David C. Harrowven

Find an error

Name: David C. Harrowven

Organization: University of Southampton , England

Department: School of Chemistry

Title: Professor(PhD)

TOPICS

Organic Chemistry

Chemicals
References

The development of a short route to the API ropinirole hydrochloride

Co-reporter:Zeshan Yousuf, Andrew K. Richards, Andrew N. Dwyer, Bruno Linclau and David C. Harrowven

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 42) pp:10532-10539

Publication Date(Web):28 Aug 2015

DOI:10.1039/C5OB01739D

A four-step, three-stage synthesis of the API ropinirole hydrochloride has been developed from a commercially available naphthalene derivative. The new route has half the step-count and twice the overall yield of the current manufacturing process. Key features of the synthesis are a regioselective Birch reduction and an ozonolysis with concomitant ring closure to induce the required ring contraction.

Exploring Diradical Chemistry: A Carbon-Centered Radical May Act as either an Anion or Electrophile through an Orbital Isomer

Co-reporter:Dr. Théo P. Gonçalves;Dr. Mubina Mohamed; Richard J. Whitby;Dr. Helen F. Sneddon; David C. Harrowven

Angewandte Chemie International Edition 2015 Volume 54( Issue 15) pp:4531-4534

Publication Date(Web):

DOI:10.1002/anie.201411334

Abstract

Diradical intermediates, formed by thermolysis of alkynylcyclobutenones, can display radical, anion, or electrophilic character because of the existence of an orbital isomer with zwitterionic and cyclohexatrienone character. Our realization that water, alcohols, and certain substituents can induce the switch provides new opportunities in synthesis. For example, it can be used to shut down radical pathways and to give access to aryl carbonates and tetrasubstituted quinones.

Exploring Diradical Chemistry: A Carbon-Centered Radical May Act as either an Anion or Electrophile through an Orbital Isomer

Co-reporter:Dr. Théo P. Gonçalves;Dr. Mubina Mohamed; Richard J. Whitby;Dr. Helen F. Sneddon; David C. Harrowven

Angewandte Chemie 2015 Volume 127( Issue 15) pp:4614-4617

Publication Date(Web):

DOI:10.1002/ange.201411334

Abstract

Organoytterbium Ate Complexes Extend the Value of Cyclobutenediones as Isoprene Equivalents

Co-reporter:Emma Packard;Dr. David D. Pascoe;Dr. Jacques Maddaluno;Théo P. Gonçalves; David C. Harrowven

Angewandte Chemie International Edition 2013 Volume 52( Issue 49) pp:13076-13079

Publication Date(Web):

DOI:10.1002/anie.201307193

Organoytterbium Ate Complexes Extend the Value of Cyclobutenediones as Isoprene Equivalents

Co-reporter:Emma Packard;Dr. David D. Pascoe;Dr. Jacques Maddaluno;Théo P. Gonçalves; David C. Harrowven

Angewandte Chemie 2013 Volume 125( Issue 49) pp:13314-13317

Publication Date(Web):

DOI:10.1002/ange.201307193

Macrocylic bisbibenzyl natural products and their chemical synthesis

Co-reporter:David C. Harrowven and Sarah L. Kostiuk

Natural Product Reports 2012 vol. 29(Issue 2) pp:223-242

Publication Date(Web):16 Nov 2011

DOI:10.1039/C1NP00080B

Covering: 1995 to June 2011 The macrocyclic bisbibenzyl family of natural products are commonly found in liverworts and other bryophytes, though the recent isolation of riccardin C from a primrose extract has demonstrated their existence in higher flowering plants. Each has a core comprising four aromatic rings and two ethano bridges, being derived in Nature from two molecules of lunularin. Sub-classes are distinguished by the connectivity between these lunularin units, while individual natural products are distinguished by the hydroxy- and/or alkoxy-substituents decorating the core structures. Further diversification results from halogenation and oxidation, which may lead to dimerization or the creation of additional rings. The review provides a timely update to a previous Natural Product Reports article by Keseru and Nógrádi (Nat. Prod. Rep. 1995, 12, 69–75) and largely focuses on new additions to the family and the strategies used to effect their chemical synthesis.

An Ammonia-Triggered Stereocontrolled Conversion of a -Lactone to the Central Tetrahydropyran of Pederin, Psymberin, and Onnamides DF

Co-reporter:William J. Buffham;Nigel A. Swain;Sarah L. Kostiuk;Théo P. Gonçalves

European Journal of Organic Chemistry 2012 Volume 2012( Issue 6) pp:1217-1222

Publication Date(Web):

DOI:10.1002/ejoc.201101543

Abstract

The onnamides, pederin, and psymberin have each attracted attention because of their potent biological activity and interesting structural features. A short (eight steps) and efficient stereocontrolled route to the central tetrahydropyran ring in these natural products has been developed from (S)-malic acid. The key sequence involves the conversion of a γ-lactone to a tetrahydropyran structure triggered by the addition of ammonia.

