Richard C. D. Brown

Electrochemical Deprotection of para-Methoxybenzyl Ethers in a Flow Electrolysis Cell

Co-reporter:Robert A. Green, Katherine E. Jolley, Azzam A. M. Al-Hadedi, Derek Pletcher, David C. Harrowven, Oscar De Frutos, Carlos Mateos, David J. Klauber, Juan A. Rincón, and Richard C. D. Brown

Organic Letters April 21, 2017 Volume 19(Issue 8) pp:

Publication Date(Web):April 4, 2017

DOI:10.1021/acs.orglett.7b00641

Electrochemical deprotection of p-methoxybenzyl (PMB) ethers was performed in an undivided electrochemical flow reactor in MeOH solution, leading to the unmasked alcohol and p-methoxybenzaldehyde dimethyl acetal as a byproduct. The electrochemical method removes the need for chemical oxidants, and added electrolyte (BF4NEt4) can be recovered and reused. The method was applied to 17 substrates with high conversions in a single pass, yields up to 92%, and up to 7.5 g h–1 productivity. The PMB protecting group was also selectively removed in the presence of some other common alcohol protecting groups.

A Short Diastereoselective Total Synthesis of (±)-Vibralactone

Co-reporter:Alexander J. Leeder, Robert J. Heap, Lynda J. Brown, Xavier Franck, and Richard C. D. Brown

Organic Letters 2016 Volume 18(Issue 23) pp:5971-5973

Publication Date(Web):October 31, 2016

DOI:10.1021/acs.orglett.6b03007

A total synthesis of the (±)-vibralactone has been achieved in 11 steps and 16% overall yield from malonic acid. Key steps include a highly diastereoselective allylation of an α-formyl ester containing an all carbon α-quaternary center, a Pd-catalyzed deallylative β-lactonization, and an aldehyde-selective Wacker oxidation of a terminal alkene.

N-Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes

Co-reporter:Robert A. Green, Derek Pletcher, Stuart G. Leach, and Richard C. D. Brown

Organic Letters 2016 Volume 18(Issue 5) pp:1198-1201

Publication Date(Web):February 17, 2016

DOI:10.1021/acs.orglett.6b00339

A flow process for N-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate N-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71–99%), productivities (up to 2.6 g h–1), and current efficiencies (65–91%) were realized for 19 amides.

N-Heterocyclic Carbene-Mediated Oxidative Electrosynthesis of Esters in a Microflow Cell

Co-reporter:Robert A. Green, Derek Pletcher, Stuart G. Leach, and Richard C. D. Brown

Organic Letters 2015 Volume 17(Issue 13) pp:3290-3293

Publication Date(Web):June 15, 2015

DOI:10.1021/acs.orglett.5b01459

An efficient N-heterocyclic carbene (NHC)-mediated oxidative esterification of aldehydes has been achieved in an undivided microfluidic electrolysis cell at ambient temperature. Productivities of up to 4.3 g h–1 in a single pass are demonstrated, with excellent yields and conversions for 19 examples presented. Notably, the oxidative acylation reactions were shown to proceed with a 1:1 stoichiometry of aldehyde and alcohol (for primary alcohols), with remarkably short residence times in the electrolysis cell (<13 s), and without added electrolyte.

trans-2-Tritylcyclohexanol as a Chiral Auxiliary in Permanganate-Mediated Oxidative Cyclization of 2-Methylenehept-5-enoates: Application to the Synthesis of trans-(+)-Linalool Oxide

Co-reporter:Ali M. Al Hazmi, Nadeem S. Sheikh, Carole J. R. Bataille, Azzam A. M. Al-Hadedi, Sam V. Watkin, Tim J. Luker, Nicholas P. Camp, and Richard C. D. Brown

Organic Letters 2014 Volume 16(Issue 19) pp:5104-5107

Publication Date(Web):September 16, 2014

DOI:10.1021/ol502454r

The permanganate-mediated oxidative cyclization of a series of 2-methylenehept-5-eneoates bearing different chiral auxiliaries was investigated, leading to the discovery of trans-2-tritylcyclohexanol (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ∼97:3). Chiral resolution of (±)-TTC, prepared in one step from cyclohexene oxide, afforded (−)-(1S,2R)-TTC (er >99:1), which was applied to the synthesis of (+)-trans-(2S,5S)-linalool oxide.

