Formation of glycols with Syn Addition

Osmium tetroxide

Syn addition

KMnO4cold, dilute, slightly alkaline

also KMnO4

Anti glycols

PhCO3H, a peracid

O

H+

O

H

H2O

HO

OH

Using a peracid, RCO3H, to form an epoxide which is opened by aq. acid.

Peracid: for example, perbenzoic acid

O O

OH

The protonated epoxide is analagous to the cyclic bromonium ion.

epoxide

An example

chiral, optically active

(S)-3-methylcyclohex-1-ene

PhCO3HO + O

aq. acid

OH

OH

OH

OHOH

OH

OH

OH

Are these unique?

Diastereomers, separable (in theory) by distillation, each optically active

OzonolysisR3

R4

R1

R2

1. O3

2. (CH3)2SR4

R3

O

R1

R2

O+

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

C8H12

ozonolysysO

O

O

O

Simply remove the new oxygens and join to make double bonds.But there is a second possibility.

O

O

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

O O

O

Suggest a reasonable structure for the unknown.

Hydrogen Deficiency = 8. Four pi bonds/rings.

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.

To construct unknown cross out the oxygens and then connect. But there are many ways the connections can be made.

a

bc

d

a-b & c-d

a b

c

da-c & b-d

ac

d

b

a-d & b-c

ad

c

b

Look for a structure that obeys the isoprene rule.

Mechanism

OO

O OO

O OO

O OO

O

Consider the resonance structures of ozone.

These two, charged at each end, are the useful ones to think about.

Electrophile capability.

Nucleophile capability.

Mechanism - 2

OO

O OO

O OO

O OO

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 - 2The 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

Heats of Hydrogenation

Incr

easi

ng s

ubst

itutio

n

Red

uced

hea

t of

Hyd

roge

natio

n

By same reasoning higher degree of substitution provide lower heat of hydrogenation and are, therefore, more stable.

Acid Catalyzed Polymerization

Principle: Reactive pi electrons (Lewis base) can react with Lewis acid. Recall

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.

+ HH

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.

the carbocation is an acid!

+

Examples of Synthetic Planning

Give a synthesis of 2-hexanol from any alkene.OH

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

Br2

BrBr

H

Br

Br

rotate lower unit

Br H

Br H

meso

This worked! How about starting with the cis?

cis

Br2

H Br

Br H

racemic mixture

+ enantiomer

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

C RA

cis

Br2H Br

Br H

racemic mixture

+ enantiomer

Characteristics can be changed in pairs and C A R will remain true.

Want meso instead?? Have to use trans. Two changed!!

AT M

trans

Br H

Br H

meso

Br2

Alkynes

Structure

sp hybridization

Acidity of Terminal Alkynes

Other strong bases that will ionize the terminal alkyne:

Not KOH

Stronger base

Weaker base

Important Synthetic Method: Dehydrohalogenation

1. Dehydrohalogenation…

An alkyl halide can eliminate a hydrogen halide molecule, HX, to produce a pi bond.

RCH=CHR + HX RCHXCH2RStrong base

Also, if we start with a vinyl halide and a very strong base (vinyl halides are not very reactive).

RCH=CHBr RCCHNaH

Or rewriting

RCHBrCH2R RCH=CHRbase

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

Synthetic planning (Retrosynthesis)

CH3

prop-1-yne

Target molecule.

Br

H

CH3

NaNH2NaNH2

CH3

Br

H

H H

BrCH3

Br2

Trace the reactions sequence from the desired product back to ultimate reactants.

H

HH

H

CBut typical of synthetic problems side reaction occurs to some extent and must be taken into account.

Overall Sequence converts alkene alkyne

Work Backwards…..

Starting reactant

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

ROH + PX3 RX

Reactions: alkyne with halogen

No regioselectivity with Br2.

Stereoselective for trans addition.

RCCR + Br2 RBrC=CBrR

Reactions: Addition of HX

The expected reaction sequence occurs, formation of the more stable carbocation.

Markovnikov orientation for both additions.

Now for the mechanism….

MechanismThe 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

Similar to formation of an anti-Markovnikov alcohol from an alkeneStep 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.

sia2BH

Less exposed site.

More exposed site.

overall: R R'

BH3 H2O2, NaOHRCH2CR'

o

R R'

H BStep 1 Step 2

Aldehyde not ketone.

Tautomerism, enol carbonyl

Overall…

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.

H

OH

enol

H

B

H2O2

NaOHH

O

Hcatalyzed bybase or acid

either an aldehyde or a ketone

internal alkyne ketone (possibly a mixture, next slide)

Terminal alkyne aldehyde

ExamplesAs before, for a terminal alkyne.

Used to insure regioselectivity.

Get mixture of alkenyl boranes due to low regioselectivity.

But for a non-terminal alkyne frequently will get two different ketones

Reduction, Alkyne Alkene

You can use a reduced activity catalyst (Lindlar), Pd and Pb, which stops at the alkene. You obtain a cis alkene.

1. Catalytic Hydrogenation

Syn addition

If you use catalysts which are also effective for alkene hydrogenation you will get alkane.

Reduction - 2

2. Treatment of alkenyl borane with a carboxylic acid to yield cis alkene.

BH3

H B

hex-3-yne

CH3CO2H

3. Reduction by sodium or lithium in liquid ammonia to yield the trans alkene.

Instead of H2O2 / NaOH

Alkenyl borane

Plan a Synthetic SequenceRetrosynthesis

Synthesize butan-1-ol from ethyne. Work backward from the target molecule.

OH

butan-1-ol

Target molecule

Is read as “comes from”.

A big alkyne can be formed via nucleophilic substitution. This is the chance to make the C-C bond we need.

Do a “disconnect” here.

Br

bromoethane

ethyne

Catalytic Lindlar reduction

Catalytic reduction Lindlar

Addition of HBr.

Convert ethyne to anion and react with EtBr.

1. BH3

2. H2O2, NaOH

Now, fill in the “forward reaction” details

Major problem: make big from small. Be alert for when the “disconnect” can be done.

Ask yourself! Do we know how to join any two molecules together to yield an alcohol?

Not yet! So how can we get it?How about joining molecules to get an alkene? Not yet!! So how can we get an alkene?

Can we get an alkyne from smaller molecules?

YES!