 Welcome to this course on Transition Metal Organometallics in Catalysis and Biology. In continuing with our earlier discussion, we would be looking at examples of ring closing in ion metathesis reaction. In short, these reactions are called RCEYM ring closing in ion metathesis reaction. And then we will try to finish off all the related examples with regard to this reaction. And then if we have time, we are going to start another new topic, another new interesting reactions, which are alkene and alkyne oligomerization reactions. Now in keeping with the theme of this course, which was intended to highlight all the industrial scale applications of organometallic reactions and catalysis in particular, these alkene and alkyne oligomerization reactions is another Nobel Prize award winning discovery that we are going to take up next after olefin metathesis, which was also awarded a Nobel Prize. So now we go back to our discussion on ring closing in ion metathesis reaction. We have looked into several examples in the earlier lecture about ring closing in ion metathesis reaction. What we have learned so far is that ring closing in ion metathesis reaction is an intramolecular reaction, where the substrate happens to have both the olefin as well as the alkyne bond. So to insert closing in ion metathesis or ring, this reaction what we have learned in short is that the substrate has both the alkene and the alkyne components, and the reaction is intramolecular metathesis reaction. Hence the preferred mode of reaction is that it is preferred under high dilution conditions in order to suppress intermolecular cross metathesis reaction reaction, and these cross metathesis reactions may occur between the alkyne two of these molecules. It can be alkyne cross metathesis, intermolecular cross metathesis or even alkyne intermolecular cross metathesis, and this is pretty much suppressed by performing this RCEYM reaction under high dilution conditions. The last thing is that these are important properties that we have been learning about this RCEYM. The first is that this is the intramolecular reaction preferred under high dilute conditions and suppresses the cross metathesis reaction. The second thing is that the favorable pathway or preferred pathway involves in first mechanism, which means that the active species is formed on the olefin first, and the active species is the metal carbene species as shown over here, and that further reacts with the alkyne subsequently, this reacts with the alkyne subsequently to give the corresponding RCEYM product. This is the active species for this ring closing in ion metathesis reaction. This is exactly a few points that we take home from our discussion on ring closing in ion metathesis reaction. In this regard, we have looked into other possibilities, for example, we have looked into the possibility of reaction happening in the alkyne or at this alkyne site giving the active species, and that mechanism is called ion first mechanism. But we have also noted that the ion first possibility will have a lot of regioisomers, so there is a lack of regio selectivity, whereas these reactions as observed are highly selective, which points to the in first mechanism. In this context, we have discussed various other possibilities, which have been proposed, but have not gained popularity with regard to the mechanism, the active species as well as the conditions in which these reactions are carried out. With our discussion on ring closing in ion metathesis, today we are going to look at two more examples of RCEYM reaction, but they are taken in a context of more complex maneuver with regard to organic synthesis, particularly tandem reactions, which involves RCEYM along with other reactions, for example, it might as well be a cycloaddition or other reactions which in tandem with RCEYM some complex substrate has been obtained. Let us start with these examples that I have been referring to. In this, let us take a look at this example of tandem RCEYM, in which there is a cycloaddition reaction proceeding along with the ring closing metathesis reaction examples. The one that we would be referring to have been used for synthesizing highly substituted bicyclic compound octahydrobenzo C as a pin 3-ion. So, this is given as in over here, the reaction is shown over here R1, and after several maneuver, the final product is this compound, and this complex synthesis was reported by Blakert in 1999. So, this synthesis is a very nice way of making this complex molecule involved using these two strategies, once a RCEYM ring closing RCEYM involved this ring closing RCEYM reaction. This complex example was synthesized using this ring closing in ion metathesis along with a tandem cycloaddition reaction. So, we are going to take a look at the mechanism for this formation as it is given below. This involved first the reaction of the substrate, some polymer support these reacting with C2, and the reaction would proceed as shown here, and then this would give the product as shown here. Now, this is the active species, but will not propagate, so then the reaction would proceed, the one which would be necessary would be the one that would proceed along the other conformation. Please note the conformation over here, as over here they are just the rivers. Now, this would then react further to give, and now that would rearrange to give the product. So, the point to note is that of these two possibilities, this is the correct pathway that gave the active species on this substrate. So, the next step involves the reaction of this substrate with further the product, and this is shown in the next slide. Now, this substrate would then react with the alkyne substrate, which is R1 to give as shown here. Now, this would subsequently undergo rearrangement as shown here, so double bond between 4 and 5 R1. Now, this would then react with olefin to give the corresponding metathesis product along with the elimination of CR2, the active species. So, once this is formed, then this is reacted with methyl aluminum dichloride in presence of this alpha beta unsaturated carbonyl compound R2. So, a cycloaddition reaction follows suit as shown over here, and the reaction proceeds to give this product, which then is reacted with amine in tubital NH4 reagent to give this amide in it R3. Finally, this cyclization with a tri methyl aluminum and tri ethylamine cyclization involves this reaction with this amine over here to unfollowed by detachment from the ring, give the desired product as shown here in R3 R1 in 20% yield. So, this is a very interesting reaction, and even though the yield 20% seems low, but in the context of such a complex molecule, 7-membered, 6-membered bicyclic amide functionality compound, so such a complex molecule being formed in multiple sequence standards step speaks well about this yield of even 20%, which otherwise may seem very low, but this is not trivial in this particular case, because such a complex molecule has been formed. Now, another important highlight of this reaction is that it undergoes this in-ine metathesis reaction, ring closing in-ine metathesis reaction. So, this reaction happens in the first half and then this cycloaddition reaction, which happens resulting in the formation of the 6-membered ring, and that sort of shows the beauty of this reaction. So, to put these two reactions, which have happened more appropriately, they are called in-ine metathesis, not the ring closing, because the two substrates are not the alkene and the alkyne moiety are on two different substrates. So, this is an intermolecular in-ine mechanism metathesis reaction. So, this is the intermolecular reactions, and then as the alkene and alkyne are on two different substrates. So, with this, we come to an end of today's discussion, where we have taken up an example and worked it out showing the different orientation in which the metal carbene species may react with the substrate, and what we have seen is a tandem reactions of cycloaddition as well as in-ine metathesis with regard to the earlier discussion on ring closing in-ine metathesis reaction, and how these active species leads to a very complex product, which is shown over here even in 20 % yield. So, with that, we come to a conclusion of today's lecture, where we have seen a tandem reaction as it preceded by this in-ine metathesis and cycloaddition reaction. We are going to take up a bit more detail, another interesting example of this in-ine metathesis reaction, when we meet next on this lecture series. Till then, goodbye and thank you.