One-pot enyne ring-closing metathesis–Diels–Alder reactions for the synthesis of polycyclic sulfamides

Co-reporter:Joseph T. Hill-Cousins, Sofia S. Salim, Youssef M. Bakar, Richard K. Bellingham, Mark E. Light, Richard C.D. Brown

Tetrahedron 2014 70(23) pp: 3700-3706

Publication Date(Web):

DOI:10.1016/j.tet.2014.04.014

Total Synthesis of the Tetracyclic Lupin Alkaloid (+)-Allomatrine

Co-reporter:Samuel V. Watkin, Nicholas P. Camp, and Richard C. D. Brown

Organic Letters 2013 Volume 15(Issue 17) pp:4596-4599

Publication Date(Web):August 27, 2013

DOI:10.1021/ol402198n

(+)-Allomatrine (1) has been synthesized using an imino-aldol reaction and N-acyliminium cyclization as key steps. Strategically, use of the tert-butylsulfinimine derivative of (E)-4-(trimethylsilyl)but-2-enal enabled the staged formation of three C–C bonds, a C–N bond, and the four stereogenic centers within the target.

A Resin-Linker-Vector Approach to Radiopharmaceuticals Containing 18F: Application in the Synthesis of O-(2-[18F]-Fluoroethyl)-L-tyrosine

Co-reporter:Dr. Amy C. Topley;Valerio Isoni;Dr. Thomas A. Logothetis;Dr. Duncan Wynn;Dr. Harry Wadsworth;Dr. Alex M. R. Gibson;Imtiaz Khan;Dr. Neil J. Wells; Cécile Perrio; Richard C. D. Brown

Chemistry - A European Journal 2013 Volume 19( Issue 5) pp:

Publication Date(Web):

DOI:10.1002/chem.201202474

Abstract

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide ¹⁸F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [¹⁸F]-fluoride ion. Three model linker-vector molecules 7 a–c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8 a–c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8 a, b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY≈60 %) of the ¹⁸F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[¹⁸F]-fluoroethyl)-L-tyrosine ([¹⁸F]-FET), delivering protected [¹⁸F]-FET in >90 % RCY. Acid deprotection gave [¹⁸F]-FET in an overall RCY of 41 % from the RLV.

TEMPO-Mediated Electrooxidation of Primary and Secondary Alcohols in a Microfluidic Electrolytic Cell

Co-reporter:Dr. Joseph T. Hill-Cousins;Dr. Jekaterina Kuleshova;Robert A. Green;Dr. Peter R. Birkin; Derek Pletcher;Toby J. Underwood;Dr. Stuart G. Leach; Richard C. D. Brown

ChemSusChem 2012 Volume 5( Issue 2) pp:326-331

Publication Date(Web):

DOI:10.1002/cssc.201100601

Abstract

A general procedure for the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated electrooxidation of primary and secondary alcohols modified for application in a microfluidic electrolytic cell is described. The electrocatalytic system utilises a buffered aqueous tert-butanol reaction medium, which operates effectively without the requirement for additional electrolyte, providing a mild protocol for the oxidation of alcohols to aldehydes and ketones at ambient temperature on a laboratory scale. Optimisation of the process is discussed along with the oxidation of 15 representative alcohols.

Syntheses of 13C2-labelled 11Z-retinals

Co-reporter:Neville J. McLean, Axel Gansmuller, Maria Concistre, Lynda J. Brown, Malcom H. Levitt, Richard C.D. Brown

Tetrahedron 2011 67(43) pp: 8404-8410

Publication Date(Web):

DOI:10.1016/j.tet.2011.07.092

Enantioselective Formal Synthesis of Eurylene: Synthesis of the cis- and trans-THF Fragments Using Oxidative Cyclization

Co-reporter:Nadeem S. Sheikh, Carole J. Bataille, Tim J. Luker and Richard C. D. Brown

Organic Letters 2010 Volume 12(Issue 11) pp:2468-2471

Publication Date(Web):May 11, 2010

DOI:10.1021/ol100513y

A formal synthesis of eurylene is described, where both cis- and trans-THF-containing fragments were prepared using diastereo- and chemoselective permanganate-mediated oxidative monocyclizations of trienes.

