 Hello everyone. I once again welcome you all to the MSP lecture series on Transmittal Chemistry. Now, since couple of last lectures we have been discussing about the oxidative addition and reductive elimination reactions. Let me continue from where I had stopped in my previous lecture. So I showed you how CH bond can be activated and how CC bond can be activated and what are the difficulties we come across. Now let us look into another important method of addition of substrate molecules. That means here we are considering polar molecules. When we consider polar molecules having an electronegative atom, how it follows a pathway that is different from the neutral molecules we considered. So neutral molecules I showed you CH I showed you H2 and even SIH bond addition and similarly one can also think of BH and all those things. Now let us look into the second mechanism that is followed by polar molecules that is called nucleophilic oxidative addition. So at the end of this one you will be knowing why we call this one as nucleophilic oxidative addition. So here if you see I have considering a square planar complex and now Rx is brought, Rx bond is polarised. When it is polarised what we have is R plus and X minus and addition of Rx to the square planar complex is a slow step and also this is a rate determining step here. So in this what would happen is now once bond is polarised, so the electron it moves and it becomes X minus, X minus it becomes and then it becomes X plus. When it is X plus it attacks here we have this dz square with two electrons. Now this attacks this one and then this generates a five coordinated species and now you can see here we have positive charge. We have a orbital with MT because the electrons are already given from metal to these two. To generate now you can see this is an anionic ligand, this is also an anionic ligand. So oxidation is halfway through. So now basically what happens this one attacks this position here and then the reaction is completed in the next step. This is fast. So that means this nucleophile is attacking here because of this one it is called nucleophilic oxidative addition reaction. So this is the path followed by most of the polar substrate molecules. So how to assess this reaction? For example, what are the factors that contribute to the rate of this reaction? So electron releasing ligands that means electron rich metals which are in a position to readily lose a couple of electrons that means metal should be more nucleophilic in order to make it more nucleophilic. So polar solvents if you use that increases the rate because polarizer transition state is there and inversion is observed carbon. These three things are important. So electron rich metal that is to in case of previous concerted addition also and then polar solvents should be used and then if you take a chiral molecule inversion is observed carbon. You can see from this one we are taking chiral compound here and you should focus here and now since it is added in a trans one so this is how the addition takes place here. So as a result what happens the configuration is changed. So that means inversion happens if any substrate molecule is added which is chiral in nature what happens in the oxidatively added product inversion can be observed. So now the third one radical pathways. Radical pathways is always followed by metals where we have odd electron systems such as cobalt 2 D7 system or manganese 0 D7 system exclusively follow radical pathway mechanism. It does not mean that other electronic configurations having even number of electrons do not follow it is not like that even a D8 system can also follow sometime radical pathways. So that means only thing is we should assess to know whether a radical pathway is followed or a concerted method is followed or nuclear philic oxidative addition method is followed. Of course distinguishing between concerted addition and nuclear philic addition would be very easy because the moment we look into substrate molecule we can tell whether it is a polar molecule or non-polar molecule if it is polar yes it is it follows nucleophilic oxidative addition if it is non-polar it follows concerted method. So that means between radical and nucleophilic addition we have to follow certain tests that means if the reaction shows ambiguity about the pathway that is followed we have to do this following experiments what we have to see is we have to see whether the rate increases with initiators such as peroxides oxygen or light and in case if we add radical scavengers then the rate should decrease and of course if the reaction follows radical pathway we can exclusively see resimization of stereochemistry at chiral carbon center if we consider any chiral carbon substrate then there will be resimization. So these three would tell us about the path followed by a particular polar molecule. So then what are the steps that are involved in a typical radical process let us look into it initially we have to use an initiator I write INIT and then this interacts with of course if I consider iridium D8 system to begin with we have a plus 1 species in the next step it interacts with substrate molecule Rx and generates a radical and this radical reacts with iridium 2 2 species 3 species and now it is still it is radical is coming 2 species and now iridium 2 species further reacts with another molecule to have plus so it continues. So these are the few steps that are followed and they are very similar to a typical radical reaction we come across in stereochemistry when R is tertiary or secondary but not for primary so you should remember this radical pathway is favored for R a tertiary carbon R secondary carbon but not for a primary carbon that means if we have CH3CH2PH. Now let us look into the reductive elimination so far we discussed about oxidative addition and two type of oxidative addition we saw now let us look into the reductive elimination so this is a typical reductive elimination process to begin with we have n plus 2 state is there and 6 coordination is there and it may be 18 electron species now after