David M. Hodgson

Asymmetric Induction in C-Alkylation of Tropane-Derived Enamines: Congruence Between Computation and Experiment

Co-reporter:Yifei Li, Kelvin E. Jackson, Andrew Charlton, Ben Le Neve-Foster, Asma Khurshid, Heinrich-K. A. Rudy, Amber L. Thompson, Robert S. Paton, and David. M. Hodgson

The Journal of Organic Chemistry October 6, 2017 Volume 82(Issue 19) pp:10479-10479

Publication Date(Web):September 27, 2017

DOI:10.1021/acs.joc.7b01954

Quantum chemical studies of C-ethylation of 1-methyl- and 1,4,4-trimethyl-tropane-derived enamines predict good (89:11 er, B3LYP) and high (98:2 er, B3LYP) levels, respectively, of asymmetric induction in the resulting α-alkylated aldehydes. The nonracemic tropanes were synthesized using Mannich cyclization strategies (Robinson-Schöpf and by way of a Davis-type N-sulfinyl amino bisketal, respectively), and ethylation of the derived enamines was found to support the predicted sense and magnitude of asymmetric induction (81:19 er and 95:5 er, respectively). A comparison of several computational methods highlights the robustness of predicted trends in enantioselectivity, enabling theory to guide synthesis.

Total Synthesis and Structural Revision of the Cytotoxin Aruncin B

Co-reporter:Aubert Ribaucourt and David M. Hodgson

Organic Letters 2016 Volume 18(Issue 17) pp:4364-4367

Publication Date(Web):August 16, 2016

DOI:10.1021/acs.orglett.6b02120

The sodium salts E-15 and Z-15 of the originally proposed dihydropyran acid structure of aruncin B (1) were prepared through ring-closing alkene metathesis (RCM) and ethoxyselenation–selenoxide elimination, but acid sensitivity of these salts, together with inconsistencies in the spectral data, suggested a significant structural misassignment. A β-iodo Morita–Baylis–Hillman reaction to give Z-iodo ester 24, followed by Sonogashira cross-coupling–5-exo-dig lactonization, provided concise access to a Z-γ-alkylidenebutenolide 18, which possessed data corresponding to those originally reported for aruncin B.

Recent applications in natural product synthesis of dihydrofuran and -pyran formation by ring-closing alkene metathesis

Co-reporter:Reece Jacques, Ritashree Pal, Nicholas A. Parker, Claire E. Sear, Peter W. Smith, Aubert Ribaucourt and David M. Hodgson

Organic & Biomolecular Chemistry 2016 vol. 14(Issue 25) pp:5875-5893

Publication Date(Web):25 Apr 2016

DOI:10.1039/C6OB00593D

In the past two decades, alkene metathesis has risen in prominence to become a significant synthetic strategy for alkene formation. Many total syntheses of natural products have used this transformation. We review the use, from 2003 to 2015, of ring-closing alkene metathesis (RCM) for the generation of dihydrofurans or -pyrans in natural product synthesis. The strategies used to assemble the RCM precursors and the subsequent use of the newly formed unsaturation will also be highlighted and placed in context.

Amine Protection/α-Activation with the tert-Butoxythiocarbonyl Group: Application to Azetidine Lithiation–Electrophilic Substitution

Co-reporter:David M. Hodgson, Claire L. Mortimer, and Jeffrey M. McKenna

Organic Letters 2015 Volume 17(Issue 2) pp:330-333

Publication Date(Web):December 23, 2014

DOI:10.1021/ol503441d

tert-Butoxythiocarbonyl (Botc), the long-neglected thiocarbonyl analogue of Boc, facilitates (unlike its alkoxycarbonyl cousin) α-lithiation and electrophile incorporation on N-Botc-azetidine. N,N,N′,N′-endo,endo-Tetramethyl-2,5-diaminonorbornane proved optimal as a chiral ligand, generating adducts with er up to 92:8. Facile deprotection, under conditions that left the corresponding N-Boc systems intact, was achieved using either TFA or via thermolysis in ethanol.

α- and α′-Lithiation–Electrophile Trapping of N-Thiopivaloyl and N-tert-Butoxythiocarbonyl α-Substituted Azetidines: Rationalization of the Regiodivergence Using NMR and Computation

Co-reporter:Kelvin E. Jackson, Claire L. Mortimer, Barbara Odell, Jeffrey M. McKenna, Timothy D. W. Claridge, Robert S. Paton, and David M. Hodgson

The Journal of Organic Chemistry 2015 Volume 80(Issue 20) pp:9838-9846

Publication Date(Web):September 24, 2015

DOI:10.1021/acs.joc.5b01804

1H NMR and computational analyses provide insight into the regiodivergent (α- and α′-) lithiation–electrophile trapping of N-thiopivaloyl- and N-(tert-butoxythiocarbonyl)-α-alkylazetidines. The magnitudes of the rotation barriers in these azetidines indicate that rotamer interconversions do not occur at the temperature and on the time scale of the lithiations. The NMR and computational studies support the origin of regioselectivity as being thiocarbonyl-directed lithiation from the lowest energy amide-like rotameric forms (cis for N-thiopivaloyl and trans for N-tert-butoxythiocarbonyl).

Generation and Electrophile Trapping of N-Boc-2-lithio-2-azetine: Synthesis of 2-Substituted 2-Azetines

Co-reporter:David M. Hodgson, Christopher I. Pearson, and Madiha Kazmi

Organic Letters 2014 Volume 16(Issue 3) pp:856-859

Publication Date(Web):January 10, 2014

DOI:10.1021/ol403626k

s-BuLi-induced α-lithiation–elimination of LiOMe from N-Boc-3-methoxyazetidine and further in situ α-lithiation generates N-Boc-2-lithio-2-azetine which can be trapped with electrophiles, either directly (carbonyl or heteroatom electrophiles) or after transmetalation to copper (allowing allylations and propargylations), providing a concise access to 2-substituted 2-azetines.

