Introduction to Organometallic Chemistry

so uh ladies and gentlemen uh welcome to the lecture organic synthesis 1 stric Organo metallics and of course a special welcome to Sandra and the rcast team who will um uh video cast uh the lecture throughout the whole semester so this lecture is the first part and the second part with the title catalytic Organo metalics is scheduled for the summer semester so now to chometric organometallics when we have a look at the periodic system of elements and unfortunately in this lecture hole there is no one uh well then we notice an awful lot of metals and you might get the impression that it could be some kind of nightmare if you have to choose a metal for your purposes for your synthesis on the other hand the awful lot of metals offers us the opportunity to find a suitable one and indeed yeah for well almost any given synthetic problems involving Organo metallics you will find some organometallics reagents with the um correct properties you need and moreover you have the uh opportunity to trigger the reactivity by adding further ligans but this is of course more used uh in terms of uh catalytic Organo metallics so but um the the uh possibilities which are imminent in organometallic synthesis makes that so uh successful first example so we have an alic Organo metallic species two substituents here and we let that react with carbon dioxide and after hydrolysis we will obtain either this carboxilic acid or the one with the quinary center if the metal is potassium and Al pottassium species we will get a product ratio of 90 to 10 so let's change the metal to a grar re agent in that case it was found that it will result in a one to 99 ratio well somehow this is a rather strange result why clearly the Organo potassium potassium compound is much more reactive than a green greenia reagent nevertheless the more reactive reagent leads to the thermodynamically more stable product clearly with the grinia reagent 99% of the thermodynamically less stable product means this reaction to that product is clearly kinetically controlled we can explain that we have a closer look to the structures that are involved in case of the potassium species we have a potassium that is called ordinated to the alic an i well it is an extremely polar bond it is a pi complex actually it is a tripto p complex because the potassium is B found to the three centers coordinated to the three centers we can also call it an ata3 complex this is a usual abbreviation for that case so highly reactive system and now it is clear that at that terminal carbon we has we have um well A Minor St hindrance compared to this Center and therefore it is clear that the CO2 can more easily attack at that Center resulting finally in this also thermodynamically more stable Compound on the other hand the grard reagent in this case the Magnesium is more covalently bound to the terminal position in this case it is an ater one complex or a sigma complex in contrast to the pi complex in that case we have the mag with the Magnesium the electrophilic center magnesium is as you know a Louis acid while in greenia reagent usually ether molecules are coordinated to the magnesium but in equilibrium an ether molecule pops off giving three that coordination site and then the CO2 coordinates to the magnesium and through a six membered transition state the CC bond is formed well and this is of course the magnesium carboxilate and after acidic hydrolysis we have the final product so this example makes uh clear that it is indeed useful to choose between different metals because we have clearly uh different selectivities Al the corresponding Al lithium species is in this case similar now it's it's in between between potassium and the grar whereas the AL zinc behaves in this case at least similar to the grinia agent so a basic concept which is regarded to be rather useful in choosing the right reagents for for synthesis uh you know already is the hsab concept concept or hsab uh principle and the name the abbreviation derives from heart soft acid base principle it was introduced in uh the early 1960s by Pearson as an extension of the Louis acid base concept so Lis as you know defines acids as electron pair acceptors well you can use the Expression electrophile as a synonym and a l base is than of course an electron pair donator or you can use also word nucleophile now to Pearson's extension he differentiates between hard acids soft acids and well there is of course something in between medium or B line acids and he introduced the same differentiation to the Louis basis again hard medium and soft so how did he characterize the expression heart so a hard Louise acid is generally small has a high charge density and is weakly polarizable or I would say hardly polarizable so on soft uh simply is the opposite yeah so okay let's draw that to the Blackboard soft big low charge density and uh strongly polarizable or I think this becomes more clear if we put on some some uh examples for instance an a heart acid so what is really small has a high charge density and is weakly polarizable the record holder of course is a proton that's it yeah so H+ in this category we have also lithium plus could see also magnesium 2+ and iron 3+ soft while Metals in the oxidation state zero can we nevertheless Lis acids but are rather soft ruis acids nickel plus but also padium 2 of a silver C ion and medium well there we have then iron 2+ zinc 2+ and copper 2+ is also regarded as medium now to the basis fluide the fluoride and ion is the Prototype of a hard base Hydrox and ion is also a hard base although relatively a bit more soft than floid than Amon ammonium ammonia NH3 well a hard base we have a free electron pair and we have an element there with a high electro negativity nevertheless it is basic it is more basic than that that means this is more nucle philic than than that yeah so all those are regarded to be relatively hard Al although of course NH3 is more soft than a fluid and also here in this