Chapter 4 Stereochemistry and Chirality Flow chart for determining ...

Chapter 4 Stereochemistry and Chirality
if different
connectivity
ISOMERS
CONSITUTIONAL
ISOMERS
if they have
same connectivity
CONFORMATIONAL
ISOMERS
ENANTIOMERS
if a rotation about σ
bond makes
them identical
if they are
nonsuperimposable
mirror images
STEREOISOMERS
CONFIGURATIONAL
ISOMERS
if bonds must be broken and
reformed to make them identical
if they are not
nonsuperimposable
mirror images
Z, E ISOMERS
(DIASTEREOMERS)
if they have
no stereogenic
centers
DIASTEREOISOMERS
Flow chart for determining the relationship between isomers.
1

Symmetry Elements
A mirror plane in Cartesian coordinates that includes the y and z axis
means that for every point {x,y,z} there is a corresponding point {–x,y,z}. Ifa
molecule has a mirror plane, then for every atom on one side of the plane there
is an equivalent atom that is the mirror equivalent on the opposite side of the
plane. When two identical groups are on one carbon, there is an internal mirror
plane passing through the molecule.
H
H
H
O
H
H
H
H
H
2

Symmetry Elements (continued)
An inversion center takes every point {x,y,z} to an equivalent point
{–x,–y,–z}:
Br
CH 3
H
H
H
H
H 3 C
Br
3

Chirality
The word "chirality" (from the Greek) refers to the property of "handedness".
To first approximation your right and left hands are mirror images that cannot
be superimposed on top of each other.
4

Chirality (continued)
Molecules that lack both a mirror plane and an inversion center can have nonsuperimposable
mirror images and are said to be chiral. A chiral center
usually is a tetrahedral carbon with four different groups attached to it. Chiral
carbons are also referred to as stereocenters, stereogenic centers, or
asymmmetric centers.
1-Bromo-1-chloroethane is chiral:
1
H
H
4
3
2
H 3 C
Br
Cl
Br
Cl
CH 3
H
H
H 3 C
Br
Cl
H 3 C
Cl
Br
H
CH 3
H 3 C
Br
Cl
H
Br
Cl
5

Chirality (continued)
Any molecule that has an internal mirror plane is achiral.
Cl
Br
H
H
H 3 C CH 3
Cl
Cl Br Br
H 3 C CH 3
Cl
Cl
Br Br
A molecule that has an inversion center is achiral.
Br
CH 3
H 3 C
Br
H
H
H
H
H
H
H
H
H 3 C
Br
Br
rotate 90°
CH 3
Br
CH 3
H
CH 3
H
H
H
H
H
Br
Br
H
H 3
C
Br
H 3 C
H
rotate 180°
6

Chirality (continued)
Further examples of achiral and chiral molecules:
HO
OH
H
H
Br
Br
H
Cl
Cl
H
achiral achiral achiral
HO
OH
Cl
H CH 3
Br
H 3 C
H
Cl
Cl
H
Br
chiral chiral chiral
7

Stereoisomers: Enantiomers
Molecules that are mirror images but are not superimposable are called
enantiomers. Enantiomers are stereoisomers. That is, they are isomers that
have the same connectivity, but have groups that occupy different regions of
space.
Enantiomers have the same physical properties (e.g. melting points,
boiling points, etc) but differ in the way they interact with other chiral objects
(e.g. polarized light or different chiral molecules).
It is possible to have a molecule with no chiral center that is chiral.
Consider 1,3-dimethylallene, shown below:
H 3 C
•
H
H
•
CH 3
H
CH 3
H 3 C
H
H 3 C
H
•
H
CH 3
H 3 C
H
•
H
CH 3
H 3 C
•
H
H
•
H
H
CH 3
H 3 C
CH 3
8