Total synthesis of cis-reticulatacin-10-ones A and B: absolute stereochemical assignment

Co-reporter:Sherif B. Abdel Ghani, Lynda J. Brown, Bruno Figadère and Richard C. D. Brown

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 20) pp:4543-4545

Publication Date(Web):23 Aug 2010

DOI:10.1039/C0OB00259C

cis-Reticulatacin-10-ones A and B were synthesised as a predefined mixture of diastereoisomers (dr ∼ 1:9) in nine steps from the acid chloride 8, and without the use of hydroxyl protecting groups. Comparison of the chiral HPLC chromatogram of the synthetic sample with that of the natural product isolated from the roots of the tropical fruit tree Annona muricata L. showed the natural product to be a mixture of A and B diastereoisomers (dr ∼ 1:1).

Synthesis of the positron-emitting radiotracer [18F]-2-fluoro-2-deoxy-D-glucose from resin-bound perfluoroalkylsulfonates

Co-reporter:Lynda J. Brown, Nianchun Ma, Denis R. Bouvet, Sue Champion, Alex M. Gibson, Yulai Hu, Alex Jackson, Imtiaz Khan, Nicolas Millot, Amy C. Topley, Harry Wadsworth, Duncan Wynn and Richard C. D. Brown

Organic & Biomolecular Chemistry 2009 vol. 7(Issue 3) pp:564-575

Publication Date(Web):2008/12/08

DOI:10.1039/B816032E

A new approach to the synthesis of 2-fluoro-2-deoxy-D-glucose (FDG, [19/18F]-3) is described, which employs supported perfluoroalkylsulfonate precursors 33–36, where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [19F]fluoride ion afforded protected FDG [19F]-18 as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [19F]-18 was shown to produce [19F]FDG. The method has been applied to the efficient radiosynthesis of the imaging agent [18F]FDG, and was shown to produce the radiochemical tracer in good radiochemical yield (average 73%, decay corrected).

Synthesis of the non-adjacent bis-THF core of cis-sylvaticin using a double oxidative cyclisation

Co-reporter:Riaz A. Bhunnoo, Heather Hobbs, Dramane I. Lainé, Mark E. Light and Richard C. D. Brown

Organic & Biomolecular Chemistry 2009 vol. 7(Issue 5) pp:1017-1024

Publication Date(Web):28 Jan 2009

DOI:10.1039/B813201A

A short synthesis of the non-adjacent bis-THF core of the Annonaceousacetogenincis-sylvaticin (1) is described. C2 Symmetrical (Z,E,E,Z)- and (E,E,E,E)-tetraenes 5 and 6 were synthesised in six and three steps respectively from (1E,5E,9E)-cyclododeca-1,5,9-triene. Subsequent permanganate promoted asymmetric bi-directional oxidative cyclisation of tetraene 5 was used to create the non-adjacent bis-THF core of 1, installing seven of the nine stereogenic centres present in the natural product in a single step. Desymmetrisation of the oxidative cyclisation product by mono-tosylation gave access to a C11–C32 fragment of cis-sylvaticin.

A biaryl cross-coupling strategy for functionalisation of benzocrown ethers

Co-reporter:Sally Dixon, Richard C. D. Brown and Philip A. Gale

Chemical Communications 2007 (Issue 34) pp:3565-3567

Publication Date(Web):06 Aug 2007

DOI:10.1039/B709861H

Preparation of (di)benzocrown-substituted aryl-zinc or -boron reagents and their palladium-catalysed cross-coupling with functionalised aryl halides is described for convenient synthesis of novel crown ether systems.

A Solid-Phase Route to 18F-Labeled Tracers, Exemplified by the Synthesis of [18F]2-Fluoro-2-deoxy-D-glucose

Co-reporter:Lynda J. Brown Dr.;Denis R. Bouvet Dr.;Sue Champion Dr.;Alex M. Gibson Dr.;Yulai Hu Dr.;Alex Jackson Dr.;Imtiaz Khan Dr.;Nianchun Ma Dr.;Nicholas Millot Dr.;Harry Wadsworth Dr.;Richard C. D. Brown Dr.

