Lecture 4 and 5

a) Elimination of HX 1. from an alkyl halide (E2, regiochemistry of reaction, stereospecific reaction)

2. dehydration of an alcohol (E1, stereoselective reaction)

b) Wittig Reaction Mechanism. Explanation of stereoselectivity with stabilized and unstablized

ylids.

c) Julia Olefination Mechanism. Stereoselective reaction. One-step Julia Olefination.

d) Peterson Reaction Elimination under acidic and basic condition. Stereospecific reactions.

e) Alkyne Syntheses Double elimination of HBr from 1,2-dibromoalkanes. Deprotonation and

alkylation of terminal alkynes.

a) Elimination of HX 1. from an alkyl halide (E2, regiochemistry of reaction, stereospecific reaction)

2. dehydration of an alcohol (E1, stereoselective reaction)

Elimination of HX

Using either a halogen of HOH that can generate an alkene

1 – Start with alkyl halides – via E2 mechanism

Treat it with a base and get an elimination of protonated base and Br -

Hydrogen and Bromine have been arranged to be antiperiplanar, this configurations ensures
maximum overlap between C-H sigma orbital with C-Br sigma star orbital, good orbital arrangement.

2- Dehydration of alcohol – via E1 mechanism (treat with acid)

Took this alcohol and treated it with acid, it will

1 - protonate on the oxygen

2 – H2O leaves to generate a tertiary carbocation which is very stable

3 – Deprotonation to form the same alkene as above

The more substituted alkene forms because have 6H + on the 2 methyl groups, which you can also
technically remove, get the more sub alkene because it is the more thermodynamically favourable
product. The reason it forms is because the relevant deprotonations passes through a lower energy
transition state.

In specific examples the dehydration of an alcohol or an elimination of HX from an organohalide is an

efficient example of making an alkene. However, many occasions where methods don’t work very
well.

a)

Tertbutyl alcohol

1 – protonate it to form the cation

2 – Get departure of water to generate T butyl carbo cation,

3 - have 9 H+ free on each terminal carbon atom, each of which could fall off and it will all generate
the same alkene

Example where dehydration of alcohol works very well

b)
Isomer of A

1 – Oxygen is protonated

2 – water leaves to generate secondary carbocation which isn’t as stable as the tertiary carbocation

Expect the more sub alkene to form but could form one of two stereoisomers which are cis and trans
(E/Z)

Reaction is to some extent stereoselective and there is a lower energy transition state for the
protonation to form the E alkene (trans)

c)

Both a and b were E1

Mixture of 3 products

Don’t get very good yields because have to separate very hard because have same functionality and
molecular mass. So need a better way of making alkenes, to control the Cis or trans isomers.

Going to look at three reactions that can control which isomer they make.

b) Wittig Reaction Mechanism. Explanation of stereoselectivity with stabilized and unstablized

ylids.

Summary of mechanism

Step 1:

Take an organo halide preferable a primary organo halide going to do an SN2 reaction on it using
triphenyl phosphine, excellent Nu, so reaction is easy to carry out to form a phosphonium salt.

Step 2:
Takin a base such as Bu-Li or NaH (not that strong but pretty strong). Remove proton on Carbon next
to phosphorous atom to generate that molecular fragment which overall is neutral carries both
positive and negative charge (zwitterion) when positive and negative charge are on adjacent atoms
that zwitter ion is called an ylid. It is possible to draw an alternative resonance form, that will turn to
known as phosphorane, use the negative charge to form a double bond.

Step 3:

Simpler to use the ylid form in same reaction pot that you use to generate ylid add a carbonyl
compound

1 – Used a carbonyl compound that removes issue of what isomer you’re going to get. So take
acetone The negative charge of the ylid can attack at the carbonyl carbon that carries a delta positive
charge and forms a tetrahedral intermediate

3 – Negative and positive charge on oxygen and phosphorous atoms so form a bond and that forms a
4 membered ring. P can form 5 bonds, plausible intermediate. Ring structure is oxaphsphetane at
room temp not stable so it collapses into 2 fragments one of which is what were trying to get to,
which is the alkene no E/Z isomerism, and the other is is triphenyl phosphine oxide.