An Efficient Flow-Photochemical Synthesis of 5H-Furanones Leads to an Understanding of Torquoselectivity in Cyclobutenone Rearrangements

Co-reporter: David C. Harrowven;Mubina Mohamed;Théo P. Gonçalves; Richard J. Whitby;David Bolien;Dr. Helen F. Sneddon

Angewandte Chemie 2012 Volume 124( Issue 18) pp:4481-4484

Publication Date(Web):

DOI:10.1002/ange.201200281

An Efficient Flow-Photochemical Synthesis of 5H-Furanones Leads to an Understanding of Torquoselectivity in Cyclobutenone Rearrangements

Co-reporter: David C. Harrowven;Mubina Mohamed;Théo P. Gonçalves; Richard J. Whitby;David Bolien;Dr. Helen F. Sneddon

Angewandte Chemie International Edition 2012 Volume 51( Issue 18) pp:4405-4408

Publication Date(Web):

DOI:10.1002/anie.201200281

CH activation and CH2 double activation of indolines by radical translocation: Understanding the chemistry of the indolinyl radical

Co-reporter:David C. Harrowven, Kerri J. Stenning, Sally Whiting, Toby Thompson and Robert Walton

Organic & Biomolecular Chemistry 2011 vol. 9(Issue 13) pp:4882-4885

Publication Date(Web):07 Apr 2011

DOI:10.1039/C1OB05527E

CH activation and CH2 double activation of indolines at C2 may be achieved efficiently through radical translocation. The fate of the C2 indolinyl radical is dictated by the substitution at C3. Fragmentation, cyclisation and tandem cyclisation reactions leading to indole, azaheterocycle and azapropellane formation, respectively, are reported.

New Insights into Cyclobutenone Rearrangements: A Total Synthesis of the Natural ROS-Generating Anti-Cancer Agent Cribrostatin6

Co-reporter:Mubina Mohamed;Théo P. Gonçalves; Richard J. Whitby;Dr. Helen F. Sneddon; David C. Harrowven

Chemistry - A European Journal 2011 Volume 17( Issue 49) pp:13698-13705

Publication Date(Web):

DOI:10.1002/chem.201102263

Abstract

Aryl- and heteroarylcyclobutenone rearrangements proceed in excellent yield under continuous-flow conditions. The former shows a Hammett correlation with σ_I providing strong evidence that electrocyclisation is the rate-determining step and has a late transition state. The reaction has been modelled by using DFT and CCSD(T) methods, with the latter giving excellent correlation with the experimental rate constant. A short and efficient total synthesis of cribrostatin 6, an anti-neoplastic and anti-microbial agent, provides a topical demonstration of the value of this method.

Unified Syntheses of Cavicularin and RiccardinC: Addressing the Synthesis of an Arene Adopting a Boat Configuration

Co-reporter:Dr. Sarah L. Kostiuk;Dr. Timothy Woodcock;Dr. Leo F. Dudin;Dr. Peter D. Howes; David C. Harrowven

Chemistry - A European Journal 2011 Volume 17( Issue 39) pp:10906-10915

Publication Date(Web):

DOI:10.1002/chem.201101550

Abstract

Concise syntheses of the natural products cavicularin (ten steps) and riccardin C (seven steps) are reported. Key features of the new synthetic route are a convergent strategy to assemble acyclic precursors and a sequence of regioselective reduction and halogenation steps to facilitate Wittig macrocyclisation and transannular ring contraction reactions.

Potassium carbonate–silica: a highly effective stationary phase for the chromatographic removal of organotin impurities

Co-reporter:David C. Harrowven, Dennis P. Curran, Sarah L. Kostiuk, Ian L. Wallis-Guy, Sally Whiting, Kerri J. Stenning, Bencan Tang, Emma Packard and Lana Nanson

Chemical Communications 2010 vol. 46(Issue 34) pp:6335-6337

Publication Date(Web):03 Aug 2010

DOI:10.1039/C0CC01328E

Organotin impurities in product mixtures can be reduced from stoichiometric levels to ∼15 parts per million by column chromatography using 10% w/w anhydrous potassium carbonate–silica as a stationary phase.

Thermally Induced Cyclobutenone Rearrangements and Domino Reactions

Co-reporter:David C. Harrowven ;David D. Pascoe;Ian L. Guy Dr.

