I have an admission to make.
I am not an organic chemist and I’m sure Bob Grubbs would agree with that and a lot of my organic friends.
I’m an inorganic chemist but I’m interested in organic problems.
And I’d like to tell you today really about what we’ve done in the last 3 years or so, maybe 4 years.
I didn’t talk about any of this the last time I talked.
If I talked about this subject at the last Lindau Nobel Laureate meeting, I’m not sure.
But in any case it’s all about advances in this field like olefin metathesis.
Most of you have at least heard the name probably, if you don’t actually know much about it.
So let me tell you where it all started.
That’s a good place to start. So I was at DuPont.
So I’m in an unusual situation of having spent some time in industry, for 3 years.
Back at that time DuPont allowed people to do
whatever they thought was remotely relevant and to basically do something, find, discover something.
Of course these days you have to predict what you’re going to discover.
But back then you didn’t have to do that.
So it was a lot simpler.
And a lot more exciting I might point out.
So up here I have the place it all started and that was with a reaction that really is a very simple one.
It’s an organometallic reaction.
It’s an attempt to make a penta-alkyl of tantalum with a very bulky alkyl.
This is called... Well, it’s a t-butyl substitute with methyl or neopentyl ligand.
And what happens when you try to make that through some relatively routine sort of displacement of chloride,
you get a compound, beautiful compound, very high yield.
But it was pretty clear that it was not a penta-alkyl.
And I won’t have time to go into that.
What happened is that the penta-alkyl was an intermediate probably.
And then it decomposed.
It couldn’t decompose intermolecularly because these big alkyls were just too big.
They didn’t allow any intermolecular reactions.
And so that then set up and there are many other details why this was set up for an intramolecular reaction,
one having to do with the t-butyl group and opening up that methyl carbon-carbon angle.
There’s an intramolecular, basically depropagation by a very nucleophilic carbon next door.
And what that gave rise to is neopentane and then a methyl-carbon double bond as shown here.
So this is trineopantal-neopentilidine.
And at the time I was actually interested in some interesting phosphorus compounds called ilids and noticed
that phosphorus and tantalum are in the same group.
Or at least they were, group 5a and 5b at that time.
So this was a remarkable compound.
When I left DuPont in 1975, I decided to try to duplicate what I had done here in the form of molybdenum, tungsten and rhenium.
Because at that time in the early ‘70s there was a great interest in this bizarre reaction
which strangely enough first was reported at DuPont in the form of a patent by Herb Eleuterio in 1956.
So I left in ’75. So that’s 20 years.
About the last 5 years of my period then in that saga, let’s say between 1970 and 1975,
people were very interested in the mechanism of this reaction because it was not known.
And what was the issue is whether 2 carbons exchange with themselves sort of like a cyclobutane intermediate
or whether it was some other odd carbon mechanism.
It turns out to be an odd carbon mechanism.
And the first person to write that down was Yves Chauvin in 1971.
And I didn’t know about this paper.
Many other people didn’t know about the paper.
There were other people who came up with the suggestion.
But it was in fact Yves Chauvin who first wrote it down. Now, that was interesting.
The problem is that there were no metaloorganic things.
I show the metal-carbon double here but there is nothing on the metal.
We knew what the metal was, molybdenum, tungsten or rhenium.
It could be either heterogeneous or homogeneous.
But we had no idea, at least to my knowledge, except for some sort of cartoons written down at will, what the actual compound was.
Of course it’s not the single compound but just generally, what is it?
So between ’75 and ’86 then I count that as a point
where I first published an example of what I call a well-defined tungsten compound.
And between that, those 2 times, I spent the time developing tantalum chemistry
and showed that it could actually do this reaction,
this so called metathesis reaction where you scramble the ends of olefins.
But not very well. And then other things happened that I’ll tell you about.
And then the next speaker is going to tell you about...
Grubbs is going to tell you about ruthenium.
He managed to make ruthenium do some things that... many of the important things that molybdenum, tungsten and rhenium will do.
But its different oxidation state of the metal.
So you don’t want to just let entropy take over, you want to guide these reactions.
And to do that it’s best in an equilibrium if you take out one of the compounds like ethylene.
