Electrophilic Addition to Alkenes

Based on

Clayden’s Organic Chemistry, Chapter 19

Nucleophilic addition reaction (Chapters 5 and 9)

Nucleophilic substitution reaction (Chapters 10, 11 and 15)

Elimination reaction (Chapter 15)

The aims of this chapter are to …..

• Reactions of simple, unconjugated alkenes with electrophiles

• Converting C=C double bonds to other functional groups by

electrophilic addition

• How to predict which end of an unsymmetrical alkene reacts

with the electrophile

• Stereoselective and stereospecific reactions of alkenes

• How to make alkyl halides, epoxides, alcohols, and ethers

through electrophilic addition

E- and Z-alkenes can be made by stereoselective addition

to alkynes

Alkynes react with some reducing agents stereoselectively to give either the Z

double bond or the E double bond

the two hydrogen atoms add to the

alkyne in a syn fashion and the

alkene produced is a Z-alkene

Wittig reaction is not entirely Z-selective, and it generates

some E-isomer. Lindlar-catalyzed reduction, on the other

hand, generates pure Z-alkene

E selective reduction of alkynes uses Na in liquid NH3

The best way of ensuring anti addition of hydrogen across any triple bond is to

treat the alkyne with sodium in liquid ammonia.

Alkenes React with Bromine

Alkenes decolourize bromine

water: alkenes react with bromine.

The product of the reaction is a

dibromoalkane

Neither the alkene nor bromine is charged, but Br2 has a low-energy empty orbital

(the Br–Br s*), and is therefore an electrophile. The Br–Br bond is exceptionally

weak, and bromine reacts with nucleophiles like this.

alkene must be the nucleophile, and its HOMO is the C=C p bond

When it reacts with Br2, the alkene’s filled

p orbital (the HOMO) will interact with the

bromine’s empty s* orbital to give a

product. But what will that product be?

The highest electron density in the p orbital is right in the middle, between the two

carbon atoms, so this is where we expect the bromine to attack. The only way the

p HOMO can interact in a bonding manner with the s* LUMO is if the Br2

approaches end-on.

electrophilic

addition to the

double bond,

because bromine

is an electrophile.

bromonium ion is an electrophile,

and it reacts with the bromide ion

lost from the bromine in the

addition step

Attack of Br– on a bromonium ion is a

normal SN2 substitution, hence the

nucleophile maintains maximal overlap with

the s* of one of the two C–Br bonds by

approaching in line with the leaving group

but from the opposite side, resulting in

inversion at the carbon that is attacked.

Oxidation of Alkenes to Form Epoxides

Drawing similarity: We can view epoxides as the oxygen analogues of

bromonium ions, but unlike bromonium ions they are quite stable.

Most commonly used epoxidizing agents are peroxy-carboxylic acids. Peroxy-acids

(or peracids) have an extra oxygen atom between the carbonyl group and their

acidic hydrogen—they are half-esters of hydrogen peroxide (H2O2).

Peracids are rather less acidic than carboxylic acids because their conjugate

base is no longer stabilized by delocalization into the carbonyl group reagent.

The most commonly used peroxy-acid is known as meta-ChloroPeroxyBenzoic

Acid or m-CPBA because it is a safely crystalline solid

Peracids are rather less acidic than carboxylic acids because their conjugate

base is no longer stabilized by delocalization into the carbonyl group reagent.

But they are electrophilic at oxygen, because attack there by a nucleophile

displaces carboxylate, a good leaving group.

alkene attacks the peroxy-acid from the centre of the HOMO, its p orbital

curly arrow mechanism:

nucleophilic p bond contributes electrons

on to oxygen of the weak, electrophilic

polarized O–O bond

a proton is transferred from the epoxide oxygen to

the carboxylic acid by-product

Epoxidation is Stereospecific

Since both new C–O bonds are formed on the same face of the alkene’s p bond,

the geometry of the alkene is reflected in the stereochemistry of the epoxide. The

reaction is therefore stereospecific

More Substituted Alkenes Epoxidize Faster

More substituted double

bonds are also more

nucleophilic because alkyl

groups are electron-

donating and they stabilize

the carbocations

Interaction of s orbital of

C-C or C-H bond with the

p orbital of the alkene will

raise the HOMO of the

alkene

Electrophilic Addition to Unsymmetrical Alkenes is Regioselective

bromine atom ends up on the more substituted carbon

Markovnikov’s rule: The hydrogen ends up attached to the carbon of the double

bond that had more hydrogens to start with.