reductive elimination what happens so slowly there will be bond will be established these two entities are brought close to each other they start interacting and a bond is established and then eventually this will be eliminated and then now it gains 2 electrons and also it loses 2 ligands so coordination number decreases oxidative state decreases and we get back the starting compound prior to the oxidative addition what we had was this one and if the rate at which oxidative addition happens and reductive elimination also happens then we can say this called microscopic reversibility for example if a XY is added and if the XY is eliminated and the rate in both the cases are very similar then it is called microscopic reversibility because this is exactly opposite of oxidative addition reaction important this reductive elimination is very very important in organic synthesis especially when we are doing cross coupling reactions cis orientation is required for concerted elimination cis orientation the two leaving group should be cis to each other on a metal center and this because whether it follows initially concerted addition or nucleophilic addition reductive elimination is always a concerted three bond concerted process as a result cis orientation is very important in case due to some reason if we get trans position two moieties that are supposed to be get eliminated and we should find a way to perform isomerization so that trans to cis isomerization happens prior to reductive elimination and always proceeds with retention of stereochemistry at carbon the only in case of nucleophilic oxidative addition inversion takes place and then whatever the configuration we have and at the end of reductive elimination configuration is retained. Let us look into the stereochemistry of reductive elimination here so a chiral compound is chosen along with a metal having two methyl groups and two tertiary phosphines so here paradigm is in place to state so here nucleophilic oxidative addition has taken place so inversion has happened already okay so now you should remember this is a polar so nucleophilic oxidative addition means they will be added to the trans positions what we have here is bromide so now oxidative addition is completed now we are talking about concerted reductive elimination so now it should not change already you can see the configuration has changed now configuration has changed inversion has already happened now this inversion is retained in the next step that is during concerted reductive elimination what we get is so methyl group is coming here H will be here and D will be here and of course plus what we get is so you can see here so that means during reductive elimination retention one can see if you are using chiral molecules under what circumstances one can perform reductive elimination very easily can be seen here if you have bulky ligands if you have bulky ligands are there due to the steric crowding what happens reductive elimination will be very facile and of course if the metal is in higher access state it will try to get reduced okay as a result again reductive elimination will be very facile and besides these things what is important is what kind of ancillary ligands we are using on the metal the so called silent spectator ligands or ancillary ligands they have a role very important role so that means ancillary ligands capable of stabilizing lower access states is what important that means we should have ligands which are non classical in nature that means we should have ligands which are capable of functioning as sigma donors as well as pi acceptors you should remember when the reductive elimination happens metal will be coordinatively unsaturated and then more electrons will be there in that case what happens they can be inter electron repulsion that that will try to destabilize the metal in that case what happens we should have sufficient ligands having back bonding capacity so that they can release some of the repulsion by taking electrons to their appropriate back bonding orbitals in that context carbon monoxide allkeins and a variety of phosphines play an important role so this is about reductive elimination and then the nature of reductive elimination can be again assessed whether it is intra reductive elimination or inter molecular reductive elimination through some crossover experiments what happens for example if cc bond formation is there not necessarily both the carbon atoms should come from the same metal in cis or they can come from two adjacent metal atoms also that means although we know we have to confirm from further experiments for that one what we call it as crossover experiments are ideal then how to perform this crossover experiment let me show you that one let us consider two species again I am considering this tertiary phosphine having two methyl groups in one case it is deuterated and another case it is simple methyl groups so what we will do is we will take a one is to one mixture one is to one mixture of these two complexes and heat it okay when we heat it let us not worry about what happens to the metal center let us look into what kind of organic products we can get from this reaction three possibilities are there one is cd3 coupling to give deuterated ethane another one is simple ethane and third possibility is ch3 cd3 so when we analyze the product obtained in this reaction we can account for this one we can account for this one but this would be missing so that indicates if this is missing means the process the reductive elimination has proceeded via intramolecular process not intermolecular so that information comes if it is in inter then they would have very nicely combined so that product is not obtained so this is called crossover experiment in many other reactions also one can think of this kind of experiment to consolidate our climb about the type of product formed in a particular reaction so now let us look into bimolecular reactions and of course already I discussed in the beginning a few bimolecular reactions a typical bimolecular reaction I have shown here so metals which do not