©2018 by Ed Anderson Group.

Pre-2015

TOTAL SYNTHESIS

40. Enantioselective Synthesis of the Predominant AB Ring System of the Schisandra Nortriterpenoid Natural Products

Birgit Gockel, Shermin S. Goh, Emma J. Puttock, Hannah Baars, Guilhem Chaubet and Edward A. Anderson

Org. Lett., 2014, 16, 4480-4483

DOI: 10.1021/ol502027m

An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a β-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.

METHODOLOGY

39. Synthesis of Cyclic Alkenylsiloxanes by Semihydrogenation: A Stereospecific Route to (Z)-Alkenyl Polyenes

Bryony L. Elbert, Diane S. W. Lim, Haraldur G. Gudmundsson, Jack A. O'Hanlon and Edward A. Anderson

Chem. Eur. J., 2014, 20, 8594-8598

DOI: 10.1002/chem.201403255

Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes—a reaction previously plagued by poor stereoselectivity. The silanes, which can be synthesized on multigram scale, undergo Hiyama–Denmark coupling to give (Z)‐alkenyl polyene motifs found in bioactive natural products. The ring size of the silane is crucial: five‐membered cyclic siloxanes also couple under fluoride‐free conditions, whilst their six‐membered homologues do not, enabling orthogonality within this structural motif.

METHODOLOGY

38. Carbopalladation of bromoene-alkynylsilanes: mechanistic insights and synthesis of fused-ring bicyclic silanes and phenols

Marie-Caroline A. Cordonnier, S. B. Jennifer Kan, Birgit Gockel, Shermin S. Goh and Edward A. Anderson

Org. Chem. Front., 2014, 1, 661-673

DOI: 10.1039/C4QO00123K

The palladium-catalyzed cascade cyclization of silylated bromoenynes and alkenylstannanes provides a straightforward route to a range of bicyclic silylated cyclohexadienes. Mechanistic insights into aspects of carbopalladation and unusual palladium-mediated isomerizations have been obtained through the detection of reaction intermediates, the isolation of byproducts, and reaction monitoring by VT NMR spectroscopy. The utility of the bicyclic products is illustrated through oxidation to bicyclic enones and phenols.

METHODOLOGY (WITH PROF ROB PATON)

37. Ligand Bite Angle-Dependent Palladium-Catalyzed Cyclization of Propargylic Carbonates to 2-Alkynyl Azacycles or Cyclic Dienamides

David S. B. Daniels, Alison S. Jones, Amber L. Thompson, Robert S. Paton and Edward A. Anderson

Angew. Chem. Int. Ed., 2014, 53, 1915-1920

DOI: 10.1002/anie.201309162

The regioselectivity of the palladium‐catalyzed cyclization of propargylic carbonates with sulfonamide nucleophiles is critically dependent on the bite angle of the bidentate phosphine ligand. Ligands with small bite angles favor attack on the central carbon atom of an allenylpalladium intermediate to afford cyclic dienamide products, whereas the use of those with large bite angles leads to alkynyl azacycles, with high stereoselectivity. A computational analysis of the reaction pathway is also presented.

METHODOLOGY

36. Palladium-catalyzed cyclization of bromoenynamides to tricyclic azacycles: synthesis of trikentrin-like frameworks

Craig D. Campbell, Rebecca L. Greenaway, Oliver T. Holton, Helen A. Chapman and Edward A. Anderson

Chem. Commun., 2014, 50, 5187-5189

DOI: 10.1039/C3CC45634J

Palladium-catalyzed cascade cyclization of bromoenynamides equipped with an additional alkyne or ynamide substituent affords azatricyclic products. Using 5- to 7-membered ring tethers, this chemistry offers a regiospecific route to highly-functionalized azacycles. Elaboration to the trikentrin B skeleton is achieved from the arylsilane cyclization products.

METHODOLOGY

35. Palladium- and Ruthenium-Catalyzed Cycloisomerization of Enynamides and Enynhydrazides: A Rapid Approach to Diverse Azacyclic Frameworks

P. Ross Walker, Craig D. Campbell, Abid Suleman, Greg Carr and Edward A. Anderson

Angew. Chem. Int. Ed., 2013, 52, 9139-9143

DOI: 10.1002/anie.201304186

I want to ride my azacycle: The title reaction of enynamides affords a wide diversity of azacycles. The reactions are high‐yielding, highly stereoselective, and proceed rapidly under mild reaction conditions. Equivalent transformations using enynhydrazides offer new routes to pyrazole and indazole scaffolds. Boc=tert‐butoxycarbonyl, EWG=electron‐withdrawing group, Ns=4‐nitrobenzenesulfonyl, Ts=4‐toluenesulfonyl.