Methods for direct generation of α-alkyl-substituted aldehydes

Co-reporter:David M. Hodgson, Andrew Charlton

Tetrahedron 2014 70(13) pp: 2207-2236

Publication Date(Web):

DOI:10.1016/j.tet.2013.11.046

Intramolecular Oxonium Ylide Formation–[2,3] Sigmatropic Rearrangement of Diazocarbonyl-Substituted Cyclic Unsaturated Acetals: A Formal Synthesis of Hyperolactone C

Co-reporter:David M. Hodgson, Stanislav Man, Kimberley J. Powell, Ziga Perko, Minxiang Zeng, Elena Moreno-Clavijo, Amber L. Thompson, and Michael D. Moore

The Journal of Organic Chemistry 2014 Volume 79(Issue 20) pp:9728-9734

Publication Date(Web):October 3, 2014

DOI:10.1021/jo501893r

Rh(II)-catalyzed oxonium ylide formation–[2,3] sigmatropic rearrangement of α-diazo-β-ketoesters possessing γ-cyclic unsaturated acetal substitution, followed by acid-catalyzed elimination–lactonization, provides a concise approach to 1,7-dioxaspiro[4.4]non-2-ene-4,6-diones. The process creates adjacent quaternary stereocenters with full control of the relative stereochemistry. An unsymmetrical monomethylated cyclic unsaturated acetal leads to hyperolactone C, where ylide formation–rearrangement proceeds with high selectivity between subtly nonequivalent acetal oxygen atoms.

An approach to hyperolactone C and analogues using late stage conjugate addition on an oxonium ylide-derived spirofuranone

Co-reporter:David M. Hodgson, Elena Moreno-Clavijo, Sophie E. Day and Stanislav Man

Organic & Biomolecular Chemistry 2013 vol. 11(Issue 32) pp:5362-5369

Publication Date(Web):12 Jul 2013

DOI:10.1039/C3OB41251B

A stereocontrolled synthesis of norphenyl hyperolactone C together with its utility as a direct precursor to the anti-HIV agent hyperolactone C and analogues by addition of organolithiums, are described. Preliminary studies to access this key building block in a catalytic enantioselective manner are also reported.

C-Alkylation of Chiral Tropane- and Homotropane-Derived Enamines

Co-reporter:David M. Hodgson, Andrew Charlton, Robert S. Paton, and Amber L. Thompson

The Journal of Organic Chemistry 2013 Volume 78(Issue 4) pp:1508-1518

Publication Date(Web):January 29, 2013

DOI:10.1021/jo3025972

The synthesis and alkylation of chiral, nonracemic tropane- and homotropane-derived enamines is examined as an approach to enantioenriched α-alkylated aldehydes. The two bicyclic N auxiliaries, which differ by a single methylene group, give opposite senses of asymmetric induction on alkylation with EtI and provide modestly enantioenriched 2-ethylhexanal (following hydrolysis of the alkylated iminium). The observed stereoselectivity is supported by density functional studies of ethylation for both enamines.

α-Lithiation–Electrophile Trapping of N-Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2-Substituted 3-Hydroxyazetidines

Co-reporter:David M. Hodgson, Christopher I. Pearson, and Amber L. Thompson

The Journal of Organic Chemistry 2013 Volume 78(Issue 3) pp:1098-1106

Publication Date(Web):January 10, 2013

DOI:10.1021/jo3025225

α-Lithiation of N-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good trans-diastereoselectivity, aside from deuteration, which gives the cis-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a trans-selective manner. These studies also suggest that the stereochemical outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (cis or trans to the hydroxyl group) is initially removed.

syn-β-Hydroxyallylic Silanes from Terminal Epoxide α-Lithiation–Silylation and Alkenylation: Application to the Tetrahydrofuran Portion of the Lytophilippines

Co-reporter:David M. Hodgson and Saifullah Salik

Organic Letters 2012 Volume 14(Issue 17) pp:4402-4405

Publication Date(Web):August 16, 2012

DOI:10.1021/ol3018853

Lithiation–in situ silylation of terminal epoxides using lithium 2,2,6,6-tetramethylpiperidide in combination with phenyldimethyl(or diethyl)silyl chloride provides a direct process for the synthesis of trans-α,β-epoxysilanes, which undergo α-ring opening with alkenylcoppers to give syn-β-hydroxyallylic silanes. The chemistry is applied in an annulation approach to the C10–C19 tetrahydrofuran-containing portion of the lytophilippines.

Synthesis of the anti-trypanosomal agent (±)-hydroxyanthecotulide by Cr(II)-catalysed allylation and Meyer–Schuster rearrangement

Co-reporter:David M. Hodgson, Eric P. A. Talbot and Barry P. Clark

Chemical Communications 2012 vol. 48(Issue 51) pp:6349-6350

Publication Date(Web):22 May 2012

DOI:10.1039/C2CC32283H

The first synthesis of the bioactive sesquiterpene lactone hydroxyanthecotulide is achieved in 7 steps, involving a stereocontrolled Cr(II)-catalysed reaction of 3-(bromomethyl)furan-2(5H)-one with enynal 9 and a mild Au(I)-catalysed Meyer–Schuster rearrangement.

Convergent synthesis of conjugated 1,2-disubstituted E-allylic alcohols from two aldehydes and methylenetriphenylphosphorane

Co-reporter:David M. Hodgson and Rosanne S. D. Persaud

Organic & Biomolecular Chemistry 2012 vol. 10(Issue 39) pp:7949-7951

Publication Date(Web):30 Aug 2012

DOI:10.1039/C2OB26346G

β-Lithiooxyphosphonium ylides, made in situ from an aldehyde and methylenetriphenylphosphorane, react with a second aldehyde to form E-allylic alcohols. α-Branching and α,β-unsaturation in the second aldehyde, together with the lack of further substitution on the phosphorane carbon play important roles in selectivity. A range of these aldehydes, in addition to aromatic aldehydes as the second aldehyde also provided synthetically useful access to E-allylic alcohols.

Disubstituted Z-allylic esters by Wittig–Schlosser reaction using methylenetriphenylphosphorane

Co-reporter:David M. Hodgson and Tanzeel Arif

Chemical Communications 2011 vol. 47(Issue 9) pp:2685-2687

Publication Date(Web):12 Jan 2011

DOI:10.1039/C0CC04429F

β-Lithiooxyphosphonium ylides, generated in situ from aldehydes and methylenetriphenylphosphorane, react with halomethyl esters to form disubstituted allylic esters in good yields and with high Z-selectivity.

Stereoselective Synthesis of β-(Hydroxymethylaryl/alkyl)-α-methylene-γ-butyrolactones

Co-reporter:David M. Hodgson, Eric P. A. Talbot, and Barry P. Clark

Organic Letters 2011 Volume 13(Issue 10) pp:2594-2597

Publication Date(Web):April 13, 2011

DOI:10.1021/ol200711f

Zinc or a chromium(II) source with 3-(bromomethyl)furan-2(5H)-one (3) and an aldehyde gives β-(hydroxymethylaryl/alkyl)-α-methylene-γ-butyrolactones 5 in good yields and high diastereoselectivities. The methodology is demonstrated in concise syntheses of (±)-hydroxymatairesinol (8) and (±)-methylenolactocin (10) by subsequent arylboronate conjugate addition and translactonization, respectively.