have two accessible access states with a difference of two electrons possibly on the other hand if they have two accessible oxidation states with a difference of one electron for example copper one copper two cobalt two cobalt three iron two iron in such cases one can anticipate bimolecular reductive elimination how that happens for example you take a molecule like this where we have a substrate x is there and another one we have a substrate y is there and what we are doing is reductive elimination so in this process through the establishment of a metal metal bond they will come close to each other and x y is eliminated this is a typical bimolecular reductive elimination and of course if we take this molecule and add this one we can get these two species that is bimolecular oxidative addition that I already showed you in my previous lecture one of the previous lectures so this is how one can imagine a bimolecular reductive elimination that is happening with species where we have metals which have a difference of one electron having two accessible oxidation states so results in mm bond formation and this is one electron reduction per metal and of course this kind of binuclear species unless these substrate molecules are capable of leaving this mm bond to add oxidatively you cannot use it in catalysis and if the as I mentioned if the species is capable of splitting this one reversibly okay then only we can use a binuclear process of course there are quite a bit of metal complexes are used in catalysis which follow binuclear reductive mechanism so this results in a new mm bond formation and this is one electron reduction per metal many examples go by radical process in these things where as I mentioned one electron process is there most of them follow radical mechanism can also occur in cases where intramolecular reductive elimination is expected so that means in some cases where intramolecular reductive elimination is expected also can follow this one binuclear method so for example if you consider this one here let us take two such species having H and CH3 here like this and as I mentioned they can come something like this and methane can be eliminated and of course here it does not follow this mechanism to give this con okay so that means basically here what you can see is if this is formed one can think that yes it is following a binuclear radical mechanism otherwise what happens you would have ended up with asmium tetracharbonyl complex so that means this shows that it follows binuclear method and what are the types of reductive elimination we come across you can see here RH so CH coupling can be seen and CC coupling can be seen and again here CH coupling can be seen and here CC coupling can be seen and here you can see carbon to silicon bond formation can be seen and binuclear reductive elimination for example you take this molecule here yeah so take this molecule on heating it can generate a species something like this or if you take a manganese compound like this with benzoil group or air CO and with combining with another metal hydride you can see this is a typical binuclear reductive process in this one you can see this species coming out through the formation of MN2CO10. Let me show you couple of more reactions here to make you familiar with this oxidative additional reductive elimination process. Let us consider this Na2 FeCO4 on several locations when question is asked whether this molecule can undergo oxidative addition or not many say no yes this can undergo oxidative addition despite it is an 18 electron species but I also showed you enough examples where an 18 electron species undergoes oxidative addition reaction so for example you take this one and treat with halide alkyl halide or aryl halide it forms yes in this fashion this can undergo oxidative addition and of course here Fe was in minus 2 state and here if you see Fe is in zero state so one electron is given one electron is taken here so it is zero state and here it was 18 electron here also it is 18 electron species. Let us try to see catalytically important reactions of course catalyst is needed here of course the moment I write these two substrate molecules and reagent you know that what kind of reaction this is so this gives if I just this one this is called Suzuki mirror Suzuki coupling reaction and if you take again air X and plus add 18 species again of course in all these reactions without saying without saying it goes that we are using a typical palladium complex or something this is still a reaction this is called Kosugi Megita still a reaction this is called Negasi reaction and of course you are familiar with this reaction as well I would say reaction of an alkali halide within alkyne catalyst is there even if I do not write you understand that you assume that there is a catalyst this is called Kumuda Kumuda and Koryu Tamil it is always good to write all the names of discoverers involved in this one it is not right to say simply Suzuki reaction we should tell always mirror Suzuki reaction and also a HEC reaction Mizaraki HEC reaction I do couple of other reactions I would write quickly so reaction of reaction of an alkyne halide with Grignard reagent is called Kumuda okay this this this is called sorry this is this reaction Kumuda this one is Sonogashira Sonogashira reaction this is addition of an alkyne halide to acetylene and in the last one in the series I am going to write Hiyama reaction we are using a silyl reagent called Hiyama so I think whatever I have discussed so far under these two topics oxidative addition reductive elimination would be enough to get some clear idea and understanding of these two reactions of course one can always go to textbooks to see similar reactions to understand in a better way at some point of time if you want to do some catalysis okay this is an ideal beginning to learn these things with this okay let me stop the discussion in my next lecture I should start discussion on another important topic in our ionic reaction mechanism so until then have an excellent time reading chemistry thank you for your kind attention