Angewandte Chemie 2007 Volume 119(Issue 6) pp:

Publication Date(Web):20 DEC 2006

DOI:10.1002/ange.200603394

Strahlende Synthese: Ein Weg zu ¹⁸F enthaltenden Radiopharmazeutika führt über das Ersetzen eines Sulfonatlinkers durch [¹⁸F]Fluoridionen und das Freisetzen des Radiomarkierers von einem festen Träger (siehe Schema; EOM=Ethoxymethyl). Auf diesem Weg ließ sich ein vielfach genutztes Bildgebungsagens, [¹⁸F]Fluor-2-desoxy-D-glucose, in guter radiochemischer Ausbeute und hoher chemischer Reinheit herstellen.

A Solid-Phase Route to 18F-Labeled Tracers, Exemplified by the Synthesis of [18F]2-Fluoro-2-deoxy-D-glucose

Co-reporter:Lynda J. Brown Dr.;Denis R. Bouvet Dr.;Sue Champion Dr.;Alex M. Gibson Dr.;Yulai Hu Dr.;Alex Jackson Dr.;Imtiaz Khan Dr.;Nianchun Ma Dr.;Nicholas Millot Dr.;Harry Wadsworth Dr.;Richard C. D. Brown Dr.

Angewandte Chemie International Edition 2007 Volume 46(Issue 6) pp:

Publication Date(Web):20 DEC 2006

DOI:10.1002/anie.200603394

Scintillating synthesis: ¹⁸F-Containing radiopharmaceuticals can be prepared by using [¹⁸F]fluoride ions to displace a sulfonate linker and release a radiotracer from a solid support (see scheme; EOM=ethoxymethyl). The method has allowed the synthesis of the widely used imaging agent [¹⁸F]fluoro-2-deoxy-D-glucose in good radiochemical yield and with high chemical purity.

Natural cis-solamin is a mixture of two tetra-epimeric diastereoisomers: biosynthetic implications for Annonaceous acetogenins

Co-reporter:Yulai Hu, Alex R. L. Cecil, Xavier Frank, Christophe Gleye, Bruno Figadère and Richard C. D. Brown

Organic & Biomolecular Chemistry 2006 vol. 4(Issue 7) pp:1217-1219

Publication Date(Web):24 Feb 2006

DOI:10.1039/B601943A

The anti-tumour natural product cis-solamin has been shown to occur as a mixture two of tetra-epimeric diastereoisomers 1A and 1B, whereas solamin (6) was isolated as a single diastereoisomer; the biosyntheses of 1A/B and 6 are likely to involve enzyme-mediated cyclohydrations of the bis-epoxide acetogenins anti-diepomuricanin A2 and syn-diepomuricanin A1 respectively, where addition of water occurs regioselectively at either C15 or C20.

A metal–oxo mediated approach to the synthesis of 21,22-diepi-membrarollin

Co-reporter:Yulai Hu and Richard C. D. Brown

Chemical Communications 2005 (Issue 45) pp:5636-5637

Publication Date(Web):21 Oct 2005

DOI:10.1039/B512126D

A synthesis of 21,22-diepi-membrarollin (14) is described, which employed sequential metal–oxo mediated oxidative cyclisations to introduce six of the seven stereogenic centres.

Synthesis and derivatisation of a novel spiro[1-benzofuran-2,4′-piperidin]-3-one scaffold

Co-reporter:Rowan A. Wilson, Lai Chan, Robin Wood and Richard C. D. Brown

Organic & Biomolecular Chemistry 2005 vol. 3(Issue 17) pp:3228-3235

Publication Date(Web):03 Aug 2005

DOI:10.1039/B507339A

The synthesis of a novel spiro[1-benzofuran-2,4′-piperidin]-3-one scaffold 6 has been achieved in five steps with an overall yield of 47%. The versatility of the spiropiperidine scaffold in the context of library synthesis is exemplified by selective and sequential derivatisation of the amino and aryl bromide functional groups, including the development of multi-step telescope reaction matrices.

Developments in Furan Syntheses

Co-reporter:Richard C. D. Brown Dr.

Angewandte Chemie International Edition 2005 Volume 44(Issue 6) pp:

Publication Date(Web):23 DEC 2004

DOI:10.1002/anie.200461668

Diversely substituted furans can be prepared from alkynones and alkynoate esters by means of mechanistically novel cycloisomerization and reductive cyclization processes, respectively. Even tetrasubstituted furans can be prepared by cycloisomerization of alkynones, or from allenyl ketones through a Pd-catalyzed cross-coupling-cyclization approach (see scheme; DMA=N,N-dimethylacetamide).