Stereoisomers: Diastereomers
Stereoisomers that are not enantiomers are called diastereomers.
H 3 C
C 2 H 5
Cl
Br
Br Cl
H 3 C
C 2 H 5
Br
Br
Cl Cl
For a molecule with multiple chiral centers, the number of possible
stereoisomers is given by:
x = 2 n
where x is the number of possible isomers and n is the number of chiral centers.
Thus, for molecules with two chiral centers there are four possible
stereoisomers. (e.g. cholesterol, which has eight stereogenic centers, has 256
possible stereoisomers!! )
9

Stereoisomers: Meso compounds
Another type of stereoisomer is called a meso compound.
• A meso compound contains at least two stereogenic centers, yet the
molecule itself is not chiral.
• Meso compounds contain an internal plane of symmetry.
H 3 C CH 3
Cl
Cl Br Br
H 3 C CH 3
Cl
Cl
Br Br
.
10

Cahn-Ingold-Prelog Convention for Assigning Absolute Configurations
The rules for assignment of priorities in order to assign absolute configuration
are based on the same set of rules for assigning E and Z stereochemistry. Use
the Cahn-Ingold-Prelog scheme to assign priorities to the groups attached to
the carbon atom as follows:
I. Consider each group attached to the carbon in question separately.
II. Rank the priority of the substituent on the carbon as follows.
A. The atom with the higher molecular weight takes top priority. If
there are two isotopes of the same atom, the isotope with the higher
mass takes priority.
B. If this does not distinguish, then move down the chain of the
substituent assigning priorities until you reach the first point of
difference.
III. Multiple bonds count as multiples of that same atom.
IV. Once the priorities have been assigned, rotate the molecule in space so
that the lowest priority group is pointing back.
V. Connect the three remaining groups in order of decreasing priority and
examine the direction of the resulting rotation.
VI. Clockwise rotation is termed R (rectus; right) and counterclockwise
rotation is termed S (sinister; left).
• Alternatively, if the lowest priority is NOT in the back simply switch the
group that is lowest priority with another group. You have just made the
mirror image of the molecule. Now assign R or S to the compound as it
IS drawn, and then SWITCH THE R AND S LABEL TO GET THE
ORIGINAL COMPOUNDS.
11

Cahn-Ingold-Prelog Convention for Assigning Absolute Configurations
H
Cl
H 3 C
Br
Cl
120° rotation
H 3 C
H
Br
4
2
120° rotation
1
4
3
2
3
1
Counterclockwise = S
12

Fischer Projections
The conversion of a perspective drawing to a Fischer projection requires
rotating the molecule so that the "top" and "bottom" groups are oriented back,
away from you as is shown for the two molecules below.
H
H
H 3 C
OH
H 3 C
OH
CH 2 OH
CH 2 OH
HO
H
H
HO
H
OH
H
OH
CHO
CH 2 OH
H
HO
H
H
H
OH
OH
CH 2 OH
CHO
OH
A Fischer projection can be used to assign absolute configuration (R or S).
4
4
3
1
3
1
2
4
R
2
4
1
3
1
3
2
S
2
13

A rotation of three groups, as shown below, is equivalent to rotating the
molecule around a single bond (here the CH 3 -C central bond).
H 3 C
H 3 C
HOH 2 C
H
HO
CH 2 OH
OH
H
A 180 degree rotation of the entire molecule regenerates the identical
configuration.
OH
OH
H
CH 2 OH
H
CH 2 OH
CH 3
CH 3
S
CH 3
H 3 C
HOH 2 C
H
HOH 2 C
H
OH
S
OH
Are we having fun yet
14

A 90 degree rotation of the entire molecule generates the enantiomer of the
original molecule.
H
H
H 3 C
OH
H 3 C
OH
CH 2 OH
R
CH 2 OH
OH
OH
H
CH 2 OH
H
CH 2 OH
CH 3
S
CH 3
If you flip the molecule out of the page, you generate the enantiomer of the
original molecule.
H
H
H 3 C
OH
H 3 C
OH
CH 2 OH
R
CH 2 OH
H
H
CH 2 OH
HO CH 3
S
CH 2 OH
HO CH 3
15

