 Welcome to this course on Transition Metal Organometallics in Catalysis and Biology. We have been discussing about olefin metathesis reaction in the past few lectures and in particular in the last two lectures we have been focusing on ring closing metathesis reaction. Now one thing which we have noticed that this olefin metathesis reactions are thermonutrile reactions in the sense that the energy released is almost equal to the energy needed for carrying out the reaction. So, there is no enthalpy gain during the course of the reaction and because of which this is not an enthalpy driven process. However, we had seen that there are various other factors which guide or drive the reaction forward. For example, in the case of ring opening polymerization, it is the release of ring strain that drives the reaction forward. Similarly, in case of the reverse ring closing metathesis, what we had observed is the formation of large macro cycle where ring strain becomes insignificant and the formation of gaseous product like ethylene resulting from the two terminal alkene which gets reacted to each other as a process of olefin metathesis. That drives the reaction. There are instances where the release of ring strain carries the reaction forward as in the case in ring opening metathesis whereas in ring closing metathesis it is the formation of ethylene molecule which drives the reaction forward because ethylene gas quickly gets out of the reaction vessel. The same thing is observed for other metathesis reactions. For example, in ring opening metathesis polymerization, R.O.M.P. or even in some of the cross metathesis reactions, these evolution of ethylene is seen as a driving force for getting the reaction forward. With that, let us now focus on ring closing metathesis reaction. In continuation with yesterday's or previous lecture, what we had observed that ring closing metathesis are mainly used for making rings which are large macro cycles and when there is a possibility of forming more than one ring or there is a possibility of forming multiple rings, what we had observed in our last discussion is the fact that the larger ring with lesser ring strain is the one which is favored and it is the one which is observed. Today, we move on with some more examples of ring closing metathesis examples for this substrate. These are acyclic amide tetra in derivatives. One can envision these having four double bonds has multiple choices for undergoing this ring closing metathesis. What we see is that the one which would undergo the ring closing metathesis depends on the variety of factors including in this particular case, including in the substituent which is present over here. For example, if R is equal to hydrogen, then the major product of this reaction becomes bicyclic six-membered ring as is shown over here and that involves the ring closing metathesis occurring between these two alkanes to give the following bicyclic compound, and this is the major product, and these are called bicyclic delta-lactam. However, if R is equal to alkyl, then what happens is strikingly different, then the metathesis occurs between these two olefins which are on the nitrogen as well as these two resulting in two five-membered rings as is shown over here, and these are called encyclopentenyl valmalactam. What we see over here is that a story of differential reactivity in one case, in the first case when R equals hydrogen, then these two olefins undergo metathesis reactions, ring closing metathesis to give this bicyclic amylactam, whereas when R becomes alkyl substituents, then the olefins on the same ligands, same side undergo ring closing metathesis to give this encyclopentyl gamma-lactam. This is a very interesting bit, and what we see is the same story of differential reactivity occurring in many substrates which have multiple double bonds, and in some cases the ones which would give larger microcycles is what is observed than the smaller one. A nice example in continuation with this discussion is described below. This is for the substrate, which has four double bonds, and it is a complex structure, which I am going to draw over here. This is a protection group. For this, there is a possibility of various kinds of ring closing metathesis that occur, but the one which is favored is the one which results in larger macrocycles, and that is between these two olefins. This can be nicely written as shown here. The metathesis sort of takes place between these two olefins resulting in the desired substrate product, which has a larger microcyle as shown over here. This is a large macrocyle, and it is aptly called macrocyle alkene. There exist other possibilities as well. For example, one can think of metathesis undergoing between these two olefins, and in that case one can think of a structure or orientation, something like in this case the other possibility is that one can think of a metathesis like this, and that would result in a five-membered ring, and that would give a product, so that would have the following carbons bearing as is shown over here. But fortunately, this product is not formed, not observed, this five-membered alkene, and this is possibly because of the issue of larger ring strain being present in small-membered cyclic structure, then it is in the big cyclic structure. What we see, which is becoming evident over and over again is that this RCM is a very powerful reaction, but they have a particular purpose, and the purpose is that these are effective only for creating large macrocyles, which has very less ring strain. For example, the one which is favored over here, this microcyclic alkene is about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, so it is a 14-membered ring. What we see is that this 14-membered microcyclic alkene is favored as opposed to the other product, which could have been formed from metathesis of different alkenes, and those structures are not favored in ring-closing metathesis. Now, the ring-closing metathesis also goes beyond the domain of achiral reactions to achiral reactions, as is shown here in the few examples, and these are called asymmetric ring-closing metathesis, and in short, they are called ACRM, A-R-C-M. A nice example of this is demonstrated below. Now, the catalyst use is quite elaborate, like in other catalysts, this one is quite, it is a molybdenum imido carbene complex with tbutyl dimethyl, so these are two R's as a bulky group, and then the carbene fragment, which is also bulky with two methyl and one phenyl, so this catalyst was reported by Hoveyda in 2001, and this reaction at 22 degree centigrade in 5 minutes gives the desired product, which involves the metathesis between this olefin and this olefin, resulting in the formation of a 5-membered ring, 1, 2, 3, 4, 5. The corresponding product is a cyclic ether plus vinyl alkene. This reaction is highly stereospecific results in R-stereochemistry in 90% yield and 99% E. Now, to note here also is the fact that there exists a possibility of other ring closing metathesis reaction happening, which is between these two olefins, but that would result in highly constrained cyclopropane ring, which would be something like this. This product which will be is never observed, not observed, not formed. What we see in ring closing metathesis over and over again is that there exists always a possibility of differential reactivity and the reaction, which gives rise to product with micro cycles with lesser ring strain is the one, which is favored. Here in this case, we saw that a 5-membered ring was favored as opposed to a 3-membered ring over here. That is what highlights these ring closing metathesis reactions. We are going to take a look at another example of asymmetric ring closing metathesis or ARCM examples. Now, this is for this particular alkene amine and this is also amidecarbene complex of tungsten as is drawn over here. These are elaborate ligand architectures, a benzene ring and a cyclohexyl ring fused and also bulky CHPH2 substituents bound to tungsten amide, phenyl amide with two methyls on the phenyl ring and the carbene bound to tungsten with two methyl and phenyl. This is the elaborate carbene catalyst. The way it reacts is the reaction that occurs between this and this olefin resulting in a 6-membered ring, which can be envisioned if I draw it in this representation. Here, the numbered atoms are, which will undergo metathesis to give the corresponding product, which is shown over here, this macrocyclic compound. This is another example of asymmetric ring closing metathesis, and with this, we come to the end of discussion of today's lecture on various aspects of ring closing metathesis. We have looked into various examples, a chiral as well as the chiral one, and we have also noted the main feature, which is visible in all of the reactions is that the formation of larger macrocyclic through ring closing mechanism is favored in cases, where there is less of a ring strain. In terms of getting products with respect to ring closing metathesis reactions, one sees that when there are multiple opportunities of ring closing metathesis, they exist on a substrate with different alkenes. The one which is favored will have comparatively a less ring strain and larger macrocycles in that process. With this, we come to today's discussion on ring closing metathesis reaction. We are going to take this metathesis reaction in much more details when we meet in the subsequent lecture. With that, I once again thank you for being with me in this lecture and look forward to being with you in the next lecture when we take up various other examples of ring closing metathesis that exist and discuss them in great detail. Till then, thank you and goodbye.