Post on 24-Dec-2015
Dr. Wolf's CHM 201 & 202 17- 1
17.1217.12The Wittig ReactionThe Wittig Reaction
Dr. Wolf's CHM 201 & 202 17- 2
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 3
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
Imine formationImine formation
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Dr. Wolf's CHM 201 & 202 17- 4
The Wittig ReactionThe Wittig Reaction
Synthetic method for preparing alkenes.Synthetic method for preparing alkenes.
One of the reactants is an aldehyde or ketone.One of the reactants is an aldehyde or ketone.
The other reactant is a phosphorus ylide.The other reactant is a phosphorus ylide.
(C(C66HH55))33PP CC++
AA
BB
••••––
(C(C66HH55))33PP CC
AA
BB
A key property of ylides is that they have a A key property of ylides is that they have a negatively polarized carbon and are nucleophilic. negatively polarized carbon and are nucleophilic.
Dr. Wolf's CHM 201 & 202 17- 5
Figure 17.12 Charge distribution in a ylideFigure 17.12 Charge distribution in a ylide
Dr. Wolf's CHM 201 & 202 17- 6
The Wittig ReactionThe Wittig Reaction
(C(C66HH55))33PP CC++
AA
BB
••••––
++
++CC CC
RR
R'R'
AA
BB
(C(C66HH55))33PP OO++
••••––••••
••••
CC OO
RR
R'R'
••••
••••
Dr. Wolf's CHM 201 & 202 17- 7
ExampleExample
++
++ (C(C66HH55))33PP OO++
••••––••••
••••
(C(C66HH55))33PP CHCH22
++ ––
••••OO••••
••••
CHCH22
DMSODMSO
(86%)(86%)
dimethyl sulfoxide (DMSO) or tetrahydrofuran dimethyl sulfoxide (DMSO) or tetrahydrofuran (THF) is the customary solvent(THF) is the customary solvent
Dr. Wolf's CHM 201 & 202 17- 8
MechanismMechanism
CC OO
RR
R'R'
••••
••••
P(CP(C66HH55))33
++CC
AA
BB––••••
OOCC
CC P(CP(C66HH55))33
RR
R'R'
BB
AA
•••• ••••
Step 1Step 1Step 1Step 1
Dr. Wolf's CHM 201 & 202 17- 9
MechanismMechanism
OOCC
CC P(CP(C66HH55))33
RR
R'R'
BB
AA
•••• ••••
Step 2Step 2Step 2Step 2
P(CP(C66HH55))33++
––OO•••• ••••••••
R'R'RR
AA BB
CC
CC++
Dr. Wolf's CHM 201 & 202 17- 10
17.1317.13Planning an Alkene Synthesis viaPlanning an Alkene Synthesis via
the Wittig Reactionthe Wittig Reaction
Dr. Wolf's CHM 201 & 202 17- 11
Retrosynthetic AnalysisRetrosynthetic Analysis
There will be two possible Wittig routes toThere will be two possible Wittig routes toan alkene.an alkene.
Analyze the structure retrosynthetically.Analyze the structure retrosynthetically.
Disconnect the doubly bonded carbons. One Disconnect the doubly bonded carbons. One will come from the aldehyde or ketone, thewill come from the aldehyde or ketone, theother from the ylide.other from the ylide.
CC CC
RR
R'R'
AA
BB
Dr. Wolf's CHM 201 & 202 17- 12
Retrosynthetic Analysis of StyreneRetrosynthetic Analysis of Styrene
CC66HH55CHCH CHCH22
HCHHCH
OO
++(C(C66HH55))33PP CHCCHC66HH55
++ ––
••••
CC66HH55CHCH
OO
++ (C(C66HH55))33PP CHCH22
++ ––
••••
Both routesBoth routesare acceptable.are acceptable.
Dr. Wolf's CHM 201 & 202 17- 13
Preparation of YlidesPreparation of Ylides
Ylides are prepared from alkyl halides by aYlides are prepared from alkyl halides by atwo-stage process.two-stage process.
The first step is a nucleophilic substitution.The first step is a nucleophilic substitution.Triphenylphosphine is the nucleophile.Triphenylphosphine is the nucleophile.
