2) NaBH4, NaOH
H2SO4
dilute
1) BH3, THF
2) H2O2, NaOH
KMnO4
-OH, cold
1) O3
2) Me2S
1) RCO3H
OsO4
Br2
H2O
Addition of
Hydrogen halide (HX)
Hydroboration-Oxidation
Oxymercuration
Acid-catalyzed hydration
Halogenation
Halohydrin Formation
Hydrogenation
Ozonolysis
HX
HBr
ROOR
NBS
Br
Radical Addition
of HBr
Br2
H2
Pd/C
OH
OH OH
HH
OH
O
O
+H
OH
OH
+
OH
HO
OH
OH
+
OH
HO
HO
OH
+
OH
OH
Br
Br
+Br
Br
HO
Br
+OH
Br
Syn Dihydroxylation
Syn Dihydroxylation
Anti Dihydroxylation
OH
+
X
Only HBr works for Anti-Markovnikov addition. The reaction goes through
a radical mechanism with syn and anti additions.
Allylic Bromination +
Br
Br
+
Br
1) Hg(OAc)2
NaHSO3
O
+En
Epoxide 2) H3O
H2O
Trans diols - enantiomers
(MCPBA)
+
Enantiomers
Simmons–Smith reaction
CH2I2
Zn, CuCl
H2
C
+En
Additions to Alkenes
The reaction goes through a regioselective formation of a carbocation. This is the
Markovnikov's rule stating that the proton binds to the less substituted carbon because
by doing so the more substituted/stable carbocation is formed. The halide can attack the
carbocation from both faces, thus a mixture of enantiomers is produced.
X
H
XX
+
+
H
3ocarbocation
more stable
2o
X
HX
Enantiomers
*Notice that an alkenewith a chi ralcenter will produce a mixture of diastereomers.
Br Br Br Br
HHHH
++ +
NBS is used to brominate the allylic position of the do uble bond.
So, for the regiochemistry of the bromination, you can simply
identify the allylic positions and place the bromine there.
However, the reaction is not as straightforward! It involves r esonance-stabilization of t he allylic radicals and other
regioisomers are alsoformed. In addition, the lacko fstereochemical control makes predicting all the possible products
quite difficult. You can check https://www.chemistrysteps.com/allylic-bromination/ for more details.
Acid-catalyzed hydration follows the Markovnikov's rule. However,
rearrangements are possible because of the carbocation intermediates. HOH
Dilute H2SO4, H+OH
H
H
Hhydride
shift
H
HH
H
H2O
2o3o
OH
OH
expected observed
Syn and anti addition.
1) Hg(OAc)2, EtNH2
2) NaBH4
Same product as acid-catalyzed hydration. The main reason for using Oxymercuration is preventing possible rearrangements that
happen during acid-catalyzed hydration.
The mechanism goes through a three-membered ring which can r eactwith other nucleophiles such as alcohols, amines and thiols. HN
Hg +En
+En
1) EtNH2
OAc
Unlike H2SO4andHg(OAc)2,Hyd roboration-Oxidation is used for Anti-Markovnikov hydroxylation.
Hydroboration is a concerted, syn addition, so the Hand OH appear o n the same side in the product.
For better stereoselectivity, bulky dialkylboranes such as 9-BBN (R2BH general formula) are used.
1) BH3, THF
+En
HBH2
+En
HOH
Like for any other exercise,
numbering the carbon chain will
help a lot!
1
2
3
456
1) O3
2) Me2S
1
2
3
4
5
6
O
O
H
The syn dihydroxylation with KMnO4works only
at lowered temperatures. If heat is applied, the
double bond is cleaved:
KMnO4
warm
O
O
+
H
O
OH
OH
HO
glycol ketone aldehyde-oxidized
acid
O+
ketone
An epoxide is a strained three-membered,
cyclic ether that can be reacted with many other
nucleophile since epoxides are very reactive. Nu
OH
O
+En
1) Nu
+En
In epoxide opening, the nucleophilic attack generally occurs at the more
substituted carbon atom for weaknucleophiles and at the less substituted
carbon atom for str ong nucleophiles.
2) H2O
Stereochemistry is the key in halogenation of a double bond. A three-membered ring intermediate
(bridged halonium ion) is formed uponaddition of the first halogen and the second onecan only
add from the opposite side.Thus, trans enantiomers formed by anti addition.
Br2
Br
Br +En
+En
Br
Br
Same mechanism as bromination. Only the bridgedhalonium ion is attacked by the water here.
Key point for regiochemistry: the water attacks the more substitut ed carbon of the ring.
Key point for stereochemistry: the Br and OH are trans since H2O attacks from t he opposite side. OH
Br +En
+En
Br
H2O
Other catalysts such as Pt or Ni can also be used forcat alytichydrogenation
of alkenes. It is a syn addition.
For homogeneous reactions, Wilkinson's catalyst is used instead of metals.
It is a stereospecific reaction and depending on the
configuration of the alkene, cis or trans productis obtained:
There is no stereoselectivity and a maximum
number of stereoisomers can be formed.
O+
O
To predict the structure of star ting alkene,
connect the two carbons of car bonyl with a
double bond:
connect
1
2
3
41231
23
1
2
3
4
Rh(Ph3P)3Cl
H2(1 atm)
Wilkinson's catalyst
Carried out in solution
RR
CH2I2
Zn, CuCl
(Z) Cis
R
CH2I2
Zn, CuCl R
R
H2
C
(E) Trans
R
R
R
H2
C
2) H2O2, NaOH
X= F, Cl, Br. I
