86

On the 15th October 2008, the University ofBath, U.K., hosted a half-day symposium entitled “Metals in Synthesis 2008 (MIS-08)”. The sympo-sium was held in honour of Professor MasakatsuShibasaki (Graduate School of PharmaceuticalSciences, The University of Tokyo, Japan) (1), thewinner of a prestigious Royal Society of Chemistry(RSC) Centenary Lectureship. Professor Shibasakiwon the Lectureship for his numerous seminalcontributions to the discovery and development ofasymmetric catalysts for organic synthesis. As partof the lectureship tour, Professor Shibasaki visitedsix U.K. universities: the Universities of Sussex,Bath, Warwick, York, Strathclyde andSouthampton, and was presented with the RSCCentenary Lectureship medal at MIS-08 at theUniversity of Bath (2).

The MIS-08 symposium was organised by JohnS. Fossey (then at the University of Bath, now atthe University of Birmingham, U.K., and co-author of this review) and aimed to showcase someof the U.K.’s leading talents in metal-mediated syn-thesis. As such, three other speakers, ProfessorJonathan M. J. Williams (University of Bath, U.K.)(3), Michael Willis (University of Oxford, U.K.) (4)and Paul Davies (University of Birmingham, U.K.)(5), were invited to present their most recent andexciting results. This was followed by a well attend-ed poster session where researchers from all overthe U.K. presented highlights of their work.

Conference Highlights The MIS-08 symposium began in the University

of Bath’s main University Hall lecture theatre infront of a packed audience of delegates from allover the U.K. Gareth Price, the head of theUniversity of Bath’s chemistry department (6), wel-comed delegates and handed over to the chair ofthe first session, Christopher Frost (University of

Bath, U.K.) (7). Frost has developed his ownmetal-mediated tandem catalysis strategies fororganic synthesis (8, 9). He gave an especiallywarm welcome to the first speaker, his formerPh.D. supervisor, Professor Jonathan Williams.

Professor Williams’ presentation detailed hismethodology of ‘hydrogen borrowing’ for the for-mation of carbon–carbon and carbon–nitrogenbonds. In this chemistry, ruthenium or iridium cat-alysts temporarily remove hydrogen (H2) from analcohol to give an aldehyde. This aldehyde maythen react to give an alkene (in a Wittig-like reac-tion) or with an amine to give an imine. The earlier‘borrowed’ hydrogen is returned to the substrate,furnishing products in which the oxygen of thealcohol starting material is replaced with a –CH2Rcarbon or an –NHR nitrogen, Figure 1 (10–14).These procedures allow alcohols to be used asalkylating agents in place of more conventional,but often toxic or mutagenic, alkyl halides. Theusefulness of this methodology has been demon-strated by application to drug molecule synthesis.

Next, Michael Willis discussed developmentssurrounding intermolecular hydroacylation

Platinum Metals Rev., 2009, 53, (2), 86–90

Metals in Synthesis 2008 (MIS-08)PGM-CATALYSED PROCESSES FOR ORGANIC SYNTHESIS

Reviewed by Wenbo Chen* and John S. Fossey**School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.; Email: *w.chen.4@bham.ac.uk;

**j.s.fossey@bham.ac.uk

DOI: 10.1595/147106709X439225

Fig. 1 Mechanism for the formation of C–C and C–Nbonds via a ruthenium- or iridium-mediated removal ofH

2

from an alcohol

R OH

R O R AR'

R AR'

alkene formation

or imine formation

M

MH2

C-C or C-N bond formation

M=Ru or Ir

A=C or N

C–C or C–N bond formation

Alkene formation

or imine formation

(+ H2NR' )

A = C or N

M = Ru or Ir

'

'

reactions with respect to reactivity and enantiose-lectivity. He detailed atom-economical reactionsthat involved rhodium(I)-catalysed addition ofaldehydes across C–C multiple bonds, in conjunc-tion with catalytic C–H activation and C–C bondformation. He elaborated on the impressive scopeof intermolecular chelation (β-S- or β-O-substitut-ed aldehyde) controlled alkene and alkynehydroacylation, Figure 2 (15–17). Willis thenshowed that this process could be applied to somerather elegant asymmetric examples.

