Magical Power of d-block Transition Metals as Exemplified by Catalytic Highly Asymmetric C-C Bond Formation
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Lindau Nobel Laureate Meetings283 / 340
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00:00
NobeliumChemistryChemical engineeringChemistryLecture/Conference
00:33
NobeliumMetalPotenz <Homöopathie>Transition metalCarbon dioxideReducing agentWalkingAzo couplingProcess (computing)IceMetalPlant breedingMDMATransition metalComputer animationLecture/ConferenceMeeting/Interview
02:21
Potenz <Homöopathie>MetalTransition metalNobeliumAlkaneAcylAlkyneOrganische VerbindungenÜbergangszustandIonenbindungChemical compoundBlock (periodic table)Transition metalComputer animationLecture/Conference
02:59
Transition metalMetalPotenz <Homöopathie>NobeliumAlkaneAlkyneAcylWursthülleChemical elementPalladiumElectronegativitySolutionNickelAzo couplingMetalOxycodonFlocculationProcess (computing)Phase (waves)StratotypLecture/ConferenceMeeting/Interview
04:31
AlkaneAcylPotenz <Homöopathie>MetalTransition metalAlkyneMetalAddition reactionPalladiumNickelHalogenFunctional groupStratotypAzo couplingLecture/Conference
05:05
NobeliumPotenz <Homöopathie>MetalTransition metalColumbia RecordsAlkaneAcylAlkyneWursthülleFunctional groupProlineThermoformingKupplungsreaktionMeeting/InterviewLecture/Conference
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Green chemistryMetalTransition metalChemical elementChemical compoundOrganische VerbindungenAzo couplingPlant breedingOrganische VerbindungenChemical compoundYield (engineering)WaterfallLecture/ConferenceMeeting/InterviewComputer animation
07:27
Chemical compoundOrganische VerbindungenGreen chemistryMetalTransition metalChemical elementLecture/ConferenceComputer animationMeeting/Interview
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11:23
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12:15
NobeliumPeriodic acidOrganische VerbindungenÜbergangszustandOrganische VerbindungenHydrierungAddition reactionMeeting/InterviewComputer animationLecture/Conference
12:55
NobeliumFlameLecture/ConferenceMeeting/Interview
13:29
MetalPlant breedingAzo couplingGrignard-ReaktionSong of SongsMan pageChemical elementValence (chemistry)Tidal raceEpidermal growth factorLecture/ConferenceMeeting/Interview
14:15
NobeliumMetalBeerAzo couplingPlant breedingGrignard-ReaktionAlcopopMixing (process engineering)Motion (physics)FireHalideOrganische VerbindungenFunctional groupMeeting/InterviewComputer animation
14:54
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15:22
Chemical bondPlant breedingAzo couplingElimination reactionNobeliumMetalMaskierung <Chemie>DistortionCHARGE syndromeElektrostatische WechselwirkungElectron donorElektronenakzeptorMultiprotein complexDewar benzeneAtomic orbitalIonenbindungSynergyFunctional groupBlock (periodic table)Transition metalGemstoneBase (chemistry)Process (computing)RedoxReduction potentialGesundheitsstörungZellmigrationKreuzmetatheseAlkeneKlinisches ExperimentBase (chemistry)AreaNickelMetalPolymerReducing agentBronzeElimination reactionMethylgruppeZellmigrationPalladiumGesundheitsstörungÜbergangszustandHydrogenMetastasisWalkingChemical compoundOrgan donationBlock (periodic table)PeriodateIceAzo couplingFarmerOperonFunctional groupWursthülleIonenbindungRapidController (control theory)SpeciesPipetteAtomic orbitalSong of SongsProcess (computing)Mixing (process engineering)Sea levelSmoking (cooking)Plant breedingBoronCarbon (fiber)KoordinationspolymerisationHydroborierungHydro TasmaniaZirkonTransition metalHeteroatomCarbokationElectronCombine harvesterChemische SynthesePharmacyDegree of polymerizationAlkeneMolekülorbitalPlatinLecture/ConferenceComputer animation
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Crown etherTetrahydrofuranAzo couplingKoordinationspolymerisationPolyolefinAcidCan (band)Dipol <1,3->Action potentialTuberculosisPermacultureFood additiveYield (engineering)Functional groupAlkeneElektronentransferEtherAldehydeDimethylformamidTrimethylsilylPlant breedingLipasenAcetylationZunderbeständigkeitPheromoneExon-Exon-Junction-ComplexStereochemistryChemical structureYield (engineering)ZirkoniumCarcinoma in situIonenbindungMoleculeWater purificationAluminiumProcess (computing)PolyolefinWursthülleTool steelWalkingSense DistrictDoppelbindungThermoformingChemical compoundHydrophobic effectGrowth mediumPolymerSystemic therapyKohlenhydratchemieHope, ArkansasComputer animationLecture/Conference
