Conjugated Dienes & Cycloadditions - Organic chemistry Group... · Conjugated Dienes & Cycloadditions. ... Synthesis of Conjugated Dienes. ... Organic Chemistry OnLine ©2000 ∆

Organic Chemistry OnLine ©2000

© 2000, Paul R. YoungUniversity of Illinois at Chicago, All Rights Reserved

Conjugated Dienes &Cycloadditions


CH3CH3

CH3

OH

Vitamin A: Retinol

A conjugated system consists of a series ofadjacent sp or sp2 centers such that there can

be overlap of -electrons.


Vitamin A: Retinol

CH3CH3

CH3

OH

A conjugated system consists of a series ofadjacent sp or sp2 centers such that there can

be overlap of -electrons.


Conjugated systems poses a series ofadjacent sp2 or sp centers

Simple Conjugated Systems


Alkene p-orbitals overlapto form a system



Conjugated double bondsoverlap to form a

continuous system

Alkene p-orbitals overlapto form a system



Conjugated double bondsoverlap to form a

continuous system

The overlap presents anenhanced barrier to

rotation around singlebonds in conjugated

systems.



NBS

CCl4

Br

(CH3)3CO-

(CH3)3COH

Synthesis of Conjugated Dienes


(CH3)3CO-

(CH3)3COH

Br

NBS

CCl4

H

Br



(CH3)3CO-

(CH3)3COH

Br

NBS

CCl4

Br H



(CH3)3CO-

(CH3)3COH

Br

NBS

CCl4



(CH3)3CO-

(CH3)3COH

Br

NBS

CCl4



(CH3)3CO-

(CH3)3COH

Br

NBS

CCl4

Br

δ

δ



Ionic Addition Reactions of ConjugatedDienes

+ HBr

Br

Br

1,2 addition

1,4 addition

12

3

4


+ HBr

Br

Br

1,2 addition

1,4 addition

12

3

4

Ionic Addition Reactions of ConjugatedDienes


Protonation on the terminal carbon generates the allylic carbocationwith cationic character on both carbons #1 and 3

1,4 addition

CH2

H

δδ

Br-

CH2

H

allylic carbocation

Br

CH2

H

+ HBr


1,2 & 1,4 Ionic Addition Reactions ofConjugated Dienes

The 1,2- addition product forms rapidly at lowtemperatures.




The 1,4-addition product is predominant at highertemperatures.





Even at low temperatures, 1,4-addition products willpredominate if given enough time.





Even at low temperatures, 1,4-addition products willpredominate if given enough time.

The addition of HBr to butadiene is reversible and isolated1,2-addition product will convert to the 1,4-product athigher temperatures or at longer times.


lower activation energy’faster reaction

high activation energy,slower reaction

Br

Br

Ene

rgy

Effect of Temperature and Time on ProductDistribution


lower activation energy’faster reaction

high activation energy,slower reaction

Br

Br

Ene

rgy



∆G˚ ∆G˚

Ene

rgy

Therefore, 1,2 addition isfaster, but forms a less stableproduct, while 1,4 addition is

slower, but gives a morestable product.


smaller ∆G˚, lessfavored at equilibrium,but formed faster

larger ∆G˚, morefavored at equilibrium,but formed more slowly

Br

Br


∆G˚ ∆G˚

smaller ∆G˚, lessfavored at equilibrium,but formed faster

larger ∆G˚, morefavored at equilibrium,but formed more slowly

Br

Br

Ene

rgy

...at equilibrium (ThermodynamicControl) the more stable 1,4

addition product will be favored,but if you examine the initialproduct distribution, the more

rapidly formed 1,2 product willpredominate (Kinetic Control).



