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Immobilisation of Ru-based metathesis catalysts and related aspects of olefin metathesis

Nieczypor, P.

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Citation for published version (APA):Nieczypor, P. (2004). Immobilisation of Ru-based metathesis catalysts and related aspects of olefin metathesis.

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Download date: 21 Jun 2020

Chapter r

GeneralGeneral Introduction to Olefin Metathesis

Keuwords',Keuwords', Olefin Metathesis / Metal Carbenes / Organic synthesis

Abstract:: The subject of olefin metathesis is briefly reviewed. The birth, growth and

maturationn of olefin metathesis is discussed exemplifying the early discoveries, the

presentt set of available catalysts and the chemical transformations in which

metathesiss plays an important role, both in polymer science and organic synthesis.

CHAPTERR 1

Thee term metathesis, derived from the Greek words ueia (meta = change) and TITEUI

(titemii = place), functions in modern English with two meanings.1 In linguistics it describes

usuallyy unintentional transposition of the letters or syllables of a word. In chemistry it refers

too a chemical reaction in which different kinds of molecules exchange parts to form other

kindss of molecules. In the latter, broad definition three specific chemical processes are

described: :

ion metathesis, or double decomposition, in which the ions of two compounds exchange

partnerss according to the equation A®B© + C®D© -+ A«De + C®Be;

a-bond metathesis in which a ligand a-bonded to a metal is replaced through reaction

withh the a-bond of an incoming ligand without a change in the oxidation state;

olefin (alkene, but also alkyne) metathesis where swapping of substituents at double and triplee bond between two olefinic molecules occurs induced by a catalyst.

Thiss dissertation deals with the aspects of the latter category that has developed tremendouslyy in the recent years. First, let's embark on a short voyage through the history that ledd to the metathesis as we find it today.

1.11 Historical Backgrounds Thee story of olefin metathesis had its origins in the industrial laboratories in the late

1950'ss where an 'anomalous' polymerisation of olefins using the Ziegler-type catalysts M0O3/AI2O3/L1AIH44 and Mo(VAl203/Et3Al was observed.2 Several papers followed, describingg the production of unsaturated polymers or disproportionation of linear olefins by variouss catalytic systems.3 Then Calderon realised that these processes belonged to one and thee same reaction and placed them under the label of olefin metathesis.4 He made his conclusionss basing also on the results obtained in his laboratory with the WCVEtAlCk/EtOH systemm that performed well in both processes.5

Initially ,, the bulk of the research was done employing simple metal salts or multicomponentt systems of early transition metals, often supported on various materials, silicaa and alumina being the most popular.6 However, this 'black box' chemistry lacked the evidencee of active species and was based on a trial and error approach in finding new catalysts.. Studies using deuterium or 14C labelled alkenes (and ,4C labelled alkynes) proved thee alkylidene (alkylidyne) species migration during metathesis.50'7 Chauvin supposed then thee involvement of metal alkylidenes in the reaction,8 having in mind the preparation of first metall carbon multiple bond complexes, named after their discoverer as Fisher carbenes, e.g. [W{=C(OMe)Me}(CO)s].99 Alkylidene analogues of the Fisher carbene, composed only of carbonn and hydrogen atoms and named Schrock carbenes, were also isolated.10 Studies on one off these alkylidenes - [W(=CPh2)(CO)s3, prepared by Casey and Burkhardt,IJa delivered the finall experimental support for the proposed metathesis mechanism, although the activity of thiss catalyst was very low. First, the creators of the latter complex found that it produces 1,1-diphenylethenee in the reaction with 2-methylpropene.ll b Subsequently, the group of Katz122 performed detailed mechanistic studies on the metathesis of cycloalkenes and

2 2

GENERALL INTRODUCTION TO OLEFIN METATHESIS

2-pentenee employing [W{=C(OMe)Ph}(CO)5] and [W(=CPh2)(CO)5], further corroborated by findingss in the group of Grubbs,13 that explained all the experimental results yet unaccounted forr by Chauvin's proposal. The revelation of the metathesis mechanism and the role of metal carbeness as the propagating species prompted an increase in effort towards the synthesis of singlee component organometallic alkylidene (carbene) complexes and their subsequent applicationn in metathesis.