Entwicklungen in der Furansynthese

Co-reporter:Richard C. D. Brown Dr.

Angewandte Chemie 2005 Volume 117(Issue 6) pp:

Publication Date(Web):23 DEC 2004

DOI:10.1002/ange.200461668

Unterschiedlich substituierte Furane werden ausgehend von Alkinonen und Alkincarbonsäureestern in mechanistisch neuartigen Cycloisomerisierungen und reduktiven Cyclisierungen gewonnen (siehe Schema; DMA=N,N-Dimethylacetamid). Durch Cycloisomerisierung von Alkinonen oder Pd-katalysierte cyclisierende Kupplung von Allenylketonen sind sogar vierfach substituierte Furane erhältlich.

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.

Ring-closing metathesis: development of a cyclisation–cleavage strategy for the solid-phase synthesis of cyclic sulfonamides

Co-reporter:Jean-Dominique Moriggi, Lynda J. Brown, José L. Castro and Richard C. D. Brown

Organic & Biomolecular Chemistry 2004 vol. 2(Issue 6) pp:835-844

Publication Date(Web):16 Feb 2004

DOI:10.1039/B313686H

A series of novel 7-membered cyclic sulfonamides have been synthesised using a solid-phase cyclisation–cleavage RCM strategy. Model solution studies indicated the sulfonamides were suitable substrates for RCM using the Grubbs' catalyst 2. Starting from either 2-carboxyethyl polystyrene (21) or Merrifield resin, various seven-membered sulfonamides were prepared in good to excellent yields at low catalyst loadings (2.5–5 mol%) using a flexible spacer between the polymer and the substrate. In addition, a novel double-armed linker was shown to allow efficient RCM cleavage of sulfonamides with as little as 1 mol% of the ruthenium alkylidene complex 2.

One-Pot Ring-Closing Metathesis-Alkene Cross Metathesis Reactions of Sulfamide-Linked Enynes

Co-reporter:Sofia S. Salim;Richard K. Bellingham;Richard C. D. Brown

European Journal of Organic Chemistry 2004 Volume 2004(Issue 4) pp:

Publication Date(Web):4 FEB 2004

DOI:10.1002/ejoc.200300725

Ring-closing metathesis (RCM) of sulfamide-linked enynes 7, 11 and 12 containing disubstituted alkynes afforded a series of novel 7-membered cyclic sulfamides 13−15 in good yield. Substrates 5, 9 and 10 containing mono-substituted alkynes gave either simple RCM products 18a−c or those arising from combinations of enyne RCM and olefin cross metathesis 16/17a−c depending on the reaction conditions. Notably, in the presence of two equivalents of styrene or ethyl acrylate, substrates 5, 9 and 10 containing terminal alkynes underwent selective enyne-RCM-olefin-cross metathesis to provide cyclic sulfamides 17a−c and 19b,c in yields of 54−83%. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Solid-phase synthesis of 4-methylene pyrrolidines and allylic amines using palladium-activated allylic linkers

Co-reporter:Richard C. D. Brown, Martyn L. Fisher and Lynda J. Brown

Organic & Biomolecular Chemistry 2003 vol. 1(Issue 15) pp:2699-2709

Publication Date(Web):26 Jun 2003

DOI:10.1039/B303752E

The solid-phase synthesis of 4-methylene pyrrolidines and allylic amines has been achieved using palladium-catalysed nucleophilic cleavage of allylic linkages. Six pyrrolidines were synthesised in five steps from a carboxyethyl resin 20, where the key transformations included a Lewis-acid promoted imino-Sakurai type reaction and reductive alkylation prior to the final palladium-catalysed cyclisation cleavage of the allylic carboxylate linkage. Allylic carboxylate resin 22 was also shown to undergo “traceless” cleavage using various hydride sources in the presence of catalytic palladium. A more robust allylic ether linkage was also investigated. Starting from a phenol resin 36, a number of 3-aryl-allylamines were prepared using a palladium-catalysed nucleophilic cleavage reaction.