TOTAL SYNTHESIS

34. Metal-Catalyzed Syntheses of Abridged CDE Rings of Rubriflordilactones A and B

Shermin S. Goh, Hannah Baars, Birgit Gockel and Edward A. Anderson

Org. Lett., 2012, 14, 6278-6281

DOI: 10.1021/ol303041j

The development of complementary palladium- and cobalt-catalyzed approaches to tricyclic arylsilanes suitable for elaboration into the CDE ring systems of rubriflordilactones A and B is reported. Microwave conditions are required to effect a cobalt-catalyzed triyne cyclotrimerization, which critically depends on the substitution pattern of the triyne termini. Mild conditions to elaborate these arylsilanes to the CDE cores of the natural products are described.

METHODOLOGY

33. Reductive Cyclization of Bromoenynamides with Alcohols as Hydride Source: Synthesis and Reactions of 2-Amidodienes

Rebecca L. Greenaway, Craig D. Campbell, Helen A. Chapman and Edward A. Anderson

Adv. Synth. Catal., 2012, 354, 3187-3194

DOI: 10.1002/adsc.201200703

Under basic conditions in alcoholic solvents, bromoenynamides undergo palladium‐catalyzed cyclization to cyclic 2‐amidodienes in good to excellent yields. This process represents the first use of an alcohol as a hydride source in an alkyne carbopalladation/termination sequence, with the site selectivity of the reduction showing a strong dependence on the tethering ring size (5–8), and the nature of the alcohol and base. Reaction of the dienes with a range of dienophiles (including alkenes, alkynes and arynes) under various conditions gives bi‐ and tricyclic azacycles, which can be further oxidized to the aromatic azacycles.

METHODOLOGY

32. Synthesis of Phenols via Fluoride-free Oxidation of Arylsilanes and Arylmethoxysilanes

Elizabeth J. Rayment, Nick Summerhill and Edward A. Anderson

J. Org. Chem.2012, 77, 7052-7060

DOI: 10.1021/jo301363h

Rapid, efficient methods have been developed to prepare phenols from the oxidation of arylhydrosilanes. The effects of arene substituents and fluoride promoters on this process show that while electron-deficient arenes can undergo direct oxidation from the hydrosilane, electron-rich aromatics benefit from silane activation via oxidation to the methoxysilane using homogeneous or heterogeneous transition metal catalysis. The combination of these two oxidations into a streamlined flow procedure involving minimal processing of reaction intermediates is also reported.

REVIEW

31. Synthesis of Vinylsilanes

Diane S. W. Lim and Edward A. Anderson

Synthesis, 2012, 7, 983-1010

DOI: 10.1055/s-0031-1289729

Vinylsilanes are versatile synthetic building blocks, which in recent years have played an increasing role in the synthesis of complex molecules. This article provides an overview of regio- and stereoselective methods for the preparation of vinylsilanes, focusing­ on the most flexible and synthetically practical routes to each substitution pattern.

METHODOLOGY

30. Palladium-Catalyzed Cascade Cyclization of Ynamides to Azabicycles

Rebecca L. Greenaway, Craig D. Campbell, Oliver T. Holton, C. Adam Russell and Edward A. Anderson

Chem. Eur. J., 2011, 17, 14366-14370

DOI: 10.1002/chem.201102880

Cascade reactions: A modular assembly of azabicycles by using a cascade cyclization/Suzuki coupling/6π‐electrocyclization of bromoenynamides is reported (see scheme). The reaction offers a wide substituent scope on the bicyclic aminodiene products, which can be selectively oxidized as a general approach to aromatic azabicycles.

METHODOLOGY

29. Palladium-Catalyzed Asymmetric Synthesis of 2-Alkynyl Oxacycles


David S. B. Daniels, Amber L. Thompson and Edward A. Anderson

Angew. Chem. Int. Ed., 2011, 50, 11506-11510

DOI: 10.1002/anie.201105720

Oxyacetylene: Unusual palladium‐catalyzed cyclizations of cyclic and acyclic propargylic carbonates give 2‐alkynyl oxacycles. The reactions proceed with very high stereoselectivity for both syn‐ and anti‐disubstituted furans and pyrans, and with exceptional regioselectivity. In addition, two‐directional cyclizations of bis‐propargylic carbonate substrates yield bifurans with complete stereocontrol for all diastereomers.