Fischer projections are also very convenient for identifying whether pairs of
molecules are identical, enantiomers or diastereomers.
For example:
H
H
HO
CH 2 OH
Enantiomers
HOH 2 C
OH
H 3 C
OH
HO
CH 3
H
H
Diastereomers
Diastereomers
Diastereomers
H
H
HO
CH 2 OH
Enantiomers
HOH 2 C
OH
HO
CH 3
H 3 C
OH
H
H
16

In summary:
• Exchanging any two groups around a Fischer projection generates the
enantiomer of the original compound.
• Rotating 90° generates enantiomers.
• Flipping the molecule out of the page generates enantiomers.
• Rotating 180° regenerates the same molecule.
• Rotating three groups is like a rotation about a bond and does not change
the configuration.
• Exchanging groups twice regenerates the original stereochemistry.
Review:
• A molecule with one chiral center will be chiral.
• A molecule need not have a chiral center to be chiral.
• A molecule with an inversion center cannot be chiral.
• A molecule with one or more internal mirror planes cannot be chiral.
A molecule can have more than one chiral center and not be chiral (if the chiral
centers are symmetry related by a mirror plane or an inversion center).
17

If you have a molecule with two chiral centers with different sets of things
attached (1 and 2) either which can be R or S, there are four possible molecules
that can result:
(1R, 2S), (1R, 2R), (1S, 2S), (1S, 2R).
• Since for a single chiral center R and S are related by mirror symmetry then
if in a molecule all possible centers are switched from R to S and vice versa,
then the resultant molecule will be an enantiomer of the original molecule.
• If one or more chiral centers, but not all centers are switched from R to S, the
molecules will not be related by mirror images, and therefore are not
enantiomers.
Such molecules are called diastereomers and they have
different physical and chemical properties.
This is illustrated in the example below:
1
2
Cl
Cl
OH Diastereomers OH
(1R, 2R) (1S, 2R)
Enantiomers
Enantiomers
Diastereomers
(1S, 2S) (1R, 2S)
Diastereomers
Cl
OH
Cl
OH
18

If you have a molecule with two chiral centers with the same sets of things
attached (1 and 2) either which can be R or S, four possible molecules that can
result:
(1R, 2S), (1R, 2R), (1S, 2S), (1S, 2R)
The following relations will hold as illustrated below:
OH
H 3 C H
H 3 C
1 OH
H
2 H
OH
H 3 C
H 3 C
OH
H
Enantiomers
(1R, 2R) (1S, 2S)
Diastereomers
Diastereomers
(1R, 2S) (1S, 2R)
Identical, MESO
H 3 C
H 3 C
H 3 C
H
OH
OH
H
H 3 C
OH
H
H
OH
The chemical and physical properties of diastereomers can be completely
different. Thus, they will react at different rates and can have different melting
and boiling points etc.
The properties of enantiomers will be identical (so long as they are not
interacting with a chiral perturbation as will be described in more detail later).
Thus, they react with achiral materials at the same rates and have identical
melting points.
19

Disubstituted Cyclohexanes
Cis and trans isomers can be drawn as planar views that are convenient for
looking for symmetry elements. Thus cis 1,2-dimethylcyclohexane can be
drawn as shown below. Note: that the isomers with both methyl groups up out
of the page is related to that with both into the page by rotating 180° about an
axis as shown below:
Note also that in the planar view there is a mirror plane perpendicular to the
page bisecting the C-C bonds with the methyl groups attached, thus we
conclude that the molecule is achiral. This is not obvious looking at the mirror
image in the chair form until you take into account that the molecule is
conformationally flexible and a rotation followed by a chair-chair-flip makes
the mirror images congruent.
20

otate 120°
chair-chair
flip
noncongruent
rotate 120°
Note that if you cooled cis 1,2-diethycyclohexane to a temperature at which the
chair-chair flip was extremely slow, then the two mirror images would be
nonconguent and in principle you could separate each of the enantiomers.
In contrast the trans form of 1,2-dimethylcyclohexane has no mirror plane
when drawn in the planar form. It does however have a two-fold axis of rotation
which relates the up and down methyl groups.
Since there is no mirror (and no inversion center) the trans form is chiral and
we would therefore expect the mirror image not to be superimposable on the
original molecule as shown below.
rotate 120°
rotate 180°
noncongruent
noncongruent
21

