Chapter 1 Introduction

Transcription

1 Chapter 1 Itroductio 1 The olefi metathesis reactio is a powerful sythetic tool that scrambles the carbo atoms of carbo carbo double bods ad creates ew carbo carbo double bods. The mechaism of the reactio was proposed by Chauvi i 1971, ad it is still accepted today (Scheme 1.1). 1 The key compoet to ay olefi metathesis reactio is a trasitio metal species bearig a metal carbo double bod (carbee or alkylidee). A alkee approaches the alkylidee (1) ad udergoes a [2+2]-cycloadditio that geerates a ew carbo carbo bod ad affords a metallocyclobutae (2). A retro-[2+2], where differet bods break tha were formed, geerates a ew olefi ad a ew metal alkylidee. 1 2 Scheme 1.1. Accepted olefi metathesis mechaism. This simple trasformatio has bee used i a wide variety of ways to sythesize simple orgaic molecules, complex atural products, supramolecules, ad polymers. 2 Some of the commo reactios are show i Figure 1.1. Cross-metathesis (C), rigopeig/cross metathesis (ROC), ad rig-closig metathesis are used i small molecule sythesis, ad acyclic diee metathesis polymerizatio (ADET) ad rig-

2 opeig metathesis polymerizatio (ROP) are processes that geerate oligomers ad polymers. These reactios are reversible, ad i may cases the drivig force for product formatio is the release of gaseous by-products such as ethylee or the release of rig strai. 2 Reactios used i small molecule sythesis cross-metathesis (C) R R2 1 rig-opeig/cross metathesis (ROC) R1 rig-closig metathesis (RC) Reactios used i polymer sythesis acyclic diee metathesis polymerizatio (ADET) rig-opeig metathesis polymerizatio (ROP) Figure 1.1. Commo olefi metathesis reactios. Although the olefi metathesis reactio has bee kow sice the 1960s, 3 it was ot util the developmet of well-defied, homogeeous catalysts that it foud applicatios i orgaic sythesis. There are may trasitio metal alkylidees that catalyze olefi metathesis reactios to some degree, but complexes based o titaium, molybdeum, ad rutheium receive the most use. 4 The differet metals impart differet reactivities to the alkylidees, ad, eve withi a family of complexes derived from oe metal, small adjustmets i the ligad eviromet cause large chages i catalyst behavior. Geerally, early trasitio metal alkylidees are more oxophilic tha late metals complexes, ad this property has a large impact o the chemoselectivity of the catalyst.

3 The most commoly used titaium alkylidees are geerated i situ from either Tebbe s reaget (3) 5 or dimethyltitaocee (4) 6 (Scheme 1.2). These compouds form a titaium methylidee, which ca catalyze the ROP of straied olefis. Other alkees ca react with titaium methylidees to afford titaacyclobutaes, but a efficiet catalytic cycle does ot typically occur. The low reactivity of titaium alkylidees allowed them to act as model systems ad provide valuable isight ito the olefi 3 metathesis reactio. 7 Due to their high oxophilicity ad the stability of the Ti O bod, these complexes will react stoichiometrically with aldehydes, ketoes, esters, lactoes, ad amides to afford methyleated products. 8 Although these complexes are ot typically used as olefi metathesis catalysts, they have foud a place i orgaic sythesis as carboyl methyleatig agets. Ti Al pyridie or THF Ti CH 2! Ti e e (catalytic) Cp 2 Ti CH 2 O OEt 5 (stoichiometric) OEt Cp 2 Ti=O Scheme 1.2. Reactios of titaium methylidees. ay differet molybdeum ad tugste alkylidees have bee sythesized, 9 ad the catalyst that is used most ofte is It is much more active that the titaium catalysts i performig olefi metathesis, ad it has bee applied to orgaic ad polymer sythesis. The mai disadvatage of the molybdeum-based catalysts is their air ad moisture sesitivity as well as their reactivity with oxyge-cotaiig fuctioal groups.