category alcoholates medium bromite somewhere here also chloride I had forgotten and soft clearly the iodide a big an or conjugated an ions enolate conjugated systems are big systems strongly polarizable should be regarded as soft Lis acids or soft nucleophiles thiolates phosphines hydrides are in this category and what is rather important for us in this lecture organometallic reagents alul or ar and ions that means Al metal species so now to the core statement of the hard soft asset base principle I will write down that core statement soft acids react faster and form stronger bonds with soft bases whereas hard acids while react faster and form stronger bonds with hard bases okay so what is the explanation a hard hard interaction what could it be well for instance a lithium plus and an F minus reaction of a lithium plus and an F minus would be driven by the electrostatic charge okay so um hard hard interaction is charge controlled and uh two centers with opposite charge of an high density will react rather fast with each other if we put aside salvation effects of course on the other hand soft soft interaction according to this principle is also favored this is regarded to be controlled by Frontier orbital interaction well the first one is easy to understand the second one you have to think a bit about that so for instance um a soft and Ion with a soft an iron we have to look at the energy level of the highest occupied molecular orbital the soft and iron has the homo on a relatively high energy level this I think is easy to understand just take into account the opposite a fluoride electr negative it uh holds to its uh electron pairs the electron pairs of the fluoride are on a low energy level that means with a soft an iron it has to be the opposite okay uh a soft a soft leis acid or cut IR omo energy level are a low relatively low no relatively high energy level relatively high with a cat iron we have to take a look at the lowest onacup molecular orbital this is of course uh the frontier orbital and in this case the lumo is the energy level of the lumo is relatively low well for instance as an example the alic Caton alic Caton uh well rather well medium or relatively big uh electron system compared to an H Plus or lithium plus it is conjugated it is polarizable so the alic cat ion is a prototype of a soft cat ion and because of the conjugation you have the lumo in a relatively low energy level you could easily put on an electron forming an alic radical okay so and the homo on a relatively high level the lumo of the Louis acid on a rather low level that means they have almost the same energy level and then it's easy to transform electron density It just fits forming than of course um uh rather stable covalent uh bonds and it's a rather fast reaction so this model here is called or known as the kopman zalm concept okay at this point let us go back to this core statement once again soft acids react faster and form stronger bonds with soft bases the expression reacts faster of course addresses the kinetics of a reaction and form stronger bonds this expression addresses addresses the thermodynamics so I think this sounds great if the hard soft as it base Concept in we have the impression that uh we both we we we address both kinetics and thermodynamics all this is of course not true kinetics and thermodynamics are clearly neglected within the hard soft acid base uh concept we just don't defer differentiate between kinetics and thermodynamics and uh well this is clearly an over simplification and that's the reason why a lot of chemists are not in favor of heart soft asset base concept and I think the best review article criticizing this uh concept was uh published about two years ago by Herbert Meer from the LMU in Munich and it was uh published in an shimi international Edition 2011 on page 6470 and it's about 3 35 pages long and the article has the interesting title farewell to the hsab treatment of ambident reactivity well very interesting article and he is right in a lot of uh points however if you use the hsab concept as some kind of qualitative guid line as some kind of rule of thump it will help a lot and still makes sense so it's time for some examples an AEL cat ion of course highly electrophilic electrophilic a hard electrophile so a hypothetic reaction with a hard base let's have a look for a hard base heart base we have for instance an alcoholate should result in an aster and we all know an aster is a rather stable compound of course not alone based on the hard soft interaction but it has something to do with a conjugated system there yeah so but let's check does the hard soft ASD based principle the Pearson principle work out in uh similar cases if we add a soft base for instance an iodite or a thiolate well what do we get then a carboxilic acid iodite or such a tho Aster well you can handle those iodides no problem but that both compounds are far more reactive against hydrolysis with uh water for instance now an interesting argument is what about the fluoride fluoride is clearly a hard base harder than the alcoholate and in that case we should discuss the stability of the carboxilic acid fluoride well looks a bit suspicious to all of us and it was also a surprise for me to find that carboxilic acid fluorides are more stable against hydrolysis as car carboxilic acid chlorides chlorides so acidic acid fluoride is more stable against uh the interaction with water hydrolysis as acidic acid chloride okay then carboxilic acid chlorides well next type of reaction a n trial a n trial is regarded to be an hard electrophile so heart Louis acid at the car carbon Center and a hard Louis base the fre electron pair at the nitrogen plus hydrogen fluid with the hard base fluide here will react in an addition process and gives this aminium no uh this uh Ean of an carboxilic acid fluoride which of course will react with additional HF to form the aminium salt so again the concept Works heart acid heart base also the other way round heart acid the