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Chiralität <Chemie>Nobelium
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NobeliumComputer animation
Transcript: English(auto-generated)
00:14
So, when I graduated from college, I joined the company and then realized that our company,
00:28
the industrial organizations, need a new kind of technology, chemical technology, a new reaction. And I came up with a list of 10, but at the top was a CO2 reduction,
00:49
which I have not done so far yet, but I have been doing my mind. Okay, and a couple of few steps down, I suggested cross coupling, just R1 metal, where R1 is a minus
01:19
and plus R2X, X is a halogen, and then R2 is effectively plus. And then by mixing these two,
01:29
in other words, the cross coupling, we should be able to prepare R1 tied to R2. I made some attempts without catalyst, and I learned that it is one of the worst
01:47
kind of reaction. And indeed, we even learned that these reactions are known, but most of the time they don't do the right thing, so we should stay away from them. But
02:01
I wonder. And the timing was probably about right. And with the incorporation of transition metal catalysis, a bunch of us, including myself, I may have presented the extensive results, 1976, that may have been the earliest one. But anyway,
02:24
so that's what I want to talk about. De-block transition metals as catalyst for organic reactions or organic synthesis. Okay, so what we have done is summarized here. And on the left,
02:45
I was just talking about, so many organic compounds can be represented by this thing with a carbon-carbon bond somewhere. You can have as many as you want, but we want to take care of the simplest case with one bond like that. How to
03:07
synthesize this one? If you chop this thing, then you get R1 and R2, and then these are much more readily available than these in many cases. Okay,
03:20
if we put X electronegative elements like this halogens or trifluoxine, then R1 will be charged positive. R1 plus. On the other hand, if you put metal here, then R2 will be negative, R2 minus.
03:41
So by mixing these two, we should be able to expect that these two will cross couple. With this naive notion in mind, I started our series at Syracuse University when I was an assistant professor in the early 1970s. Everything failed. Most everything failed.
04:07
And I kept wondering, what's wrong? Well, what was missing is this catalyst. Eventually, we landed on nickel first, but palladium turned out to be a good solution for me anyway.
04:25
So here we have palladium containing catalyst. This can undergo so-called oxidative addition reaction, so I don't go through this one in detail. And then here, these two can exchange
04:45
metal and halogen. So in other words, R2 goes here, X goes here, and that will drive actually some thermodynamic driving force. Okay, at this point, metal such as nickel or palladium
05:02
grabs these two groups, and then they bang each other, and then they cross couple, because this is thermodynamically more favorable in many cases, at just this point, this segment. And then this can recycle, and then can go on and on. So I had this plan first,
05:27
and then at the Syracuse University in 1976, Dr. Baba Magroub, with ample experience with palladium, he called me when I was playing with Professor Brown,
05:46
Charlie Brown in California, IBM Research Center, and he said, we got it by phone. So I asked, what? Well, you know that thing. He was so excited,
06:04
he couldn't describe over the phone, but that was how we discovered in 1976 cross coupling reactions. And believe me, many others followed. Okay, so
06:25
when I received the Nobel Prize, Japanese government agencies called me, and they asked me, what should we do? What should we be doing? So I gave them a list of 10 items. At the top of
06:45
the list, I put CO2 reduction, which we were hearing, and considerable progress had been made, but for some reason, I couldn't do many good things. But second, I said nanoscale material
07:06
development investigation. In the third position, I put this cross coupling, including cross coupling, to synthesize any organic compounds in high yield
07:24
efficiencies, selectivity, economy, and safety. If you read this one, Y, and this one, E, this one, S, Y, E, S. I forgot who the presidential candidate was. Anyway, I think Jack Kennedy.