Synthesis of the Anti-HIV Agent ()-HyperolactoneC by Using Oxonium Ylide FormationRearrangement

Co-reporter: David M. Hodgson;Dr. Stanislav Man

Chemistry - A European Journal 2011 Volume 17( Issue 35) pp:9731-9737

Publication Date(Web):

DOI:10.1002/chem.201101082

Abstract

Starting from readily available (S)-styrene oxide an asymmetric synthesis is described of the naturally occurring anti-HIV spirolactone (−)-hyperolactone C, which possesses adjacent fully substituted stereocenters. The key step involves a stereocontrolled Rh^II-catalysed oxonium ylide formation–[2,3] sigmatropic rearrangement of an α-diazo-β-ketoester bearing allylic ether functionality. From the resulting furanone, an acid-catalysed lactonisation and dehydrogenation gives the natural product.

Convergent Synthesis of Trisubstituted Z-Allylic Esters by Wittig−Schlosser Reaction

Co-reporter:David M. Hodgson and Tanzeel Arif

Organic Letters 2010 Volume 12(Issue 18) pp:4204-4207

Publication Date(Web):August 19, 2010

DOI:10.1021/ol101843q

β-Lithiooxyphosphonium ylides, generated in situ from aldehydes and Wittig reagents, react readily with halomethyl esters to form trisubstituted Z-allylic esters. The methodology was applied to a total synthesis of the geranylgeraniol-derived diterpene (6S,7R,Z)-7-hydroxy-2-((E)-6-hydroxy-4-methylhex-4-enylidene)-6,10-dimethylundec-9-enyl acetate (12).

Epoxide Opening-Induced Tandem 8-Azabicyclo[3.2.1]octane to 6-Azabicyclo[3.2.1]octane Rearrangement−Iminium Allylation: Synthesis of (±)-Peduncularine

Co-reporter:David M. Hodgson, Ruth E. Shelton, Thomas A. Moss and Mouloud Dekhane

Organic Letters 2010 Volume 12(Issue 12) pp:2834-2837

Publication Date(Web):May 14, 2010

DOI:10.1021/ol100943j

An efficient Lewis acid induced nitrogen-driven rearrangement iminium-trapping cascade from an epoxytropinone 3 gives a 7-allylated 6-azabicyclo[3.2.1]octan-3-one 2, which is converted into the alkaloid (±)-peduncularine (1).

Synthetic and computational studies on the tricarboxylate core of 6,7-dideoxysqualestatin H5 involving a carbonyl ylide cycloaddition–rearrangement

Co-reporter:David M. Hodgson, Carolina Villalonga-Barber, Jonathan M. Goodman and Silvina C. Pellegrinet

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 17) pp:3975-3984

Publication Date(Web):02 Jul 2010

DOI:10.1039/C004496B

Reaction of diazodiketoesters 17 and 28 with methyl glyoxylate in the presence of catalytic rhodium(II) acetate generates predominantly the 6,8-dioxabicyclo[3.2.1]octanes 29 and 30, respectively. Acid-catalysed rearrangement of the corresponding alcohol 31 favours, at equilibrium, the 2,8-dioxabicyclo[3.2.1]octane skeleton 33 of the squalestatins–zaragozic acids. Force field calculations on the position of the equilibrium gave misleading results. DFT calculations were correct in suggesting that the energy difference between 31 and 33 should be small, but did not always suggest the right major product. Calculation of the NMR spectra of the similar structures could be used to assign the isomers with a high level of confidence.

Transition States and Origins of 1,4-Asymmetric Induction in Alkylations of 2,2,6-Trialkylpiperidine Enamines

Co-reporter:JoannM. Um;NaeemS. Kaka Dr.;DavidM. Hodgson ;K.N. Houk

Chemistry - A European Journal 2010 Volume 16( Issue 21) pp:6310-6316

Publication Date(Web):

DOI:10.1002/chem.201000046

Abstract

The asymmetric C-alkylation of chiral enamines derived from terminal epoxides and lithium 2,2,6-trialkylpiperidides has previously been shown to provide α-alkylated aldehydes by intermolecular nucleophilic substitution in good levels of asymmetric induction. We now report a computational study of the origins of asymmetric induction in these reactions. Computational modeling with density functional theory (B3LYP/6-31G(d)) agrees closely with the experimental observations. This stereoselectivity is attributed to a preferential conformation of the enamine and the piperidine ring that places the C-6 alkyl substituent in an axial position due to A^1, 3 strain. Preferential attack occurs away from the axial group, for steric reasons. The effects of changing the C-6 substituent from methyl to isopropyl were studied, and twist transition states were found to contribute significantly in the latter alkylations.

LithiationElectrophilic Substitution of N-Thiopivaloylazetidine

Co-reporter:DavidM. Hodgson ;Johannes Kloesges

Angewandte Chemie International Edition 2010 Volume 49( Issue 16) pp:2900-2903

Publication Date(Web):

DOI:10.1002/anie.201000058

LithiationElectrophilic Substitution of N-Thiopivaloylazetidine

Co-reporter:DavidM. Hodgson ;Johannes Kloesges

Angewandte Chemie 2010 Volume 122( Issue 16) pp:2962-2965

Publication Date(Web):

DOI:10.1002/ange.201000058

Radical deoxygenation of 3-azatricyclo[2.2.1.02,6]heptan-5-ols to 2-azabicyclo[2.2.1]hept-5-enes and 1,2-dihydropyridines

Co-reporter:David M. Hodgson, Matthew L. Jones, Christopher R. Maxwell, Andrew R. Cowley, Amber L. Thompson, Osamu Ichihara, Ian R. Matthews

Tetrahedron 2009 65(37) pp: 7825-7836

Publication Date(Web):

DOI:10.1016/j.tet.2009.07.022

Catalytic enantioselective tandem carbonyl ylide formation—intramolecular cycloaddition with unsaturated α-diazo-β,ε-diketo sulfones

Co-reporter:David M. Hodgson, Rebecca Glen, Alison J. Redgrave

Tetrahedron: Asymmetry 2009 Volume 20(6–8) pp:754-757

Publication Date(Web):7 May 2009

DOI:10.1016/j.tetasy.2009.02.031

The synthesis and 1,3-dipolar cycloaddition reactions of unsaturated α-diazo-β,ε-diketo sulfones 7 using chiral rhodium catalysts (up to 71.5:28.5 er) are described.7-(Phenylsulfonyl)-11-oxatricyclo[5.3.1.01,5]undecan-8-oneC16H18O4Ser = 71.5:28.5 (by chiral HPLC)[α]D25=+13.6 (c 1.0, CH2C12)Source of chirality: Rh (S)-valine-derived catalystAbsolute configuration: unknown7-(Methylsulfonyl)-11-oxatricyclo[5.3.1.01,5]undecan-8-oneC11H16O4Ser = 66.5:33.5 (by chiral GC)[α]D25=+3.1 (c 1.05, CH2C12)Source of chirality: Rh (S)-valine-derived catalystAbsolute configuration: unknown