1,3-dimethylcyclohexane
• If we consider cis and trans 1,3-dimethylcyclohexane then we see again that
the cis isomer has a mirror plane and the trans isomer does not.
• Note also that in the chair form both the axial-axial, and the equatorialequatorial
forms have mirrors as drawn and thus are achiral even when each
form is frozen out at low temperature.
chair-chair
flip
22

Equivalence
Homotopic hydrogens: If you have two identical molecules each with a
methylene group of the form X- CH(1)H(2)-X, and you replace one of the
hydrogens of the H(1) in one molecule with a dummy atom (Y) and then you
independently replace the H(2) in the other molecule with a dummy atom(Y), if
then the two molecules thus created will be identical to each other, the
hydrogens are said to be homotopic. (e.g. The protons on a methyl group are
homotopic)
H
X
C
X
H
Y
H
X
C
X
X
C
X
H
Y
Identical
Enantiotopic: If you have a methylene group of the form X- CH 2 -Z, and you
replace one of the hydrogens of the CH 2 with a dummy atom and then you
independently replace the other hydrogen of the CH 2 group with a dummy
atom (Y), the two molecules thus created will be enantiomers of each other.
The protons are said to be enantiotopic. In a nonchiral environment
enantiotopic protons are equivalent. However, in a chiral environment such as
a chiral solvent, they can, in principle, have different chemical shifts.
H
Z
C
X
H
Y
H
Z
C
X
Z
C
X
H
Y
Enantiomers
23

Diastereotopic: If you have a methylene group for example, in a chiral
molecule X- CH 2 -Z* (where the * indicates that Z is a chiral group), and you
replace one of the hydrogens of the CH 2 with a dummy atom (Y) and then you
independently replace the other hydrogen of the CH 2 group with a dummy
atom the two molecules thus created will be diastereomers to each other. Thus,
in principle, the two hydrogens should have different chemical shifts.
H
Z*
C
X
H
Y
H
Z*
C
X
Z*
C
X
H
Y
Diastereomers
24

On The Interaction of Enantiomers with Chiral Perturbations:
A chiral perturbation is any physical or chemical perturbation that has a
handedness.
• Let us assume that we have a pair of chiral acids that are enantiomers. If a
solution is made up of equal amounts of the R and S isomers, the mixture is
said to be racemic.
• If sodium hydroxide is added to the solution, then the acids will be
deprotonated and will result in a racemic solution of the carboxylate anions.
• We then crystallize them with a chiral cation as shown below:
H 3 C
Enantiomers
H 3 C
H
H 3 C
R
COO
H 3 C
H
S
COO
H 3 C
H 3 C
H
N
S
H 3 C
H 3 C
H 3 C
H 3 C
H
H 3 C
R
COO
H 3 C
H
N
S
H 3 C
H
S
COO
H 3 C
H
N
S
Diastereomers
25

• In such a case the two salts that are formed are diastereomers. (Remember:
they will have different physical properties including melting points and
solubility)
• As a result of these different physical properties, one salt may preferentially
crystallize from the solution leaving the other behind. If the crystallized salt
is isolated and then acidified, the chiral acid of just one of the enatiomers
will be regenerated. Such as process is call a chemical resolution of
enantiomers.
Note: There are many examples of interactions of chiral molecules with
chiral perturbations leading to diastereomeric interactions.
• Different molecules can be separated by chromatography. If the stationary
phase is chiral, then each enantiomer in a racemic solution will interact
differently with the stationary phase since the interactions will be
diastereomeric. As a result, each enantiomer may move through the chiral
material at a different speed. Thus, a chiral resolution can be effected.
26