So you can couple 2 thermal olefins to make ethylene and then an internal olefin,
that’s called homometathesis or homocoupling, related to carbon-carbon single bond coupling but double bond coupling.
You can do a cross metathesis where you hope to stop this sort of reaction and make the R prime molecule.
You can open up strained rings and make polymers.
That’s called ring opening metathesis polymerisation.
That I think Bob Grubbs came up with that acronyms. It’s a very apt one.
That was done long before in fact people knew what the catalysts were
because they could do that with the classical systems or what are called the classical systems.
And then you could make rings, you could sort of do this in reverse.
You could make rings ejecting this olefin and so on if that ring is not too strained.
The problem at the time was that of course if you go to equilibrium you make roughly 80% trans double bonds.
Even here where you make rings, if it’s big enough you can make a trans double bond.
So that was a problem. How do you make the higher energy, about 2 k cals or so.
How do you make the higher energy olefin because nature likes to do that?
Get a little more energy for reactions, a little more reactive molecule when you’re faced with an equilibrium situation.
So that’s what I want to describe to you today.
How do you do that? This is the first generation,
what are called the first generation of catalysts with the metals molybdenum and tungsten.
You have an imido group here which is very bulky.
It prevents bimolecular decomposition.
You have a bulky alkoxide, 2 of them.
You have initially at least a bulky alkyladine and neopantyladine.
That of course changes during the reaction. That’s the reaction itself.
But we got a long way with these molecules.
We could make polymers. We could do a lot of interesting reactions.
And very often you might see in the literature that this is Schrock’s catalyst.
As if there is one catalyst.
There isn’t just one catalyst and it’s not mine. It’s just one of many.
So activities to some degree, although still not easy, selectivity still not cis and trans,
can be controlled with these molecules.
The next step or the next generation is really an asymmetric version of that.
So making products then that are chiral, enantiomerically pure using a chiral catalyst,
enantiomerically pure catalyst was the object
by simply connecting the 2 oxygens with some enantiomerically pure biphenylate or binaphylate
and carry out enantiomerically pure reactions.
So the catalyst can then make a product that is one enantiomer.
And it does that very well ejecting ethylene in this process.
And you get a product of very high yield, 97% or greater than 97% ee.
Now the way this works is that the substrate attacks the carbon-nitrogen-oxygen phase.
I could have said that for the previous catalyst also and makes the metallocyclobutane of some shape.
We don’t know exactly what that is or didn’t at the time.
I should note that if this is a racemic biphenylate or binaphylate...
In 1993 we showed that you could ring open metathesize strained olefins and make polymers
that had only cis double bonds connecting the units.
And then, as I’ll talk about later, it was a very tactic.
It had one structure, isotacticity.
So, I should have paid more attention to what these molecules did with polymers.
These have to be norbornenes or substituted norbornadines to generate that tacticity although there are others that would do it.
But that’s what we used as sort of the demonstration in terms of the molecule employed.
The third generation is the compound shown here, a MonoAlkoxide Pyrrolide.
Now how did we do that or why did we do that?
We weren’t actually interested in that.
So the first thing I showed you was a completely eureka type moment.
This is... I’m not very interested in that type of moment
because what we wanted to do was to make the bisalkoxides by using these pyrrolides
and these amines of pyrrol to receive protons and generate bisalkoxides.
But then we looked at this and decided that that is indeed an interesting molecule.
Of course you follow whatever is the most interesting path.
And maybe we had sort of exhausted our interest in bisalkoxides.
I don’t know. But we thought this was an interesting molecule. And it is.
One of the interesting things is that there are 4 different things attached to the metal.
So it’s a mixture, a one to one mixture of those 2 enantiomers.
Now people, specially people like Henry Bruner who had spent his lifetime
thinking about what it means to do catalyses with a metal that is itself a chiral centre.
Now you can attach a chiral ligand, enantiomerically pure ligand.
And then you have diastereomers.
But just because there are 4 different groups that should certainly very greatly affect how the molecule
that you’re interested in, in our case an olefin, comes into the metal.
And we’ve shown that it’s pretty much this.