Asymmetric Synthesis of -Alkylated Aldehydes using Terminal Epoxide-Derived Chiral Enamines

Co-reporter:DavidM. Hodgson ;NaeemS. Kaka

Angewandte Chemie 2008 Volume 120( Issue 51) pp:10106-10108

Publication Date(Web):

DOI:10.1002/ange.200804369

Asymmetric Synthesis of -Alkylated Aldehydes using Terminal Epoxide-Derived Chiral Enamines

Co-reporter:DavidM. Hodgson ;NaeemS. Kaka

Angewandte Chemie International Edition 2008 Volume 47( Issue 51) pp:9958-9960

Publication Date(Web):

DOI:10.1002/anie.200804369

Synthesis of azabicyclic systems using nitrogen-directed radical rearrangements

Co-reporter:David M. Hodgson and Leonard H. Winning

Organic & Biomolecular Chemistry 2007 vol. 5(Issue 19) pp:3071-3082

Publication Date(Web):02 Aug 2007

DOI:10.1039/B707566A

Radical rearrangements are important transformations in organic synthesis. The stabilisation of α-nitrogen radicals is shown to be a useful effect for the control of radical rearrangements and is applied to the synthesis of a variety of azabicyclic frameworks. The utility of this method is illustrated in the synthesis of bioactive targets.

Lithiation-Induced Migrations from Nitrogen to Carbon in Terminal Aziridines

Co-reporter:David M. Hodgson ;Philip G. Humphreys;Zhaoqing Xu Dr.;John G. Ward Dr.

Angewandte Chemie 2007 Volume 119(Issue 13) pp:

Publication Date(Web):15 FEB 2007

DOI:10.1002/ange.200604920

Einfach entschützt: Lithium-2,2,6,6-tetramethylpiperidid löst in Aziridinen mit N-Boc- oder N-Phosphonat-Schutzgruppen eine regio- und stereoselektive Wanderung der Schutzgruppe vom N- zum C-Atom aus. Die Produkte sind präparativ nützliche trans-Aziridinylester bzw. trans-Aziridinylphosphonate.

Highly Chemo- and Stereoselective Intermolecular Coupling of Diazoacetates To Give cis-Olefins by Using Grubbs Second-Generation Catalyst

Co-reporter:David M. Hodgson ;Deepshikha Angrish

Chemistry - A European Journal 2007 Volume 13(Issue 12) pp:

Publication Date(Web):9 FEB 2007

DOI:10.1002/chem.200601692

Highly stereoselective formation of cis-2-ene-1,4-diesters by homo- and heterocoupling of α-diazoacetates in the presence of Grubbs second-generation catalyst is demonstrated. The dual reactivity of the catalyst in alkene metathesis and diazocoupling has been exploited in the synthesis of 12–26-membered macrocyclic dienyl dilactones by one-pot carbene dimerisation/ring-closing metathesis.

Lithiation-Induced Migrations from Nitrogen to Carbon in Terminal Aziridines

Co-reporter:David M. Hodgson ;Philip G. Humphreys;Zhaoqing Xu Dr.;John G. Ward Dr.

Angewandte Chemie International Edition 2007 Volume 46(Issue 13) pp:

Publication Date(Web):15 FEB 2007

DOI:10.1002/anie.200604920

Benefiting from deprotection: Lithium 2,2,6,6-tetramethylpiperidide induces N-Boc or N-phosphonate terminal aziridines to undergo regio- and stereoselective N-to-C migration of the protecting group, giving synthetically valuable trans-aziridinylesters and trans-aziridinylphosphonates.

One-pot cross-metathesis/tandem carbonyl ylide formation–intramolecular cycloaddition of an unsaturated 2-diazo-3,6-diketoester

Co-reporter:David M. Hodgson, Deepshikha Angrish and Agnès H. Labande

Chemical Communications 2006 (Issue 6) pp:627-628

Publication Date(Web):18 Jan 2006

DOI:10.1039/B515943A

Dicarbonyl-stabilised diazo functionality is tolerated during alkene cross-metathesis using Grubbs' catalyst, but undergoes subsequent tandem carbonyl ylide formation–intramolecular 1,3-dipolar cycloaddition on addition of catalytic Rh2(OAc)4 in a one-pot operation.

3-Hydroxypyrrolidines from epoxysulfonamides and dimethylsulfoxonium methylide

Co-reporter:David M. Hodgson, Matthew J. Fleming, Zhaoqing Xu, Changxue Lin and Steven J. Stanway

Chemical Communications 2006 (Issue 30) pp:3226-3228

Publication Date(Web):22 Jun 2006

DOI:10.1039/B606583J

N-Tosyl-protected 3-hydroxypyrrolidines are prepared by reaction of dimethylsulfoxonium methylide with readily available epoxysulfonamides.

Oxapolycycles from One-Pot Cross-Metathesis/Carbonyl Ylide Formation-Intramolecular Cycloaddition of α-Diazo-β-keto Esters

Co-reporter:David M. Hodgson;Deepshikha Angrish

Advanced Synthesis & Catalysis 2006 Volume 348(Issue 16-17) pp:

Publication Date(Web):27 NOV 2006

DOI:10.1002/adsc.200600306

Chemoselective cross-metathesis of unsaturated α-diazo-β-keto esters using Grubbs’ 2^nd generation catalyst, followed by Rh₂(OAc)₄-catalysed tandem carbonyl ylide formation-intramolecular cycloaddition is demonstrated. The two different catalytic metallocarbene transfer reactions have also been successfully carried out in a one-pot procedure, which allows rapid generation of molecular complexity in a single operation.

Dimerization of Lithiated Terminal Aziridines

Co-reporter:David M. Hodgson Dr.;Steven M. Miles Dr.

Angewandte Chemie 2006 Volume 118(Issue 6) pp:

Publication Date(Web):27 DEC 2005

DOI:10.1002/ange.200503303

Aus zwei mach eins: Die Dimerisierung enantiomerenreiner terminaler Aziridine durch Lithiierung liefert effizient N-geschützte 2-En-1,4-diamine mit vollständiger Selektivität für das E-Olefin (siehe Schema). Die Nützlichkeit der Methode wurde durch die Synthese von (R,S,S,R)-2,5-Diamino-1,6-diphenylhexan-3,4-diol demonstriert, der zentralen Einheit vieler äußerst potenter HIV-Protease-Inhibitoren und asymmetrischer Katalysatoren.