The Interaction of Chiral Molecules with Light
• Plane polarized light is light wherein the electric field oscillates in one plane.
• Plane polarized light can be thought of being made up of a superposition of
two chiral and opposite circularly polarized electric fields.
• If we now consider each hand of the circularly polarized light interacting
with one enantiomer of the chiral carboxylate that we considered above, we
see that the interaction of the light with the molecule is a diastereomeric
interaction.
• Accordingly, the index of refraction (speed of light in the solution relative to
that of light in a vacuum) for the left and right circularly polarized light will
be different. Thus, one hand of the circularly polarized light will get slowed
down more.
H 3 C
H 3 C
H
H 3 C
R
COO
H
H 3 C
R
COO
diasteriomeric interaction with each
hand of circularly polarized light
27

• As a result when the light passes through a cell containing a non-racemic
assembly of chiral molecules, the phase shift of one hand of the circularly
polarized light relative to the other will result in the plane of light being
rotated by angle α. Such a solution is optically active. 0
in
α
out
• Since a racemic solution has equal amounts of chiral molecules that have
opposite configurations, for each molecule rotating the light in one direction,
there will be a molecule of opposite configuration rotating the light in the
opposite direction. Thus, the two rotations will cancel, and there will be no
net rotation of light. Such a solution is not optically active. = 0
Note: A solution of a meso compound is not chiral, and it is not racemic. A
racemic solution is made up of an equal mixture of chiral molecules. Since a
meso compound is not chiral, it is not optically active. = 0
28

Amine Inversions
Tertiary amines substituted with three different groups in frozen configurations
are chiral. Thus, their mirror images are not superimposable.
H 3 C
N
H
CH 2OH
HOH 2C
H
N
CH 3
.
However there is a process called amine inversion wherein the substituents on
the nitrogen distort through a plane transition state such that there is an
inversion of configuration:
H 3 C
H
CH 2 OH
H 3 C
N
H
CH 2 OH
H 3 C
N
H
CH 2 OH
29

Such a process creates the enantiomer of the original molecule:
H 3 C
N
H
CH 2 OH
HOH 2 C
H
N
CH 3
H 3 C
N
H
CH 2 OH
• This inversion process, which is an equilibrium, will take a single chiral
isomer into a racemic mixture. Any process that allows one chiral isomer to
interconvert with its enantiomer is termed racemization.
• Since amine inversion can be fast at room temperature, it is often impossible
to isolate one enantiomer of chiral amines. For example in ammonia the
barrier for inversion is 5.8 kcal/mol (the rate at ambient temperature is about
2 x 10 11 / sec), and for methylamine the barrier for inversion is 4.8 kcal/mol.
If a chiral amine has the nitrogen tied down into a bicyclic ring system, then it
would be impossible for the nitrogen to invert without introducing an
unreasonable amount of strain into the molecule. In such cases, it should be
possible to isolate one enantiomer:
1
N
3
2
R
It is possible to assign configurations to chiral amines. Simply use the Cahn-
Ingold-Prelog convention and always assign the lone pair the lowest priority.
30

Stereoselective and Stereospecific Reactions.
• Regioselective reaction: A reaction in which one structural isomer is
formed preferentially over another. (In some cases, this preference can be
extremely lopsided such that essentially only one isomeric product is
formed. In such cases, this is termed a regiospecific reaction.)
• Stereoselective reaction: Is a reaction in which one stereoisomer in a
mixture is created or consumed more quickly than other, such that one
stereoisomeric product is preferentially formed.
Note: a reaction can be moderately or very stereoselective.
• Stereospecific reaction: A reaction in which relative chemistry of starting
materials defines, due to the mechanism of the reaction relative
stereochemistry of the products is stereospecific
Note: all stereospecific reactions are stereoselective, but the reverse is not
necessarily so.
Consider the reaction of Br 2 with Z, and E-2-butene:
H 3 C
BrH
Br 2
CH 3
H 3 C
CH 3
Br H
meso
H 3 C CH 3 Br 2
HBr
H 3 C
CH 3
Br H
R,R
BrH
CH
H 3 C
3
HBr
S,S
Here the mechansim, i.e. anti addition of the bromine to the double in combination
with the stereochemistry of the starting materials (cis or trans) determines the
stereochemistry of the products.
31