METHODOLOGY

28. One-Step Preparation of Functionalized (E)-Vinylsilanes from Aldehydes


Diane S. W. Lim and Edward A. Anderson

Org. Lett., 2011, 13, 4806-4809

DOI: 10.1021/ol201833u

Functionalized (E)-vinylsilanes have been prepared in one step from a wide range of aldehydes, via a chromium(II)-mediated olefination with novel dihalomethylsilane reagents, in moderate to excellent yields and with excellent stereoselectivity.

EMERGING AREA

27. Cascade polycyclisations in natural product synthesis


Edward A. Anderson

Org. Biomol. Chem. 2011, 9, 3997-4006

DOI: 10.1039/C1OB05212H

The efficient, stereocontrolled construction of polycyclic ring systems has long presented a formidable challenge to synthetic chemists. Cascade reactions offer a ‘quick fix’—building multiple rings in a single step—and often dramatically shorten a synthetic route. In this Emerging Area article, a selection of the most recent and impressive examples of applications of this tactic to natural product synthesis are discussed, which demonstrate the ambition and achievements of the modern synthetic chemist.

TUTORIAL REVIEW

26.Recent advances in the use of temporary silicon tethers in metal-mediated reactions


Sonia Bracegirdle and Edward A. Anderson

Chem. Soc. Rev. 2010, 39, 4114-4129

DOI: 10.1039/C0CS00007H

This tutorial review describes the use of temporary silicon tethers in metal-mediated organic reactions, a strategy which although well-established in traditional organic synthesis is still a blossoming field in the organometallic arena. The benefits of silicon-tethering are manifold: the reactivity, selectivity, and efficiency of organometallic processes can all be dramatically enhanced, often with unique regio- and stereochemical outcomes compared to the analogous intermolecular transformations. In addition, the residual silicon functionality can undergo a wide range of chemistry subsequent to the tethered reaction, creating further synthetic opportunities.

METHODOLOGY

25. Arylsilane Oxidation - New Routes to Hydroxylated Aromatics. (Front Cover)


Sonia Bracegirdle and Edward A. Anderson

Chem. Commun. 2010, 46, 3454-3456

DOI: 10.1039/B924135C

An efficient route to hydroxylated aromatics has been developed, via the oxidation of aryl organosilanes under functional group-tolerant and relatively mild conditions, using sub-stoichiometric amounts of fluoride promoters.

TOTAL SYNTHESIS

24. A Palladium-mediated Cascade Cyclisation Approach to the CDE Cores of Rubriflordilactone A and Lancifodilactone G.


Marie-Caroline A. Cordonnier, S. B. Jennifer Kan and E. A. Anderson

Chem. Commun. 2008, 5818-5820

DOI: 10.1039/B814360A

Palladium-mediated cascade cyclisation reactions have been applied to the synthesis of the CDE-ring cores of two anti-HIV natural products, rubriflordilactone A and lancifodilactone G.

METHODOLOGY

23. A Cascade Palladium-mediated Cross-coupling / Electrocyclization Approach to the Construction of Fused Bi- and Tricyclic Rings


S. B. Jennifer Kan and Edward A. Anderson

Org. Lett., 2008, 10, 2323-2326

DOI: 10.1021/ol8007952

A versatile palladium-catalyzed cyclization/cross-coupling/electrocyclization strategy for the synthesis of fused bi- and tricyclic ring systems is described. Excellent yields of the polycyclic products are obtained with a range of tethering ring sizes and functionality, including an unprecedented 5,6,4,5-fused tetracycle. The reaction mechanism features two unusual palladium-mediated isomerizations prior to electrocyclization.

REVIEW (WITH PROF IAN PATERSON)

22. Total synthesis of (+)-spirastrellolide A methyl ester: Challenges and discoveries


Ian Paterson, Philip Maltas and Edward A. Anderson

Pure Appl. Chem., 2013, 85, 1133-1147

DOI: 10.1351/PAC-CON-13-01-01

This review focuses on recent synthetic efforts by our group towards spirastrellolide A methyl ester, a complex marine macrolide containing two spiroacetal ring systems that shows promising anticancer properties. The evolution of a flexible, modular strategy leading to the first total synthesis of (+)-spirastrellolide A methyl ester, and the associated challenges overcome, are highlighted, particularly in dealing with the initial structural ambiguities. This work enabled the development of an improved second-generation synthesis, which revealed a critical dependence of the key macrolactonization step on the nature of the protecting groups in the linker region between the spiroacetal motifs.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