Electrophilic Addition to Dienes

protonation gives a

stable delocalized

allylic cation

Why not protonate the other double bond?

cation is attacked at

the less hindered end

Cation obtained by protonating

the other double bond is also

allylic, but it cannot benefit

from the additional stabilization

from the methyl group

Overall, the atoms H and Br are added to the ends of

the diene system

The same appears to be the case when dienes are brominated with Br2.

At lower temperatures, the bromine

adds across one of the double

bonds to give a 1,2-dibromide. –

kinetic product

when the reaction is heated,

the 1,4-dibromide is formed -

thermodynamic product

Bromide is a good nucleophile and a good leaving group and, so SN1 can take place

in which both the nucleophile and the leaving group are bromine

Electrophilic Addition to Alkenes

(part 2)

Based on

Clayden’s Organic Chemistry, Chapter 19

Unsymmetrical Bromonium Ions Open Regioselectively

when a bromination is done in a

nucleophilic solvent - eg water or

methanol, solvent molecules compete with

the bromide to open the bromonium ion

alcohols are much worse nucleophiles than

bromide but, because the concentration of

solvent is so high, the solvent gets there

first most of the time

An ether is formed by attack of methanol only at

the more substituted end of the bromonium ion

Methanol attacks the bromonium ion where it is most hindered, so there must be

some effect at work more powerful than steric hindrance.

bromine begins to leave, and a partial

positive charge builds up at carbon. bromine begins to leave, and a partial

positive charge builds up at carbon.

The departure of bromine can get to a

more advanced state at the tertiary

end than at the primary end, because

the substituents stabilize the build-up

of positive charge.

bromine begins to leave, and a partial

positive charge builds up at carbon.

The departure of bromine can get to a

more advanced state at the tertiary

end than at the primary end, because

the substituents stabilize the build-up

of positive charge. The products of

bromination in water are called

bromohydrins

Regioselectivity of Epoxide Opening Can Depend on the Conditions

Although epoxides, like bromonium ions, contain strained three-membered rings,

they require either acid catalysis or a powerful nucleophile to react well

acid-catalysed reaction

- protonation by acid produces a positively charged intermediate. - protonation by acid produces a positively charged intermediate. The two alkyl

groups make possible a build-up of charge on the carbon at the tertiary end

of the protonated epoxide,

- protonation by acid produces a positively charged intermediate. The two alkyl

groups make possible a build-up of charge on the carbon at the tertiary end

of the protonated epoxide, and methanol attacks here, just as it does in the

bromonium ion

- protonation by acid produces a positively charged intermediate. The two alkyl

groups make possible a build-up of charge on the carbon at the tertiary end

of the protonated epoxide, and methanol attacks here, just as it does in the

bromonium ion

- opening happens at the more substituted end

base-catalysed reaction

- no protonation of the epoxide, and so no build-up of positive charge;

With epoxides, even with

acid catalysts, SN2

substitution at a primary

centre is very fast.

- no protonation of the epoxide, and so no build-up of positive charge;

- without protonation, the epoxide oxygen is a poor leaving group, and leaves only

if pushed by a strong nucleophile:

- no protonation of the epoxide, and so no build-up of positive charge;

- without protonation, the epoxide oxygen is a poor leaving group, and leaves only

if pushed by a strong nucleophile: reaction becomes pure SN2. Steric hindrance

becomes the controlling factor, and methoxide attacks only the primary end of the

epoxide.

With epoxides, even with

acid catalysts, SN2

substitution at a primary

centre is very fast. It is very

difficult to override the

preference of epoxides

unsubstituted at one end to

react at that end

Regiochemistry of the ring opening depends : dominance ofsteric or electronic factors

Ring-opening of epoxides

Base-catalyzed reactions:

- nucleophile provides the driving force for ring opening;- ring opening involves breaking epoxide bond at the less-substituted carbon

Acid-catalyzed reactions:

- protonated O weakens C-O bond;- if C-O bond is largely intact at the TS, nucleophile will attach to less-substituted C;- If C-O rupture is more complete in TS, nucleophile will attach to more-substituted C

For chloronium, bromonium and iodonium ions, Markovnikov orientation usually prevails because the bridging bonds are relatively weak

Electrophilic Additions to Alkenes Can be Stereoselective

epoxide ring opening is stereospecific: it is an SN2 reaction, and it goes with

inversion

Similarly,

Besides bromine, N-bromosuccinimide, or NBS can be used to generate the

bromonium ion

a small amount of HBr is

enough to get the reaction

going, and every addition

reaction produces another

molecules of HBr which

liberates more Br2 from

NBS. NBS is a source of

‘Br+’.