proton and heart base here the nitrogen the addition reaction Works try that with hydrogen iodide and it won't work so now to a bit more interesting examples carbony compounds the oxygen hard base for carbon is regarded to be a hard acid here we have a substrate which has alide functionality and a tosilate within the same molecule this carbon a hard electrophile this carbon with the tosilate leaving group is also an electrophile also regarded to be rather hard electrophile although somehow softer than that yeah so softer not soft softer than this position here we have a tho phenolate thiolates are soft nucleophiles especially if conjugated to uh an aromatic system so this is soft and on the other hand a cyanide as a relatively hard H well both are soft both are soft systems but this is of course harder than that or this softer than that so both soft but this is relatively hard compared to the thiolate and indeed that thiolate selectively reacts with the softer position simply a nucleophilic substitution as an as in two process with the thionite a completely different pathway reaction pathway is observed it detects the harder Electro philic Center so that means we get this intermediate and now an intr molecular sn2 process is observed with uh the alcoholate as the nucleophilic center and that carbon as the the electrophilic center resulting in this product so enolates as ambident ambident nucleophiles enolates with the two misic structures of course the oxygen is the heart nucleophilic center and the carbon is the soft nucleophilic centers that mean means the artsoft ASD base concept suggests that hard electrophiles should form a bond to the oxygen and soft electrophiles should form a bond to the carbon so is that true as it turned out it is somewhat an over interpretation of the heart soft acid base concept because we enolate of cyoh hexone plus bromo methane in the gas phase has been tested to give exclusively the O alation product although the methyl the bromomethane is regarded to be rather um soft this is somewhat contradictionary uh to what we expect from the hardsoft ASD base concept another example is lithium enolates have been shown by the famous daa zeach from sirish University who invented uh reactivates of reactivity he found that under the ri reaction conditions lithium enolates with eil chlorides in thf at low temperature - 100° to - 80° react under CC Bond formation also contradictionary to what we expect from the from the uh Pearson concept um and indeed there are numerous examples known where normally the isolation takes a place uh at the oxygen can easily form that it depends on the reaction conditions so um this is contradictionary or it has gives the impression but it's contradictionary to the uh hardsoft ASD base principle but as I said predicting this is soft and therefore it has to react here is an over interpretation of it you can use it as a rule of thump if you make for instance a test reaction and you find with a bromite you have a certain uh um product ratio with the hardsoft acid base principle you can then predict how the product ratio will change if you change from the bromide to the chloride to the iodide or to the toate so you need one um experimental result to um yeah well to make a um prediction based on the H uh hsab concept and this can be very useful we will see that in a couple of more examples a sodium enolate with atile compound and X is a leaving group would anticipate two products well here this and trans maybe the O alation product and the calculation product so let's form a table with percentage of O alation and it depends very much on the solvent which is used hmpt as a solvent hexamethyl phosphoric acid triamide first with uh the iodite just 15% o culation with a bromite we have more 40% ulation the chloride butil chloride is more hard electrophile than the bromite so we should get even more oh alation and indeed it turns out to be right 67% the toate 85 and then let's go to the fluoride 96% o ulation the fluide B fluide flane one flu Bane is uh the hardest electrophile here so it gives indeed the best yield of the ulation product the best percentage right something wrong okay it's okay good um well let's change to DMSO W 10% 23% 46% well here we have 44% and the fluoride has not been tested generally lower percentage of O alation but hmpt and DMSO both are rather polar solvents similar but this is much more polar let's go to a far less polar solvent di ether just 1% of o ulation in the case of the iodite then five with a bromide 18 18% with a chloride and philate 20% so and uh well okay this means 80% it's not the lower yield it's then 80% of uh the calculation generally we can say that if we have dissociated dissociated enolates naked isolate enolates separated from the counter cut Iron by the solvent which is indeed the case in hmpt and similarly in DMSO and maybe a bit also in DMF then we have a high oxygen carbon ratio if you have ion pairs well then we will get an intermediate result and if we have higher Aggregates as frequently obs oberved in eus as solvents then we have a low oxygen carbon ratio so that means or that shows that the solvent has indeed a tremendous influence on the outcome of the reaction however again if we have tested here the bromite gives a 23% yield of O alation and we want to increase the uh amount of O calculation well we know that uh we will get a better result if we go to to the chloride or to the tosilate but uh nevertheless we could even more influence the outcome with changing the solvant that's what we should learn from this example another interesting case is the alation of the enolate of acidic acid ACO acidic acid eser in this case the potassium enolate has been tested in the reaction with uh ethyl haloid again in hmpt in order to examine the influence of the leaving group on the ratio between O alation and C alation so X and v c ratio iodite the softest eth uh electrophile which has been tested 0.15 that means we have a far more CC Bond formation