21. The stereocontrolled total synthesis of spirastrellolide A methyl ester. Fragment coupling studies and completion of the synthesis


Ian Paterson, Edward A. Anderson , Stephen M. Dalby , Jong H. Lim and Philip Maltas

Org. Biomol. Chem., 2012, 10, 5873-5886

DOI: 10.1039/C2OB25101A

The spirastrellolides are a novel family of structurally unprecedented marine macrolides which show promising anticancer properties due to their potent inhibition of protein phosphatase 2A. In the preceding paper, a modular strategy for the synthesis of spirastellolide A methyl ester which allowed for the initial stereochemical uncertainties was outlined, together with the synthesis of a series of suitably functionalised fragments. In this paper, the realisation of this synthesis is described.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

20. The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments


Ian Paterson, Edward A. Anderson , Stephen M. Dalby , Jong H. Lim and Philip Maltas

Org. Biomol. Chem., 2012, 10, 5861-5872

DOI: 10.1039/C2OB25100K

Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

19. A Second-Generation Total Synthesis of Spirastrellolide A Methyl Ester


Ian Paterson, Philip Maltas, Stephen M. Dalby, Jong H. Lim and Edward A. Anderson

Angew. Chem. Int. Ed., 2012, 51, 2749-2753

DOI: 10.1002/anie.201108594

Marine macrolides: An improved second‐generation total synthesis of the anticancer macrolide spirastrellolide A methyl ester has been achieved. The synthesis features a uniformly high level of stereocontrol combined with more expedient fragment assembly, and demonstrates a critical dependence of the crucial macrolactonization step on the substitution pattern of the C22–C24 linker region.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

18. Total Synthesis of Saliniketals A and B.

Ian Paterson, Mina Razzak and Edward A. Anderson


Org. Lett., 2008, 10, 3295-3298

DOI: 10.1021/ol801148d

A stereocontrolled total synthesis of the orthinine decarboxylase inhibitors saliniketals A and B is described. Key features of the 17-step route include the use of two boron aldol/reduction sequences to control six of the nine stereocenters, an intramolecular Wacker-type cyclization to install the bicyclic acetal core, and a late-stage Stille coupling to append the requisite (2Z,4E)-dienamide.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

17. Total Synthesis of Pteridic Acids A and B

Ian Paterson, Edward A. Anderson, Alison D. Findlay, Christopher S. Knappy
Tetrahedron, 2008, 64, 4768-4777

DOI: 10.1016/j.tet.2008.01.132

A convergent synthesis of pteridic acids A and B, epimeric spiroacetal polyketides with potent plant growth promoter properties, is described. The use of boron aldol methodology efficiently achieved the stereocontrolled construction of advanced C1–C11 and C12–C16 subunits, which were coupled to generate a linear (Z)-enone precursor that underwent spiroacetalization with HF·pyridine, providing pteridic acids A and B after saponification.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

16. Total Synthesis of Spirastrellolide A Methyl Ester - Part 2: Subunit Union and Completion of the Synthesis


Ian Paterson, Edward A. Anderson, Stephen M. Dalby, Jong H. Lim, Julien Genovino, Philip Maltas, Christian Moessner

Angew. Chem. Int. Ed., 2008, 47, 3021-3025

DOI: 10.1002/anie.200705566

Succumbing to synthesis: The stereocontrolled total synthesis of spirastrellolide A methyl ester is reported. The union of two key C1–C16 and C17–C40 subunits is followed by macrolactonization and late‐stage side chain attachment by a cross‐metathesis reaction and a π‐allyl Stille coupling reaction with a C43–C47 stannane, thus confirming the 46R configuration. The full configuration and conformation of the 38‐membered macrolide is revealed by single‐crystal X‐ray analysis of an advanced pentaol intermediate.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

15. Total Synthesis of Spirastrellolide A Methyl Ester - Part 1: Synthesis of an Advanced C17-C40 Bis-spiroacetal Subunit

Ian Paterson, Edward A. Anderson, Stephen M. Dalby, Jong H. Lim, Julien Genovino, Philip Maltas, Christian Moessner