An efficient synthesis of endo,exo-furofuranone derivatives

Co-reporter:Nigel A. Swain, Richard C. D. Brown and Gordon Bruton

Chemical Communications 2002 (Issue 18) pp:2042-2043

Publication Date(Web):13 Aug 2002

DOI:10.1039/B206150C

The ring openings of 1-acetyl-4-phenyl-3-oxabicyclo[3.1.0]hexane afforded α-acetyl-γ-butyrolactones that underwent a novel diazo-transfer reaction, followed by C–H insertion, to provide a series of endo,exo-furofuranone analogues.

An Asymmetric Phase-Transfer Dihydroxylation Reaction

Co-reporter:Riaz A. Bhunnoo;Yulai Hu Dr.;Dramane I. Lainé Dr. Dr.

Angewandte Chemie 2002 Volume 114(Issue 18) pp:

Publication Date(Web):13 SEP 2002

DOI:10.1002/1521-3757(20020916)114:18<3629::AID-ANGE3629>3.0.CO;2-I

1,2-Diole durch asymmetrische Phasentransferkatalyse: Durch eine neue, asymmetrische Dihydroxylierung von Enonen mit Permanganat unter Phasentransferbedingungen sind 1,2-Diole mit hohen Enantiomerenüberschüssen zugänglich (siehe Schema: z. B. R¹=nBu, R²=(p-OMe)C₆H₄).

An Asymmetric Phase-Transfer Dihydroxylation Reaction

Co-reporter:Riaz A. Bhunnoo;Yulai Hu Dr.;Dramane I. Lainé Dr. Dr.

Angewandte Chemie International Edition 2002 Volume 41(Issue 18) pp:

Publication Date(Web):16 SEP 2002

DOI:10.1002/1521-3773(20020916)41:18<3479::AID-ANIE3479>3.0.CO;2-O

Enantiomerically enriched 1,2-diols can be prepared, in good enantiomeric excesses, by using a novel asymmetric dihydroxylation of enones with permanganate under phase-transfer conditions (see scheme: e.g. R¹=nBu, R²=(p-OMe)C₆H₄).

Asymmetric Permanganate-Promoted Oxidative Cyclization of 1,5-Dienes by Using Chiral Phase-Transfer Catalysis

Co-reporter:Richard C. D. Brown Dr.;John F. Keily

Angewandte Chemie 2001 Volume 113(Issue 23) pp:

Publication Date(Web):28 NOV 2001

DOI:10.1002/1521-3757(20011203)113:23<4628::AID-ANGE4628>3.0.CO;2-N

Bis zu vier neue Stereozentren werden bei der phasentransferkatalysierten oxidativen Cyclisierung achiraler Diene mit Permanganat mit Kontrolle der relativen und absoluten Konfiguration in einem Schritt aufgebaut (siehe Schema).

Asymmetric Permanganate-Promoted Oxidative Cyclization of 1,5-Dienes by Using Chiral Phase-Transfer Catalysis

Co-reporter:Richard C. D. Brown Dr.;John F. Keily

Angewandte Chemie International Edition 2001 Volume 40(Issue 23) pp:

Publication Date(Web):28 NOV 2001

DOI:10.1002/1521-3773(20011203)40:23<4496::AID-ANIE4496>3.0.CO;2-F

Up to four new stereocenters are created with control of the relative and absolute stereochemistry in a single step in the unusual phase-transfer-catalyzed oxidative cyclization of achiral dienes with permanganate (see scheme).

Diastereoselective synthesis of tetrahydrofuran-containing fragments by the permanganate oxidation of 1,5,9-trienes

Co-reporter:Richard C. D. Brown, Robert M. Hughes, John Keily and Anne Kenney

Chemical Communications 2000 (Issue 18) pp:1735-1736

Publication Date(Web):25 Aug 2000

DOI:10.1039/B004307I

The permanganate oxidation of several readily accessible 1,5,9-trienes occurs regioselectively to provide very short diastereoselective routes to substituted octahydro-2,2′-bifuranyl systems.

