hey everyone, it's Professor Dave
let's all about Robinson annulation
if we remember our latin, annulation comes from annulum which means ring
so this is a reaction, a very good one, in fact a nobel prize winning reaction
in which we are able to generate ring systems
which are very important because a lot of natural products are polycyclic, they have a lot of rings
so if we are going to mimc natural products we are going to need to be able to build rings
the robinson annulation is actually a combination of these other enolate reactions we've been looking at
it is actually a Michael addition followed by an intramolecular Aldol condensation
we'll see what that means here, so this is the reaction that Robinson did
we're going to look at this substrate, and we're going to generate an enolate just like we did
for the aldol and the michael. the reason that we're going to extract this proton over the ones here or here
which also could be used to enolize, this actually has the lowest pKa on the molecule
because if it deprotonates here, the electron density can participate in resonance not just up and into
this carbonyl but down and into this carbonyl as well
further delocalization means additional stabilization
so that's why this proton ends up being the most acidic proton on the molecule. so that's the one we're going to
deprotonate. we will arbitrarily have that go up to this carbonyl here, so there is our enolate.
the first thing this is going to do is it's going to attack this molecule here, so remember this is the
alpha-beta unsaturation that we remember from a substrate in any michael addition
so the first step of michael addition, this pi bond goes here, and there's the first attachment
we have formed this new carbon-carbon bond right there, that is the first step of any michael addition
and we have attached this carbon fragment here. so let's just protonate that, grab a proton from a water molecule
and there is our enol, remember the enol from the michael addition, and we are going to tautomerize
once again, this is just energetically favorable, we are swapping out better, higher energy-containing bonds
for the lesser ones, so this is going to be a better situation, that's the tautomerization
and there is our 1,4 michael addition. if this was carbon 1, 2, 3, 4, we've got that 1,4-dione.
this is our michael addition product. so that's step one, we've done one part of it.
now, the interesting thing, if we are going to deprotonate again, let's say we deprotonate at this position.
so i'll draw in one of the implied hydrogens, and hydroxide will go and grab this, this bond will go here
and we will generate another enolate
what we're going to do now is something pretty interesting, whereas in solution
a substrate typically has to swim around to find something to interact with, here we have a
much more kinetically favorable situation
we have the opportunity to do an intramolecular reaction. that is when a molecule reacts with itself.
this enolate sees something that it can react with in its immediate vicinity, there is this carbonyl here
enolates interact with carbonyls, we are going to be able to save a lot of time and just have this go ahead
and react right there on the other portion of the molecule. so this carbon will go attack that carbon
and this is the new bond right here
so this is an intramolecular aldol condensation
we are doing a 1,2 addition so this is directly attacking a carbonyl carbon, there's no alpha-beta unsaturation
so it's aldol, it's not the michael, this is what we're going to end up getting, and then we will protonate again
just as we did, and we'll go ahead and protonate again, giving us the hydroxyl
and the last step of the aldol condensation, we know is going to be an elimination
that gives us the unsaturation right there, so that's our robinson annulation product
so this is a very powerful reaction for a number of reasons, we are utilizing chemistry
that nature uses itself, that is the aldol condensation, that is the michael addition
and we were able to go from this to a much larger structure, it's a much more complex molecule
and that could be a starting point to go ahead and fuse an additional ring and make some kind of
steroid-resembling compound or something like that
so we have generated a new six-membered ring, that's a very powerful reaction, the robinson annulation.
thanks for watching, guys. subscribe to my channel for more tutorials
and as always feel free to email me with questions