Angew. Chem. Int. Ed., 2008, 47, 3016-3020

DOI: 10.1002/anie.200705565

Out of the blue: The marine macrolide spirastrellolide A is a potent and selective inhibitor of protein phosphatase 2A and a lead for anticancer therapies. A flexible and modular synthetic strategy has been developed with two routes for the construction of the DEF bis‐spiroacetal subunit. The optimized Suzuki coupling approach results in the efficient preparation of a C17–C40 aldehyde that forms the cornerstone of the first total synthesis.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

14. Synthesis of an advanced C10-C32 spiroacetal fragment and assignment of the absolute configuration of spirangien A

Ian Paterson, Alison D. Findlay and Edward A. Anderson

Angew. Chem. Int. Ed. 2007, 46, 6699-6702

DOI: 10.1002/anie.200702735

A bit on the side: A highly convergent and flexible synthetic strategy has been developed for spirangiens A and B that made use of a common stereotetrad building block and led to an advanced C10–C32 spiroacetal fragment, thus enabling the unambiguous assignment of the absolute configuration of these potent cytotoxic polyketide metabolites isolated from the myxobacterium Sorangium cellulosum.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

13. Synthesis of two diastereomeric C1-C22 fragments of spirastrellolide A

Ian Paterson, Edward A. Anderson, Stephen M. Dalby, Julien Genovino, Jong H. Lim and Christian Moessner

Chem. Commun. 2007, 0, 1852-1854.

DOI: 10.1039/B700827A

The optimisation of a synthetic strategy towards the ABC segment of the cytotoxic macrolide spirastrellolide A is reported, together with its application to the synthesis of two diastereomeric C1–C22 fragments for stereochemical correlation purposes with a putative spirastrellolide degradation product.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

12. Progress towards a total synthesis of spirastrellolide A

Ian Paterson, Edward A. Anderson, Stephen M. Dalby, Jong H. Lim, Olivier Loiseleur and Christian Moessner

Pure Appl. Chem., 2007, 79, 667-676

DOI: 10.1351/pac200779040667

Progress toward a total synthesis of spirastrellolide A, a 38-membered marine macrolide, is reported. Syntheses of two diastereomers of the C1-C25 region, and an evolving Sharpless dihydroxylation strategy toward a C26-C40 fragment, are described. The syntheses exploit boron-mediated aldol chemistry to install key stereocenters, and feature late-stage thermodynamically controlled spiroacetalizations.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

11. Synthesis of the DEF-bis-spiroacetal of spirastrellolide A exploiting a double asymmetric dihydroxylation / spiroacetalisation strategy


Ian Paterson, Edward A. Anderson, Stephen M. Dalby, Jong H. Lim, Philip Maltas and Christian Moessner

Chem. Commun., 2006, 0, 4186-4188

DOI: 10.1039/B612697A

An efficient synthesis of the C26–C40 tricyclic [5,6,6]-bis-spiroacetal segment of the marine macrolide spirastrellolide A has been developed, exploiting a novel double Sharpless asymmetric dihydroxylation/spiroacetalisation sequence.

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

10. Synthesis of the C1–C21 southern hemisphere of the originally proposed structure of spirastrellolide A


Ian Paterson, Edward A. Anderson and Stephen M. Dalby

Synthesis, 2005, 19, 3225-3228

DOI: 10.1055/s-2005-918449

A stereocontrolled synthesis of the C1-C21 [6,6]-spiro­acetal-containing domain of the originally assigned structure of spirastrellolide­ A is reported, exploiting asymmetric boron aldol methodology and an alkyne addition to a C17 aldehyde. Comparison of the 1H NMR data obtained for this synthetic fragment with that for the corresponding region of spirastrellolide suggested some stereochemical reassignment was required.

PERSPECTIVE ARTICLE (WITH PROF IAN PATERSON)

9. The renaissance of natural products as drug candidates

Ian Paterson and Edward A. Anderson

Science, 2005, 310, 451-453

DOI: 10.1126/science.1116364

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

8. Toward the synthesis of spirastrellolide A: Construction of two C1-C25 diastereomers containing the BC-spiroacetal.


Ian Paterson, Edward A. Anderson, Stephen M. Dalby and Olivier Loiseleur

Org. Lett., 2005, 7, 4125-4128

DOI: 10.1021/ol051405x

TOTAL SYNTHESIS (WITH PROF IAN PATERSON)

7. Toward the Synthesis of Spirastrellolide A:  Construction of a Tetracyclic C26−C40 Subunit Containing the DEF-Bis-Spiroacetal


Ian Paterson, Edward A. Anderson, Stephen M. Dalby, and Olivier Loiseleur

Org. Lett., 2005, 7, 4121–4124

DOI: 10.1021/ol051403c

A stereocontrolled synthesis of the fully elaborated C26−C40 tricyclic [5,6,6]-bis-spiroacetal of spirastrellolide A containing the C28 chlorine substituent is reported, exploiting asymmetric Sharpless dihydroxylation and boron-mediated allylation methodology.