The formations of this by product is what drives the reaction forward, the P=O double bond is very
strong and so that is the driving force. The enthalpy released upon formation , drives reaction.

Picked acetone so there would be 2 methyl groups on one of the carbon atoms on the alkene and so
no isomerism, but if taken aldehyde where one of the methyl groups is replaced with a proton.
Could generate E/Z isomer.

How do you control which one you get?

Do this by choosing what the R group in the organo halide is, if the R group is simply an alcohol
group, generate something called an unstabilised ylid.

So if you have an unstabilised ylid where you use a simple alkyl from a simply alkyl halide, this gives
you Z alkenes. This is the case because of the way the ylid approaches the carbonyl compound that’s
added in step 3, its believed the ylid which we tend to draw as phosphorane, and the carbonyl group
such as benzaldehyde approach with the two double bonds at 90 degrees to one another and they
actually overlap.

This is being controlled by sterics, keep larger groups away from each other, the PPh3 is huge, 3
benzenes rings

If spin phsopharane around so bigger groups are close together its sterically unfavourable, so the
bulky groups are kept as far away as possible while maintaining 90 degree of double bonds.

Curly arrow to describe whats happening in terms of electron flow.:

1 – Break pi bonds and making O-P single bond

2 - and a C-C single bond, doesn’t matter whether it’s the electron from the C=O double bond that
are forming the O-P single bond or the C-C bond so can draw arrows the other way round
Don’t move any of the atoms in the first instance, just get rid of two double bonds and insert two
new single bonds that have been created.

Rotate 180, pull P atoms down so its in the same plane as the O and the two C atoms. H sticking up
and R group sticking down.

3 +4 - So when oxo phosphetane collapses to generate the triphenyl phsphine oxide end up with the
phenyl group from benzaldehyde and the R group from phosphorane ylid, alkyl halise on the same
side of the C=C because on same face of the intermiediate oxo phsophotane

Ph and R group below the ring when loked at from above to syn oxophosphotane

Now using stabilised ylids

So a normal ylid is that you have a negative charge next to a positive charge,

already draw resonance structure where theres a C=P double bond and all ylids have that structure,

however if you have an anion stabilising group can draw further resonance structures and those are
stabilised ylids, eg stabilise negative charge onto the ester group, alternatively if you have an
aromatic ring can draw multiple resonance strucutres where you delocalise negative charge onto
benzene ring, so these are examples of stabilised ylids.

Stabilised ylids give you E alkenes, not clear cut on why it occurs what people do agree with is that
this therefore must occur

via anti oxophosphotanes because when it collapses it gives you trans. Multiple explanations on how
you get to the anti oxophosphoatnes.
With unstabilised ylids the wittig reactions gives Z alkenes but with stabilised, it gives E alkenes. Still
controversial about why

Old explanation

In every case, this is what happens. Get syn oxophosphotane, but in the case of a stabilised ylid, then
this is a stable intermediate. Which allows it to ho back to the starting material, instead of it being an
irreversible process you can decompose the oxophosphotane back to the starting materials, then
that allows for the rearrangement of the carbonyl and the phosphorane into a higher energy
transition state which then goes and eventually gives you anti-oxophosphotane

This is not true for ylids that contain an ester group to stabilise the negative charge but only
explanation that exists for benzene rings.

New explanation

Works for carbonyl based stabilised ylids, actually these ylids it transpires that the lowers E
transition state is infact that. The big difference between this TS and the other one is instead of
having smaller group H next to bulky group of the carbonyl, now put the bigger group CO2Rnext to
Ph, still minimising steric repulsion between the very bulky PPh3 group and the large substituent on
the carbonyl Ph, jus tlike previously . Now also minimising repulsion between EN groups. (Chi), trying
to keep clouds of electrons away from each other. Overrides the simple steric argument. Between
ESTER and bulky substituent on carbonyl.