+ HBrCH3

kinetic product

thermodynamic product


+ HBrCH3

Br

Br

kinetic product

thermodynamic product


Br

Br

H

H

3˚ carbocation initiallyformed; product also has

less steric hindrance

2˚ carbocation initiallyformed


Cycloaddition Reactions

The Diels-Alder Reaction


+heat

+heat

+heat

O

CH3

C

O

CH3

4 + 2 Cycloaddition Reactions

a diene... ...and adienophile


4 + 2 Cycloaddition Reactions

a diene... ...and adienophile

+heat

+heat

+heat

O

CH3

C

O

CH3


heat

O

CH3

C

O

CH3

a diene a dieneophile

Cycloaddition reactions work best with dienes containingelectron donating substituents and dienophiles containing

electron withdrawing substituents.


s-cis s-trans

free rotation

s-cis stereochemistry is required for a4+2 cycloaddition reaction


concertedtransition

state


a diene

a dieneophile

CNNC NC CN


















Organic Chemistry OnLine ©1999Organic Chemistry OnLine ©2000



Drawing the cyclohexene as a “chair” allows thestereochemistry of attached groups to be clearly described;the cyclohexene ring, however, is actually distorted due to

the 120˚ bond angles of the sp2 centers.



C

CH

HH

H

C

CH

CH

H

H

O

C

CH

CH

H

CH3

O

C

CH

CH

H

OCH3

O

C

C

H

H CO

C

O

O

C

CC

CH

H

C

O

C

O

H

H

C

CH

CH

H

NC

C

COOCH3

H

poor

Common Dienophiles


H

H

H

H

H

H

H

H

H

H

H

H

...benzene can be formed from a 2+2+2 cycloaddition reaction


CN

+

COOCH3+

CHO

+

C

O

CH3+


CN

+

COOCH3+

CHO

+

C

O

CH3+

CN


CN

+

COOCH3+

CHO

+

C

O

CH3+

CN

COOCH3


CN

+

COOCH3+

CHO

+

C

O

CH3+

CN

COOCH3

CHO


CN

+

COOCH3+

CHO

+

C

O

CH3+

CN

COOCH3

CHO

C

O

CH3


O

O

CN+

+

C

O

CH3+


O

O

CN+

+

C

O

CH3+

H

CN


O

O

+

C

O

CH3+

H

CN+

H

CN


O

O

+

C

O

CH3+

H

CN+ CN

H


O

O

CN+

+

C

O

CH3+

H

CNendo isomer


CN

H

CN

HCN

CNH

CN

H

CN

+

exo

endo

not observed


O

O

H

H

H

CHO

H

CHO

Consider the reaction ofcyclopentadiene with

butanedial...


O

O

H

H

H

CHO

H

CHO


butanedial...


O

O

H

H


butanedial...


O

O

H

H


butanedial...


With the carbonyl groupslined up underneath the

double bonds of the diene,there can be -

interactions between thediene and the electron

withdrawing groups onthe dienophile.

O

O

H

H


O

O

H

H

H

CHO

H

CHO


O

O

CN+

+

C

O

CH3+

H

CNendo isomer


O

O

CN+

+

C

O

CH3+

H

CN

O

O


O

O

CN+

+

C

O

CH3+

H

CN

O

OC

O

H3CH


C

O

H3CHC

O

H3CH


C

O

H3CHC

O

H3CH


O

O

CN+

+

C

O

CH3+

H

CN

O

OC

O

H3CH


CH3

CH3

HH

+

CHO

H


+

CHO

H

HH

CH3

CH3


CH3CH3H H

H

CHO

+

CHO

H

HH

CH3

CH3


CH3CH3H H

H

CHO

CH3

CH3

HH

+

CHO

H


CH3

CH3

HH

H

CHO

CH3

H

H H

OHCCH3

CH3 HH CH3

H

CHO

trans stereochemistry

CHO

H+

CH3

CH3

HH

CH3CH3H H

H

CHOrotate up


+

CH3

HH3C

H


+

CH3

HH3C

HCH3

HH3C

H

rotate up H


+

CH3

HH3C

HCH3

HH3C

H

H HH3C CH3

H

H3C

H

H3C

rotate up H

H3C

CH3

H

cis stereochemistry


cis trans

trans trans

H

H3C

CH3

H

CH3

HH3C

H+

CH3

CH3

HH

+

CHO

H

CH3

CH3

HH

H

CHO

1,4-trans

1,4-cis

14

14


trans

cis

cis

trans

trans

trans

1,4- trans

1,4- cis

1,2- cis

1,2- trans


+


+


H

H

CH3

H3C+

trans dienophile trans adduct


+

CH3

H

H

H3C

H

H

CH3

H3C

trans-trans diene cis adduct


HNC

H

NCH

CN

O

H

O

NH2

Suggest a synthesis foreach of the following

utilizing a 4 + 2cycloaddition reaction:


HNC

H

NCH

CN

O

H

O

NH2


HNC

H

NCH

CN

O

H

O

NH2

+

CN


HNC

H

NCH

CN

O

H

O

NH2

+

CN


HNC

H

NCH

CN

O

H

O

NH2

+

CN

O+

C

O

NH2


HNC

H

NCH

CN

O

H

O

NH2

+

CN

O+

C

O

NH2


HNC

H

NCH

CN

O

H

O

NH2

+

CN

O+

C

O

NH2

+

CN

NC


H

O

CH3

O

O

HH

O

O

Suggest a synthesis foreach of the following

utilizing a 4 + 2cycloaddition reaction:


H

O

CH3

O

O

HH

O

O


H

O

CH3

O

O

HH

O

O

+heat


H

O

CH3

O

O

HH

O

O

+heat


H

O

CH3

O

O

HH

O

O

+heat

+C

O

CH3


H

O

CH3

O

O

HH

O

O

+heat

+C

O

CH3


H

O

CH3

O

O

HH

O

O

+heat

+C

O

CH3

O+ O

O

O


H

Cl

H

H

O

CH3

O

H3C

H3C CH3

Suggest a synthesis for themolecule shown above utilizinga 4 + 2 cycloaddition reaction:


H

Cl

H

H

O

CH3

O

H3C

H3C CH3

The molecule is a diketone, we can make ketones by:


H

Cl

H

H

O

CH3

O

H3C

H3C CH3


a) ozonolysis or oxidation of an alkene


H

Cl

H

H

O

CH3

O

H3C

H3C CH3


a) ozonolysis or oxidation of an alkeneb) hydration of an alkyne


H

Cl

H

H

O

CH3

O

H3C

H3C CH3



Because ozonolysis will give us both carbonyls at once,that is our first choice.


H

Cl

H

H

O

CH3

O

H3C

H3C CH3



Because ozonolysis will give us both carbonyls at once,that is our first choice.

12

3

45

6


H

Cl

H

H

O

CH3

O

H3C

H3C CH3

H3C

H3C

H

Cl

O3; Zn/H+

1

23

4

5

6


H

Cl

H

H

O

CH3

O

H3C

H3C CH3

H3C

H3C

H

Cl

O3; Zn/H+

Cl

4+2


H3C

H3CCl

H

H

H3C

H

H3C

Suggest a synthesis for themolecule shown above utilizing a4 + 2 cycloaddition reaction:


The molecule is a saturated alkyl halide, we must use acycloaddition reaction which will yield an alkene. We couldtherefore make this molecule by either:

H3C

H3CCl

H

H

H3C

H

H3C



H3C

H3CCl

H

H

H3C

H

H3C

a) reduction of an alkene



H3C

H3CCl

H

H

H3C

H

H3C

a) reduction of an alkeneb) addition of HCl to an alkene



H3C

H3CCl

H

H

H3C

H

H3C

a) reduction of an alkeneb) addition of HCl to an alkene

Because the double bond will form between the carbons ofthe diene, reduction of that double bond is our firstchoice.


H3C

H3CCl

H

H

H3C

H

H3C

Cl

H

H3C

H3C

H2/Pt


H3C

H3CCl

H

H

H3C

H

H3C

Cl

H

H3C

H3C

H2/Pt

4+2

Cl


COOHHOOC

Br

Suggest a synthesis for themolecule shown above utilizing a4 + 2 cycloaddition reaction:


The molecule is a dicarboxylic acid. The only way we knowto make carboxylic acids is by:

COOHHOOC

Br



COOHHOOC

Br

oxidation of an alkene



COOHHOOC

Br





CC

Br

HH


H

Br

MnO4/H+

COOHHOOC

Br


H

Br

MnO4/H+

4+2

Br

COOHHOOC

Br


H

H3CH

CN

Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.


