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)
Dec 23, 2015
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.