than Co Bond formation in this case bromite 0.65 we get more reaction a bit more reaction at the oxygen with a chloride we already have a turnaround more o culation than C calculation and then consequently with a talate we get a rather high amount of O calculation so uh now to organometallic species so where we have a carbon metal Bond methyl group sitting at a metal than an eal group ethyl group an isopropyl group and tasy B group those are all regarded as soft bases at a carbon Center but from the methyl species to the ter B uh species they get softer so this one is harder and this is softer simply because it is bigger and the anionic charge is uh stabilized through that molecule one example although this with this example one should be a bit careful however if we choose to let this react with methyl grineer we will get predominantly the one two addition product changing to the isopr GR will give us predominantly the 14 addition product or it's called conjugate addition product well we have in that alphabeta unsaturated uh Ketone two electrophilic centers one of the carbonal group this is the hard electrophile and this Center the conjugated one is regarded to be the soft one and while you can interpret that in terms of the heart soft assd base concept this is harder reacts here this is softer reacts there uh but maybe some uh yeah one has to in the explanation this is not certainly not a me good mechanistic explanation you should take in a mechanistic explanation uh also into account aeric hindrance steric steric interaction of course um nevertheless let's have a look at a similar reaction cyclohexanone plus tary ble lithium this clearly gives this product so and this tells us that well the structure of the carbon nucleophile is less influential than the nature of the metal lithium is harder than the Magnesium so hardeners lithium harder than a grard reagent and this is how harder than well any Cate again cyc exone first methyl lithium secondly hydrolysis will result in the alic alcohol and uh while uh coup rate for instance this one hydrolized after CC Bond formation will give the conjugate addition product until now we have um only interpreted uh this in terms of the artsoft acid base principle in focusing of the carbon Center we could also interpret it focusing on the metal lithium a lithium cat iron harder than a copper cat and therefore the lithium cat is a Lis acid coordinates preferentially at the three electron pairs of the oxygen it's already sitting there okay on the other hand the CATE might preferentially coordinate to the electron density of that double bond and indeed uh Nobert kower from our neighboring University Dortmund a couple of years ago found some interesting examples proved that with uh NMR spectroscopy that the cprit are indeed coordinating to that double bond two further examples for today more complicated ones an isolated peridine and isolated with a counter anine presumably simply a chloride so where do we have electrophilic centers here so of course this carbon is very electrophilic and this is certainly the hardest electrophilic Center here in this uh aromatic system a conjugated uh system we could write down some uh misic structures with positive charge there and there and there of course this uh um visualizes then that we have electrophilic centers here in the uh author position of a nitrogen and also in the par position these in the conjugated systems are of cuse regarded to be much softer than that yeah and uh well okay here and there we have a soft position and there this is even softer okay so reaction and between Lithium at minus 78° was found out to react exclusively almost exclusively at this carbon well this is in accord what we have already seen here with arithium species and it simply set free the purine and formed at Aster next test was done with a grineer reagent reagent and magnesium bromite also at min -78° and here we observed predominantly the reaction at the soft and softer positions what is the result in that case this and the par isomer was found in the ratio 67 to 33 of course this means there is no real discrimination between the author and the par position because we have uh the offer position twice and we per position only once it's just the ratio of one to one to one yeah and this is the result then so the Organo magnesium discriminates between the heart center and the soft centers but not between soft and softer going to uh softer Organo metallic reagent and Organo zinc Which is less reactive and they have done the reaction at higher temperature zero de and the copper uh compound Organo copper would would react similarly in that CA in this this case they achieved a r ratio of 19 to 81 that means with the less reactive Organo zinc you indeed can discriminate between the soft and the softer position and get predominantly here the reaction in the power position last example for today once again we enol enolate of 13 dicarbon compound in focus is the reaction with an Alo compound an Alo electrophile with the c alculated product as the Target first attempt simply with Al bromite gave a 30% yield of the target compound interesting is the result with an Alo acetate which is not reactive to This nucleophile Not That reactive to this nucleophile in moderate reaction conditions but adding a catalyst a padium zero catalyst then this product was isolated in a 94% yield well actually this is this is uh the so-called 2 G reaction and the padium zero Catalyst as a very soft nucleophile reacts with the alil acetate forming such an Alo padium complex and this is indeed a very very soft electr file and this gives then the high yield we will see more of these catalytic systems of course uh in in summer semester so okay I think uh we should finish for today see you tomorrow with uh remarks on uh basic reaction types in organometallic stric organometallics chemistry thanks for listening see you tomorrow

