 Hello and welcome you all to today's lecture. I hope you had the opportunity to go through what I discussed in the last class related to the introduction to organic synthesis etc. Now, we will have a brief recap of the last lecture where we discussed sulfur based oxidations starting with conblume oxidation where we saw the importance of DMSO in oxidation. We discussed in this oxidation the activation of halides or tosylate with DMSO eventually leading to the oxidation and forming carbonyl compounds and of course, we discussed some mechanism. Now, then we also discussed Moffet-Pittner oxidation which involved the use of dicyclohexyl carbodyl myde which activated DMSO and allowed the formation of an intermediate that reacts with the alcohol and eventually leads to the formation of the carbonyl compound. As a extension of this particular concept, Barton used phosphgene to activate DMSO and then oxidation of alcohols were discussed by us. Of course, we saw that the phosphgene being very low boiling compound and not easy to handle was of course, a drawback. Now, all these cases what was the mechanism that was basically reported by Torsal which allowed through deuterium labeling to confirm that the reaction proceeds via an intramolecular mechanism and not an intermolecular mechanism something we had discussed at the beginning of the course where we discussed in the first lecture the mechanism of the oxidation based on chromium. Now, Parikhand during then reported activation of DMSO using a complex of this type which is called as pyridine sulphur trioxide complex where the sulphur species here acts as an electrophile to activate DMSO to form this intermediate and that allows oxidation to take place. So, basically what we had discussed was that DMSO is activated by an electrophile whether it is a DCC or whether it is phosphgene or whether it is pyridine sulphur trioxide to form an intermediate of this kind where the oxygen of the DMSO is basically reacting with the electrophile to form a leaving group and so alcohol then reacts with the sulphur here and this leaving group goes off to form this intermediate which then upon reaction with triethylamine as a base leads to the formation of aldehyde as we discussed and as confirmed by the torsion studies that the hydrogen from the methyl group gets first removed as a proton and generate an anion which then intramolecularly picks up this hydrogen and then the oxidation takes place. Now, these type of studies have led to even more popular oxidations on similar concepts. Now, today we will discuss these oxidations. The first one is Cori-Chem oxidation that was developed in 1972 where they used dimethyl sulfide and n-chlorosuccinimide as a reagent combination to give something similar type of species and therefore conceptually it is very similar to what we have discussed so far. And then Swern oxidation which is a very popular oxidation it was reported in 1978 where Swern used DMSO and oxylyl chloride to activate DMSO and leads to the same kind of intermediate and similar type of oxidation but of course this is more popular for reasons that I will discuss today. Now, once again we look at what is this conceptual similarity between the oxidation of DMSO type and Cori-Chem type of oxidation is in Cori-Chem type of oxidation of course we see that there is a dimethyl sulfide that gets activated by n-chlorosuccinimide or chlorine where sulfur makes a sulfur-chlorine bond and we get this species with the chloride ion or this succinimide ion as counter ion. So and then the oxidation occurs. So as you can see that there is a similarity conceptual similarity between these two. This is the DMSO species which is activated by an electrophile where Oe is leaving group and here directly the divalent sulfur leads to a species similar to this where there is a leaving group. So conceptually they are like this that you have an electrophilic sulfur species having a leaving group like X here and of course having a counter ion. Now this species can come from DMSO or DMS that is dimethyl sulfide depending on what the activating agent is. Now, if we now look at it very carefully then it looks that they are basically conceptually having a similar type of intermediates. In corn bloom oxidation as we saw the DMSO interacts with halide or tosylate and give this intermediate directly and we are not reacting with an alcohol but we are reacting with a halide or a tosylate which could be a derivative of an alcohol and we get an intermediate like this which of course leads to the formation of aldehyde. In the DMSO based oxidation what we have seen the DMSO then gets activated by the electrophile to form the species to which alcohol reacts to form similar type of species which is formed here by the reaction of DMSO with the halide or tosylate and then of course rest of the things are similar. In the case of DMS based oxidation what we have seen is that we get similar type of intermediate like here which then react with an alcohol to form similar type of intermediate as corn bloom by oxidation which then eventually leads to the aldehyde. So this is the similarity between the 3 types of oxidation. So today we will look at little more carefully the Kori-Kim oxidation. What is done is to react a dimethyl sulfide with chlorine to form this chloro dimethyl sulfonium chloride or it is reacted with n-chlorosuccinimide to form this particular intermediate which then reacts with the succinimide ion to form another sulfonium ion intermediate to this particular sulfonium ion intermediate or to this particular sulfonium ion intermediate which is chloro dimethyl sulfonium chloride the alcohol attacks and then this particular intermediate is formed the kind of intermediate that we have seen in earlier oxidations. Then of course the treatment of this