—— 1950

discoveryy of olefin metathesis

Chauvinn proposes metal alkylidene based mechanism

single-component t catalystss developed

firstt Ru alkylidene made

mechanismm of 8 investigated

phosphine-freee mono(NHC) catalystss developed

1960 0

RuCI3(hydrate)) performs ROMP

1970 0

evidencee for Chauvin's mechanismm found

1980 0

1990 0 synthesiss of Mo alkylidene (6)

synthesiss of Ru(=CHPh)CI2(PCy3)2 (8)

20000 rnono(NHC) catalysts 9 and 10 made

Schemee 1. The timeline of development of olefin metathesis (adapted from reference 51h).

1.22 Weil-Defined Homogeneous Metathesis Catalysts Gradually,, more and more homogeneous, early transition metal complexes in the form

off metal carbenes, a number of them first requiring activation by a Lewis acid, entered the scenee of metathesis. Some of the most prominent systems are: Tebbe reagent 1, Osborn tungstenn carbene 2 activated by gallium bromide,15 Schrock tantalum alkoxide carbene 3, tungstenn carbene etherate 4 by Basset and co-workers.17

Cp-- , / \ ,.-Me Cpp CI Me

1 1

Br r O,,, I

Br r

++ GaBr,

Ar r

O O

Ar—O—Ta a

O O

Ar r

Arr = 2,6-/-Pr(C6H3)

3 3

3 3

CHAPTERR 1

Yet,, their application to a broader spectrum of reagents was hampered by their high sensitivityy that required strictly dry and anaerobic reaction conditions. This also precluded theirr application for highly functionalised substrates and this drawback could only be partly alleviatedd by protection of the functional groups of the alkene in question. A further developmentt from the Schrock's laboratory was the preparation of currently the most popular metathesiss catalysts based on early transition metal carbon multiple bond complexes. The new classs of metal carbenes was built around tungsten 518 and molybdenum 6,19 consisting of an imidoo dialkoxy neopentyl alkylidene. The tungsten trialkoxy neopentyl alkylidyne 720 is still, afterr more than twenty years since its discovery, the most widely used catalyst for alkyne metathesis. .

^ ^

W) ) Mo) )

Thee reputation enjoyed by complex 6 stems from its very high activity in various types off metathesis allowing the coupling of sterically encumbered tri- and tetrasubstituted alkenes. Remarkably,, chiral analogues of 6 that have recently been prepared provide products of high enantiomericc purity.21 Despite or actually because of their excellent activity, this type of catalystt has to be handled under inert atmosphere and a number of functional groups, such as hydroxyll or formyl, are rendered incompatible.

1.33 Ruthenium Carbene Metathesis Catalysts Thee first ruthenium carbene complexes introduced by Grubbs and co-workers,22 e.g.

Ru(=CHPh)Cl2(PCy3)22 (8),22cd resolved the shortcomings of the molybdenum complexes to a greatt extent, however, at the cost of much lower activity. The rather low activity of the first generationn ruthenium carbenes, especially in the more difficult cases of substituted olefins, drovee the researchers to the quest for better ruthenium-based catalysts. It turned out that the replacementt of one of the phosphine moieties in 8 by a more strongly donating imidazolium carbenee ligand (NHC - N-heterocyclic carbene)23 yields much more active catalysts of type Ru(=CHR)Cl2(PCy3)LL (where L is a NHC ligand: 9, L = IMes,24 10, L = H2IMes,25 both bearingg mesityl groups on ligand nitrogen atoms). These second generation catalysts broadenedd the scope of the Ru based catalysts, especially in the case of sterically demanding reactionss where catalyst 8 fails. A further improvement in terms of catalyst longevity was madee by serendipitous discovery of Hoveyda and co-workers that the introduction of styrenyl etherr moiety produces complexes l l 26 and 1227 of a particular stability.

4 4

GENERALL INTRODUCTION TO OLEFIN METATHESIS

PCy-, , CU,, I 3

CKII Ï PCy3 3

Ph h

/ = \ \ M e s - N ^ N ~ ~

Cl„ .. I

PCy3 3

'Mess Mes' ' N--

Ph h

PCy, , Mess CI,, '

CI-,, I ^ ,

%=,%=, or i y ^

'Mes s

^ = \ \ CI I

of of RUITN N

P^J P^J 10 0 11 1 12 2

Severall other ruthenium carbene catalysts have also been presented in light of the fact thatt there is currently no superior catalyst for all the metathetic transformations. Indeed, small structurall changes in the catalyst design often give unexpected improvements in activity and stability.30aa To highlight some of these complexes: the indenylidene 13,28 the extremely fast initiating,, six-coordinate dipyridine Ru carbenes of type 14,29 the bulky-substituted version of thee second generation Grubbs catalyst 15,30 which performs extraordinary well in the self metathesiss of terminal olefins,30b variants of Hoveyda-type catalyst: 16,31 chiral binaphtyl-substitutedd 17,32 and 18 made from commercially available building blocks,33 Schiff-base-containingg carbenes of type 19,34 a class of cationic, cymene-allenylidene precatalysts 20.