so uh ladies and gentlemen uh welcome to the lecture organic synthesis 1 stric Organo metallics and of course a special welcome to Sandra and the rcast team who will um uh video cast uh the lecture throughout the whole semester so this lecture is the first part and the second part with the title catalytic Organo metalics is scheduled for the summer semester so now to chometric organometallics when we have a look at the periodic system of elements and unfortunately in this lecture hole there is no one uh well then we notice an awful lot of metals and you might get the impression that it could be some kind of nightmare if you have to choose a metal for your purposes for your synthesis on the other hand the awful lot of metals offers us the opportunity to find a suitable one and indeed yeah for well almost any given synthetic problems involving Organo metallics you will find some organometallics reagents with the um correct properties you need and moreover you have the uh opportunity to trigger the reactivity by adding further ligans but this is of course more used uh in terms of uh catalytic Organo metallics so but um the the uh possibilities which are imminent in organometallic synthesis makes that so uh successful first example so we have an alic Organo metallic species two substituents here and we let that react with carbon dioxide and after hydrolysis we will obtain either this carboxilic acid or the one with the quinary center if the metal is potassium and Al pottassium species we will get a product ratio of 90 to 10 so let&#39;s change the metal to a grar re agent in that case it was found that it will result in a one to 99 ratio well somehow this is a rather strange result why clearly the Organo potassium potassium compound is much more reactive than a green greenia reagent nevertheless the more reactive reagent leads to the thermodynamically more stable product clearly with the grinia reagent 99% of the thermodynamically less stable product means this reaction to that product is clearly kinetically controlled we can explain that we have a closer look to the structures that are involved in case of the potassium species we have a potassium that is called ordinated to the alic an i well it is an extremely polar bond it is a pi complex actually it is a tripto p complex because the potassium is B found to the three centers coordinated to the three centers we can also call it an ata3 complex this is a usual abbreviation for that case so highly reactive system and now it is clear that at that terminal carbon we has we have um well A Minor St hindrance compared to this Center and therefore it is clear that the CO2 can more easily attack at that Center resulting finally in this also thermodynamically more stable Compound on the other hand the grard reagent in this case the Magnesium is more covalently bound to the terminal position in this case it is an ater one complex or a sigma complex in contrast to the pi complex in that case we have the mag with the Magnesium the electrophilic center magnesium is as you know a Louis acid while in greenia reagent usually ether molecules are coordinated to the magnesium but in equilibrium an ether molecule pops off giving three that coordination site and then the CO2 coordinates to the magnesium and through a six membered transition state the CC bond is formed well and this is of course the magnesium carboxilate and after acidic hydrolysis we have the final product so this example makes uh clear that it is indeed useful to choose between different metals because we have clearly uh different selectivities Al the corresponding Al lithium species is in this case similar now it&#39;s it&#39;s in between between potassium and the grar whereas the AL zinc behaves in this case at least similar to the grinia agent so a basic concept which is regarded to be rather useful in choosing the right reagents for for synthesis uh you know already is the hsab concept concept or hsab uh principle and the name the abbreviation derives from heart soft acid base principle it was introduced in uh the early 1960s by Pearson as an extension of the Louis acid base concept so Lis as you know defines acids as electron pair acceptors well you can use the Expression electrophile as a synonym and a l base is than of course an electron pair donator or you can use also word nucleophile now to Pearson&#39;s extension he differentiates between hard acids soft acids and well there is of course something in between medium or B line acids and he introduced the same differentiation to the Louis basis again hard medium and soft so how did he characterize the expression heart so a hard Louise acid is generally small has a high charge density and is weakly polarizable or I would say hardly polarizable so on soft uh simply is the opposite yeah so okay let&#39;s draw that to the Blackboard soft big low charge density and uh strongly polarizable or I think this becomes more clear if we put on some some uh examples for instance an a heart acid so what is really small has a high charge density and is weakly polarizable the record holder of course is a proton that&#39;s it yeah so H+ in this category we have also lithium plus could see also magnesium 2+ and iron 3+ soft while Metals in the oxidation state zero can we nevertheless Lis acids but are rather soft ruis acids nickel plus but also padium 2 of a silver C ion and medium well there we have then iron 2+ zinc 2+ and copper 2+ is also regarded as medium now to the basis fluide the fluoride and ion is the Prototype of a hard base Hydrox and ion is also a hard base although relatively a bit more soft than floid than Amon ammonium ammonia NH3 well a hard base we have a free electron pair and we have an element there with a high electro negativity nevertheless it is basic it is more basic than that that means this is more nucle philic than than that yeah so all those are regarded to be relatively hard Al although of course NH3 is more soft than a fluid and also here in this category alcoholates medium bromite somewhere here also chloride I had forgotten and soft clearly the iodide a