Paul Davies followed up with an impressivestory of how his metal-activated reactions encom-pass activation of alkynes towards nucleophilicattack and the use of alkynes as masked ylides.When activated by gold or platinum catalysts, thealkynes can potentially react as an alkylidene car-benoid by the pull-push nature of the catalyticactivation, Figure 3 (18, 19).

Davies went on to describe a one-pot cascadereaction catalysed by gold, which exploited his

masked ylide protocol. The reaction proceeds viarearrangement of propargylic carboxylates in thepresence of sulfides, to give 2-substituted 4-allyl-2,3-dihydrothiophenes, Figure 4 (20).

After a short break, John Fossey opened thesecond session and introduced ProfessorMasakatsu Shibasaki. At this point Mike Willistook to the floor once again for his second officialrole of the day: as a member of the ExecutiveCommittee of the Organic Division of the RSC,the privilege of presenting Professor Shibasakiwith the Centenary Lectureship medal fell to him,Figure 5.

Professor Shibasaki proceeded to deliver hislecture entitled ‘Recent Progress in AsymmetricTwo Centre Catalysis’. He began by revealing therequirement for enhanced activation modes incatalysis, and proposed that dual activation or ‘twocentre’ catalysis has the potential to afford newreactivities and higher selectivities, particularly inasymmetric transformations. He provided detailsof asymmetric two centre catalysis promotedsimultaneously by Lewis acid complexes (withmetals such as aluminium, titanium, lanthanum,gallium or zinc) and Brönsted bases or by Lewisacids in conjunction with Lewis bases (for exampleS=O, P=O), Figure 6 (21).

Excellent results were achieved in a wide rangeof bond-forming transformations, with high enan-tiomeric excess and high yields possible under dualactivation conditions (22–28). Furthermore, themethods have been used in the practical synthesisof a key intermediate for ranirestat, AS-3201, ahighly potent aldose reductase inhibitor, Figure 7(29, 30).

Platinum Metals Rev., 2009, 53, (2) 87

SMe

H

O

S

Rh

O

Me

L

H

O

OMe

SMe O

OMe

O

96% yield

Rh(I)MeS

MeS

[Rh(dppe)]ClO4

10 mol%

DCE

60ºC, 2 h

71% yield

Fig. 2 Rhodium-catalysed addition of aldehydes acrossC–C multiple bonds in conjunction with catalytic C–Hactivation and C–C bond formation

AuCl (5 mol%)

DCE, 70ºC

OPiv

Ph

S

S

PivO

Ph

OPiv = pivaloyl

Fig. 3 Push-pull catalytic activation of alkynesinto alkylidene carbenoids catalysed by gold orplatinum (18)

Fig. 4 One-pot gold-catalysed cascade reactionto form 2-substituted 4-allyl-2,3-dihydrothiophenes

MM M

Pull Push+

+

+

M+

.. ..

DCE = dichloroethane

Poster Session and Prizes Following an invigorating question and answer

session, Fossey brought the seminar to a close andinvited delegates to the poster session and winereception held in the University’s Department of

Chemistry. The poster session was an opportunityfor more than thirty young scientists to presenttheir work and discuss ideas with the other dele-gates. The Japan Society for the Promotion ofScience (JSPS) was the main sponsor of the postersession and wine reception, which allowed it to dis-tribute details of its exchange programmesconnecting U.K. and Japanese researchers and facil-itating bilateral research projects. Professor YukoFurukawa, Director of the JSPS’s London Officeattended the event. Full details of JSPS programmesfor pre- and postdoctoral fellows may be obtainedfrom the JSPS London Office’s website (31).