/ P r r

1.44 Mechanism of Metathesis Withh the discovery of a new, 'anomalous' polymerisation process2'3 the question had

risen:risen: how does this process operate? The early explanation attempts were more intuitive than anythingg built on sound experimental proofs, in view of the scarcity thereof.36 Mechanistic studiess by, inter alia, Mol et a/.,7a'b Clark and Cook,7c Calderon et al.5c and Dall'Asta et al.7d'e

allowedd Chauvin to propose a mechanism that is still consistent with experimental

5 5

CHAPTERR 1

observationss and this is now referred to as 'Chauvin's mechanism'. He pinpointed the importantt metallacyclobutane step, which is common to all the catalysts functioning in the metathesiss of olefins. Nevertheless, the individual complexes do differ in the formation of the catalyticallyy active species.

Schemee 2 presents the accepted mechanism of metathesis for ruthenium carbene complexess as determined mainly by the extensive studies in the group of Grubbs.3739 Initially, twoo possible catalytic cycles for this type of catalyst were presented: a dissociative and an associativee one. Experimental evidence proved the former to be operative. Strictly speaking, rutheniumm carbenes like complex 8 are pre-catalysts that can enter the catalytic cycle upon decoordinationn of one of the ligands, usually a phosphine or the oxygen atom of styrenyl ether moietyy in the case of 11 or 12. The vacant site in the 14-electron species is quickly filled by coordinationn of the double bond of an alkene RCH=CH2, forming species A that undergoes a formall [2+2] cycloaddition to produce metallacyclobutane B. This can collapse either back to speciess A in a non-productive step or to C in a productive step. In the latter case, a styrene moleculee is expelled and a second RCH=CH2 molecule coordinates giving species D that transformss to metallacyclobutane E upon [2+2] cycloaddition.

PCy, , -PCy3 3

++ RCH=CH,

C I ' ' PCy3 3

1 1

Ph h ++ PCy3

-- RCH=CH2

> u - - H H

RCH=CH, ,

RR s

Schemee 2. The mechanism of metathesis for Ru carbenes exemplified on cross metathesis of an alkene RCH=CH22 by thee first generation Grubbs catalyst 8.

Iff the alkene in the transition state D coordinates with the R group next to the PCy3 moietyy then metallacyclobutane E results, which then cycloreverts to species D in a non-productivee metathesis step. With the proper geometry of the metallacyclobutane as in E, cycloreversionn and decoordination gives cross metathesis product RCH=CHR (S). The

6 6

GENERALL INTRODUCTION TO OLEFIN METATHESIS

methylenee carbene F with coordinated RCH=CH2 follows similar steps via G to push out the secondd cross metathesis product - ethene. If the ethene is allowed to escape the reaction medium,, this step becomes irreversible and drives the reaction towards the propagating speciess D. The catalytic cycle is completed and can start again.

1.55 Metathetic Transformations Withh the new very active and robust metathesis catalysts in hand, a variety of chemical

transformationss of molecules containing double and triple bonds have been achieved. Since thee metathesis process is energetically neutral and thus reversible, one obtains a mixture of bothh substrates and products in a thermodynamical equilibrium. By the judicious choice of substratess and/or reaction conditions this intrinsic problem can be circumvented, so one productt can be made selectively. Many substrate combinations are successful giving rise to severall genres of metathetical transformations. They can be categorised by the kind of starting materialss used and the outcome of the reaction.

Thee energy gain from the release of ring strain in cyclic alkenes, e.g. norbornene derivatives,, is the driving force behind Ring Opening Metathesis Polymerisation (ROMP). Inn the most favourable reaction conditions, the polymers are formed in a, so called, living polymerisationn manner where a single species acts as active catalyst without chain terminationn or chain transfer processes, leading to almost monodispersed material. Most metathesiss catalytic systems operate in close to the living manner and polydispersity indexes closee to one are common, as opposed to 'normal' e.g. heterogeneous Ziegler-Natta-type polymerisationn catalysts, where indexes of 10-20 are typically observed. Additionally, ROMP co-polymerisationn is also possible.