07:48
Yes, yes, Obama. So I got this Y, E, S. I have never found a second Y word.
08:03
Just feed me if you have one, a good one. So mine is still Y, E, S, E, S. Yes, S. So we are still trying to go forward, but anyway, I have to rush.
08:24
So is this the one? This thing doesn't want to, huh? Hmm. In problem. Oh, this one.
08:40
So eventually, I came to the conclusion that we should learn, first of all, the periodic table will, because that refine, that's like a world map or something. We cannot go, well, we can go to the moon or something, but this is our playground stage. Okay. And I studied in my own
09:13
way, and I have noted that there are a fair number of radioactive elements, and I didn't want
09:23
to confront with these radioactivity issues, but here and there, you can see, so I have eliminated, deleted them, or put them aside, and there are some intrinsically toxic elements, no matter how you use them. Beryllium is one of them. Cadmium. Mercury is also dangerous.
09:47
You may see it in a thermometer, that's okay, but okay, I have to rush. My clock is telling me. So I have put aside all these. Then I realized that avoiding all
10:06
these things, F block transition metals, they are, many of them are radioactive and so on. We still have, we still have a fair number of green ones. Of course, these are what I would
10:25
call organic kinds of element. In other words, your desired products contains many of these. Not all of them all the time. So we must use them and we must have them. But beyond that,
10:45
blue ones, blue ones are so-called main groove metals. They can be used. They are, many of them are sufficiently cheap and they're sufficiently safe. So I put them, I painted them blue.
11:05
But then, okay, avoiding these toxic, intrinsically toxic ones or intrinsically inert ones. We had these, but then I kept looking at this part and they look very attractive as you know.
11:24
This gold, platinum and so on. Very attractive, but they are very expensive. So I kept looking at it, kept looking at them, looking at them. Then I realized that
11:43
pollution control device people already, a couple of centuries ahead of me, they decided to use the And of course, we all are asked to use. If you don't follow the rule, then you may be put in jail
12:05
or something like that in the worst situations. So I became very, very serious. And then eventually I concluded that these are the ones, so-called
12:21
de Broglie transition metals, that they can substantially revamp the traditional synthetic organic chemistry. Of course, catalytic hydrogenation and a few others are known. So that was my starting point. And
12:44
to the extent that we use effectively, there is still a lot of additional room for exploiting them in organic synthesis. Well, and so this is in
13:11
St. Andrews. I always get confused. Not St. Andrews, but St. Petersburg.
13:26
Moskovsky Avenue. So these names get confused. So the person who is seated is Mendeleev, as you can imagine. And then he increased the number of elements known and
13:50
identified and so on from about 80 to 90. And now 100, 10, 120. But single person
14:03
discovered 11 elements. That's about 10% of the universe, 10% of the whole periodic table. So he's my forever, he's my hero. But if you have a chance to visit St. Petersburg, I urge you to stop by this place. And then there's a museum right by. Anyway.
14:26
Okay. So my first notion was to mix, prepare and mix organometals R1M and then
14:41
halide or other electrophiles R2X. Without the catalyst, the results I got is shown here. Looks bright, but miserable. Almost completely useless. So by and large, organic groups R1 and R2
15:03
can be classified into about close to 10 categories here and same thing or nearly the same thing here. And we tried randomly many, many, many combinations and hardly anything would work without the catalyst. And then we decided to resort to catalyst without knowing what they are
15:33
and how to do it and so on in the main, but by trial and error and so on. And then we learn
15:41
quickly and we are the first to come up with this kind of cross coupling results. So the key is the use of palladium. Well, as we were struggling, nickel came to the scene.
