Formation of glycols with Syn Addition
Osmium tetroxide
Syn addition
also
KMnO4
KMnO4
cold, dilute, slightly alkaline
Anti glycols
Using a peracid, RCO3H, to form an epoxide which is opened by aq. acid.
H+
PhCO3H, a peracid
H2O
O
O
H
HO
epoxide
The protonated epoxide is analagous
to the cyclic bromonium ion.
O
O
OH
Peracid: for example, perbenzoic acid
OH
An example
PhCO3H
O
+
O
(S)-3-methylcyclohex-1-ene
aq. acid
chiral, optically active
OH
OH
OH
OH
OH
OH
Diastereomers, separable (in theory) by
distillation, each optically active
OH
OH
Are these
unique?
Ozonolysis
R3
R1
1. O3
R1
R3
O
R4
R2
2. (CH3)2S
R4
+
O
R2
Reaction can be used to break larger molecule down into smaller parts
for easy identification.
Ozonolysis Example
For example, suppose an unknown compound had the formula C8H12 and upon
ozonolysis yielded only 3-oxobutanal. What is the structure of the unknown?
The hydrogen deficiency is 18-12 = 6.
6/2 = 3 pi bonds or rings.
The original compound has 8 carbons and the ozonolysis product has only 4
Conclude: Unknown  two 3-oxobutanal.
Unknown ozonolysys
C8H12
O
O
O
O
O
Simply remove the new oxygens and join to make double bonds.
But there is a second possibility.
Another Example
2. An unknown compound (derived from the gall bladder of the gila monster) has the formula
C10H14 . When subjected to ozonolysis the following compound is isolated
O
Suggest a reasonable structure for the unknown.
d
Hydrogen Deficiency = 8. Four pi
bonds/rings.
O
a
O
c
Unknown has no oxygens. Ozonolysis
product has four. Each double bond
produces two carbonyl groups. Expect
unknown to have 2 pi bonds and two rings.
b
O
To construct unknown cross out the oxygens and then connect. But there are many
ways the connections can be made.
a-b & c-d
d
a-d & b-c
a-c & b-d
c
a
c
Look for a structure
that obeys the
isoprene rule.
d
d
a
c
b
a
b
b
Mechanism
Consider the resonance structures of ozone.
Electrophile
capability.
Nucleophile
capability.
O
O
O
O
O
O
O
O
O
O
O
O
These two, charged at
each end, are the useful
ones to think about.
Mechanism - 2
O
O
O
O
O
O
O
O
O
O
O
O
Mechanism - 3
Mechanism - 4
Hydrogenation
No regioselectivity
Syn addition
Heats of Hydrogenation
Consider the
cis vs trans
heats of
hydrogenation
in more
detail…
Heats of Hydrogenation - 2
The trans alkene has a lower heat of hydrogenation.
Conclusion:
Trans alkenes with lower heats of hydrogenation are more stable than cis.
We saw same kind of reasoning when we talked about heats of combustion of
isomeric alkanes to give CO2 and H2O
By same reasoning higher degree of substitution provide lower heat of
hydrogenation and are, therefore, more stable.
Reduced heat of Hydrogenation
Increasing substitution
Heats of Hydrogenation
Acid Catalyzed Polymerization
Principle: Reactive pi electrons (Lewis base) can react with Lewis acid. Recall
H
+ H
Which now reacts with a Lewis base,
such as halide ion to complete addition
of HX yielding 2-halopropane
Variation: there are other Lewis bases available. THE ALKENE.
+
the carbocation is an acid!
The new carbocation now reacts with a Lewis base such as
halide ion to yield halide ion to yield 2-halo-4-methyl
pentane (dimerization) but could react with another
propene to yield higher polymers.
Examples of Synthetic Planning
OH
Give a synthesis of 2-hexanol from any alkene.
Planning:
Alkene is a hydrocarbon, thus we have to introduce the OH group
How is OH group introduced (into an alkene): hydration
What are hydration reactions and what are their characteristics:
•Mercuration/Reduction: Markovnikov
•Hydroboration/Oxidation: Anti-Markovnikov and syn addition
What alkene to use? Must involve C2 in double bond.
Which reaction to use with which alkene?
Markovnikov rule can be
applied here. CH vs CH2.
Want Markovnikov!
Use
Mercuration/Reduction!!!
Markovnkov Rule cannot be
used here. Both are CH.
Do not have control over
regioselectivity.
Do not use this alkene.
For yourself : how would you make 1 hexanol, and 3-hexanol?
Another synthetic example…
How would you prepare meso 2,3 dibromobutane from an alkene?
Analysis:
Alkene must be 2-butene. But wait that could be either cis or trans!
We want meso. Have to worry about stereochemistry
Know bromine addition to an alkene is anti addition (cyclic bromonium ion)
trans
cis
Br2
Br2
Br
Br
H
H
Br
rotate lower unit
+ enantiomer
Br
H
Br
Br
H
Br
H
Br
meso
This worked! How about
starting with the cis?
racemic mixture
This did not work, gave us
the wrong stereochemistry!
Addition Reaction General Rule…
Characterize Reactant as cis or trans, C or T
Characterize Reaction as syn or anti, S or A
Characterize Product as meso or racemic mixture, M or R
Relationship
Characteristics can be
changed in pairs and C A R will
remain true.