Dimerization of Lithiated Terminal Aziridines

Co-reporter:David M. Hodgson,Steven M. Miles

Angewandte Chemie International Edition 2006 45(6) pp:935-938

Publication Date(Web):

DOI:10.1002/anie.200503303

Maleates from diazoacetates and dilactones from head-to-head dimerisation of alkenyl diazoacetates using Grubbs' 2nd-generation ruthenium carbene catalyst

Co-reporter:David M. Hodgson and Deepshikha Angrish

Chemical Communications 2005 (Issue 39) pp:4902-4904

Publication Date(Web):31 Aug 2005

DOI:10.1039/B510829B

Grubbs' 2nd-generation ruthenium carbene catalyst homocouples diazoacetates to maleates and also catalyses head-to-head dimerisation of alkenyl diazoacetates giving dienyl dilactones.

Use of allene in 1,3-dipolar addition to a carbonyl ylide: syntheses of 3-hydroxy-cis-nemorensic acid and nemorensic acid

Co-reporter:David M. Hodgson and Frédéric Le Strat

Chemical Communications 2004 (Issue 7) pp:822-823

Publication Date(Web):24 Feb 2004

DOI:10.1039/B316908A

1,3-Dipolar addition of allene to the carbonyl ylide derived from 6-diazoheptane-2,5-dione is the key step in syntheses of 3-hydroxy-cis-nemorensic acid and nemorensic acid.

Unsaturated 1,2-amino alcohols and ethers from aziridines and organolithiums

Co-reporter:David M. Hodgson, Bogdan Štefane, Timothy J. Miles and Jason Witherington

Chemical Communications 2004 (Issue 19) pp:2234-2235

Publication Date(Web):24 Aug 2004

DOI:10.1039/B409486G

Organolithium-induced ring-opening of aziridines of 2,5-dihydrofuran (5 and 8) and 1,4-dimethoxybut-2-ene (16, 17 and 23) gives 3-substituted 2-aminobut-3-en-1-ols 9–15 and amino ethers 18–20 and 24–26.

Catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoester-derived carbonyl ylides with alkene dipolarophiles

Co-reporter:David M. Hodgson;Tobias Brückl;Rebecca Glen;Agnès H. Labande;Deborah A. Selden;Alexander G. Dossetter;Alison J. Redgrave

PNAS 2004 Volume 101 (Issue 15 ) pp:5450-5454

Publication Date(Web):2004-04-13

DOI:10.1073/pnas.0307274101

Catalyzed cascade reactions that generate molecular complexity rapidly and in an enantioselective manner are attractive methods for asymmetric synthesis. In the present article, chiral rhodium catalysts are shown to effect such a transformation by using a range of 2-diazo-3,6-diketoesters with bicyclo[2.2.1]alkenes and styrenes as reaction partners. The reactions are likely to proceed by formation of a catalyst-complexed carbonyl ylide from the diazo compound, followed by intermolecular cycloaddition with the alkene dipolarophile. It was possible to obtain high levels of asymmetric induction [up to 89% enantiomeric excess (ee) and 92% ee for the two chiral catalysts investigated]. Enantioselectivity is not highly sensitive to substituent variation at the ketone that forms the ylide; however, branching does improve ee. Observations of dipolarophile-dependent enantiofacial selectivity in the cycloadditions indicate that the dipolarophile can be intimately involved in the enantiodiscrimination process.

Enantioselective alkylative double ring-opening of epoxides derived from cyclic allylic ethers: synthesis of enantioenriched unsaturated diols

Co-reporter:David M. Hodgson, Matthew A. H. Stent, Bogdan Štefane and Francis X. Wilson

Organic & Biomolecular Chemistry 2003 vol. 1(Issue 7) pp:1139-1150

Publication Date(Web):17 Feb 2003

DOI:10.1039/B212404A

A screen of external chiral ligands has led to enantioselective organolithium-induced alkylative double ring-opening of 3,4-epoxytetrahydrofuran 1 with n-BuLi to give 3-methyleneheptane-1,2-diol 3 in 75% yield and 55% ee in the presence of bisoxazoline 10, and in up to 60% ee in the presence of (−)-sparteine 2. Extending the alkylative double ring-opening reaction to epoxides derived from oxabicyclo[n.2.1]alkenes (n = 2, 3) results in the formation of cycloalkenediols, which, when carried out in the presence of (−)-sparteine 2 affords products in up to 85% ee.

Development of two processes for the synthesis of bridged azabicyclic systems: intermolecular radical addition–homoallylic rearrangements leading to 2-azanorborn-5-enes and neophyl-type radical rearrangements to 2-azabenzonorbornanes

Co-reporter:David M. Hodgson, Magnus W. P. Bebbington and Paul Willis

Organic & Biomolecular Chemistry 2003 vol. 1(Issue 21) pp:3787-3798

Publication Date(Web):22 Aug 2003

DOI:10.1039/B306717N

Radical thiol additions to 7-azanorbornadienes give 7-thio-substituted 2-azanorbornenes and Barton deoxygenations of 7-azabenzonorbornanols give 2-azabenzonorbornanes. The processes both involve novel nitrogen-directed radical rearrangements. The kinetics and mechanisms of the reactions are also discussed.

Enantioselective synthesis of epoxides by α-deprotonation—electrophile trapping of achiral epoxides

Co-reporter:David M. Hodgson, Timothy J. Buxton, Iain D. Cameron, Emmanuel Gras and Eirene H. M. Kirton

Organic & Biomolecular Chemistry 2003 vol. 1(Issue 23) pp:4293-4301

Publication Date(Web):24 Oct 2003

DOI:10.1039/B309717J

Enantioselective α-deprotonation of achiral epoxides 1, 21, and 26 using organolithiums in the presence of (−)-sparteine 2 and subsequent electrophile trapping gives access to enantioenriched trisubstituted epoxides 9–17, 22, 23, 27 and 28 (in up to 86% ee).