If you allow the TS to react, best to draw next step without moving any of the artoms in the first
instance. Get rid of two double bonds and change to single. The look to rotatepuling P down to the
same plane as the three atoms that are going to make up the oxo phosphetane. Bc pulled P atom
down the CO2R is up and H is down, H atoms are on diff atoms of the oxophosphotane so this is an
anti-oxophosphetane which will decompose to give E alkene. Triphenyl phosphine oxide.
Julia Olefination (Stereoselective) – E alkenes

Start with sulfone, react that with a base like BuLi (strong base). Removes one of the two H atoms on
the carbon next to sulphur

1 - the electrons flow from bond through the Bu group to pick up the H so the by product is butane
gas. The reason it deprotonates at that C atom is because the H are acidic because the negative
charge delocalises into either of the two O atoms bonded to the sulphur

2 – Then add an aldehyde to the deprotonated sulfone and that negative charge is quite Nu and it
will attack the carbonyl carbon which has a delta positive charge and hence generate a tetrahedral
intermediate

3 - If you avoid having any water there you can leave that negatively charged oxygen deprotonated
and you can add in a third reagent (benzoyl chloride),. Electrophilic carbonyl group and then can
then collapse the tetrahedral intermediate instantly and kick out chloride as leaving group.

Can isolate the product, now have functionality that can be eliminated to make C=C use a reducing
agent (Na/Hg) (miss steps out of reducing), reduce of sulfone group and generate a carbanion which
can then eliminate a good leaving group to get E alkene.

The stereoselectivity of the reactions the fact you get an E alkene comes from the confirmation at
the reducing agent stage, so the least hindered confirmation of the anion gives the E isomer on
elimination.
Peterson Olefination – Stereospecific – if you change the configuration (stereochemistry) of the
starting materials get a diff stereochemistry of the product.

Acidic and Basic condition Peterson Reactions

Acidic

Take Alpha silyl alcohol, have a silyl group on carbon next to alcohol. If take that molecule and treat
w strong acid end up with the trans alkene.

have the OH and the silyl group antiperiplanar to one another. Protonate OH to make it into a good
Leaving group and water is a good enough Nu to attack the Si. Break the C-Si bond electrons flow to
make C=C double bond with the elimination of OH2 +

If take the diastereomer and treat with strong acid get cis alkene. To get the correct arrangement of
antiperiplanar between the silyl group and the departing OH groups the propyl groups are on the
same side of what will become the C=C.

Leaving group has to be antiperiplanar to where the attack is happening. E2 elimination

Basic Conditions
Take the same molecule and use first stereoisomer, rotate around the central C=C bond, to form a
higher energy confirmation, one which is accessible. Where the OH and MeSi on the same side of
the C bond so they’re in plane with one another. Treat with KH which is a K cation and Hydride ion so
it’s a base and it will deprotonate the alcohol.

The forms a 4 membered ring, which then collapses. C-O bond goes to O only and the electrons in
the C-Si bond go to form the C=C

Gives you Z alkene. Diastereoisomer is the same mechanism you just don’t rotate it. If you have
access to an entiopure silyl alcohol can access either cis or trans or E/Z alkene by choosing correct
conditions.

2 ways to synthesise alkynes

1)

Take a 1-2 dibromo alkane react w two eq of NaNH2 (amide) to generate the alkyne double E2
elimination, wants us to know the mechanism.

2)

Less general starts with an alkyne, method to generate non terminal alkynes, react terminal alkyne
to generate a nonterminal alkyne, reacts on the fact that alkynes are quire acidic, because alkynes
are sp hybridised, great deal of s character which means when you deprotonate an alkyne that
negative charge is held in an sp orbital, 50% s character means there’s a much higher probability of
electron being at the nucleus. Bc electron in an S orbital has a non 0 probability of being at the
nucleus, unlike the other orbitals.

React alkyne with Bu-Li to deprotonate and then with organo bromine to generate alkyne.