Enantiomeric and Diastereomeric Transition States
Achiral molecule reacts with an achiral reactant: If an achiral molecule or
intermediate interacts with an achiral reactant then the transition state will be
either be achiral or enantiomeric (if a chiral center is being formed).
Br
H 3 C
Br
H
CH 2 CH 3
H 3 C
Br
H
CH 2 CH 3
R
+
H 3 C CH 2 CH 3
H
Br
S
Enantiomeric transition states have the same energy. Thus, the R and S isomer
will form at identical rates and a racemic mixture will always result.
R
S
R
Achiral
S
Chiral molecule reacts with a chiral reactant: If a chiral molecule or
intermediate interacts with a chiral reactant then the transition state will be
diastereomeric.
Ph
R
H
CH 3
R
R
Ph
R
H
CH 3
H
B
H
Ph
H
CH 3
B
B
H
CH 3
S
H
PH
CH 3
S H
H
Ph
B
H
CH 3
H
Ph
B
32

Enantiomeric and Diastereomeric Transition States (continued)
Therefore, each transition state will be a different energy and the diasteriomeric
products will be formed at different rates, and they will have different energies.
R RR
S RR
S and R
S RR
R RR
Achiral molecule reacts with a chiral resolved reagent: If an achiral
molecule interacts with a chiral resolved reagent (such as an enzyme) in such a
manner that in the transition state one or more chiral centers is being formed,
then the transition states for the R or S center will be diastereomeric. Therefore,
the R and S product will form at different rates.
fumarase
S
fumarase
S
OH
H 2 O
H
OOC
Achiral
COO
H
H
OOC
HO
H
Achiral
COO
H
OOC
H
S
CH 2 COO
34

Enantiomeric and Diastereomeric Transition States (continued)
R RR
S RR
S and R
S RR
R RR
In the case of an enzyme this stereoselectivity (i.e. the preferential formation of
one stereoisomer over another) can be very high such that in biological systems
often only one isomer is formed.
This means that the two diastereomeric transition states are most likely different
in energy by 3 kcal/mol or more.
Tremendous effort has been devoted toward developing reagents and catalysts
for use in organic synthesis that work in much then same manner such that a
chemist can select the chiral configuration of a given center. (A Nobel Prize
was awarded for this last year).
35

Inversion of Configuration
In a nucleophilic substitution reaction that is concerted (i.e. bonds are being
made and broken at the same time), the nucleophile (Nu) attacks the molecule
from the side opposite from the group that will leave (called the leaving group,
LG) (left).
A
B
A
B
B
A
Nu
LG
Nu
LG
Nu
LG
C
C
C
• As this happens the other groups distort to accommodate the incoming
group and the molecule goes through a transition state that is basically
symmetrical (middle).
• Then as the bond forming step with the nucleophile is completed and the
leaving group departs, the geometry of the rest of the molecule continues to
relax in such a way to restore tetrahedral geometry about the central carbon
atom (right).
• This process involves a net inversion of configuration as illustrated in the
example below.
Cl
H 3 C
H
Cl
δ
Cl
H CH 3
δ
Cl
Cl
CH 3H
Cl
D
D
D
S
R
• Note that with this degenerate substitution of Cl - for Cl - the configuration is
inverted.
36