Total Syntheses of (−) Epilupinine and (−)-Tashiromine Using Imino-Aldol Reactions

Co-reporter:Amanda C. Cutter ; Iain R. Miller ; John F. Keily ; Richard K. Bellingham ; Mark E. Light

Organic Letters () pp:

Publication Date(Web):July 11, 2011

DOI:10.1021/ol2015048

Short routes to enantiomerically pure indolizidine and quinolizidine alkaloids have been developed using imino-aldol reactions of enolates derived from phenyl 5-chlorovalerate. High levels of syn selectivity (dr ∼13–16:1) were obtained using lithium enolates of phenyl esters in combination with tert-butylsulfinyl imines. The imino-aldol adducts were deprotected and cyclized to afford (−)-epilupinine ((−)-2) and (−)-tashiromine ((−)-1) in two further steps.

Synthesis of the non-adjacent bis-THF core of cis-sylvaticin using a double oxidative cyclisation

Co-reporter:Riaz A. Bhunnoo, Heather Hobbs, Dramane I. Lainé, Mark E. Light and Richard C. D. Brown

Organic & Biomolecular Chemistry 2009 - vol. 7(Issue 5) pp:NaN1024-1024

Publication Date(Web):2009/01/28

DOI:10.1039/B813201A

A short synthesis of the non-adjacent bis-THF core of the Annonaceousacetogenincis-sylvaticin (1) is described. C2 Symmetrical (Z,E,E,Z)- and (E,E,E,E)-tetraenes 5 and 6 were synthesised in six and three steps respectively from (1E,5E,9E)-cyclododeca-1,5,9-triene. Subsequent permanganate promoted asymmetric bi-directional oxidative cyclisation of tetraene 5 was used to create the non-adjacent bis-THF core of 1, installing seven of the nine stereogenic centres present in the natural product in a single step. Desymmetrisation of the oxidative cyclisation product by mono-tosylation gave access to a C11–C32 fragment of cis-sylvaticin.

Synthesis of the positron-emitting radiotracer [18F]-2-fluoro-2-deoxy-D-glucose from resin-bound perfluoroalkylsulfonates

Co-reporter:Lynda J. Brown, Nianchun Ma, Denis R. Bouvet, Sue Champion, Alex M. Gibson, Yulai Hu, Alex Jackson, Imtiaz Khan, Nicolas Millot, Amy C. Topley, Harry Wadsworth, Duncan Wynn and Richard C. D. Brown

Organic & Biomolecular Chemistry 2009 - vol. 7(Issue 3) pp:NaN575-575

Publication Date(Web):2008/12/08

DOI:10.1039/B816032E

A new approach to the synthesis of 2-fluoro-2-deoxy-D-glucose (FDG, [19/18F]-3) is described, which employs supported perfluoroalkylsulfonate precursors 33–36, where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [19F]fluoride ion afforded protected FDG [19F]-18 as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [19F]-18 was shown to produce [19F]FDG. The method has been applied to the efficient radiosynthesis of the imaging agent [18F]FDG, and was shown to produce the radiochemical tracer in good radiochemical yield (average 73%, decay corrected).

Total synthesis of cis-reticulatacin-10-ones A and B: absolute stereochemical assignment

Co-reporter:Sherif B. Abdel Ghani, Lynda J. Brown, Bruno Figadère and Richard C. D. Brown

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 20) pp:NaN4545-4545

Publication Date(Web):2010/08/23

DOI:10.1039/C0OB00259C

cis-Reticulatacin-10-ones A and B were synthesised as a predefined mixture of diastereoisomers (dr ∼ 1:9) in nine steps from the acid chloride 8, and without the use of hydroxyl protecting groups. Comparison of the chiral HPLC chromatogram of the synthetic sample with that of the natural product isolated from the roots of the tropical fruit tree Annona muricata L. showed the natural product to be a mixture of A and B diastereoisomers (dr ∼ 1:1).

A biaryl cross-coupling strategy for functionalisation of benzocrown ethers

Co-reporter:Sally Dixon, Richard C. D. Brown and Philip A. Gale

Chemical Communications 2007(Issue 34) pp:NaN3567-3567

Publication Date(Web):2007/08/06

DOI:10.1039/B709861H

Preparation of (di)benzocrown-substituted aryl-zinc or -boron reagents and their palladium-catalysed cross-coupling with functionalised aryl halides is described for convenient synthesis of novel crown ether systems.

Richard C. D. Brown

TOPICS

Abstract

Abstract