Synthesis and evaluation of 4,4′,6,6′-tetrasubstituted binaphtholphosphate dirhodium(II) complexes as catalysts in enantioselective carbonyl ylide formation–cycloaddition reactions

Co-reporter:David M. Hodgson, Deborah A. Selden, Alexander G. Dossetter

Tetrahedron: Asymmetry 2003 Volume 14(Issue 24) pp:3841-3849

Publication Date(Web):12 December 2003

DOI:10.1016/j.tetasy.2003.09.029

The synthesis of tetrakis[4,4′,6,6′-tetrasubstituted-1,1′-bi-2-naphtholphosphate]dirhodium(II) complexes, and their use as catalysts in the enantioselective tandem carbonyl ylide formation–intramolecular 1,3-dipolar cycloaddition of an unsaturated 2-diazo-3,6-diketoester, generating cycloadduct in up to 86% ee, is described.Graphic(S)-4,4′,6,6′-Tetraoctynyl-1,1′-bi-2-naphtholC52H62O2[α]D=+78.9 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetra(2-phenylethynyl)-1,1′-bi-2-naphtholC52H30O2[α]D=+137.5 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetra(2-phenylethyl)-1,1′-bi-2-naphtholC52H46O2[α]D=+15.0 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetra(4-n-butylphenyl)-1,1′-bi-2-naphtholC60H62O2[α]D=+68.9 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetraoctyl-1,1′-bi-2-naphtholC52H78O2[α]D=+16.3 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetraoctyl-1,1′-bi-2-naphthol phosphateC52H77O4P[α]D=+119 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetra(4-n-butylphenyl)-1,1′-bi-2-naphthol phosphateC60H61O4P[α]D=+82.4 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetraphenyl-1,1′-bi-2-naphthol phosphateC44H29O4P[α]D=+76.5 (c 0.33, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(S)-4,4′,6,6′-Tetra(2-phenylethyl)-1,1′-bi-2-naphthol phosphateC52H45O4P[α]D=+104 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: STetrakis[(S)-4,4′,6,6′-tetraoctyl-1,1′-bi-2-naphthol phosphate]dirhodium(II)C208H304O16P4Rh2[α]D=−6.9 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: STetrakis[(S)-4,4′,6,6′-tetra(2-phenylethyl)-1,1′-bi-2-naphthol phosphate]dirhodium(II)C208H176O16P4Rh2[α]D=−14.8 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: STetrakis[(S)-4,4′,6,6′-tetra(4-n-butylphenyl)-1,1′-bi-2-naphtholphosphate]dirhodium(II)C240H240O16P4Rh2[α]D=+219 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S(1S,5R,7S)-7-Carbo-tert-butoxy-11-oxa-tricyclo[5.3.1.0]undecan-8-oneC15H22O4Ee=86%[α]D=−12.4 (c 1, CHCl3)Source of chirality: RhII (S)-BINOL-derived catalystAbsolute configuration: 1S,5R,7S (from X-ray analysis of (−)-borneol ester)Tetrakis[(S)-4,4′,6,6′-tetraphenyl-1,1′-bi-2-naphthol phosphate]dirhodium(II)C176H112O16P4Rh2[α]D=+215 (c 1, CHCl3)Source of chirality: (S)-BINOLAbsolute configuration: S

Catalytic enantioselective intermolecular cycloadditions of a 2-diazo-3,6-diketoester-derived carbonyl ylide with alkyne and strained alkene dipolarophiles

Co-reporter:David M. Hodgson, Agnès H. Labande, Rebecca Glen, Alison J. Redgrave

Tetrahedron: Asymmetry 2003 Volume 14(Issue 7) pp:921-924

Publication Date(Web):4 April 2003

DOI:10.1016/S0957-4166(03)00036-3

Catalytic enantioselective tandem carbonyl ylide formation-cycloaddition reactions of tert-butyl 2-diazo-3,6-dioxoheptanoate 7 with alkyne and strained alkene dipolarophiles to afford the corresponding cycloadducts with up to 92% ee are described.Graphic1-tert-Butyloxycarbonyl-5-methyl-7-phenyl-8-oxabicyclo[3.2.1]oct-6-en-2-oneC19H22O4Ee=61% (by chiral HPLC)[α]D24=−171.0 (c 1.0, CHCl3)Source of chirality: Rh (R)-BINOL-derived catalystAbsolute configuration: unknown(1α,4α,4aβ,5α,9α,9aβ)-Decahydro-5-tert-butyloxycarbonyl-9-methyl-5,9-epoxy-1,4-methano-6H-benzocyclohepten-6-oneC18H26O4Ee=92% (by chiral GC)[α]D27=+58.9 (c 1.0, CHCl3)Source of chirality: Rh (R)-BINOL-derived catalystAbsolute configuration: unknown(1α,4α,4aβ,5α,9α,9aβ)-1,4,4a,5,7,8,9,9a-Octahydro-5-tert-butyloxycarbonyl-9-methyl-5,9-epoxy-1,4-methano-6H-benzocyclohepten-6-oneC18H24O4Ee=83% (by chiral GC)[α]D27=+76.2 (c 1.0, CHCl3)Source of chirality: Rh (R)-BINOL-derived catalystAbsolute configuration: unknown

Enantioselective total synthesis of (–)-xialenon A

Co-reporter:David M. Hodgson, Jean-Marie Galano and Martin Christlieb

Chemical Communications 2002 (Issue 20) pp:2436-2437

Publication Date(Web):24 Sep 2002

DOI:10.1039/B208485F

The first total synthesis of (−)-xialenon A (1) via conjugate allylation of a 1,5-cyclooctadiene-derived bicyclo[3.3.0]octenone 3 and an α′-hydroxylation on the more hinderd face of enone 9 using hypervalent iodine chemistry, is described.

Enantioselective Alkylative Double Ring Opening of Epoxides: Synthesis of Enantioenriched Unsaturated Diols and Amino Alcohols

Co-reporter:David M. Hodgson Dr.;Christopher R. Maxwell;Timothy J. Miles;Edyta Paruch Dr.;Matthew A. H. Stent;Ian R. Matthews Dr.;Francis X. Wilson Dr.;Jason Witherington Dr.

Angewandte Chemie International Edition 2002 Volume 41(Issue 24) pp:

Publication Date(Web):12 DEC 2002

DOI:10.1002/anie.200290003

Enantioselective Alkylative Double Ring Opening of Epoxides: Synthesis of Enantioenriched Unsaturated Diols and Amino Alcohols

Co-reporter:David M. Hodgson Dr.;Christopher R. Maxwell;Timothy J. Miles;Edyta Paruch Dr.;Matthew A. H. Stent;Ian R. Matthews Dr.;Francis X. Wilson Dr.;Jason Witherington Dr.

Angewandte Chemie 2002 Volume 114(Issue 24) pp:

Publication Date(Web):12 DEC 2002

DOI:10.1002/ange.200290002

Enantioselective Alkylative Double Ring Opening of Epoxides: Synthesis of Enantioenriched Unsaturated Diols and Amino Alcohols

Co-reporter:David M. Hodgson Dr.;Christopher R. Maxwell;Timothy J. Miles;Edyta Paruch Dr.;Matthew A. H. Stent;Ian R. Matthews Dr.;Francis X. Wilson Dr.;Jason Witherington Dr.