Acyclicc Diene Metathesis Polymerisation (ADMET)40"'41 is a second metathetical methodd for making polymers. Dienes are polymerised upon release of a low molecular weight,, volatile alkene, usually ethene, which departs from the reaction environment. The polymerr chain can grow further, usually in a living manner, by reaction with a double bond of aa second diene molecule. However, when the latter process occurs intramolecularly, we are in factt dealing with Ring Closing Metathesis (RCM),42 which yields a cyclic alkene upon ring closure.. The latter reaction is favoured for a,co-dienes that can form five- to seven-membered rings,rings, while the former is preferred for dienes with a longer spacer between the two double

7 7

CHAPTERR l

bonds,, e.g. 1,9-decadiene. Where necessary, there are methods known to steer the reaction to thee other, less favoured direction. RCM has a remarkable impact on organic synthesis making itt one of the most useful tools in carbon-carbon bond formation reactions.

AA cyclic olefin can also undergo a ring opening process, denominated as Ring Opening Metathesiss (ROM),43 when allowed to react with an acyclic alkene in the presence of an activee metathesis catalyst. A positive pressure of ethene is often used for this purpose (etheno-lysis)) shifting the equilibrium towards ct,oo-dienes from the unstrained cycloalkenes. Ethenolysiss is also employed in degradation of internal olefins into terminal ones.44

Metathesiss between two olefinic partners is known as Cross Metathesis (CM)45 and ROMM might be considered a variant of this. In the case of CM, one encounters the problem of poorr selectivity due to self-metathesis of two molecules of the same alkene. With the careful choicee of the substrates, the catalyst and reaction conditions used, one can canalise the reactionn towards the desired product. Though often unwanted, the self-metathesis (dimerisation,, disproportionation) is also of synthetic interest with regard to symmetrically substitutedd alkenes.

CM M - H 2 O C H 22 , V

++ 4p H2C=CH2 \ /

ethenolysis s

Similarr reaction pathways can be envisaged for alkynes when employing appropriate metall carbynes and examples of each of the mentioned types are known, even if not as numerouss as for alkenes.46 The alkyne RCM is of the most importance in organic synthesis sincee it allows synthesis of an exclusively Z- or E-cycloalkene after selective hydrogenation off cycloalkyne.47 The E/Z selectivity is still an important issue with regard to the alkene metathesiss catalysts. The metathesis catalysts usually employed are the Schrock tungsten alkylidynee (/-BuO)3W=CCMe3 (7),20 or sterically hindered molybdenum(III) amido complexess of type [Mo{(?-Bu)(Ar)N} 3] activated upon treatment with a halogen donor.47a'b

Thee metal carbenes are also active catalysts in ene-yne metathesis. Two main types

cann be individuated: an intermolecular process in which a diene is formed from an alkene and

ann alkyne, and an intramolecular one, where a cycloalkene with a vinyl group attached to the

doublee bond usually results upon cyclisation of an co-alken-a-yne.

o o e? ?

8 8

GENERALL INTRODUCTION TO OLEFIN METATHESIS

Compoundss with several double and triple carbon-carbon bonds incorporated can undergoo tandem or domino metathesis.50 The metathesis of the metal carbene/carbyne with thee most reactive/accessible multiple bond starts a chain of the metathesis reaction proceeding fromfrom the most to the least reactive/accessible multiple bond. Design of such polyunsaturated carbonn chains, the metathesis of which proceeds along a selective cascade pathway is a remarkablee achievement. The domino processes can also occur in a multicomponent system when,, for example, the first, inter- or intramolecular metathesis triggers the successive metathesiss steps, respectively intra- or intermolecular.

Thee described homogeneous catalysts have found wide application in organic synthesis andd also in polymer chemistry. The organic chemists especially have made effective use of thee ruthenium carbene catalysts 8 - 2 0 because of their ease of preparation, resistance towards oxygenn and moisture, and compatibility with many functional groups. The success of such catalystss has now made metathesis a standard tool in the organic chemistry repertoire for carbon-carbonn bond formation. For further, more comprehensive reading on olefin metathesis andd related chemistry, the reader is advised to consult the numerous general review articles andd monographs, especially the recently published, monumental, counting 1234 pages, 'the motherr of all reviews' — Handbook of Metathesis.51"53

1.66 The Outline of the Thesis Thee development of homogeneous catalysts built upon the ruthenium centre has given

ann enormous impetus for employing metathesis in synthetic organic chemistry. Despite some greatt achievements, several facets of olefin metathesis are still unexplored, unresolved or not fullyy understood. We have tried to tackle some of them in this thesis.