big an or conjugated an ions enolate conjugated systems are big systems strongly polarizable should be regarded as soft Lis acids or soft nucleophiles thiolates phosphines hydrides are in this category and what is rather important for us in this lecture organometallic reagents alul or ar and ions that means Al metal species so now to the core statement of the hard soft asset base principle I will write down that core statement soft acids react faster and form stronger bonds with soft bases whereas hard acids while react faster and form stronger bonds with hard bases okay so what is the explanation a hard hard interaction what could it be well for instance a lithium plus and an F minus reaction of a lithium plus and an F minus would be driven by the electrostatic charge okay so um hard hard interaction is charge controlled and uh two centers with opposite charge of an high density will react rather fast with each other if we put aside salvation effects of course on the other hand soft soft interaction according to this principle is also favored this is regarded to be controlled by Frontier orbital interaction well the first one is easy to understand the second one you have to think a bit about that so for instance um a soft and Ion with a soft an iron we have to look at the energy level of the highest occupied molecular orbital the soft and iron has the homo on a relatively high energy level this I think is easy to understand just take into account the opposite a fluoride electr negative it uh holds to its uh electron pairs the electron pairs of the fluoride are on a low energy level that means with a soft an iron it has to be the opposite okay uh a soft a soft leis acid or cut IR omo energy level are a low relatively low no relatively high energy level relatively high with a cat iron we have to take a look at the lowest onacup molecular orbital this is of course uh the frontier orbital and in this case the lumo is the energy level of the lumo is relatively low well for instance as an example the alic Caton alic Caton uh well rather well medium or relatively big uh electron system compared to an H Plus or lithium plus it is conjugated it is polarizable so the alic cat ion is a prototype of a soft cat ion and because of the conjugation you have the lumo in a relatively low energy level you could easily put on an electron forming an alic radical okay so and the homo on a relatively high level the lumo of the Louis acid on a rather low level that means they have almost the same energy level and then it&#39;s easy to transform electron density It just fits forming than of course um uh rather stable covalent uh bonds and it&#39;s a rather fast reaction so this model here is called or known as the kopman zalm concept okay at this point let us go back to this core statement once again soft acids react faster and form stronger bonds with soft bases the expression reacts faster of course addresses the kinetics of a reaction and form stronger bonds this expression addresses addresses the thermodynamics so I think this sounds great if the hard soft as it base Concept in we have the impression that uh we both we we we address both kinetics and thermodynamics all this is of course not true kinetics and thermodynamics are clearly neglected within the hard soft acid base uh concept we just don&#39;t defer differentiate between kinetics and thermodynamics and uh well this is clearly an over simplification and that&#39;s the reason why a lot of chemists are not in favor of heart soft asset base concept and I think the best review article criticizing this uh concept was uh published about two years ago by Herbert Meer from the LMU in Munich and it was uh published in an shimi international Edition 2011 on page 6470 and it&#39;s about 3 35 pages long and the article has the interesting title farewell to the hsab treatment of ambident reactivity well very interesting article and he is right in a lot of uh points however if you use the hsab concept as some kind of qualitative guid line as some kind of rule of thump it will help a lot and still makes sense so it&#39;s time for some examples an AEL cat ion of course highly electrophilic electrophilic a hard electrophile so a hypothetic reaction with a hard base let&#39;s have a look for a hard base heart base we have for instance an alcoholate should result in an aster and we all know an aster is a rather stable compound of course not alone based on the hard soft interaction but it has something to do with a conjugated system there yeah so but let&#39;s check does the hard soft ASD based principle the Pearson principle work out in uh similar cases if we add a soft base for instance an iodite or a thiolate well what do we get then a carboxilic acid iodite or such a tho Aster well you can handle those iodides no problem but that both compounds are far more reactive against hydrolysis with uh water for instance now an interesting argument is what about the fluoride fluoride is clearly a hard base harder than the alcoholate and in that case we should discuss the stability of the carboxilic acid fluoride well looks a bit suspicious to all of us and it was also a surprise for me to find that carboxilic acid fluorides are more stable against hydrolysis as car carboxilic acid chlorides chlorides so acidic acid fluoride is more stable against uh the interaction with water hydrolysis as acidic acid chloride okay then carboxilic acid chlorides well next type of reaction a n trial a n trial is regarded to be an hard electrophile so heart Louis acid at the car carbon Center and a hard Louis base the fre electron pair at the nitrogen plus hydrogen fluid with the hard base fluide here will react in an addition process and gives this aminium no uh this uh Ean of an carboxilic acid fluoride which of course will react with additional HF to form the aminium salt so again the concept Works heart acid heart base also the other way round heart acid the proton and heart base here the nitrogen the addition reaction Works try that