This is still somewhat a project in process.
But it comes in on the carbon-nitrogen-oxygen phase, Interestingly enough trans to the pyrrolide.
And the first thing that’s generated in this case where I start with a mephyladine
and I add then the one terminal olefin, R’’ in red here.
We generate a metallocyclobutane that has this structure, I call the PSP’ structure.
And the interesting thing in metathesis that I really didn’t think about enough
especially since the methyl was chiral but I’m thinking about it now...
And that is that the way the olefin comes in is the way the olefin has to go out unless the olefins are dramatically different.
Like norbornene and ethylene. Probably norbornene could react in a way that is different from the product ethylene going out.
But if the olefins are similar then what comes in a certain pathway has to go out a certain pathway.
So that’s not possible when this is the product that you want to form
because it’s got to somehow turn into the similar thing by being trans to the pyrrolide.
And so what it does, it kind of rotates down and these 4 atoms flip up to this structure.
Now, nobody has seen these intermediates but that’s the proposal.
And now what you’ve done by inverting at the metal,
interestingly is that you put the product ethylene here, transfer the pyrrolide
and so it can be lost.
But in the process what you’ve done is that you’ve inverted at the metal from this chirality, whatever you want to call that.
Or let’s say to this one, S, the other possibility.
Now the intermediate in this flipping process is a trigonal bipyramid
as shown here with the alkoxide and the imido groups in the apical position.
Now that’s not the only fluxional process.
That’s the least motion mechanism.
I didn’t appreciate and I’m starting to appreciate it much more now, that 5 coordinate compounds as everybody knows,
especially d zero or things with no electrons, basically they get in the way, are highly fluxional.
Whether it’s phosphorus or tantalum, it doesn’t matter.
5 coordinate compounds are highly fluxional.
And so these metallocycles can do other types of rearrangements.
And that’s a process that’s ongoing.
And what are the consequences of that in terms of catalysis.
Of course catalysis is just making something.
You want to make something and the system figures it out.
It figures out a way to make it.
And so to be highly fluxional is probably a good thing because you can sample a lot of possibilities in that time
which is a rapid time scale.
We’re not talking about 10^8 here, we’re talking about 100 per second or something like that.
Well, that turns out to be the intermediate.
You can tell by making metallocyclobutanes.
We’ve only made them now with nothing on the carbons because those are the more stable ones.
And you have an imido group in the axial position and the alkoxide or in this case aryloxide in the other axial position.
And then you have a pyrrolide, the pyrrolide in the equatorial position.
Now it’s interesting that of course you have 4 different ligands, the carbon nitrogen, different nitrogen and oxygen ligand.
And it so happens luckily that this is, we think, the most important metallocycle.
And there are structural reasons for that. I don’t have time to go into.
And that the olefin comes in and goes through this transition state or that molecule in the process of going in
and generating a new olefin and a new alkylidene.
Now we became interested in very large aryloxides like this one.
This is a ligand prepared by Phil Power.
It has 6 isopropyl groups.
It’s a hex isopropyl 2,6 terphenoxide.
And you can see why we might want to do that.
Because if you start putting R groups on these carbons... Let’s say you want to put one on each one.
If you make a space filling model, it turns out you can’t put it down here.
You can’t put one down here. You can put it up here.
You can’t put it down there, you can put it up here.
So what that means is that you can only make and you can only make cis olefins or Z olefins as products.
And so the theory arose that that’s the way to make z olefins.
Now you’ve got 2 things.
You’ve got to make that Z olefin exactly right, you might make a mistake occasionally.
And then you have to prevent any future mistakes, isomerising Z to E, cis to trans.
And so you have to use catalysts that maybe aren’t the most active catalysts in the world.
Because that means they are very non-discriminate and they attack everything.
So these map catalysts turn out to be more efficient
but at the same time they’re actually I think a little less reactive than a bisalkoxide.
But that was the theory and so you should be able to generate Z olefins from terminal olefins for example.
And we show here, this is 2011 now, a couple of years ago, some work by Miranda Marinescu.
It’s easy to do that with that large theory that I just outlined.