Thee well-defined homogeneous metathesis catalysts are a formidable tool in the hands off an organic chemist due to the already mentioned activity, chemical robustness and functionall group tolerance (Chapter 1). The combination of these properties with better ease off handling, separation, and reusability (features of the heterogeneous catalytic systems) wouldd be advantageous. Chapter 2 presents an approach to permanently anchor Ru carbenes onn solid supports funtionalised with silver carboxylate.54 The application in metathesis, recyclingg and characterisation by EXAFS of such heterogeneous catalysts are discussed.

Twoo new aspects of homogeneous Ru carbene complexes are described in the two followingg chapters. In Chapter 3, preparation of Ru carbenes with various bidentate phosphiness is presented.55 The influence of this sort of ligands on catalytic activity and the crystall structures of three novel complexes are shown. Chapter 4 deals with synthesis of NHCC ligands bearing the very bulky adamantyl substituents.56 Both symmetrical and unsymmetricall analogues of the ligand have been prepared and the effect on the formation of Ruu carbene complexes and their metathetic activity are also dealt with.

Chapterr 5 introduces a marriage of two transformations - allylboration using triallylboronn and ring closing metathesis. This new synthetic route applied to lactams provides azaspiroalkenee scaffolds in a straightforward manner.57

9 9

CHAPTERR l

Inn the introductory section of each chapter the reader wil l find a more detailed literature

surveyy on the topics presented in this thesis.

1.77 References

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10 0

GENERALL INTRODUCTION TO OLEFIN METATHESIS

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255 M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999,1,953.

266 (a) J. P. A. Harrity, D. S. La, D. R. Cefalo, M. S. Visser, A. H. Hoveyda, J. Am. Chem. Soc. 1998, 120,120, 2343. (b) J. S. Kingsbury, J. P. A. Harrity, P. J. Bonitatebus Jr., A. H. Hoveyda, J. Am. Chem.

Soc.Soc. 1999,121,191.

277 (a) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem. Soc. 2000,122, 8168.

(b)) S. Gessler, S. Randl, S. Blechert, Tetrahedron Lett. 2000,41, 9973.

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288 (a) K. J. Harlow, A. F. Hill , J. D. E. T. Wilton-Ely, J. Chem. Soc, Dalton Trans. 1999, 285. (b) A.

Fürstner,, A. F. Hill , M. Liebl, J. D. E. T. Wilton-Ely, Chem. Commun. 1999, 601. (c) A. Fürstner,

J.. Grabowski, C. W. Lehmann, J. Org. Chem. 1999, 64, 8275. (d) A. Fürstner, O. Goth, A. Duffels,

G.. Seidl, M. Liebl, B. Gabor, R. Mynott, Chem. Eur. J. 2001, 7,4811.

299 (a) J. A. Love, J. P. Morgan, T. M. Trnka, R. H. Grubbs, Angew. Chem. Int. Ed. 2002,41,4035. (b)

M.. S. Sanford, J. A. Love, R. H. Grubbs, Organometallics 2001,20, 5314.

300 (a) A. Fürstner, L. Ackermann, B. Gabor, R. Goddard, C. W. Lehmann, R. Mynott, F. Stelzer, O.

R.. Thiel, Chem. Eur. J. 2001, 7, 3236. (b) M. B. Dinger, J. C. Mol, Adv. Synth. Catal. 2002, 344,

671. .

311 (a) H. Wakamatsu, S. Blechert, Angew. Chem. Int. Ed. 2002, 41, 794. (b) H. Wakamatsu, S.

Blechert,, Angew. Chem. Int. Ed. 2002, 41,2403.

322 (a) J. J. Van Veldhuizen, S. B. Garber, J. S. Kingsbury, A. H. Hoveyda, J. Am. Chem. Soc. 2002, 124,124, 4954. (b) J. J. Van Veldhuizen, D. G. Gillingham, S. B. Garber, O. Kataoka, A. H. Hoveyda,

J.J. Am. Chem. Soc. 2003,125, 12502. (c) A. H. Hoveyda, D. G. Gillingham, J. J. Van Veldhuizen,

O.. Kataoka, S. B. Garber, J. S. Kingsbury, J. P. A. Harrity, Org. Biomol Chem. 2004, 2, 8.

333 K. Grela, M. Kim, Eur. J. Org. Chem. 2003, 963.

344 (a) S. Chang, L. Jones II, C. Wang, L. M. Henling, R. H. Grubbs, Organometallics 1998,17, 3460.

(b)) T. Opstal, F. Verpoort, Angew. Chem. Int. Ed. 2003, 42, 2876 and references cited therein.