TOTAL SYNTHESIS (WITH PROF ERIK SORENSEN)

6. Synthesis of the Furanosteroidal Antibiotic Viridin

Edward A. Anderson, Erik J. Alexanian, Erik J. Sorensen

Angew. Chem. Int. Ed., 2004, 43, 1998-2001

DOI: 10.1002/anie.200353129

A rhodium‐catalyzed alkyne cyclotrimerization, domino electrocyclic reactions, and a hydroxy‐directed dihydroxylation are key steps in an efficient synthesis of the bioactive furanosteroid viridin from a simple acyclic triyne.

METHODOLOGY (WITH PROF A HOLMES)

5. The Claisen rearrangement approach to fused bicyclic medium-ring oxacycles.

Jonathan W. Burton, Edward A. Anderson, Paul T. O'Sullivan, Ian Collins, John E. Davies, Andrew D. Bond, Neil Feeder and Andrew B. Holmes

Org. Biomol. Chem., 2008, 6, 693-702

DOI: 10.1039/B715354F

The synthesis of five fused-bicyclic medium-ring lactones carrying identical ring-fusion to that in the polyether toxins is described using an enolate hydroxylation, intramolecular hydrosilation, Claisen rearrangement sequence.

METHODOLOGY (WITH PROF A HOLMES)

4. Synthesis of medium-ring lactones via tandem methylenation/Claisen rearrangement of cyclic carbonates


Edward A Anderson, James E.P Davidson, Justin R Harrison, Paul T O'Sullivan, Jonathan W Burton, Ian Collins, Andrew B Holmes
Tetrahedron, 2002, 58, 1943-1971

DOI: 10.1016/S0040-4020(02)00049-2


The conversion of vinyl-substituted 6- and 7-membered cyclic carbonates into 8- and 9-membered medium-ring lactones has been achieved in good yield using dimethyltitanocene in toluene at reflux. The reaction proceeds by initial formation of a ketene acetal which undergoes subsequent in situ Claisen rearrangement to provide the corresponding lactones. The preparation of the cyclic carbonates is carried out under basic conditions and hence this methodology complements our existing selenium-based methodology for the synthesis of medium-ring lactones.

METHODOLOGY (WITH PROF A HOLMES)

3. Synthesis of fused bicyclic medium-ring lactones via Claisen rearrangement.

Jonathan W. Burton, Paul T. O’Sullivan, Edward A. Anderson, Ian Collins and Andrew B. Holmes

Chem. Commun. 2000, 631-632

DOI:  10.1039/B000303O

Fused bicyclic medium-ring lactones, carrying identical ring-fusion to that in the polyether toxins, are prepared by a Claisen rearrangement sequence.

METHODOLOGY (WITH PROF A HOLMES)

2. Synthesis of medium-ring lactones via tandem methylenation/Claisen rearrangement of cyclic carbonates.

James E. P. Davidson, Edward A. Anderson, Wilm Buhr, Justin R. Harrison, Paul T. O’Sullivan, Ian Collins, Richard H. Green and Andrew B. Holmes

Chem. Commun., 2000, 629-630

DOI: 10.1039/B000299M

Tandem methylenation/Claisen rearrangement of cyclic carbonates derived from vinyl-substituted 1,3- and 1,4-diols afforded eight and nine-membered unsaturated lactones respectively.

METHODOLOGY (WITH PROF A HOLMES)

1. Medium ring stereocontrol in the functionalisation of eight-membered lactones.

Edward A. Anderson, Andrew B. Holmes, Ian Collins
Tetrahedron Letters, 2000, 41, 117-121.
DOI: 10.1016/S0040-4039(99)01988-7


Medium ring lactones with up to three substituents have been prepared as single diastereoisomers via Claisen rearrangement. Application of medium ring stereocontrol to a γ,δ-unsaturated eight-membered ring lactone prepared by this route enabled the overall diastereoselective functionalisation of all but one of the ring positions. A comparison of the ring-induced selectivity was made with that of the corresponding acyclic hydroxy ester which exhibited an overall reversal of stereoselectivity. This methodology provides access to highly substituted polyketide fragments.