Professor Furukawa drew the event to a closeby awarding prizes for the most innovative andexciting posters. The first prize of a signed copy of a book edited by Professor Shibasaki“Multimetallic Catalysts in Organic Synthesis” (32)(donated by Wiley: Chemistry – An Asian Journal)and a presentation lacquer-ware clock (from theJSPS) went to Michael Shaw, a Ph.D. student inProfessor Varinder K. Aggarwal’s group at theUniversity of Bristol, U.K., for his poster presen-tation on studies towards the synthesis of natural

Platinum Metals Rev., 2009, 53, (2) 88

Fig. 5 Dr Michael Willis (left) presents ProfessorMasakatsu Shibasaki (right) with the RSC CentenaryLectureship medal

Chiral Backbone

Brönsted base

or Lewis BaseLewis Acid

Substrate A Substrate BSubstrate A Substrate B

Chiral backbone

Brönsted base

or Lewis baseLewis acid

Fig. 6 Asymmetric two-centre catalysis promotedby Lewis acid complexes with Brönsted bases orLewis bases

HN

O

O

CO2Et

N

NBoc

Boc

OH

NH

OHN

O

OH

1.0 mol %

La(NO3)3 .XH2O, 1.0 mol %

H-D-Val-OtBu 3.0 mol %

EtOAc, 0oC, 180min

HN

O

O

NH

CO2Et

HCl .H2N

(ii)

(i)

HCl(gas)/toluene, 0oC to rt

>100 g scale

96% yield

91%ee

La(NO3)·xH2O, 1.0 mol%

H-D-Val-OtBu, 3.0 mol%

EtOAc, 0ºC, 180 min

(ii) HCl (gas)/toluene, 0ºC to RT

96% yield

91% ee

·

Fig. 7 Synthesis of an intermediatefor the aldose reductase inhibitorranirestat, AS-3201, catalysed by alanthanum complex

1.0 mol%

(R)-isomer

products (33), Figure 8. JSPS runner-up prizeswere awarded to five Ph.D. students: Paul Fordred(in Steven Bull’s group, University of Bath), MartaP. Pereira Morais (co-supervised by John Fossey,University of Bath) Simon Pridmore (ProfessorWilliams’ group, University of Bath), TomokiNishimura (Royal Society visiting scholar from theUniversity of Kitakyushu, Sakurai Laboratory,Japan) and Hannah Edwards (Christopher Frost’sgroup, University of Bath).

ConclusionsPlatinum group metals (pgms) are playing an

increasingly important role in organic synthesis,especially in the asymmetric synthesis field.Synthetic methodologies based on pgm-catalysedreactions that form new chemical bonds underprogressively milder conditions, with greater easeand increasing power, will continue to be at theheart of intriguing and useful discoveries.

Acknowledgements As well as generous support from the RSC

and the RSC Organic Division, the event was

sponsored by the University of Bath’s ‘Bridgingthe Gaps’ initiative, TCI Europe, Wiley (Chemistry– An Asian Journal) and the JSPS. This supportallowed the event to be free to attend for all.

Platinum Metals Rev., 2009, 53, (2) 89

Fig. 8 Michael Shaw (left) (Aggarwal Group, Universityof Bristol, U.K.) receives first prize for his poster at MIS-08 from Professor Shibasaki (right)

1 Shibasaki Group, The University of Tokyo:http://www.f.u-tokyo.ac.jp/~kanai/e_index.html(Accessed on 30th March 2009)

2 RSC Centenary Lecture, Professor MasakatsuShibasaki, ‘Recent Progress in Asymmetric Two CentreCatalysis’, RSC Conferences and Events:http://www.rsc.org/ConferencesAndEvents/conference/alldetails.cfm?evid=102683 (Accessed on 30thMarch 2009)

3 Professor Jonathan M. J. Williams, University of Bath:http://www.bath.ac.uk/chemistry/people/jmjwilliams/(Accessed on 30th March 2009)

4 Willis Group, University of Oxford:http://mcwillis.chem.ox.ac.uk/ (Accessed on 30thMarch 2009)

5 Davies Research Group, University of Birmingham:http://www.chem.bham.ac.uk/labs/davies/index.shtml (Accessed on 30th March 2009)

6 Gareth Price, University of Bath:http://www.bath.ac.uk/chemistry/people/price/index.html (Accessed on 30th March 2009)

7 Christopher G. Frost, University of Bath:http://people.bath.ac.uk/chpcjc/cgfrost/Home.html(Accessed on 30th March 2009)