intermediate with a base like triethylamine leads to the formation of the corresponding aldehyde or carbonyl compounds the kind of alcohol that we start with say for example if we start with the primary alcohol then we get aldehyde if we start with the secondary alcohol then we get the ketone. In place of dimethyl sulfide we can also use thioenosol that means basically what we need is a divalent sulfide. This has been published by Kori and Kim in 1972 and 73 and that is how it is called as Kori-Kim oxidation. So basically what we need is to have at least one hydrogen on the substituent on the sulfur like for example this, this is a divalent sulfur compound in which there is one hydrogen on the carbene. So if we activate this divalent sulfur compound with any electrophile like chlorine or n-chlorosuccinimide then we will get an intermediate of this kind to which if we react with alcohol like this has specifically taken this deuterated alcohol to distinguish between this hydrogen or deuterium from this particular hydrogen. So we get this intermediate to which when base is allowed to react then this particular proton will be picked up based on the mechanism that we have discussed earlier and then the intramolecular abstraction of the proton in this particular case it will be deuterium which will then lead to the formation of the corresponding deuterated aldehyde. And of course as we can see that it would lead to the formation of this di phenyl sulfide containing a deuterium here because now what has come out is of course a deuterium from here to here and of course this sulfur oxygen bond has broken therefore we get this particular sulfide. So this is how the Corikim oxidation takes place. Now we look at this one oxidation where oxyl chloride is used to activate DMSO. The oxyl chloride has a high boiling point like 61 degrees and the Bray products are water soluble. The reaction was reported in 1978. The reaction is carried out at minus 78 to minus 60 degrees and then workup is done at the room temperature. The crucial point is of course to maintain the temperature. When DMSO reacts with the oxyl chloride at minus 78 degrees and slowly it is brought to minus 60 degrees then we get a species 1 and this species 1 then reacts with the alcohol to form a species 2. Then that species reacts with triethylamine to form the corresponding aldehyde. Now one of the problems that is faced here is that oxyl chloride is hygroscopic and therefore water must be absent and in order to make sure that water is not present in the reaction medium molecular sieves are used to remove water. So basically the conditions require that we have to be very careful to remove water and also we have to maintain the temperature because of mechanistic implications that we will discuss now. So now you can see that in the mechanism of so on oxidation the DMSO reacts with oxyl chloride in this particular fashion to form oxygen carbon bond at minus 78 degrees to lead to the formation of this intermediate in which chloride ion attacks onto the sulphur and carbon dioxide carbon monoxide and of course chloride ion are released to form this intermediate onto which the alcohol attacks and then upon the loss of hydrochloric acid this intermediate is formed. Now this particular intermediate as you can see coming from DMSO oxyl chloride is similar to the intermediate that comes from dimethyl sulphide and chlorine as reported by Corey Kim. Then of course triethylamine picks up the proton from here forming an intermediate of this kind which then in an intramolecular fashion leads to the elimination of this oxygen sulphur bond and of course we get the corresponding aldehyde and dimethyl sulphide which is low boiling and then of course triethylamine hydrochloride which is auto soluble. So as you can see that we have the low boiling carbon dioxide, carbon monoxide and of course we have water soluble triethylamine hydrochloride. So we can easily work up this reaction and get essentially pure aldehyde or a ketone from the reaction. Now if the temperature is not maintained properly then some side reactions may occur. The side reactions are through a rearrangement called as Pumler rearrangement. Now if you recall this is the first intermediate that forms when DMSO reacts with oxyl chloride and then of course as we discussed the chloride ion attacks onto the sulphur and of course we get this intermediate which is similar to the intermediate that Corey Kim reported. Now what can happen is instead of alcohol attacking onto this particular sulphur chlorine as a chloride ion can pick up a hydrogen form here and this type of elimination occurs leading to the formation of this sulfonium salt in which now the chloride ion attacks onto the carbon forming this species to which then alcohol can attack directly and form this type of sulphur intermediate. This can also form directly from this species here. So instead of chlorine attacking as a chloride ion onto this carbon alcohol directly can this anion of the alcohol can directly attack onto this carbon to form this sulphur intermediate. Now this is basically the side product that can form and this is what is coming due to rearrangement which is very similar to Pumler rearrangement. Now what is Pumler rearrangement? Pumler rearrangement is that if you start with a sulfoxide and react with an electrophile like acetic anhydride then what we get is basically alpha acetoxy sulphide like here what we have got is alpha chlorosulphide. So if we start with DMSO then what we have got is alpha chlorosulphide which of course reacts with the alcohol anion in the sworn oxidation because alcohol was present in the reaction medium to form this intermediate. But this particular species is basically due to the rearrangement which is similar to what is called as Pumler rearrangement. In