with hydrogen iodide and it won&#39;t work so now to a bit more interesting examples carbony compounds the oxygen hard base for carbon is regarded to be a hard acid here we have a substrate which has alide functionality and a tosilate within the same molecule this carbon a hard electrophile this carbon with the tosilate leaving group is also an electrophile also regarded to be rather hard electrophile although somehow softer than that yeah so softer not soft softer than this position here we have a tho phenolate thiolates are soft nucleophiles especially if conjugated to uh an aromatic system so this is soft and on the other hand a cyanide as a relatively hard H well both are soft both are soft systems but this is of course harder than that or this softer than that so both soft but this is relatively hard compared to the thiolate and indeed that thiolate selectively reacts with the softer position simply a nucleophilic substitution as an as in two process with the thionite a completely different pathway reaction pathway is observed it detects the harder Electro philic Center so that means we get this intermediate and now an intr molecular sn2 process is observed with uh the alcoholate as the nucleophilic center and that carbon as the the electrophilic center resulting in this product so enolates as ambident ambident nucleophiles enolates with the two misic structures of course the oxygen is the heart nucleophilic center and the carbon is the soft nucleophilic centers that mean means the artsoft ASD base concept suggests that hard electrophiles should form a bond to the oxygen and soft electrophiles should form a bond to the carbon so is that true as it turned out it is somewhat an over interpretation of the heart soft acid base concept because we enolate of cyoh hexone plus bromo methane in the gas phase has been tested to give exclusively the O alation product although the methyl the bromomethane is regarded to be rather um soft this is somewhat contradictionary uh to what we expect from the hardsoft ASD base concept another example is lithium enolates have been shown by the famous daa zeach from sirish University who invented uh reactivates of reactivity he found that under the ri reaction conditions lithium enolates with eil chlorides in thf at low temperature - 100° to - 80° react under CC Bond formation also contradictionary to what we expect from the from the uh Pearson concept um and indeed there are numerous examples known where normally the isolation takes a place uh at the oxygen can easily form that it depends on the reaction conditions so um this is contradictionary or it has gives the impression but it&#39;s contradictionary to the uh hardsoft ASD base principle but as I said predicting this is soft and therefore it has to react here is an over interpretation of it you can use it as a rule of thump if you make for instance a test reaction and you find with a bromite you have a certain uh um product ratio with the hardsoft acid base principle you can then predict how the product ratio will change if you change from the bromide to the chloride to the iodide or to the toate so you need one um experimental result to um yeah well to make a um prediction based on the H uh hsab concept and this can be very useful we will see that in a couple of more examples a sodium enolate with atile compound and X is a leaving group would anticipate two products well here this and trans maybe the O alation product and the calculation product so let&#39;s form a table with percentage of O alation and it depends very much on the solvent which is used hmpt as a solvent hexamethyl phosphoric acid triamide first with uh the iodite just 15% o culation with a bromite we have more 40% ulation the chloride butil chloride is more hard electrophile than the bromite so we should get even more oh alation and indeed it turns out to be right 67% the toate 85 and then let&#39;s go to the fluoride 96% o ulation the fluide B fluide flane one flu Bane is uh the hardest electrophile here so it gives indeed the best yield of the ulation product the best percentage right something wrong okay it&#39;s okay good um well let&#39;s change to DMSO W 10% 23% 46% well here we have 44% and the fluoride has not been tested generally lower percentage of O alation but hmpt and DMSO both are rather polar solvents similar but this is much more polar let&#39;s go to a far less polar solvent di ether just 1% of o ulation in the case of the iodite then five with a bromide 18 18% with a chloride and philate 20% so and uh well okay this means 80% it&#39;s not the lower yield it&#39;s then 80% of uh the calculation generally we can say that if we have dissociated dissociated enolates naked isolate enolates separated from the counter cut Iron by the solvent which is indeed the case in hmpt and similarly in DMSO and maybe a bit also in DMF then we have a high oxygen carbon ratio if you have ion pairs well then we will get an intermediate result and if we have higher Aggregates as frequently obs oberved in eus as solvents then we have a low oxygen carbon ratio so that means or that shows that the solvent has indeed a tremendous influence on the outcome of the reaction however again if we have tested here the bromite gives a 23% yield of O alation and we want to increase the uh amount of O calculation well we know that uh we will get a better result if we go to to the chloride or to the tosilate but uh nevertheless we could even more influence the outcome with changing the solvant that&#39;s what we should learn from this example another interesting case is the alation of the enolate of acidic acid ACO acidic acid eser in this case the potassium enolate has been tested in the reaction with uh ethyl haloid again in hmpt in order to examine the influence of the leaving group on the ratio between O alation and C alation so X and v c ratio iodite the softest eth uh electrophile which has been tested 0.15 that means we have a far more CC Bond formation than Co Bond formation in this case