H

H3CH

CN+

CN

H3C




CN

CN


CN

CN

+

CN

CN




CH3

HH

CN

H

CH3

H

H3C


trans

cis

cis

trans

trans

trans

1,4- trans

1,4- cis

1,2- cis

1,2- trans



CH3

HH

CN

H

CH3

H

H3C



+

CN

CH3

CH3

CH3

CH3

HH

CN

H

CH3

H

H3C



HH

NC

CH3

CH3

H



HH

NC

CH3

CH3

H



HH

NC

CH3

CH3

H+

CN

CH3

CH3



CN

CN

H3C



CN

CN

H3C+

CN

CN

H3C



CH3

HH

CN

H

CH3

CH3

H



CH3

HH

CN

H

CH3

CH3

H+

CN

CH3

CH3

CH3


CH3

Cl

Cycloadditions & Isomerism Draw all of the potential isomers from the cycloadditionreaction shown below.


CH3

H

HClCH3

H

HCl

First, you must considerthat attack can occur

from either the top, or thebottom face.


CH3

H

HClCH3

H

HCl




CH3

H

HClCH3

H

HCl



H

CH3H

Cl


CH3

H

HClCH3

H

HCl



H

CH3H

Cl

H

H3CH

Cl


CH3

H

HClCH3

H

HCl



H

CH3H

Cl

H

H3CH

Cl

The compounds areenantiomers.


CH3

H

HCl

CH3

H

Cl H

H

H

H

Cl

H

H H

CH3

Therefore, all additions will lead to the formation of a pairof enantiomers.

A pair of enantiomers;a racemic mixture.


Next, the dienophile can approach the diene from either theendo (favored) or exo face.

CH3

H

ClHexo

CH3

H

Cl Hendo



CH3

H

ClHexo

CH3

H

Cl Hendo

CH3

H

HCl



CH3

H

ClHexo

CH3

H

Cl Hendo

CH3

H

HCl

H

H

H

Cl

H

H H

CH3



CH3

H

ClHexo

CH3

H

Cl Hendo

CH3

H

HCl

H

H

H

Cl

H

H H

CH3

CH3

H

ClH



CH3

H

ClHexo

CH3

H

Cl Hendo

CH3

H

HCl

H

H

H

Cl

H

H H

CH3

CH3

H

ClH

H

H

Cl

H

H

H H

CH3



CH3

H

ClHexo

CH3

H

Cl Hendo

CH3

H

HCl

H

H

H

Cl

H

H H

CH3

CH3

H

ClH

H

H

Cl

H

H

H H

CH3

(Each as a pair ofenantiomers.)


CH3

Cl

CH3

Cl

syn

anti

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

endo exo

Further, the dienophile can approach syn or anti to the methylgroup on the diene.


CH3

Cl

CH3

Cl

syn

anti

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

endo exo


H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

endo exo


CH3

Cl

CH3

Cl

syn

anti

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

endo exo


H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

endo exo

i

e


CH3

Cl

CH3

Cl

syn

anti

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

endo exo


H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

endo exo

i

e

These two are diasteromers.


CH3

Cl

CH3

Cl

syn

anti

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

endo exo


H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

endo exo

i

e


i

e


CH3

Cl

CH3

Cl

syn

anti

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

endo exo


H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

endo exo

i

e


i

e

These two are also diasteromers.


CH3

Cl

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

CH3

Cl

The two sets are isomers, but are different chemical compounds.

syn

anti

i

e

i

e

cis- and trans-3-chloro-2-methylcyclohexene

endo exo

endo exo

cis- and trans-4-chloro-2-methylcyclohexene


CH3

Cl

Cycloadditions & Isomerism Conclusion: the reaction yields two sets of diastereomersand their mirror images.

H

H

H

Cl

H

H H

CH3

H

H

Cl

H

H

H H

CH3

H

Cl

H

H

H

H H

CH3

Cl

H

H

H

H

H H

CH3

(Each compound is formed as apair of enantiomers.)

Conjugated Dienes & Cycloadditions - Organic chemistry Group... · Conjugated Dienes & Cycloadditions. ... Synthesis of Conjugated Dienes. ... Organic Chemistry OnLine ©2000 ∆

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