten. Diese Kaskaden enthalten nicht nur mechanistische Glanzstücke, sondern ermöglichen auch kompakte und elegante Synthesen komplexer Naturstoffe. Längere Kaskaden erfordern allerdings eine Vielzahl funktioneller Gruppen, die an ganz bestimmten Stellen in sorgfältig entworfenen Startmolekülen angeordnet sein müssen. Wir geben hier einen Überblick über die sagenhafte Spannweite von Kaskaden unimolekularer Radikalreaktionen und stellen ein nützliches System zur Klassifizierung solcher Kaskaden vor. Es dient zur Bewertung und zum Vergleich von Kaskadenreaktionen und hilft beim Design von Synthesen für Polycyclen. Kaskadenreaktionen von Dienen unter doppelter Cyclisierung führen zu Cyclopentylcyclopentan- oder Bicyclo[3.3.0]octanderivaten. Aus Vorstufen mit einem Ring als Templat ließen sich stereokontrolliert Triquinane und viele hierzu verwandte Verbindungen synthetisieren. Unter den Kaskadenreaktionen mit Ringspaltungen sind die zu Ringerweiterungen führenden die nützlichsten, denn sie machen auch Polycyclen mit mittleren Ringen zugänglich. Die entscheidenden Designmerkmale großartiger dreistufiger Kaskaden, mit denen Steroidgerüste teilweise oder vollständig erhalten werden, sind linear angeordnete Radikalacceptoren mit Methylgruppen an jedem fünften C-Atom in dem als Vorstufe dienenden Polyen. Die Ringspaltung ist die Umkehrung der Cyclisierung. Besonders bei symmetrischen Strukturen kann dies zu reversiblen Sequenzen führen und damit endlos sich wiederholende Kaskaden auslösen, die von wunderbar fluktuierenden Strukturen getragen werden. Das Arbeitsgebiet der „Programmierung“ organischer Moleküle, um Produktstrukturen gezielt zu erhalten, entwickelt sich rasch. Koordinierung und Klassifizierung der noch ungeordneten Datenmengen auf diesem Gebiet sollen das Design erleichtern und somit immer mehr und auch komplexere Strukturen zugänglich machen.

UV promoted phenanthridine syntheses from oxime carbonate derived iminyl radicals

Co-reporter:Roy T. McBurney, Alexandra M. Z. Slawin, Laura A. Smart, Yanping Yu and John C. Walton

Chemical Communications 2011 - vol. 47(Issue 28) pp:NaN7976-7976

Publication Date(Web):2011/06/16

DOI:10.1039/C1CC12720A

An all-purpose preparation of oxime carbonates and resultant insights into the chemistry of alkoxycarbonyloxyl radicals

Co-reporter:Roy T. McBurney, Andrew D. Harper, Alexandra M. Z. Slawin and John C. Walton

Chemical Science (2010-Present) 2012 - vol. 3(Issue 12) pp:NaN3444-3444

Publication Date(Web):2012/09/04

DOI:10.1039/C2SC21298F