bromite 0.65 we get more reaction a bit more reaction at the oxygen with a chloride we already have a turnaround more o culation than C calculation and then consequently with a talate we get a rather high amount of O calculation so uh now to organometallic species so where we have a carbon metal Bond methyl group sitting at a metal than an eal group ethyl group an isopropyl group and tasy B group those are all regarded as soft bases at a carbon Center but from the methyl species to the ter B uh species they get softer so this one is harder and this is softer simply because it is bigger and the anionic charge is uh stabilized through that molecule one example although this with this example one should be a bit careful however if we choose to let this react with methyl grineer we will get predominantly the one two addition product changing to the isopr GR will give us predominantly the 14 addition product or it&#39;s called conjugate addition product well we have in that alphabeta unsaturated uh Ketone two electrophilic centers one of the carbonal group this is the hard electrophile and this Center the conjugated one is regarded to be the soft one and while you can interpret that in terms of the heart soft assd base concept this is harder reacts here this is softer reacts there uh but maybe some uh yeah one has to in the explanation this is not certainly not a me good mechanistic explanation you should take in a mechanistic explanation uh also into account aeric hindrance steric steric interaction of course um nevertheless let&#39;s have a look at a similar reaction cyclohexanone plus tary ble lithium this clearly gives this product so and this tells us that well the structure of the carbon nucleophile is less influential than the nature of the metal lithium is harder than the Magnesium so hardeners lithium harder than a grard reagent and this is how harder than well any Cate again cyc exone first methyl lithium secondly hydrolysis will result in the alic alcohol and uh while uh coup rate for instance this one hydrolized after CC Bond formation will give the conjugate addition product until now we have um only interpreted uh this in terms of the artsoft acid base principle in focusing of the carbon Center we could also interpret it focusing on the metal lithium a lithium cat iron harder than a copper cat and therefore the lithium cat is a Lis acid coordinates preferentially at the three electron pairs of the oxygen it&#39;s already sitting there okay on the other hand the CATE might preferentially coordinate to the electron density of that double bond and indeed uh Nobert kower from our neighboring University Dortmund a couple of years ago found some interesting examples proved that with uh NMR spectroscopy that the cprit are indeed coordinating to that double bond two further examples for today more complicated ones an isolated peridine and isolated with a counter anine presumably simply a chloride so where do we have electrophilic centers here so of course this carbon is very electrophilic and this is certainly the hardest electrophilic Center here in this uh aromatic system a conjugated uh system we could write down some uh misic structures with positive charge there and there and there of course this uh um visualizes then that we have electrophilic centers here in the uh author position of a nitrogen and also in the par position these in the conjugated systems are of cuse regarded to be much softer than that yeah and uh well okay here and there we have a soft position and there this is even softer okay so reaction and between Lithium at minus 78° was found out to react exclusively almost exclusively at this carbon well this is in accord what we have already seen here with arithium species and it simply set free the purine and formed at Aster next test was done with a grineer reagent reagent and magnesium bromite also at min -78° and here we observed predominantly the reaction at the soft and softer positions what is the result in that case this and the par isomer was found in the ratio 67 to 33 of course this means there is no real discrimination between the author and the par position because we have uh the offer position twice and we per position only once it&#39;s just the ratio of one to one to one yeah and this is the result then so the Organo magnesium discriminates between the heart center and the soft centers but not between soft and softer going to uh softer Organo metallic reagent and Organo zinc Which is less reactive and they have done the reaction at higher temperature zero de and the copper uh compound Organo copper would would react similarly in that CA in this this case they achieved a r ratio of 19 to 81 that means with the less reactive Organo zinc you indeed can discriminate between the soft and the softer position and get predominantly here the reaction in the power position last example for today once again we enol enolate of 13 dicarbon compound in focus is the reaction with an Alo compound an Alo electrophile with the c alculated product as the Target first attempt simply with Al bromite gave a 30% yield of the target compound interesting is the result with an Alo acetate which is not reactive to This nucleophile Not That reactive to this nucleophile in moderate reaction conditions but adding a catalyst a padium zero catalyst then this product was isolated in a 94% yield well actually this is this is uh the so-called 2 G reaction and the padium zero Catalyst as a very soft nucleophile reacts with the alil acetate forming such an Alo padium complex and this is indeed a very very soft electr file and this gives then the high yield we will see more of these catalytic systems of course uh in in summer semester so okay I think uh we should finish for today see you tomorrow with uh remarks on uh basic reaction types in organometallic stric organometallics chemistry thanks for listening see you tomorrow

Transcript for:Introduction to Organometallic Chemistry

Transcript for:
Introduction to Organometallic Chemistry