8 C. J. Chapman and C. G. Frost, Synthesis, 2007, (1), 21

9 C. G. Frost and B. C. Hartley, Org. Lett., 2007, 9, (21),4259

10 G. Cami-Kobeci, P. A. Slatford, M. K. Whittlesey andJ. M. J. Williams, Bioorg. Med. Chem. Lett., 2005, 15, (3),535

11 P. J. Black, G. Cami-Kobeci, M. G. Edwards, P. A.Slatford, M. K. Whittlesey and J. M. J. Williams, Org.Biomol. Chem., 2006, 4, (1), 116

12 P. J. Black, M. G. Edwards and J. M. J. Williams, Eur.J. Org. Chem., 2006, (19), 4367

13 S. Burling, B. M. Paine, D. Nama, V. S. Brown, M. F. Mahon, T. J. Prior, P. S. Pregosin, M. K.Whittlesey and J. M. J. Williams, J. Am. Chem. Soc.,2007, 129, (7), 1987

14 M. H. S. A. Hamid and J. M. J. Williams, Chem.Commun., 2007, (7), 725

15 M. C. Willis, H. E. Randell-Sly, R. L. Woodward, S. J. McNally and G. S. Currie, J. Org. Chem., 2006,71, (14), 5291

16 G. L. Moxham, H. E. Randell-Sly, S. K. Brayshaw,R. L. Woodward, A. S. Weller and M. C. Willis, Angew.Chem. Int. Ed., 2006, 45, (45), 7618

17 G. L. Moxham, H. Randell-Sly, S. K. Brayshaw, A. S. Weller and M. C. Willis, Chem. Eur. J., 2008, 14,(27), 8383

References

18 Davies Research Group, University of Birmingham,School of Chemistry: http://www.chem.bham.ac.uk/labs/davies/research/ (Accessed on 30th March2009)

19 A. Fürstner and P. W. Davies, Angew. Chem. Int. Ed.,2007, 46, (19), 3410

20 P. W. Davies and S. J.-C. Albrecht, Chem. Commun.,2008, (2), 238

21 M. Shibasaki, M. Kanai and K. Funabashi, Chem.Commun., 2002, (18), 1989

22 H. Kakei, T. Sone, Y. Sohtome, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2007, 129, (44), 13410

23 T. Sone, A. Yamaguchi, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2008, 130, (31), 10078

24 S. Handa, V. Gnanadesikan, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2007, 129, (16), 4900

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26 Z. Chen, H. Morimoto, S. Matsunaga and M. Shibasaki,

J. Am. Chem. Soc., 2008, 130, (7), 217027 K. Yabu, S. Masumoto, S. Yamasaki, Y. Hamashima,

M. Kanai, W. Du, D. P. Curran and M. Shibasaki, J. Am. Chem. Soc., 2001, 123, (40), 9908

28 S. Masumoto, H. Usuda, M. Suzuki, M. Kanai and M. Shibasaki, J. Am. Chem. Soc., 2003, 125, (19), 5634

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Platinum Metals Rev., 2009, 53, (2) 90

The Reviewers

Dr Wenbo Chen is a Leverhulme Trust-funded postdoctoral research fellowworking with John S. Fossey at theUniversity of Birmingham, U.K. His work isfocused on new asymmetric motifs for C–Cbond forming catalysis. Prior to this,Wenbo was a Ph.D. student at the ShanghaiInstitute of Organic Chemistry, China,where he worked on organosulfurchemistry with Professor Long Lu.

Dr John S. Fossey is a recently appointedlecturer in chemistry at the University ofBirmingham, U.K. Prior to this, he spentthree years at the University of Bath wherehe established his research group andpublished on a range of topics, includingnickel- and cobalt-mediated chemistry.Before that, John was JSPS postdoctoralresearch fellow in the laboratories ofProfessor Shu Kobayashi (The University ofTokyo, Japan), where he worked on nickel-

catalysed reactions of enecarbamates. He obtained his Ph.D.from Queen Mary, University of London, U.K., under Dr Chris J.Richards, working on Group 10 pincer complexes as C–C bondforming catalysts. For more information please visit:http://www.chem.bham.ac.uk/staff/Fossey.shtml