18.11 effects of conjugation in a,b -unsaturated aldehydes and ketones
DESCRIPTION
18.11 Effects of Conjugation in a,b -Unsaturated Aldehydes and Ketones. Relative Stability. aldehydes and ketones that contain a carbon-carbon double bond are more stable when the double bond is conjugated with the carbonyl group than when it is not - PowerPoint PPT PresentationTRANSCRIPT
18.1118.11
Effects of Conjugation in Effects of Conjugation in
-Unsaturated Aldehydes and -Unsaturated Aldehydes and
KetonesKetones
Relative StabilityRelative Stability
aldehydes and ketones that contain a carbon-aldehydes and ketones that contain a carbon-carbon double bond are more stable when the carbon double bond are more stable when the double bond is conjugated with the carbonyl double bond is conjugated with the carbonyl group than when it is notgroup than when it is not
compounds of this type are referred to as compounds of this type are referred to as ,, unsaturated aldehydes and ketonesunsaturated aldehydes and ketones
Relative StabilityRelative Stability
CHCH33CHCH
OO
CHCHCHCH22CCHCCH33 (17%)(17%)
KK = 4.8 = 4.8
(83%)(83%)
OO
CHCH33CHCH22CHCH CHCCHCHCCH33
AcroleinAcrolein
HH22CC CHCHCHCH
OO
AcroleinAcrolein
HH22CC CHCHCHCH
OO
AcroleinAcrolein
HH22CC CHCHCHCH
OO
AcroleinAcrolein
HH22CC CHCHCHCH
OO
Resonance DescriptionResonance Description
CCOO•••• ••••
CCCC
++
––
CCOO•••• ••••
CCCC ••••
Resonance DescriptionResonance Description
CCOO•••• ••••
CCCC
++
––
CCOO•••• ••••
CCCC ••••
++
––
CCOO•••• ••••
CCCC ••••
-Unsaturated aldehydes and ketones are -Unsaturated aldehydes and ketones are more polar than simple aldehydes and ketones. more polar than simple aldehydes and ketones.
-Unsaturated aldehydes and ketones contain -Unsaturated aldehydes and ketones contain two possible sites for nucleophiles to attack two possible sites for nucleophiles to attack
carbonyl carboncarbonyl carbon
-carbon-carbon
PropertiesProperties
-Unsaturated aldehydes and ketones are -Unsaturated aldehydes and ketones are more polar than simple aldehydes and ketones. more polar than simple aldehydes and ketones.
-Unsaturated aldehydes and ketones contain -Unsaturated aldehydes and ketones contain two possible sites for nucleophiles to attack two possible sites for nucleophiles to attack
carbonyl carboncarbonyl carbon
-carbon-carbon
PropertiesProperties
CCOO•••• ••••
CCCC
Dipole MomentsDipole Moments
ButanalButanal transtrans-2-Butenal-2-Butenal
= 2.7 D= 2.7 D = 3.7 D= 3.7 D
OO OO–– ––
++
++
++
greater separation greater separation of positive and of positive and negative chargenegative charge
18.1218.12
Conjugate Addition to Conjugate Addition to
-Unsaturated Carbonyl Compounds-Unsaturated Carbonyl Compounds
1,2-addition (direct addition)1,2-addition (direct addition)
nucleophile attacks carbon of C=Onucleophile attacks carbon of C=O
1,4-addition (conjugate addition)1,4-addition (conjugate addition)
nucleophile attacks nucleophile attacks -carbon-carbon
Nucleophilic Addition to Nucleophilic Addition to -Unsaturated Aldehydes and Ketones -Unsaturated Aldehydes and Ketones
attack is faster at C=Oattack is faster at C=O
attack at attack at -carbon gives the more stable -carbon gives the more stable productproduct
Kinetic versus Thermodynamic ControlKinetic versus Thermodynamic Control
HH YY++CC CC
CC
OO
1,2-addition1,2-addition
CC CC
CC
OOHH
YY
formed fasterformed faster
major product under major product under conditions of kinetic conditions of kinetic control control (i.e. when (i.e. when addition is not readily addition is not readily reversible)reversible)
HH YY++CC CC
CC
OO
1,4-addition1,4-addition
CC CC
CC
OOHH
YY
enolenol
goes to keto form goes to keto form under reaction under reaction conditionsconditions
HH YY++CC CC
CC
OO
1,4-addition1,4-addition
keto form is isolated keto form is isolated product of 1,4-additionproduct of 1,4-addition
is more stable than is more stable than 1,2-addition product1,2-addition product CC CC
CC
OO
HHYY
HH YY++CC CC
CC
OO
1,2-addition1,2-addition
CC CC
CC
OOHH
YY
1,4-addition1,4-addition
CC CC
CC
OO
HHYY
C=O is stronger C=O is stronger
than C=Cthan C=C
C=O is stronger C=O is stronger