355 (a) A. Fürstner, M. Picquet, C. Bruneau, P. H. Dixneuf, Chem. Commun. 1998, 1315. (b) M.

Picquet,, D. Touchard, C. Bruneau, P. H. Dixneuf, New J. Chem. 1999, 23, 141. (c) A. Fürstner, M.

Liebl,, C. W. Lehmann, M. Picquet, R. Kunz, C. Bruneau, D. Touchard, P. H. Dixneuf, Chem. Eur.

J.J. 2000, 6, 1847. (d) For a review see: C. Bruneau in Ruthenium Catalysts and Fine Chemistry; C.

Bruneau,, P. H. Dixneuf, Eds.; Top. Organomet. Chem. 2004,11, pp. 125 -153.

366 (a) C. P. C. Bradshaw, E. J. Howman, L. Turner, J. Catal. 1967, 7, 269. (b) C. T. Adams, S. G.

Branderberger,, J. Catal. 1969,13, 360. (c) R. H. Grubbs, T. K. Brunck, J. Am. Chem. Soc. 1972, 94,94, 2538. (d) C. G. Biefield, H. A. Eick, R. H. Grubbs, Inorg. Chem. 1973, 12, 2166. (e) For an

overvieww see: R. H. Grubbs, Prog. Inorg. Chem. 1978, 24, 1.

377 (a) E. L. Dias, S. T. Nguyen, R. H. Grubbs, J. Am. Chem. Soc. 1997, 119, 3887. (b) M. Ulman, R.

H.. Grubbs, Organometallics 1998, 17, 2484. (c) M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am.

Chem.Chem. Soc. 2001, 123, 749. (d) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc. 2001, 123,123, 6543. (e) J. A. Love, M. S. Sanford, M. W. Day, R. H. Grubbs, J. Am. Chem. Soc. 2003, 125,

10103. .

388 For mechanistic studies of metathesis employing mass spectrometry see: (a) C. Adlhart, P. Chen,

Helv.Helv. Chim. Acta 2000, 83, 2192. (b) C. Adlhart, M. A. O. Volland, P. Hofmann, P. Chen, Helv.

Chim.Chim. Acta 2000, 83, 3306. (c) C. Adlhart, C. Hinderling,, H. Baumann, P. Chen, J. Am. Chem. Soc.

2000,122,, 8204. (d) C. Hinderling, C. Adlhart, P. Chen, Angew. Chem. Int. Ed. 1998, 37, 2685. (e)

M.. A. O. Volland, C. Adlhart, C. A. Kiener, P. Chen, P. Hofmann, Chem. Eur. J. 2001, 7,4621. (f)

Forr an overview refer to: P. Chen, Angew. Chem. Int. Ed. 2003, 42, 2832.

399 For theoretical studies see: (a) O. M. Aagaard, R. J. Meier, F. Buda, J. Am. Chem. Soc. 1998, 720,

7174.. (b) R. J. Meier, O. M. Aagaard, F. Buda, J. Mol. Catal. A: Chem. 2000, 160, 189. (c) S. M.

Hansen,, F. Rominger, M. Metz, P. Hofmann, Chem. Eur. J. 1999, 5, 557. (d) S. F. Vyboishchikov,

M.. Bühl, W. Thiel, Chem. Eur. J. 2002, 5, 3962. (e) L. Cavallo, J. Am. Chem. Soc. 2002, 124,

8965.. (f) C. Adlhart, P. Chen, Angew. Chem. Int. Ed. 2002, 41, 4484. (g) S. Fomine, S. Martinez

12 2

GENERALL INTRODUCTION TO OLEFIN METATHESIS

Vargas,, M. A. Tlenkopatchev, Organometallics 2003, 22, 93. (h) F. Bemardi, A. Bottom, G. P.

Miscione,, Organometallics 2003, 22, 940. (i) C. Costabile, L. Cavallo, J. Am. Chem. Soc. 2004, 126,126,9592. 9592.

400 For recent reviews see: (a) M. R. Buchmeiser, Chem. Rev. 2000, 100, 1565. (b) U. Frenzel, O.

Nuyken,, J. Polym. Sci. Part A: Polym. Chem. 2002,40,2895.

411 (a) D. Tindall, J. H. Pawlow, K. B. Wagener, in Alkene Metathesis in Organic Synthesis; A.

Fürstner,, Ed.; Top. Organomet. Chem. 1998, 1, pp. 183 - 198. (b) K. R. Brzezinska, K. B.