4 Carboxylic acids, primary amies, aldehydes, most alcohols, ad some ketoes react with them ad remove them from the olefi metathesis catalytic cycle. These fuctioal groups are foud i may orgaic compouds, limitig the use of the molybdeum catalysts. 4 F 3 C F 3 C N O o O e e F 3 C CF 3 6 Ph e e The mai disadvatage of the early trasitio metal catalysts preseted above is a lack of selectivity for olefis over other fuctioal groups, ad selectivity is a crucial part of ay sythetic methodology. Some of the most successful reactios used i orgaic chemistry are those that reliably react with a certai fuctioal group i a certai way ad do ot disturb the rest of the molecule. It was the developmet of rutheium olefi metathesis catalysts that bridged the gap betwee olefi metathesis ad orgaic sythesis. 11 Due to the fuctioal group tolerace of rutheium catalysts, olefi metathesis has become a selective reactio that has foud widespread use amog orgaic ad polymer chemists. Just as i the case of molybdeum, may differet metathesisactive rutheium catalysts are kow. A few of the most commo catalysts are show i Figure All three alkylidees are stable to air ad moisture, ad complexes 8 12b ad 9 12c exhibit catalytic activities similar to those of the highly active molybdeum systems.

5 5 PCy 3 Ru PCy 3 Ph N N Ru PCy 3 Ph N N Ru O Figure 1.2. Selected rutheium olefi metathesis catalysts. This brief itroductio has ot doe justice to all of the time ad effort that has bee dedicated to uderstadig olefi metathesis ad developig it ito a reliable, practical reactio. However, it has illustrated the importace of selectivity. Ulike the early trasitio metal-based alkylidees, the rutheium catalysts react preferetially with alkees over may commo fuctioal groups, so they are the catalysts of choice i sythetic orgaic chemistry. But aother questio remais: could these rutheium catalysts (or derivatives thereof) react selectively with oe alkee i the presece of more tha oe? The exploratio of chemo- ad stereoselective olefi metathesis ad its applicatio i the sythesis of importat orgaic compouds is preseted i the followig chapters of this dissertatio. As described i chapter 2, the sythesis of trisubstituted viyl boroates usig catalyst 8 was moderately successful. The lack of reactivity of catalyst 8 toward 1,1- disubstituted alkees discovered durig the work i chapter 2 afforded isight ito how to develop a chemoselective olefi metathesis reactio. The research preseted i chapter 3 focuses o the chemoselective C of substituted cojugated diees. This reactio geerates compouds that are kow to be versatile sythetic itermediates ad are foud i atural products. Chapter 4 cotais the results from a study o asymmetric rigclosig metathesis (ARC) that used chiral derivatives of 8. All of the substrates were achiral triees, ad the extet to which a catalyst reacted with oe alkee over aother

6 was determied by the eatiomeric excess of the chiral products. The applicatio of ARC i the eatioselective total sythesis of (+)-5-epi-citreoviral is preseted i 6 chapter 5. Fially, commets o the formatio of tetrasubstituted olefis usig uhidered rutheium catalysts are preseted i appedix 1, ad the results from research directed toward the geeratio of a cis-selective olefi metathesis catalyst bearig a bidetate ligad are described i appedix 2. Refereces 1 Hérriso, J.-L.; Chauvi, Y. akromol. Chem. 1971, 141, For a comprehesive review of applicatios i orgaic ad polymer sythesis, see Hadbook of etathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weiheim, Germay, 2003; Vol. 2 ad Vol (a) Truett, W. L.; Johso, D. R.; Robiso, I..; otague, B. A. J. Am. Chem. Soc. 1960, 82, (b) Natta, G.; Dall Asta, G.; azzati, G.; Passquo, J. J. Polymer Sci., Polymer Lett. 1964, B2, For a review o the history of metathesis catalyst developmet, see Hadbook of etathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weiheim, Germay, 2003; Vol (a) Tebbe, R. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc. 1978, 100, (b) Tebbe, F. N.; Parshall, G. W.; Oveall, D. W. J. Am. Chem. Soc. 1979, 101, aus, K.; Bestia, H. Justus Liebigs A. Chem. 1962, 654, 8. 7 Grubbs, R. H. I Hadbook of etathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weiheim, Germay, 2003; Vol. 1, Chapter 1.2.

7 7 8 Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112, For reviews o molybdeum ad tugste olefi metathesis catalysts, see (a) Schrock, R. R.; Hoveyda, A. H. Agew. Chem. It. Ed. 2003, 42, (b) Schrock, R. R I Hadbook of etathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weiheim, Germay, 2003; Vol. 1, Chapter Schrock, R. R.; urdzek, J. S.; Baza, G. C.; Robbis, J.; Diare,.; O Rega,. J. Am. Chem. Soc. 1990, 112, Nguye, S. T.; Trka, T.. I Hadbook of etathesis; Grubbs, R. H., Ed.; Wiley- VCH: Weiheim, Germay, 2003; Vol. 1, Chapter (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W.; J. Am. Chem. Soc. 1996, 118, (b) Scholl,.; Dig, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, (c) Carber, S. B.; Kigsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122,