Angewandte Chemie International Edition 2007 Volume 46(Issue 3) pp:

Publication Date(Web):5 DEC 2006

DOI:10.1002/anie.200603538

Four thermal-rearrangement pathways and a domino reaction leading to quinones arise from the thermolysis of cyclobutenones. The course of vinylcyclobutenone rearrangements is dictated by the nature of the substituent, R (see scheme): a cyclopentenone arises when R is an electron-rich alkene. In other cases thermolysis gives a cyclohexadienone, which may collapse with elimination to form a quinone, or tautomerize into a hydroquinone or cyclohexenedione.

Thermally Induced Cyclobutenone Rearrangements and Domino Reactions

Co-reporter:David C. Harrowven ;David D. Pascoe;Ian L. Guy Dr.

Angewandte Chemie 2007 Volume 119(Issue 3) pp:

Publication Date(Web):5 DEC 2006

DOI:10.1002/ange.200603538

Vielseitig: Aus der Thermolyse von Cyclobutenonen ergeben sich vier thermische Umlagerungen und eine Dominoreaktion unter Bildung von Chinonen. Der Verlauf der Vinylcyclobutenon-Umlagerungen wird vom Substituenten R bestimmt (siehe Schema): So entsteht ein Cyclopentenon, wenn R ein elektronenreiches Alken ist; in anderen Fällen ergibt Thermolyse zunächst ein Cyclohexadienon, aus dem sich ein Chinon, ein Hydrochinon oder ein Cyclohexendion erhalten lassen.

Efficient Phenanthrene, Helicene, and Azahelicene Syntheses

Co-reporter:David C. Harrowven ;Ian L. Guy;Lana Nanson

Angewandte Chemie 2006 Volume 118(Issue 14) pp:

Publication Date(Web):28 FEB 2006

DOI:10.1002/ange.200504287

Homolytische aromatische Substitutionen werden für die effiziente regioselektive Synthese von Helicenen, Phenanthrenen und Azahelicenen genutzt. Der Einsatz von Halogen- und Alkoxysubstituenten, um den stereochemischen Verlauf der Reaktionen zu steuern, und röntgenographische Untersuchungen der erhaltenen Helicene wie des im Bild gezeigten (rot O) werden beschrieben.

Efficient Phenanthrene, Helicene, and Azahelicene Syntheses

Co-reporter:David C. Harrowven, Ian L. Guy,Lana Nanson

Angewandte Chemie International Edition 2006 45(14) pp:2242-2245

Publication Date(Web):

DOI:10.1002/anie.200504287

Total Synthesis of Cavicularin and Riccardin C: Addressing the Synthesis of an Arene That Adopts a Boat Configuration

Co-reporter:David C. Harrowven Dr.;Timothy Woodcock;Peter D. Howes Dr.

Angewandte Chemie International Edition 2005 Volume 44(Issue 25) pp:

Publication Date(Web):18 MAY 2005

DOI:10.1002/anie.200500466

A transannular ring contraction induced by the addition of an aryl radical intermediate to a proximal arene facilitated the construction of the highly strained macrocyclic core of cavicularin (1). The precursor, an iodinated derivative of another natural product, riccardin C, was prepared from four commercially available arenes in a highly convergent sequence.

Total Synthesis of (−)-Colombiasin A and (−)-Elisapterosin B

Co-reporter:David C. Harrowven Dr.;David D. Pascoe;Daniela Demurtas;Heather O. Bourne Dr.

Angewandte Chemie International Edition 2005 Volume 44(Issue 8) pp:

Publication Date(Web):4 FEB 2005

DOI:10.1002/anie.200462268

Intramolecular cycloaddition reactions are central in the total syntheses of colombiasin A (1) and elisapterosin B (2) described, which use (−)-dihydrocarvone as the starting material. A Moore rearrangement of a vinylcyclobutene is used to initiate the cycloaddition.

Total Synthesis of (−)-Colombiasin A and (−)-Elisapterosin B

Co-reporter:David C. Harrowven Dr.;David D. Pascoe;Daniela Demurtas;Heather O. Bourne Dr.

Angewandte Chemie 2005 Volume 117(Issue 8) pp:

Publication Date(Web):4 FEB 2005

DOI:10.1002/ange.200462268

Intramolekulare Cycloadditionsreaktionen spielen bei den beschriebenen Totalsynthesen von Colombiasin A (1) und Elisapterosin B (2), die von (−)-Dihydrocarvon ausgehen, eine entscheidende Rolle. Als Auslöser der Cycloaddition fungiert die Moore-Umlagerung eines Vinylcyclobutens.

Total Synthesis of Cavicularin and Riccardin C: Addressing the Synthesis of an Arene That Adopts a Boat Configuration

Co-reporter:David C. Harrowven Dr.;Timothy Woodcock;Peter D. Howes Dr.