Wagener,, G. T. Bums, J. Polym. Sci. Part A: Polym. Chem. 1999, 37, 849. (c) J. E. Schwendeman,

A.. C. Church, K. B. Wagener, Adv. Synth. Catal. 2002, 344, 597. (d) A. C. Church, J. A. Smith, J.

H.. Pawlow, K. B. Wagener, in Synthetic Methods and Step-Growth Polymers; M. E. Rogers, T.

Long,, Eds.; Wiley, New York, 2003, Chapter 8, p. 431. (e) A. C. Church, J. H. Pawlow, K.. B.

Wagener,, Macromol. Chem. Phys. 2003,204, 32. (f) F. C. Courchay, J. C. Sworen, K. B. Wagener,

MacromoleculesMacromolecules 2003, 36, 8231. (g) T.. E. Hopkins, K. B. Wagener, J. Mol. Catal. A: Chem. 2004, 213,213, 93.

422 (a) S. K. Armstrong, J. Chem. Soc, Perkin Trans. 1 1998, 371. (b) A. J. Phillips, A. D. Abell,

AldrichimicaAldrichimica Acta 1999, 32, 75. (c) For a general review on metal mediated synthesis of medium-

sizedd cycles see: L. Yet, Chem. Rev. 2000, 100, 2963. (d) F.-X. Felpin, J. Lebreton, Eur. J. Org.

Chem.Chem. 2003, 3693. (e) A. Deiters, S. F. Martin, Chem. Rev. 2004, 104, 2199. (f) M. D.

McReynolds,, J. M. Dougherty, P. R. Hanson, Chem. Rev. 2004,104, 2239.

433 (a) J. A. Tallarico, M. L. Randall, M. L. Snapper, Tetrahedron 1997, 53, 16511. (b) J. A. Tallarico,

P.. J. Bonitatebus Jr., M. L. Snapper, J. Am. Chem. Soc. 1997, 119, 7157. (c) D. L. Wright, L. C.

Usher,, M. Estrella-Jimenez, Org. Lett. 2001,3,4275.

444 For examples see: (a) R. H. A. Bosma, G. C. N. van den Aardweg, J. C. Mol,, J. Chem. Soc, Chem.

Commun.Commun. 1981, 1132. (b) M. Sibeijn, J. C. Mol, J. Mol. Catal. 1992, 76, 345. (c) R. H. Grubbs, S.

T.. Nguyen, L. K. Johnson, M. S.Hillmyer, G. C. Fu, WO 9604289, filed 1996. (d) S. Warwel, F.

Bruse,, C. Demes, M. Kunz, M. R. Klaas, Chemosphere 2001, 39. (e) K. A. Burdett, L. D. Harris, P.

Margl,, B. R. Maughon, T. Mokhtar-Zadeh, P. C. Saucier, E. P. Wasserman, Organometallics 2004, 26,26,2027. 2027.

455 (a) M. Schuster, S. Blechert, Angew. Chem. Int. Ed. Engl. 1997, 36, 2036. (b) S. J. Connon, S.

Blechert,, Angew. Chem. Int. Ed. 2003, 42, 1900. (c) For a general model for selectivity in CM see:

A.. K. Chatterjee, T.-L. Choi, D. P. Sanders, R. H. Grubbs, J. Am. Chem. Soc 2003,125,11360.

466 For examples check: (a) A. Fürstner, C. Mathes, Org. Lett. 2001,3,221. (b) ref. 47b.

477 For examples of RCAM see: (a) A. Fürstner, K. Grela, C. Mathes, C. W. Lehmann, J. Am. Chem.

Soc.Soc. 2000,122, 11799. (b) A. Fürstner, C. Mathes, C. W. Lehmann, Chem. Eur. J. 2001, 7, 5299.

(c)) B. Aguilera, L. B. Wolf, P. Nieczypor, F. P. J. T. Rutjes, H. S. Overkleeft, J. C. M. van Hest, H.

E.. Schoemaker, B. Wang, J. C. Mol, A. Fürstner, M. Overhand, G. A. van der Marel, J. H. van

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(e)) M. Usselstijn, B. Aguilera, G. A. van der Marel, J. H. van Boom, F. L. van Delft, H. E.

Schoemaker,, H. S. Overkleeft, F. P. J. T. Rutjes, M. Overhand, Tetrahedron Lett. 2004, 45, 4379.

(f)) F. Lacombe, K. Radkowski, G. Seidel, A. Fürstner, Tetrahedron 2004, 60, 7315.