Angewandte Chemie 2002 Volume 114(Issue 22) pp:

Publication Date(Web):12 NOV 2002

DOI:10.1002/1521-3757(20021115)114:22<4489::AID-ANGE4489>3.0.CO;2-8

Enantioselektive Erzeugung und intermolekulares Abfangen eines Lithiumcarbenoids erfolgt bei der Reaktion von Epoxiden aus 2,5-Dihydrofuran, 2,5-Dihydropyrrol sowie Oxa- und Aza-bicyclo[n.2.1]alkenen (n=2, 3) mit Organolithiumverbindungen in Gegenwart externer chiraler Liganden. Diese Methode kann zur Synthese wichtiger ungesättigter Diole und Aminoalkohole verwendet werden (siehe Schema; NBoc=N-t-Butoxycarbonyl).

Enantioselective Alkylative Double Ring Opening of Epoxides: Synthesis of Enantioenriched Unsaturated Diols and Amino Alcohols

Co-reporter:David M. Hodgson Dr.;Christopher R. Maxwell;Timothy J. Miles;Edyta Paruch Dr.;Matthew A. H. Stent;Ian R. Matthews Dr.;Francis X. Wilson Dr.;Jason Witherington Dr.

Angewandte Chemie International Edition 2002 Volume 41(Issue 22) pp:

Publication Date(Web):12 NOV 2002

DOI:10.1002/1521-3773(20021115)41:22<4313::AID-ANIE4313>3.0.CO;2-B

Enantioselective generation and intermolecular trapping of a lithium carbenoid occurs in the reaction of epoxides of 2,5-dihydrofuran, 2,5-dihydropyrrole, and oxa- and aza-bicyclo[n.2.1]alkenes (n=2, 3) with organolithium compounds in the presence of external chiral ligands. This methodology leads to the synthesis of important unsaturated diol and amino alcohol functionality (see scheme; tert-butoxycarbonyl).

Chiral Epoxides by Desymmetrizing Deprotonation of meso-Epoxides

Co-reporter:David M. Hodgson Dr.;Emmanuel Gras Dr.

Angewandte Chemie International Edition 2002 Volume 41(Issue 13) pp:

Publication Date(Web):1 JUL 2002

DOI:10.1002/1521-3773(20020703)41:13<2376::AID-ANIE2376>3.0.CO;2-Q

Simple meso-epoxides can be asymmetrically functionalized: Ligand-assisted direct hydrogen–lithium exchange allows the generation of destabilized oxiranyl lithium species and their subsequent trapping by a wide array of electrophiles (see scheme; E=group formed by addition of electrophile). When carried out in the presence of (−)-sparteine as ligand, this reaction provides a new enantioselective route to epoxides.

Catalytic enantioselective rearrangements and cycloadditions involving ylides from diazo compounds

Co-reporter:David M. Hodgson, Françoise Y. T. M. Pierard and Paul A. Stupple

Chemical Society Reviews 2001 vol. 30(Issue 1) pp:50-61

Publication Date(Web):27 Nov 2000

DOI:10.1039/B000708K

This review summarizes the background and state of the art (as of June 2000) of catalytic enantioselective rearrangements and cycloadditions involving ylides from diazo compounds. The field is still in its infancy, as until a few years ago it was not considered likely that a catalyst, having decomposed a diazo compound to form an ylide, would still be able to exert an influence on subsequent transformations of the ylide. Recent developments have shown this not to be the case and a new era of synthetically important ylide transformations in organic chemistry has begun where appropriate metal–chiral (nonracemic) ligand combinations are starting to be developed to render these transformations enantioselective.

Palladium-catalysed isomerisation of vinyldisilanes to allyldisilanes

Co-reporter:David M. Hodgson, Sarah F. Barker, Laura H. Mace and Julian R. Moran

Chemical Communications 2001 (Issue 2) pp:153-154

Publication Date(Web):21 Dec 2000

DOI:10.1039/B008565K

The isomerisation of vinyldisilanes 1 to allyldisilanes 2 catalysed by palladium-on-carbon in diethyl ether under hydrogen is described.

2-Azabicyclo[2.2.1]hept-5-enes from 7-azabicyclo[2.2.1]heptadienes by tandem intermolecular radical addition—homoallylic radical rearrangement

Co-reporter:David M. Hodgson, Magnus W. P. Bebbington and Paul Willis

Chemical Communications 2001 (Issue 10) pp:889-890

Publication Date(Web):20 Apr 2001

DOI:10.1039/B101984H

Addition of thiols to 7-azabicyclo[2.2.1]heptadienes such as 16 leads exclusively to 7-thio-substituted 2-azabicyclo[2.2.1]-hept-5-enes 17 in good yields via tandem intermolecular radical addition—homoallylic radical rearrangement.

Rh(II)-binaphthol phosphate catalysts in the enantioselective intramolecular oxonium ylide formation–[3,2] sigmatropic rearrangement of α-diazo-β-ketoesters

Co-reporter:David M. Hodgson, Margarita Petroliagi

Tetrahedron: Asymmetry 2001 Volume 12(Issue 6) pp:877-881

Publication Date(Web):17 April 2001

DOI:10.1016/S0957-4166(01)00147-1

The enantioselective intramolecular oxonium ylide formation-[3,2] sigmatropic rearrangement of α-diazo-β-ketoesters 9 using catalytic (1 mol%) dirhodium tetrakisbinaphthol phosphate catalysts 1 and 2 to give benzofuranones 11 in up to 62% e.e. is described.Graphic2-Allyl-2-methyloxycarbonyl-2,3-dihydrobenzofuran-3-oneC13H12O4Ee=62% (by chiral HPLC)[α]D24=+28.0 (c 0.25, CHCl3)Source of chirality: Rh R-BINOL-derived catalystAbsolute configuration: unknown2-Allyl-2-t-butoxycarbonyl-2,3-dihydrobenzofuran-3-oneC16H18O4Ee=45% (by chiral HPLC)[α]D24=+19.6 (c 0.5, CHCl3)Source of chirality: Rh R-BINOL-derived catalystAbsolute configuration: unknown

Cover Picture

Co-reporter:David M. Hodgson Dr.;Paul A. Stupple;Françoise Y. T. M. Pierard Dr.;Agnès H. Labe Dr. and;Craig Johnstone Dr.