Angewandte Chemie 2005 Volume 117(Issue 25) pp:

Publication Date(Web):18 MAY 2005

DOI:10.1002/ange.200500466

Ein transannulare Ringverengung, die durch die Addition eines Arylradikal-Intermediats an ein benachbartes Aren ausgelöst wird, erleichterte den Aufbau des hoch gespannten makrocyclischen Kerns von Cavicularin (1). Die Vorstufe, ein iodiertes Derivat des Naturstoffs Riccardin C, wurde aus vier kommerziell erhältlichen Arenen in einer hochkonvergenten Sequenz synthetisiert.

(Bu3Sn)2–TBAF: a new combination reagent for the reduction and deuteration of aryl bromides and iodides

Co-reporter:David C. Harrowven, Ian L. Guy and Michael I. T. Nunn

Chemical Communications 2004 (Issue 17) pp:1966-1967

Publication Date(Web):12 Jul 2004

DOI:10.1039/B406103A

The combination of (Bu3Sn)2 and TBAF has been shown to reduce aromatic bromides and iodides in excellent yields under mild conditions. When the residual water in TBAF is exchanged for D2O, the halogen is replaced by a deuterium atom.

KF–Silica as a stationary phase for the chromatographic removal of tin residues from organic compounds

Co-reporter:David C. Harrowven and Ian L. Guy

Chemical Communications 2004 (Issue 17) pp:1968-1969

Publication Date(Web):12 Jul 2004

DOI:10.1039/B406041E

Through the simple expedient of using a mixture of KF and silica as the stationary phase in column chromatography, levels of organotin impurities from tributyltin hydride mediated reductions have been reduced from stoichiometric levels to ∼ 30 ppm.

Intramolecular C–H insertions adjacent to sulfur for the diastereoselective synthesis of thienofuranones

Co-reporter:Paul S. Skerry, Nigel A. Swain, David C. Harrowven, Donald Smyth, Gordon Bruton and Richard C. D. Brown

Chemical Communications 2004 (Issue 15) pp:1772-1773

Publication Date(Web):30 Jun 2004

DOI:10.1039/B402603A

A new approach to the diastereoselective synthesis of thienofuranones is described in which an intramolecular 1,5-carbenoid C–H insertion adjacent to sulfur features as a key step.

Medium ring synthesis by radical ipso-substitution

Co-reporter:David C. Harrowven, Nathalie L'Helias, Jonathan D. Moseley, Nigel J. Blumire and Stuart R. Flanagan

Chemical Communications 2003 (Issue 21) pp:2658-2659

Publication Date(Web):01 Oct 2003

DOI:10.1039/B309496K

A new approach to eight and nine membered ring synthesis is described in which a radical ipso-substitution reaction features as a key step.

Intramolecular radical additions to pyridines

Co-reporter:David C. Harrowven, Benjamin J. Sutton and Steven Coulton

Organic & Biomolecular Chemistry 2003 vol. 1(Issue 22) pp:4047-4057

Publication Date(Web):13 Oct 2003

DOI:10.1039/B309331J

Intramolecular 6-exo/endo-trig and 5-exo-trig cyclisations of aryl radical intermediates to the α-, β- and γ-carbons of pyridine have been shown to be facile processes at neutral pH. The tether conjoining the radical donor to the pyridine plays an important role in determining the outcome of the reaction. When a Z-alkene is used as a tether, ortho-cyclisation proceeds in good yield. A more complex course is followed when a saturated two carbon tether is employed, leading to products derived from hydrogen atom abstraction, ipso-cyclisation and ortho-cyclisation pathways. All attempts to effect 5-exo/endo-trig cyclisations failed. Tributyltin hydride, tris(trimethylsilyl)silane, tris(trimethylsilyl)germane and, in part, samarium(II) iodide can each be employed as mediators of the reaction.

The development of a short route to the API ropinirole hydrochloride

Co-reporter:Zeshan Yousuf, Andrew K. Richards, Andrew N. Dwyer, Bruno Linclau and David C. Harrowven

Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 42) pp:NaN10539-10539

Publication Date(Web):2015/08/28

DOI:10.1039/C5OB01739D

Potassium carbonate–silica: a highly effective stationary phase for the chromatographic removal of organotin impurities

Co-reporter:David C. Harrowven, Dennis P. Curran, Sarah L. Kostiuk, Ian L. Wallis-Guy, Sally Whiting, Kerri J. Stenning, Bencan Tang, Emma Packard and Lana Nanson

Chemical Communications 2010 - vol. 46(Issue 34) pp:NaN6337-6337

Publication Date(Web):2010/08/03

DOI:10.1039/C0CC01328E

CH activation and CH2 double activation of indolines by radical translocation: Understanding the chemistry of the indolinyl radical

Co-reporter:David C. Harrowven, Kerri J. Stenning, Sally Whiting, Toby Thompson and Robert Walton

Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 13) pp:NaN4885-4885

Publication Date(Web):2011/04/07

DOI:10.1039/C1OB05527E