488 For considerations on selective synthesis of macrocyclic (E)-alkenes see: J. Prunet, Angew. Chem.

Int.Int. Ed. 2003, 42,2826.

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CHAPTERR 1

499 For reviews see: (a) M. Mori in Alkene Metathesis in Organic Synthesis; A. Fiirstner, Ed.; Top.

Organomet.Organomet. Chem. 1998,1, pp. 133 - 154. (b) D. Sémeril, C. Bruneau, P. H. Dixneuf, Adv. Synth.

Catal.Catal. 2002,344, 585. (c) C. S. Poulsen, R. Madsen, Synthesis 2003,1.

500 For some examples consult: (a) W. J. Zuercher, M. Hashimoto, R. H. Grubbs, J. Am. Chem. Soc.

1996,, 118, 6634. (b) T.-L. Choi, R. H. Grubbs, Chem. Commun. 2001, 2648. (c) S. Blechert, C.

Stapper,, Eur. J. Org. Chem. 2002, 2855. (d) M.-P. Heck, C. Baylon, S. P. Nolan, C. Mioskowski,

Org.Org. Lett. 2001,5,1989. (e) D. J. Wallace, Tetrahedron Lett. 2003,44,2145.

511 (a) C. Pariya, K. N. Jayaprakash, A. Sarkar, Coord. Chem. Rev. 1998, 168, 1 (b) R. H. Grubbs, S.

Chang,, Tetrahedron 1998, 54, 4413. (c) A. Fiirstner, Ed. Alkene Metathesis in Organic Synthesis,

Top.Top. Organomet. Chem. 1998, /, pp. 1 - 231. (d) S. Blechert, Pure Appl. Chem. 1999, 71,1393. (e)

D.. L. Wright, Curr. Org. Chem., 1999, 3, 211. (f) For applications of olefin metathesis in

carbohydratee chemistry consult: M. Jergensen, P. Hadwiger, R. Madsen, A. E. Stütz, T. M.

Wrodnigg,, Curr. Org. Chem. 2000, 4, 565. (g) A. Fürstner, Angew. Chem. Int. Ed. 2000, 39, 3012.

(h)) T. M. Trnka, R. H. Grubbs, Ace. Chem. Res. 2001, 34, 18. (i) M. A. Rouhi, Chem. Eng. News

2002,, 80 (51), 29-38. (j) R- H. Grubbs, Ed.; Handbook of Metathesis, Wiley-VCH: Weinheim,

Germany,, 2003. (k) S. J. Connon, S. Blechert in Ruthenium Catalysts and Fine Chemistry; C.

Bruneau,, P. H. Dixneuf, Eds.; Top. Organomet. Chem. 2004, 11, pp. 93 - 124. (1) For applications

off RCM and RCAM in the synthesis of macrocyclic glycolipids refer to: A. Fürstner, Eur. J. Org.

Chem.Chem. 2004, 943.

522 For non-metathetic behaviour patterns of Ru carbene catalysts and their direct derivatives see: (a)

B.. Alcaide, P. Almendros, Chem. Eur. J. 2003, 9, 1258. (b) B. Schmidt, Eur. J. Org. Chem. 2004, 1865. .

533 For a series of annual surveys dealing with complexes containing multiple metal-carbon bonds by

J.. W. Herndon turn to: (a) Coord. Chem. Rev. 1999, 181, 177. (b) Coord. Chem. Rev. 2000, 206-

207,207, 237. (c) Coord. Chem. Rev. 2000, 209,387. (d) Coord. Chem. Rev. 2001, 214, 215. (e) Coord.

Chem.Chem. Rev. 2002,227, 1. (f) Coord. Chem. Rev. 2003,243, 3. (g) Coord. Chem. Rev. 2004,248, 3.

544 (a) P. Nieczypor, W. Buchowicz, W. J. N. Meester, F. P. J. T. Rutjes, J. C. Mol, Tetrahedron Lett.

2001,, 42, 7103. (b) P. Nieczypor, J. A. van Bokhoven, J. C. Mol, manuscript in preparation.

555 P. Nieczypor, P. W. N. M. van Leeuwen, J. C. Mol, M. Lutz, A. L. Spek, J. Organomet. Chem.

2001,, 625, 58.

566 M. B. Dinger, P. Nieczypor, J. C. Mol,, Organometallics 2003, 22, 5291.

577 P. Nieczypor, J. C. Mol, N. B. Bespalova, Y. N. Bubnov, Eur. J. Org. Chem. 2004, 812.

14 4