16:00
So we tried nickel and nickel worked, but already nickel was sufficiently developed by Professor Tamau of Kyoto University. So we decided not to pursue, but of course, below nickel in the periodic table, we have palladium and platinum. We screened them all and out came
16:23
palladium as a real winner, because look at this thing. Without a catalyst, the whole chart will look like all red like this one, but with a palladium catalyst, we can convert all those red
16:42
areas where there is this somewhat questionable recolored thing. And then there is a no-no area here and I don't go into the details, but we converted the mostly fading areas into
17:02
successfully usable areas. And here I'd like to briefly explain. Today I don't talk about all the details, but the key question is why metals? So if you learn a little bit about
17:21
this molecular orbital theory and so on, then with the two bonds here, CH bond, two electron, sorry, two electron bond, and then pi, most reactive part must be pi bond. Pi bond with the two electrons, and if you mix these two, really no fast side
17:45
reaction is observed. But we all know, we all learn that if you convert this 80 electron species to six electron species with empty orbital, carbocation, then they react very rapidly,
18:01
but these reactions tend to be very wild, uncontrolled. So not very useful in many, many other cases. But then my notion, my successful notion came when I noticed this isoelectronic relationship between carbocations and boron. So I was trained as a boron chemist
18:27
in H.C. Brown's group. So, okay, let's, well, this just shows why hydroboration goes so well cleanly, selectively, and so on. Then came hydro zirconation and others. So these results
18:45
convinced me the combination of this empty and the field non-bonding orbital, that of course is needed, but we may need to clean them up. Okay, so,
19:12
and then eventually I realized that we should use d-block transition metals. And, well,
19:25
so I was extensively reading Dewar's and Fukui's and Woodward Hoffman's rule and so on. So here it is. Here is an alkene. Here is an
19:42
empty orbital containing a d-block transition metal. And here you can see two electrons inside can go up, can be fed this way, and in turn then metals can provide two electrons
20:01
back to the other. This action, I think, is a critically important one. With this notion, you can understand why Brown's hydroboration, alkene hydroboron here, hydroboration can work well and selectively. And then later we win others, of course, you know, I should say others.
20:28
In a very, very simple way, mechanistic way, carbon metallation reactions can be done. And if this continues, that's a polymerization reaction. And so if hydrogen can be placed here,
20:44
carbon can be placed here, then I thought all kinds of metals and all kinds of heteroatoms should also be placed here. This is my way of thinking. And two up, two down. So we have discovered and developed many kinds of reactions based on this simply simple principle.
21:07
Okay. So, but among them, I was particularly attracted by d-block transition metal. And I don't have any reaction to discuss in detail. But, and then I have noted that these
21:31
are the kinds of basic reaction, reductive elimination shown here. And they work very well with d-block transition metals, such as nickel and palladium. And our choice,
21:45
after screening 20 or more d-block transition metals, came palladium. You know, palladium emerged as our choice. So I call this a Lego game way of synthesizing organic compounds.
22:03
And then we kept exploring further, and out emerged a very well known reaction, carbon metallation. Very well known because sigma-nata reaction, polymerization reaction, may be represented by this, so carbon metallation. But that's not what we really wanted,
22:29
because that's a polymerization reaction. But we can control the degree of polymerization. Then we can achieve, convert this or these, allokines and allokines into these compounds.
22:42
They turned out to be very, very useful. And very briefly, migratory insertion reactions and metastasis reaction can also be represented by this. So this way, we were clearly the first to come up with wide range of cross coupling reactions,
23:07
as these numbers indicate. But other people got so much interested in it. Especially these people, as you can see, within a few years, they came up with their version,
23:27
but most of them are actually originally our version, with boron.
23:45
With this reaction, cross coupling, we can synthesize all kinds, maybe that's overstatement, wide variety of organic compounds, in high yield and selectively.
24:06
Actually, during the course, or even before our involvement, Professor Tamao's group was developing this nickel-based version. But we went through this, and we kept
24:23
comparing, and the palladium turned out to be our choice, and then probably everybody's choice. So in terms of not so much in yield, but in terms of selectivity, look at this thing, 95% selectivity. This is essentially very close to 100% selectivity. So if you want to
24:51
and then come up with this kind of reagent, sorry, this kind of reagent here, and then this kind of reagent here. And then in the presence of palladium catalyst,
25:06
you can hook them up. That was my Nobel winning chemistry. And then I have to very, very quickly, it can be applied to many, many cases, many, many patterns.
25:23
So here you can see high yield and high turnover number. So here some of them are million or higher. So if your catalyst cost a million bucks, sorry, million dollars
25:43
per mole, if reaction turns over a million times, it's, sorry, I tell my students, buck a mole. Okay, not only that, with this kind of method, use knowing a little bit of
26:06
synthetic analysis and so on. You can tackle any kind of molecule. Look at this, very, very challenging, but we have done that. So I'm just showing this part of the synthesis.