With NBS, the concentration of Br– is always low, so alcohols compete with Br– to

open the bromonium ion even if they are not the solvent.

alcohol attacks the more hindered end of the bromonium ion as this provides greatest

stabilization of the partial positive charge in the ‘loose SN2’ transition state

Dihydroxylation: Making Trans 1,2-Diol

A good way of making 1,2-diol is to add 2 hydroxyl groups across a double bond.

Recall:

Epoxide opening goes via an SN2

reaction with stereochemical inversion

When a nucleophile opens an

epoxide, it generates an alcohol

Making Syn 1,2-Diol

- osmium tetroxide, OsO4, reacts with

alkenes to provide one –OH to each

end of the double bond;

- Both –OH groups are delivered at the

same time

N-methylmorpholine-N-oxide (NMO) reoxidizes Os(VI) back to Os(VIII)

- osmium tetroxide, OsO4, reacts with

alkenes to provide one –OH to each

end of the double bond;

- Both –OH groups are delivered at the

same time

- hydroxyl group added in a

syn fashion;

- overall product depends on

the geometry of the alkene;

- reaction is stereospecific

Breaking a Double Bond Completely: Periodate Cleavage

- two steps: (i) OsO4; (ii) sodium periodate, NaIO4

- NaIO4 also reoxidizes Os(VI) to Os(VIII), so only a catalytic amount of Os is

required

- reaction comprises 2 oxidation – first of the p and then the s bond

Ozonolysis

- ozone is unstable and is generated immediately

before use from O2 (using an ozonizer) and bubbled

into the reaction mixture;

- it adds to alkenes by a cyclic mechanism;

- the 5-membered ring with 3 oxygen atoms

collapses by breaking a weak O-O bond and a C-C

s bond, but gains 2 strong C=O bonds

- Mild reducing agent, such as dimethyl sulfide, Me2S, or triphenylphosphine, Ph3P,

removes the “spare” O

Ozonolysis can be used to generate not only aldehydes, but also other functional

groups

Adding One Hydroxyl Group: How to Add Water Across a Double Bond

The reaction works only if protonation of the alkene can give a stable, tertiary

cation. The cation is then trapped by the aqueous solvent.

Alkenes are soft nucleophiles and interact well with soft electrophiles such as

transition metal cations eg mercury(II) cation

- electrophile: +HgX or Hg2+

- bridging in the mercurinium ion is weaker than that in the bromonium ion

- even relatively feeble nucleophiles such as water and alcohols, when used

as the solvent, open the ‘mercurinium’ ion and give alcohols and ethers.

Water attacks at the more substituted end of the mercuronium ion

Oxymercuration reaction

Hydration of Alkynes

Oxymercuration works particularly well with alkynes. The conditions and product

follow the analogy of alkene hydration

product isolated from an alkyne

oxymercuration is a ketone

mercury can be removed in the presence of acid enol-keto tautomerization

Hydroboration

Borane (BH3 or HBR2)

For unsymmetrical alkenes, the boron ends up on the less substituted carbon

atom

Borane (BH3 or HBR2) adds to alkenes to make a

new C-H bond and a new C-B bond

For unsymmetrical alkenes, the boron ends up on the less substituted carbon

atom and the reaction can happened several times

- C-B bond can be oxidized to C-O bond by a mixture of NaOH and H2O2

- HO-O- adds to the empty p orbital on B

- O-O bond is weak and can break, losing HO-;

- an alkyl group on boron migrates from B to O;

- HO- displaces B

To conclude...

Electrophilic addition to

double bonds gives 3-

membered ring

intermediates with Br2,

Hg2+ and with peroxy

acids.

All three classes of three-

membered rings react with

nucleophiles to give 1,2-

difunctionalized products with

control over (1) regioselectivity

and (2) stereoselectivity.

Protonation of a double bond gives

a cation, which also traps

nucleophiles, and this reaction can

be used to make alkyl halides.