the Pumler rearrangement for example here when DMSO reacts with acetic anhydride then O minus reacts with the carbon of the acetic anhydride to form this intermediate and of course acetate ion will come out. Now just the way as chloride ion has removed the proton from here the acetate ion removes the proton from here and this acetate ion leaves off, acetic acid comes off and we generate this sulfonium ion intermediate which is what is here. Now acetate attacks onto this to form the alpha acetoxy sulphide similar to alpha chlorosulphide. So this is the similarity between the two reactions and that happens because if the temperature is not maintained then some of these side reactions can occur. Now there are a lot of interesting reactions that have been reported using the positive aspects of the Pumler rearrangement. In fact Pumler rearrangement was independently discovered. Now what is happening in the Pumler rearrangement is of course as we discussed that a sulfonium ion forms form a sulfoxide. So for example if you start with a sulfoxide like this which has an indole moiety. Now this side chain which is attached is on the third carbon of the indole and we have sulfoxide and of course a carbonyl group and in between we have two hydrogens. So we can of course write this sulfoxide like this and if we react this with an electrophile like acetic anhydride, trifluoroacetic anhydride or anything of that sort. Then what will happen is that O- will react with the electrophile, get activated as a leaving group then of course this proton will fall as we discussed earlier in the Pumler rearrangement leading to the formation of this sulfonium ion which is what is a Pumler type of intermediate. So now depending on what the electrophile is the counter ion will be. So if we start with acetic anhydride then of course we get the corresponding acetate. But generally we choose in such a reaction the electrophile in which has electron withdrawing group so that this does not become a very good nucleophile. So instead of this nucleophile attacking on to this carbon here since this species now is well suited for an intramolecular reaction and therefore the reaction occurs to trap this intermediate this species where this carbon is now electrophilic and therefore the nucleophilic carbon of the indole then attacks to this leads to the formation of this type of intermediate which then loses a proton to form the indole derivative of this type where now you can see that there is a new carbon carbon bond form and a new cyclic ring is attached to the indole. So we are going through the Pumler intermediate and making use of this to form this kind of cyclic molecules. Now what can be done with this is that now we have two hydrogens here which are alpha to the carbonyl group. We also have one hydrogen here which is alpha to the carbonyl and of course is also alpha sulfide. Now this is definitely more acidic proton and of course the hydrogen here on the nitrogen is also acidic. So if we react this particular species with two equivalents of base then we can get this particular di anion. The anion will form on the nitrogen as well as on to this carbon. Now these two anions of course can react with a species like this in which there are two living groups. So if we have something like ethylene diabromide for example, then we can get either this reacting first or this anion reacting first and eventually what will happen is you will have a C-C bond formation here and then followed by that there will be N-C bond and then of course we can proceed in either way depending on what this particular species is. We can of course have substitutions on these carbons then we will get different type of final molecule. But eventually what will happen is that we will get a ring here of this kind. So we will have not only 3 rings attached to each other. Now we have 4 rings attached to each other and now we have scope where the chemistry based on this sulfur moiety can be carried out based on this carbonyl can be carried out and various kinds of reactions and various kinds of products can be formed. So this is an interesting example of the utility of the Pumler rearrangement product or Pumler intermediate. The Swern type of oxidation can be utilized in the oxidation of this species here where there is a nitrogen. What is found is that such alcohols if they are oxidized using premium trioxide based reagents then sometimes there is an oxidation of the nitrogen directly to form the corresponding N-oxide and the alcohol is not readily oxidized. In this cases of course one can make use of Swern oxidation. But in Swern oxidation as we discussed chloride becomes a living group and then chlorine based products are formed as side products. So in order to avoid the formation of chlorine based side products some people have made use of DMSO P2O5 combination which is similar to Swern oxidation but now does not have a chloride or any such species which can give side products. So DMSO reacts with P2O5 to form an intermediate of this kind which does not have any kind of an ion that can react with the intermediates and therefore now when alcohol reacts with this intermediate then we get a species like this which is similar to the species that we have seen in Swern oxidation or other oxidations and of course we get the corresponding aldehyde. Now the part which has come out from the this sulfur based intermediate is of this type and of course this will expel two phosphate species and they are of course non-nucleophilic. So therefore this is a very interesting variation of the DMSO based oxidation or Swern type of oxidation and without having any chlorinated bi-products. So we will stop it here and look at the other aspects of oxidations next time. Till then take care and study what I have taught today. Bye.