Stereochemistry of "Carbocation" - Addition to Alkenes
C
A
D
E
B
Nu
C
Nu
A
D
B
E
C
A
Nu
E
D
B
C
A
B
D
E Nu
E
D
C
Nu
B
A
E
D
C
B
Nu
A
Nu
C
A
top or bottom
addition
D
E
B
Nu
C
A
Nu
E
D
B
D
E
C
Nu
Nu
A
B
E-Nu E-Nu E-Nu
START
HERE!!
C
A
D
B
C
A
B D
C
D
A
B
E-Nu E-Nu E-Nu
top or bottom
addition
C
A
E
D
B
Nu
A
C
E
B
D
Nu
D
C
E
Nu
Nu
B
A
Nu
C
A
E
D
Nu
B
C
A
Nu
D
E
B
A
C
E Nu
B D
A
C
E
Nu
B
D
C
D
E
B
Nu
A
C
D
E
Nu
B
A
37

Stereochemistry of Syn- Addition to Alkenes
A
Y
B
C
Y
X
C
X
Y
C
D
X
A
D
B
D
B
A
rotatate
60°
A
C
B
Y
X
D
A C
X Y
D
B
X
C
D
Y
B
A
X Y X Y X Y
START
HERE!!
A
C
B
D
C
A
B D
C
D
A
B
X Y X Y X Y
A
Y
B
A D B
C
C
D
B
A
C
X
D
Y X
X
Y
rotatate
60°
Y
C
A
X
B
D
C
Y
A
X
D
B
D
X
C
Y
B
A
38

39
B
A
C
D
A
B
D
C
D
B
C
A
B
A
C
D
E
A
B
C
D
E
Nu
E
A
B
C
D
B
Nu
A
E
C
D
D
B
C
A
E
D
B
C
A
E
Nu
B
A
C
D
E
B
C
D
E
Nu
E
A
B
C
D
B
Nu
A
E
C
D
D
B
C
A
E
D
B
C
A
E
Nu
A
E-Nu
Nu
inversion
Nu
E-Nu
E-Nu
Nu
inversion
inversion
Nu
inversion
Nu
Nu
inversion
inversion
E-Nu E-Nu E-Nu
Stereochemistry of Anti- Addition to Alkenes
START
HERE

Addition to 1-Methyl Cyclohexane
E Nu
X 2
Hg(OAc) 2
HOX
where X = Br Cl
E
Nu
E
E
Nu
substitution
with
INVERSION
E
Nu
E
Nu
E
E Nu
E
HX (DX)
HX (DX), H 2 O
HX (DX), ROH
where X = Br Cl
Nu
E
E
Nu
syn and
anti
addition
E
Nu
E
Nu
E
D
D
D
D
Nu
E
E
Nu
E
X
1. X Y
Y 2. step 2
syn addition
E
X
Y, (Y')
X
Y
H 2 BH
OOs(O) 2 O
OMn(O) 2 O
H-H, catalyst
X
Y
X
Y, (Y')
40

E Nu
H
H
X 2
Hg(OAc) 2
HOX
where X = Br Cl
E Nu
H
E
H
E
Nu
substitution
with
INVERSION
E
H
Nu
H E
H
Nu
E
H
E
H
NuH
E
H
H
Nu
H
H
E Nu
HX (DX)
HX (DX), H 2
O
HX (DX), ROH
where X = Br Cl
E Nu
H
E
H
H
E
H
Nu
syn and
anti
addition
E
H
Nu
E
H
Nu
E
H
D
D
D
D
E
Nu
H
E
Nu
H
E
H
X
Y
H
H
H 2 BH
OOs(O) 2
O
OMn(O) 2 O
H-H, catalyst
H
1. X Y
Y X 2. step 2
H
syn addition
X
H
X
Y
H
Y
Y
X
Addition to Cis Double Bonds
E
H
H
X
Y, (Y')
H
X
H
Y, (Y')
H
Y, (Y')
H
X
H
Y, (Y')
X
H
Homework draw out all the products for each of these additions for (E)-2-
pentene.
41