A
C
R
Want meso instead?? Have to
use trans. Two changed!!
Br2
H
Br
+ enantiomer
Br
H
A
T
M
cis
Br2
racemic mixture
Br
H
Br
H
trans
meso
Alkynes
Structure
sp hybridization
Acidity of Terminal Alkynes
Stronger
base
Weaker
base
Other strong bases that
will ionize the terminal
alkyne:
Not KOH
Important Synthetic Method: Dehydrohalogenation
1. Dehydrohalogenation…
An alkyl halide can eliminate a hydrogen halide molecule, HX, to produce a pi bond.
Recall that HX can be added to a double bond to make an alkyl halide.
HX can also be removed by strong base, called dehydrohalogenation.
Preparation of alkene
Strong base
RCH=CHR + HX
RCHXCH2R
Or rewriting
RCHBrCH2R
base
RCH=CHR
Also, if we start with a vinyl halide and a very
strong base (vinyl halides are not very reactive).
NaH
RCH=CHBr
RCCH
Synthetic planning (Retrosynthesis)
Work Backwards…..
Trace the reactions sequence from the desired product back to ultimate reactants.
Br
Br2
H
H
H
NaNH2
NaNH2
Br
CH3
Starting reactant
CH3
Br
H
prop-1-yne
CH3
CH3
Target
molecule.
Overall Sequence converts alkene alkyne
H
But typical of synthetic problems side reaction occurs to
some extent and must be taken into account.
C
H
H
H
More Sythesis: Nucleophilic Substitution
Use the acidity of a terminal alkyne to create a nucleophile which then initiates
a substitution reaction.
Note that we still have an acidic hydrogen and, thus, can react with another
alkyl group in this way to make RCCR’
Alkyl halides can be obtained from alcohols
Reactions: alkyne with halogen
RCCR + Br2 RBrC=CBrR
No regioselectivity with Br2.
Stereoselective for trans addition.
Reactions: Addition of HX
The expected reaction sequence occurs, formation of the more
stable carbocation.
Markovnikov orientation for both additions.
Now for the mechanism….
Mechanism
The expected reaction sequence occurs, formation of the more
stable carbocation.
Addition of the second mole, another example of resonance.
Reactions: Acid catalyzed Hydration
(Markovnikov).
Markovnikov addition, followed by tautomerism to yield, usually, a
carbonyl compound.
Reactions: Anti Markovnikov Hydration of Alkynes,
Regioselectivity
BH3
overall:
R
R'
Step 1
R
H
R'
B
H2O2, NaOH
Step 2
RCH2CR'
o
Similar to formation of an anti-Markovnikov alcohol from an alkene
Step 1, Internal Alkyne: addition to the alkyne with little or no
regioselectivity issue.
Alternatively Asymmetric, terminal, alkyne if you want to have strong
regioselectivity then use a borane with stronger selectivity for more open site of
attack.
Less exposed site.
More exposed site.
sia2BH
Aldehyde
not
ketone.
Tautomerism, enol  carbonyl
Step 2, Reaction of the alkenyl borane with H2O2, NaOH would yield an enol. Enols are
unstable and rearrange (tautomerize) to yield either an aldehyde or ketone.
catalyzed by
base or acid
H2O2
H
H
H
H
NaOH
OH
O
B
enol
either an aldehyde
or a ketone
Overall…
internal alkyne   ketone (possibly a mixture, next slide)
Terminal alkyne   aldehyde
Examples
Used to insure
regioselectivity.
As before, for a terminal alkyne.
But for a non-terminal alkyne frequently will get two different ketones
Get mixture of
alkenyl boranes
due to low
regioselectivity.
Reduction, Alkyne  Alkene
1.
Catalytic Hydrogenation
If you use catalysts which are also effective for alkene hydrogenation you
will get alkane.
You can use a reduced activity catalyst (Lindlar), Pd and Pb, which stops
at the alkene. You obtain a cis alkene.
Syn addition
Reduction - 2
2.
Treatment of alkenyl borane with a carboxylic acid to yield cis alkene.
BH3
CH3CO2H
hex-3-yne
H
B
Instead of H2O2 / NaOH
Alkenyl borane
3. Reduction by sodium or lithium in liquid ammonia to yield the trans alkene.
Plan a Synthetic Sequence
Retrosynthesis
Synthesize butan-1-ol from ethyne. Work backward from
A big the
alkyne
target
can
molecule.
be
formed via nucleophilic
Is read as “comes from”.
substitution. This is the
chance to make
thedone.
C-C
Major problem: make big from small. Be alert for
Catalytic
when the “disconnect”
can be
1. BH3
bond we need.
Lindlar
OH
2. H2O2,
reduction
NaOH
YES!
butan-1-ol
Target
molecule
Convert ethyne to anion
Do a “disconnect” here.
and react with EtBr.
Catalytic
Br
reduction
Addition
Lindlar
of HBr.
bromoethane
Now, fill in the “forward reaction” details
Can
we
get
alkyne
from
smaller
Not
How
yet!
about
Soan
joining
how
can
molecules
we
get
it?
to get
an alkene?
Ask
yourself!
Do
we
know
how
tomolecules?
join
any two Not
yet!!
So howtogether
can we to
getyield
an alkene?
molecules
an alcohol?
ethyne