And you can do it quite efficiently with some olefins at room temperature, good to reasonable conversion.
Some don’t work so well.
I should point out that with normal catalysts, what are called normal catalysts, run of the mill catalysts at that time,
anything better than about a 1 to 1 mixture was considered Z selective although it really wasn’t.
These really are Z selective greater than 99%.
Now it’s interesting today and we have a theory or a subject
I should say of this conference of green chemistry and environmentally more secure chemistry.
And what you can do is you can make chemicals from natural products like seed oils.
And we’ll hear some other examples in the next talk.
But what you can do is you can run that coupling reaction backward.
So you can take ethylene and push it into the system with the same catalyst,
because it has to go through the same intermediate.
And you can chop up olefins.
In this case these un-symmetrical olefins.
And this is oleic acid ester. So it’s a major component of many seed oils.
It happens to be the methyl ester and its Z because nature likes Z olefins as I mentioned.
It’s not that she never produces a trans one but very many Z olefins than you would expect based on thermodynamics.
Because everything is kinetic, that gives rise to them.
And so you then by the mechanism I mentioned, you get 2 pieces.
In this case methyl 9 to ZnO 8 and 1 decine.
And using the same catalyst -I’ll show you what this bicat ligand is in a minute,
it’s in the next slide- you can easily show that you can chop up 5,000 equivalents at room temperature with ethylene.
But you have to do it under pressure because ethylene is not very soluble.
And of course you want to prevent the back reaction
because then that gives a chance for cis to isomerise
or gives a chance for cis so isomerise to trans, possibly in your starting material.
To remake the starting material as well as the homometathesis product.
So you don’t want that.
And in fact this goes very cleanly.
99% to these 2 species, methyl 9 to ZnO 8 and 1decine.
And you get about a 95% yield.
But time here I don’t think is... It’s probably quite, quite short. Maybe 15 minutes.
But this was probably an overnight run.
And then when you want to work it up, of course you want to prevent the back reaction
so you have to quench the reaction, open it up quickly and quench it.
In any that’s a big deal these days.
There are seed oil companies, one is called, I think the only major one is called ...
(inaudible 19.45), near Chicago in the USA, that is using seed oils as sources of chemicals.
If the coupling of terminal olefins is Z selective then ethenolysis
since it goes through that same intermediate should be Z selective.
So we said, oh, that’s interesting. So cis olefins generally are more reactive than trans olefins.
I never knew just how much and I haven’t tried to find out in terms of hydrogenation if anybody has determined that.
But we could easily do that by just getting a mixture, 80% E 4-octene, trans 4-octene versus cis 4-octene.
And just individually taking each of those pure species and seeing what the rate of metathesis or ethenolysis was.
And it turns out to be based on the temperature. These data aren’t very accurate in my opinion.
These data at 0 degrees are probably more reliable.
But basic result is that the rate at which the cis olefin is chopped up in this reaction is about 30 to 40 times the rate
at which the trans olefin is chopped up.
Now that doesn’t sound like a very big number.
But it’s big enough if you go through the kinetics or just do the experiments to selectively consume more or less the cis olefin.
And that’s what happens. The cis olefin gets turned into 1 pentene in this reaction.
The ethylene is missing in that reaction.
Well, because it wouldn’t be balanced anyway because what’s left over is about 77%.
We started with 80% here, E.
What’s left over is pure E, greater than 99%.
And that yield is 77% out of 80% theory.
So it’s a high yield, in the 90s, 95% in terms of found versus theory.
So this was reported back in 2011.
Now we would like to make E olefins directly in a kinetic reaction.
We don’t know how... kinetic meaning of course you make it in whatever step it is,
the crucial step where you make the olefin product.
But we can’t do that yet. And so we saw this and we said, well, this is interesting.
What we could do is we could take any old mixture of olefins, E to Z, thermodynamic or not.
Here this is a benzo-allyl, benzo-ether.
That’s 11 to 1 in terms of the E,
so you’re just going to consume 1 part in 12 in this ethenolysis reaction and make the pure E olefins.
It’s hard to make pure E and Z.
Now people say oh you use Vidic reaction.
