all right let's look at direct 1,2 addition an alpha beta unsaturated ketones aldehydes and a
little bit about carboxylic acid derivatives so our most explanatory additions are going to be
our predictable will be direct addition to ketones and aldehydes and so if we look at this example
ketone we see the difference here between a 1,2 direct addition and a 1,4 conjugate addition so
we would call position one the carbonyl oxygen to define the diene system so one two three four
that's the alpha beta conjugated ketones so there's a couple ways to label it there one
two three four the Alpha and Beta positions and so we would call direct addition a nucleophile
attacking with its lone pair there that carbonyl directly all right as opposed to attacking the
four position which is conjugate so what we're gonna focus on in this lesson are nucleophiles
and substrates that focus on the one two addition is the major product you might get a little bit of
both but you're gonna typically lean towards 1,2 addition with these strong bases hard nucleophiles
as we're gonna call them that attack 1,2 and so just finishing out this mechanism we just
attacked with our nucleophile kicking up these are typically anionic for our direct addition
nucleophiles so when they attack they kick up oxygen to a minus they take a zero formal charge
and so there we look we have no leaving group on our substrate here and so we go to a second step
which is acidification we are required to acidify in order to cap off this proton so we'd then take
the proton there from hydronium just lower the pH enough to get to our protonated alcohol the
direct 1,2 addition product alright so the anions that we're going to use for nucleophiles here will
follow this mechanistic looking at us a more concrete definition here our nucleophiles that
are going to be good direct addition nucleophiles will also be strong bases so as we described for
substitution elimination the same nucleophiles apply in this situation so a strong base we
define that base the anionic form is the base the conjugate acid of its of the base form is
going to have a pKa greater than 15 for these strong bases so whatever our nucleophile is put
a proton on look up the pKa and a table if it's greater than 15 it's gonna be a good nucleophile
and a strong base also called a hard base or a hard nucleophile meaning it prefers more polar
positions the carbonyl is the most polar position on these alpha beta systems and so what things
qualify we'll enolates can qualify the enolates of a tertiary amide for example would be a good
nucleophile alpha carbon nucleophile for these the the enolate of an ester for example the enolate
sort of enolate of a nitrile looks like this right so it's a little bit different it looks a little
different than a normal enolate but it's still going to be harder nucleophile ketones we're gonna
look at in a moment aldehydes acetylides are good hard nucleophiles their pKa's are in the 20s okay
we can get some mixture with those but typically they do go 1,2 as far as major products are
concerned the amide ion is a strong base a good nucleophile so primary amines with a proton taken
off of that negative formal charge very strong base hard nucleophile grignard reagents we'll
look at lithium aluminum hydride and organolithium reagents in particular among the organometallics
the organolithiums are best when we want to zero in on that 1,2 addition product lithium aluminum
hydride much much better than sodium hydride as far as picking that 1,2 reduction so let's have
a look at some products we get from some of these and so again we're focusing on the 1,2 position of
this four carbon system here this diene system or double and guess not two alkenes but a alpha beta
unsaturated ketone has two pi bonds like a diene system we label diene in this manner as well so
let's just focus on that two position cap off our proton we put our alkyl group on with the grignard
reagent lithium aluminum hydride same thing is going to create that o- at first it's going to add
a hydrogen but with a hydrogen we're not drawing that in the skeletal structure and so we end up
with here just our alcohol okay once we protonate with an enolate suppose we made a kinetic enolate
from a unsymmetrical ketone at negative 78 degrees so we get the enolate on two alpha carbons here
but we'd prefer the less substituted side in kinetic conditions zero degrees we'd prefer
the enolate to the more substituted side but here we've created a hard nucleophile and yeah these do
add 1,2 and they add 1,4 but they also add 1,2 when they're free like this we get a mixture
really of 1,2 and 1,4 and it's hard to control it's a big problem in synthesis that a lot of
chemists have devoted their careers to solving the selectivity of how to go 1,2 how to go 1,4 with
enolate additions and so this is one I'll show you but just note that the 1,2 addition it's not
going to be as great a yield as it would be for say lithium aluminum hydride reduction like we
saw above but in general what will is that enolate collapse the Alpha carbon PI bond reaches out to
either the four position or as we're gonna show in this lesson here the 1,2 addition product a hard
nucleophile steric hindrance plays a role here even with grignard reagents if we have a bulky
substituent on the grignard if we have a bulky substituent here it can bias to the 1,4 product
as well in general though they tend to go toward the 1,2 organolithium's have a higher selectivity
to the 1,2 as well looking at this though when we add our enolate we've got to keep track of carbons
here so i'm going to redraw the alpha beta system exactly as we drew it a moment ago and then i'm
going to attach this alpha carbon here to that position that we attacked okay and so how many
carbons 1 2 3 4 5 from the Alpha 1 2 3 4 5 from the alpha carbon where is our carbonyl at it's
at the second position okay and so we've got to make sure that we're keeping track of everything
when all these carbon groups are moving around and attacking so we can draw it upside down left right
either way ultimately though when you lower the pH you will cap off this proton and we've got our1,2
addition product another note here in addition to hard nucleophiles if the alpha beta system
is more reactive than a ketone or an aldehyde in other words it's an anhydride or an acyl halide
carboxylic acid derivative the addition product to the direct 1,2 position is going to be preferred
in all cases because you've got a good leaving group so even with a weak nucleophile here we
just drew this - so the nucleophiles weak the base is weak we just used this in order to illustrate
the point here that we've got a system that will prefer to form a tetrahedral intermediate like
we're used to seeing for acid halides and then a solvent molecule or base from solution can
remove this proton forming our leaving group here our we had two good leaving groups before
now we only have one and so then we can kick off that chlorine the good leaving group what
do we get we get a carboxylic acid from that direct addition okay so anhydrides work in the
same fashion we're gonna favor that 1,2 addition every time even with a soft weaker nucleophile