26:25
That was the most challenging and difficult part. So this part was synthesized in mere eight steps from this and overall yield is almost 30%. So that was published just a few,
26:42
several years ago. So you might take a look at them if you're interested in, but the key processes is hooking these two parts using palladium as a catalyst. Nickel works, but nowhere near as good as and then for synthesis of molecule like this,
27:06
it's not acceptable. Okay, so pretty much I have done my job, I think. Where is the, so, and you can, you know, by putting these three double bonds in series like
27:29
this, and each one, if each one can be trans like this or cis like this, how many, how many do you have? Two times, two times, two times, two, that's eight of them. Okay, so let's make
27:42
eight of them to prove that you can control stereochemistry as you please, as you like. And I want you to know, you know, first overall stereoselective, overall, you know,
28:02
stereoselectivity is nearly 100%, not 100%, but you can further purify. And then yields, final coupling yields are excellent, and you can synthesize them as you wish. So we've taken care of four out of eight, fifth and sixth one, they are initially a little
28:30
more challenging because of the presence of this cis at the critical point, but turned out no problem by choosing appropriate catalyst, Pepsi, so you can remember this name.
28:49
Anyway, so with these, you know, here there is a cis double bond, this one has two cis double bonds, and they become increasingly somewhat more difficult, but not, but if you trust my numbers,
29:08
they're very, very satisfactory. So six, four gone, five, sorry, how many? Sorry, six.
29:24
Anyway, the remaining one has two cis double bonds, more cis than, and in other methods, if you have more cis double bonds, quite often,
29:41
your job becomes very, very difficult. But in this game, as you can see, purity doesn't dip down, yields somewhat, but not by much. So this has two cis double bonds, this one has three of them, and we may have quit. Yeah, that's what we have done.
30:06
So in view of time, I'll just show you the kinds of molecule. This is a CoQ10, many of you must be taking CoQ10 pills, I am also taking, without knowing the structure.
30:22
Now I know it is this. So there are actually one, two, three, four, five, six, seven, eight, nine of them stereo defined, and of course TENS1 doesn't have a stereochemistry. So these things can be synthesized in a very, very efficient way.
30:44
Oops, back. Okay, so now, can we, somewhat related to previous talk, can we possibly synthesize these natural polyolefins by sigma-nata polymerization?
31:06
Well, so we like to be able to synthesize these kinds of reasonably short, reasonably long oligomers, but in a very highly pure way. Of course, nature does it, but prior to
31:30
our work here, it was considered to be nearly impossible, and we needed to develop a new reaction. But in view of time, I'll just show, we also developed a reaction which is a one-step
31:47
sigma-nata reaction. In other words, this double bond, we treat this with zirconium containing aluminum compounds, and then R2 goes here, and aluminum goes here. I call this a
32:04
one-step sigma-nata reaction. So we can synthesize all these things. And so, okay, this one. And then once you do that, once you get this thing, then you feed this to
32:25
cross-coupling, which we have developed, and you form this bond here. And what is quite amazing is that yield-wise and selectivity-wise,
32:43
before, you know, extensive purification, actually no extensive purification necessary, these products are formed in a very highly selective way. In essentially all cases,
33:01
probably over 90%, but sometimes over 95% or beyond even. Okay, so let me just complete with something like this. So you have, if you see this kind of molecule with
33:20
stereochemistry here, before us, probably people really struggled to synthesize, but we synthesized this compound in mere five or six steps, maybe? Is this six or five? Five steps, I cannot read it. In overall yield of 34% and isomeric purity of 98% or higher.
33:55
Unprecedented, in my opinion, and rather recently. So as you can imagine,
34:01
you can synthesize all kinds of sugar kinds of molecules or you know, isoprenoid natural products. And I just point out that you can obtain the desired product
34:29
after a little chromatography, as greater than 99%, 99% or 99% pure compound. Of course,
34:41
if you wanted to purify further, you can do that, but you also want to maintain the overall yield at a reasonable level and more. So just to please my, yeah.
35:01
One minute. Okay. Am I going back? How did I go back? Well, thank you very much.