That’s a terrible, I mean I shouldn’t say it’s terrible, it’s not as good a reaction.
And of course unlike the reactions here, it’s not catalytic.
And you’re using olefins to make olefins.
So it’s a zero sum game. It’s very atom economic and everybody is happy.
You don’t make a lot of waste. And it’s catalytic and atom economic. So that’s the story.
You can make... We haven’t followed this up in any great detail.
But you can make, using the Z selective catalyst through ethenolysis pure e olefins in a 2 step process.
Now we’d like to do it directly. But we can’t yet.
Let me say something about ROMP, ring opening metathesis polymerisation.
If you take something like norbornene and you open it up,
you can get either polymers then having cis double bonds between these units or trans double bonds between these units.
And then the rings can, in this case 5 membered rings,
point in one direction all along the chain or front back, front back all along the chain in either one of these.
So those give rise to cis isotactic.
The configuration of that carbon and that carbon is the same.
That carbon and that carbon is different.
So this is syndiotactic and so forth.
Now you’d like to be able to make one structure.
It turns out that in spite of books written about ROMP and people have made a lot of polymers,
it’s very, very rare and its pure chance.
There are a couple of examples out there of making a single structure.
But you don’t know why or how.
And you can’t do it, it’s also substrate dependent.
You can’t do it with everything.
One thing works, you get one polymer and that’s it.
Now why do you want these polymers?
Well as we all know, as Ada Yonath mentioned, structure dictates properties, dictates behaviour and so forth.
If you have single structure ,then you can begin maybe to design polymers for a given purpose.
And an example that we know of is, say, isotactic polypropylene versus singular tactic polypropylene.
Those are 2 very different polyolefins.
So that... we’d like to apply that to ROMP because norbornenes and things like them, dicyclopentadiene are readily available.
They’re almost... they used to burn dicyclopentadiene because they couldn’t think of anything else to do with it.
Now, what you can do is you can hydrogenate the whole thing.
But that doesn’t get rid of the tacticity.
So what does tacticity, the way these rings point in the case of norbornene,
how does that control the structure of polymers and their properties made from these things?
So I told you that in 1993 we made cis isotactic structures using biphenylate and binaphenylate catalysts.
And we found that the MAP catalyst now because the chirality at the metal switches we think with each step.
To make an isotactic one that monomer has to come in the same metal carbon bond face each step.
The syndiotactic one has to come in the opposite face. Right left, right left to get syndiotactic.
And since the chirality of the metals changes from one to the other,
you come in from the back in this case and then after you insert one unit you come in from the front.
And then you go back to this structure and come in from the back again.
And you get sole cis because of what I mentioned and syndiotactic polymer, essentially 100% cis and syndiotactic.
So now you have the cis isotactic one and now you have the cis syndiotactic one.
You could hydrogenate them both. But that still leaves you with tacticity.
So how do those polymer properties depend on tacticity.
We don’t know the answer but that was the prediction actually
and here is the actual reaction using a fairly boring substitute, norbornediene.
But that’s just our test molecule.
So greater than 99% syndiotactic and cis.
Now in the isotactic polymer, here is an illustration of how different those 2 can be.
This is not hydrogenated but in the one that’s up there now.
The glass... Well, this is the isotactic version.
The glass transition is 115 degrees centigrade.
That’s where the polymer begins to move.
And we couldn’t see a glass transition for this one.
This is syndiotactic up to 250 degrees.
So our glass transition difference of at least roughly 135 degrees is a significant difference.
Now, this illustrates some of the games you can play now in polymer chemistry, in ROMP polymer chemistry.
So, I realise that if the chirality at the metal is switching from one to another
and you had a racemic, chiral but racemic substrate, then it’s possible that this metal would take one of the enantiomers,
one of the enantiomers of the metal would take one enantiomers of the substrate.
The chirality at the metal would change and then it would have to take the other enantiomer of the substrate
if that diastereomeric pair was the lowest energy transition state and so forth.
And that turns out to be true.
So what happens, you get a with this monomer racemic, dicarbomethoxynorbornene a cis syndiotactic.
But then this is one enantiomer and that’s the other one.
And this one and this one are the same.