than C=Cthan C=C
observed with observed with stronglystrongly basic nucleophiles basic nucleophiles
Grignard reagentsGrignard reagents
LiAlHLiAlH44
NaBHNaBH44
Sodium acetylideSodium acetylide
strongly basic nucleophiles add irreversiblystrongly basic nucleophiles add irreversibly
1,2-Addition1,2-Addition
ExampleExample
OO
CHCH33CHCH CHCHCHCH ++ HCHC CMgBrCMgBr
1. THF1. THF2. H2. H33OO++
OHOH
CHCH33CHCH CHCHCCHCHC CHCH
(84%)(84%)
observed with observed with weaklyweakly basic nucleophiles basic nucleophiles
cyanide ion (CNcyanide ion (CN––))
thiolate ions (RSthiolate ions (RS––))
ammonia and aminesammonia and amines
azide ion (Nazide ion (N33––))
weakly basic nucleophiles add reversiblyweakly basic nucleophiles add reversibly
1,4-Addition1,4-Addition
ExampleExample
KCNKCN ethanol,ethanol,
acetic acidacetic acid
(93-96%)(93-96%)
OO
CC66HH55CHCH CHCCCHCC66HH55
OO
CC66HH55CHCHCHCH22CCCC66HH55
CNCN
ExampleExample
KCNKCN ethanol,ethanol,
acetic acidacetic acid
(93-96%)(93-96%)
OO
CC66HH55CHCH CHCCCHCC66HH55
OO
CC66HH55CHCHCHCH22CCCC66HH55
CNCN
viavia
CC66HH55CHCH CCCC66HH55
CNCN••••
––OO•••• ••••
CHCH
CC66HH55CHCH CCCC66HH55
CNCN
––OO•••• ••••••••
CHCH
ExampleExample
OO CHCH33
CC66HH55CHCH22SHSH HOHO––, H, H22OO
(58%)(58%)
OO CHCH33
SCHSCH22CC66HH55
ExampleExample
viaviaOO
CHCH33
CC66HH55CHCH22SHSH HOHO––, H, H22OO
(58%)(58%)
––OO•••• ••••••••
CHCH33
SCHSCH22CC66HH55
OO CHCH33
SCHSCH22CC66HH55
CHCH33
SCHSCH22CC66HH55
––
OO•••• ••••
••••
18.1318.13
Addition of Carbanions toAddition of Carbanions to
-Unsaturated Carbonyl Compounds:-Unsaturated Carbonyl Compounds:
The Michael ReactionThe Michael Reaction
Stabilized carbanions, such as those Stabilized carbanions, such as those derived from derived from -diketones undergo conjugate-diketones undergo conjugateaddition to addition to ,,-unsaturated ketones.-unsaturated ketones.
Michael AdditionMichael Addition
ExampleExample
(85%)(85%)
OO
HH22CC CHCCHCHCCH33
CHCH33
OO
OO
OO
CHCH33
OO
OO
CHCH22CHCH22CCHCCH33
KOH, methanolKOH, methanol
++
The Michael reaction is a useful method forThe Michael reaction is a useful method forforming carbon-carbon bonds.forming carbon-carbon bonds.
It is also useful in that the product of the It is also useful in that the product of the reaction can undergo an intramolecularreaction can undergo an intramolecularaldol condensation to form a six-membered aldol condensation to form a six-membered ring. One such application is called the Robinsonring. One such application is called the Robinsonannulation.annulation.
Michael AdditionMichael Addition
ExampleExample
OO
CHCH33
OO
OO
CHCH22CHCH22CCHCCH33
NaOHNaOH
heatheat
OHOH
OO CHCH33
OO
not isolated;not isolated;
dehydrates under dehydrates under
reaction conditionsreaction conditions
ExampleExample
(85%)(85%)
OO
CHCH33
OO
OO
CHCH22CHCH22CCHCCH33
NaOHNaOH
heatheat OOOO
CHCH33
OHOH
OO CHCH33
OO
18.1418.14
Conjugate Addition of Organocopper Conjugate Addition of Organocopper
Reagents to Reagents to
-Unsaturated Carbonyl Compounds-Unsaturated Carbonyl Compounds
The main use of organocopper reagents is toThe main use of organocopper reagents is toform carbon-carbon bonds by conjugate form carbon-carbon bonds by conjugate addition to addition to ,,-unsaturated ketones.-unsaturated ketones.
Addition of Organocopper Reagents toAddition of Organocopper Reagents to-Unsaturated Aldehydes and Ketones-Unsaturated Aldehydes and Ketones
ExampleExampleOO CHCH33
(98%)(98%)
++ LiCu(LiCu(CHCH33))22
OO CHCH33
CHCH33
1. diethyl ether1. diethyl ether
2. H2. H22OO
18.1518.15
Alkylation of Enolate AnionsAlkylation of Enolate Anions
Enolate ions are nucleophiles and react withEnolate ions are nucleophiles and react withalkyl halides.alkyl halides.
However, alkylation of simple enolates does However, alkylation of simple enolates does not work well.not work well.
Enolates derived from Enolates derived from -diketones can be-diketones can bealkylated efficiently.alkylated efficiently.
Enolate Ions in SEnolate Ions in SNN2 Reactions2 Reactions
ExampleExample
CHCH33CCHCCH22CCHCCH33
OO OO
++ CHCH33IIKK22COCO33
CHCH33CCHCCHCCHCCH33
OO OO
CHCH33
(75-77%)(75-77%)