Chemistry - A European Journal 2001 Volume 7(Issue 20) pp:

Publication Date(Web):5 OCT 2001

DOI:10.1002/1521-3765(20011015)7:20<4315::AID-CHEM4315>3.0.CO;2-B

The cover picture shows a space-filling representation of a chiral dirhodium catalyst that converts diazo-containing substrates into tricyclic adducts (artwork and three-dimensional modelling by Karl Harrison, University of Oxford). The dirhodium tetrakis(binaphtholphosphate) catalyst (octopus-like, with its eight dodecyl arms providing solubility in hydrocarbon solvents) induces up to 90 % enantiomeric excess in this newly emerging asymmetric cascade process. The evolution of the catalyst for the generation and enantioselective 1,3-dipolar cycloaddition of carbonyl ylides is described in detail by D. M. Hodgson et al. on p. 4465 ff.

Development of Dirhodium(II)-Catalyzed Generation and Enantioselective 1,3-Dipolar Cycloaddition of Carbonyl Ylides

Co-reporter:David M. Hodgson Dr.;Paul A. Stupple;Françoise Y. T. M. Pierard Dr.;Agnès H. Labe Dr. and;Craig Johnstone Dr.

Chemistry - A European Journal 2001 Volume 7(Issue 20) pp:

Publication Date(Web):5 OCT 2001

DOI:10.1002/1521-3765(20011015)7:20<4465::AID-CHEM4465>3.0.CO;2-W

Catalytic, enantioselective, tandem carbonyl ylide formation/cycloaddition of 2-diazo-3,6-diketoester 2 with the use of dirhodium tetrakiscarboxylate and tetrakisbinaphtholphosphate catalysts to give the cycloadducts 3 in good yields and up to 90 % ee is described.

Synthesis of azabicyclic systems using nitrogen-directed radical rearrangements

Co-reporter:David M. Hodgson and Leonard H. Winning

Organic & Biomolecular Chemistry 2007 - vol. 5(Issue 19) pp:NaN3082-3082

Publication Date(Web):2007/08/02

DOI:10.1039/B707566A

Radical rearrangements are important transformations in organic synthesis. The stabilisation of α-nitrogen radicals is shown to be a useful effect for the control of radical rearrangements and is applied to the synthesis of a variety of azabicyclic frameworks. The utility of this method is illustrated in the synthesis of bioactive targets.

Synthetic and computational studies on the tricarboxylate core of 6,7-dideoxysqualestatin H5 involving a carbonyl ylide cycloaddition–rearrangement

Co-reporter:David M. Hodgson, Carolina Villalonga-Barber, Jonathan M. Goodman and Silvina C. Pellegrinet

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 17) pp:NaN3984-3984

Publication Date(Web):2010/07/02

DOI:10.1039/C004496B

Reaction of diazodiketoesters 17 and 28 with methyl glyoxylate in the presence of catalytic rhodium(II) acetate generates predominantly the 6,8-dioxabicyclo[3.2.1]octanes 29 and 30, respectively. Acid-catalysed rearrangement of the corresponding alcohol 31 favours, at equilibrium, the 2,8-dioxabicyclo[3.2.1]octane skeleton 33 of the squalestatins–zaragozic acids. Force field calculations on the position of the equilibrium gave misleading results. DFT calculations were correct in suggesting that the energy difference between 31 and 33 should be small, but did not always suggest the right major product. Calculation of the NMR spectra of the similar structures could be used to assign the isomers with a high level of confidence.

Synthesis of the anti-trypanosomal agent (±)-hydroxyanthecotulide by Cr(II)-catalysed allylation and Meyer–Schuster rearrangement

Co-reporter:David M. Hodgson, Eric P. A. Talbot and Barry P. Clark

Chemical Communications 2012 - vol. 48(Issue 51) pp:NaN6350-6350

Publication Date(Web):2012/05/22

DOI:10.1039/C2CC32283H

The first synthesis of the bioactive sesquiterpene lactone hydroxyanthecotulide is achieved in 7 steps, involving a stereocontrolled Cr(II)-catalysed reaction of 3-(bromomethyl)furan-2(5H)-one with enynal 9 and a mild Au(I)-catalysed Meyer–Schuster rearrangement.

Disubstituted Z-allylic esters by Wittig–Schlosser reaction using methylenetriphenylphosphorane

Co-reporter:David M. Hodgson and Tanzeel Arif

Chemical Communications 2011 - vol. 47(Issue 9) pp:NaN2687-2687

Publication Date(Web):2011/01/12

DOI:10.1039/C0CC04429F

β-Lithiooxyphosphonium ylides, generated in situ from aldehydes and methylenetriphenylphosphorane, react with halomethyl esters to form disubstituted allylic esters in good yields and with high Z-selectivity.

An approach to hyperolactone C and analogues using late stage conjugate addition on an oxonium ylide-derived spirofuranone

Co-reporter:David M. Hodgson, Elena Moreno-Clavijo, Sophie E. Day and Stanislav Man

Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 32) pp:NaN5369-5369

Publication Date(Web):2013/07/12

DOI:10.1039/C3OB41251B

A stereocontrolled synthesis of norphenyl hyperolactone C together with its utility as a direct precursor to the anti-HIV agent hyperolactone C and analogues by addition of organolithiums, are described. Preliminary studies to access this key building block in a catalytic enantioselective manner are also reported.

Convergent synthesis of conjugated 1,2-disubstituted E-allylic alcohols from two aldehydes and methylenetriphenylphosphorane

Co-reporter:David M. Hodgson and Rosanne S. D. Persaud

Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 39) pp:NaN7951-7951

Publication Date(Web):2012/08/30

DOI:10.1039/C2OB26346G

β-Lithiooxyphosphonium ylides, made in situ from an aldehyde and methylenetriphenylphosphorane, react with a second aldehyde to form E-allylic alcohols. α-Branching and α,β-unsaturation in the second aldehyde, together with the lack of further substitution on the phosphorane carbon play important roles in selectivity. A range of these aldehydes, in addition to aromatic aldehydes as the second aldehyde also provided synthetically useful access to E-allylic alcohols.

Recent applications in natural product synthesis of dihydrofuran and -pyran formation by ring-closing alkene metathesis

Co-reporter:Reece Jacques, Ritashree Pal, Nicholas A. Parker, Claire E. Sear, Peter W. Smith, Aubert Ribaucourt and David M. Hodgson

Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 25) pp:NaN5893-5893

Publication Date(Web):2016/04/25

DOI:10.1039/C6OB00593D

In the past two decades, alkene metathesis has risen in prominence to become a significant synthetic strategy for alkene formation. Many total syntheses of natural products have used this transformation. We review the use, from 2003 to 2015, of ring-closing alkene metathesis (RCM) for the generation of dihydrofurans or -pyrans in natural product synthesis. The strategies used to assemble the RCM precursors and the subsequent use of the newly formed unsaturation will also be highlighted and placed in context.

TOPICS

Abstract

Abstract