So it’s cis syndiotactic alternating.
So monomers are alternating. That’s a pretty rare thing.
I could find no other example in the literature.
Maybe someone could tell me one.
But that’s very rare. So we’re controlling these structures very closely.
One thing that happens when you make very regular structures is that, well, they’re just single molecules like everything else.
They just happen to have 100 monomers in them and 15,000 molecular weight and the NMR spectra are uncommonly sharp.
Just simple proton NMR spectra because the environments of these 2 protons are different
but they’re on the same double bond, the same here.
So you get 2 nice olefinic signals here. There’s a little bit of something there.
And there’s something in there which is actually a trans isotactic component,
the alternative structure that I don’t have time to talk about today.
You can see how nice this reaction can be.
Here’s another racemic monomer and here’s this catalyst that makes this syndiotactic.
And it’s alternating, those 2 are alternating enantiomers.
And if you run the proton NMR spectrum you see these 3 protons.
There’s nothing else there. So this is essentially 100%. I’ll go over this.
And just mention, well, I don’t know which is more important here since I’m running out of time.
I should mention... I’ll skip over that slide.
I should mention that oxo alkylidines are probably the components of classical catalysts.
And so we wanted to get closer to classical catalysts, oxo in particular.
That’s where the high oxidation state chemistry started, with oxo alkylidine, bisphosphine dichlorides.
We showed for the first time these could be used as real metathesis catalysts.
But then we thought that you really couldn’t do any of this chemistry with oxo
because it’s too small to prevent bimolecular decomposition.
So we went to these big amido groups.
I don’t know if that’s true, now that we can really manipulate and play with large ligands.
For example here’s a hexamethyl terephine oxide, dimethylpyrrolide,
molybdenum alkylidine oxophosphine complex made from that previous species.
That’s about 60% associated. That comes off at 20millimol.
So we’re essentially dealing with this 4 coordinate core as you have to be to do these reactions.
It’s very good for making Z products very selectively, greater than 99% Z.
You don’t see any of the E, mainly because of the difference between the big phenoxide here and the oxo is so great.
Everything points towards the oxo.
The metallocycles that we’ve seen are not the TBPs.
There are the square pyramids.
There’s some interesting things going on with bis phenoxy, yeah big phenoxides like this.
You can even make an oxo methylidine, the most unstable of the alkylidines.
So that’s telling us that, yeah, we can control these intermolecular reactions
and I think also intramolecular reactions and control this chemistry.
One thing we’d like to do is see what kind of Lewis acid adducts we can make.
And here’s one perfloratriphenylborone.
You take the phosphine out with one equivalent,
you bind to the oxo because it’s a Lewis base and it’s accessible unlike the amido groups.
And you can make an adduct and here’s the structure.
And that’s going to dramatically change what these molecules do.
So that’s what we’re interested in, organic chemistry.
I don’t have time to talk about but you can make fancy molecules with cis double bonds in them.
And you can do some fancy couplings making precursors to carbon-carbon bond coupling substrates.
So you can very nicely do this cross coupling with a Bpin and make a precursor then through carbon-carbon bond coupling.
It’s something called combretastatin A4.
This is an anti-tumour agent and it has to be Z.
That’s fixed in our reaction because it’s 10,000 times more reactive in preventing, killing tumours than the E version.
So with that, I just want to leave by pointing out that these are the 4 metals, molybdenum, tungsten, rhenium, ruthenium
which you’ll hear about soon.
And these are the production per year in 2009.
And these are the approximate costs in 2011 per kilogram. And these metals are rare.
And so that doesn’t mean they won’t be used for catalysis forever.
Iridium is used, platinum is used, certainly rhodium.
But those turnovers better be high.
And I don’t know if we’re ever going to get there to a million for example in turnovers. But it’s possible.
Otherwise we’re going to have to use something that’s a little more affordable.
So that’s my story. So here’s what is going to lie ahead.
Probably don’t have time to read all that.
But I’ll stop there and just point out the people who have provided money over the years and still do.
I have a small group now, 6 or 7 and these are the people who have done the most work recently that I’ve talked about.
So thank you very much.
Applause.