CHEM 203
Topics Discussed on Oct 2
Reaction of alkenes with molecular halogens (Cl2, Br2, sometimes I2, but not F2 – see below):
X
X
X
X
C
C
C
C
X = Cl, Br, sometimes I
notice how the above reaction reflects the general pattern of reactivity of olefins (notes of Sept 18)
Violent, exothermic reaction of F2 with alkenes (and organic matter in general) due to the
extreme reactivity of F2 toward carbon-based compounds, as a consequence of which the
fluorination of alkenes is not a reaction of interest
Description of the above reaction as the halogenation (chlorination, bromination, iodination, …)
of an alkene
Description of the product as the above reaction as a 1,2-dihalide or vicinal dihalide (dichloride,
dibromide, diiodide…)
Absence of rearrangements during the halogenation of olefins, ruling out the intervention of
carbocation intermediates (notes of Sept. 25)
Example:
Br
Br
Br2
no
Br
formed
Br
Mechanistic aspects of the halogenation reaction: predicted initial interaction of the π system
with a halogen molecule, e.g., Cl2, leading to a chloronium ion:
lobes of the σ*Cl–Cl orbital
(phases omitted for clarity)
C
C
Cl
Cl
populating the σ*Cl–Cl orbital
breaks the Cl–Cl bond ...
every atom has
a Lewis octet:
C Cl
+
Cl
Cl
much more stable
C
than a hypothetical ... C
chloronium ion
C with only 6 electrons:
highly unfavorable
C
notice how electrons flow from the less electronegative C to the more electronegative Cl
Chloronium, bromonium, iodonium, … halonium ions
Concerted (= simultaneous creation / breakup of two or more bonds) formation of halonium ions
Halonium ions as exceedingly reactive, strained electrophiles, which nonetheless are isolable in
some favorable cases
Lecture of Oct 2
p. 2
Rapid SN2-like reaction of the halonium (chloronium, bromonium, …) ion with halide (chloride,
bromide, …) ion through donation of an electron pair into the C–X σ* orbital:
Cl
C
large lobes of the
σ*Cl–Cl orbitals
C
Cl C
Cl
C Cl
Stereochemical aspects of the halogenation reaction: possible formation of stereoisomeric
products.
Example. The addition of Br2 to cyclohexene could produce the following stereoisomeric
products:
Br2
Br
[?]
Br
Br
&/or
A
Br
&/or
Br
&/or
Br
Br
B
C
Br
D
In products A and B the Br atoms
point in the same direction relative
to the plane containing the ring.
In products C and D the Br atoms
point in opposite directions relative
to the plane containing the ring.
The Br atoms are in a cis relationship
The Br atoms are in a trans relationship
A and B are thus cis isomers
A and B are thus trans isomers
Now . . .
Structures A and B are different projections of the same molecule; i.e., they represent the
same thing (the cis isomer)! This cis isomer is achiral, even though it possesses stereogenic
carbons; therefore, it is a meso compound.
Structures C and D are enantiomeric forms of the trans isomer: their thermodynamic properties
are identical: if they should form, they will be obtained as a 50:50 mixture.
The cis and the trans isomers are one a diastereomer of the other. But…: diastereomers
possess distinct thermodynamic properties:
could the halogenation reaction form preferentially one type of diastereomeric product ?
Terminology used to describe the stereochemical outcome of the addition of a generic agent X–Y
to a π system: syn and anti additions
Syn addition of a generic molecule X–Y to the π system of an alkene (e.g., cyclohexene): a
process during which the X and Y atoms add from the same face of the π system:
X
Y
H
syn addition
H
C
C
plane of the
olefinic system
H
of X–Y
H
C
C
H
X and Y add to the
same face (e.g., top
face) of the π bond
H
Y
X
cis - isomer
product of
syn addition
Lecture of Oct 2
p. 3
Anti addition of a generic molecule X–Y to the π system of an alkene (e.g., cyclohexene): a
process during which the X and Y atoms add from opposite faces of the π system:
X
H
anti addition
H
C
C
of X–Y
H
plane of the
olefinic system
H
C
C
X and Y add to
opposite faces
of the π bond
H
Y
product of
anti addition
X
H
trans - isomer
Y
The formation of bromonium (halonium) ions as a syn addition process:
The reaction must start with the formation of a bromonium ion without the intervention of
carbocationic intermediates. The halogen molecule "deposits" a Br atom onto the double bond
through a mechanism that involves the simultaneous motion of three electron pairs (concerted
mechanism):
σ*Br–Br orbital
Br
Br
Br
Br
H
C
C
H
H
C
C
H
then, the bromonium ion undergoes SN2-like reaction with the halide (bromide, chloride..) ion:
Br
Br
Br
"blue"
"red"
H
C
C
Br
H
H
Br
Br
H
mech.
H
large lobes
of σ*C-Br
C
C
mech.
H
H
C
C
H
Br
H
Br
only the trans-diastereomer can form
in this reaction!
H
Br
Br
The halogenation (e.g., bromination) of alkenes as an overall anti addition
consequence: the cis-isomer of the product is unavailable by any reaction yet known to us
cis-1,2-dibromocyclohexane
(unavailable by any reaction
yet known to us in CHEM 203)
Br
Br
Br
Br
trans-1,2-dibromocyclohexane:
available by bromination of
cyclohexene
The halogenation of olefins as a diastereoselective reaction (it selectively forms one diastereomer)
Lecture of Oct 2
p. 4
Achiral nature of Br2 (molecular halogens in general) and cyclohexene
Chiral nature of the product of bromination (halogenation) of cyclohexene (trans-1,2dibromocyclohexane) and consequent formation of a racemic mixture through the statistically
equally probable occurrence of the "red" and "blue" mechanisms above:
H
H
Br
(R) (R)
Br
H
Br
(S) (S)
Br
H
enantiomeric forms of
the trans-diastereomer
Principle: mechanistic constraints force the halogenation reaction of any alkene to proceed in
the anti mode.
Stereochemical outcome of the halogenation of an acyclic olefin, e.g. the chlorination of transand cis-2-butene:
Cl
H
H3C
CH3
trans-isomer
H
Cl2
antiaddn.
H
(R)
H3C
H
plane of the olefinic system
Cl
(R)
Cl
Cl
rotate about
(S)
Cl
CH3
(S)
Cl
central C–C
bond
this molecule is achiral
even though it contains
stereogenic centers:
it is a meso form
plane of symmetry
Cl
H
H3C
H
cis-isomer
CH3
antiaddn.
plane of the olefinic system
(R)
Cl
rotate about
Cl
(R)
central C–C
bond
H
Cl2
H3C
(R)
(R)
H
CH3
Cl
(R)
Cl
chiral molecule,
formed in a 50:50
(R) ratio together with
Cl
Cl
(S)
(S)
Cl
Enantiomeric relationship between the R,R- and the S,S-isomer (non-superimposable mirror
images)
Diastereomeric relationship between R,R- and the R,S-isomer or the S,S- and the R,S-isomer
(stereoisomers that are not mirror images)