(C(C66HH55))33PP •••• ++ CHCH
AA
BB
XX
++
(C(C66HH55))33PP CHCH
AA
BB
++ XX––
Dr. Wolf's CHM 201 & 202 17- 14
Preparation of YlidesPreparation of Ylides
In the second step, the phosphonium salt isIn the second step, the phosphonium salt istreated with a strong base in order to removetreated with a strong base in order to removea proton from the carbon bonded to a proton from the carbon bonded to phosphorus.phosphorus.
(C(C66HH55))33PP CC
AA
BB
++HH
basebase ••••––
(C(C66HH55))33PP CC
AA
BB
++••••
––
HHbasebase
Dr. Wolf's CHM 201 & 202 17- 15
Preparation of YlidesPreparation of Ylides
Typical strong bases include organolithium Typical strong bases include organolithium reagents (RLi), and the conjugate base of reagents (RLi), and the conjugate base of dimethyl sulfoxide as its sodium saltdimethyl sulfoxide as its sodium salt[NaCH[NaCH22S(O)CHS(O)CH33].].
(C(C66HH55))33PP CC
AA
BB
++HH
basebase ••••
(C(C66HH55))33PP CC
AA
BB
++••••
––
––HHbasebase
Dr. Wolf's CHM 201 & 202 17- 16
17.1417.14
Stereoselective Addition to Stereoselective Addition to
Carbonyl GroupsCarbonyl Groups
Nucleophilic addition to carbonyl Nucleophilic addition to carbonyl groups sometimes leads to a mixture groups sometimes leads to a mixture
of stereoisomeric products.of stereoisomeric products.
Dr. Wolf's CHM 201 & 202 17- 1720%20%
ExampleExample CHCH33HH33CC
OO
80%80%
OOHH
HH
CHCH33HH33CC
OOHH
HH
CHCH33HH33CCNaBHNaBH44
Dr. Wolf's CHM 201 & 202 17- 18
this methyl group hindersapproach of nucleophilefrom top
this methyl group hindersapproach of nucleophilefrom top
HH33B—HB—H––
preferred direction ofapproach is to less hindered(bottom) face of carbonyl group
preferred direction ofapproach is to less hindered(bottom) face of carbonyl group
Steric Hindrance to Approach of ReagentSteric Hindrance to Approach of Reagent
Dr. Wolf's CHM 201 & 202 17- 19
Biological reductions are highly stereoselectiveBiological reductions are highly stereoselective
pyruvic acid pyruvic acid SS-(+)-lactic acid-(+)-lactic acid
OO
CHCH33CCOCCO22HHNADNADHH
HH++
enzyme is enzyme is lactate dehydrogenaselactate dehydrogenase
COCO22HH
HHOO HH
CHCH33
Dr. Wolf's CHM 201 & 202 17- 20
Figure 17.14Figure 17.14
One face of the One face of the substrate can bind to substrate can bind to the enzyme better the enzyme better than the other.than the other.
Dr. Wolf's CHM 201 & 202 17- 21
Figure 17.14Figure 17.14
Change in geometry Change in geometry from trigonal to from trigonal to tetrahedral is tetrahedral is stereoselective. stereoselective. Bond formation Bond formation occurs preferentially occurs preferentially from one side rather from one side rather than the other.than the other.
Dr. Wolf's CHM 201 & 202 17- 22
in aqueous solutionin aqueous solution
RCHRCH RCHRCH RCOHRCOH
OO OHOH
OHOH
HH22OOOO
17.1517.15
Oxidation of AldehydesOxidation of Aldehydes
Dr. Wolf's CHM 201 & 202 17- 23
KK22CrCr22OO77
HH22SOSO44
HH22OO
OO
OO
CHCH
OO
OO
COHCOH
(75%)(75%)
viavia
OO
OHOH
CHCH
OHOH
ExampleExample
Dr. Wolf's CHM 201 & 202 17- 24
17.1617.16
Baeyer-Villiger OxidationBaeyer-Villiger Oxidation
of Ketonesof Ketones
Oxidation of ketones with peroxy acidsOxidation of ketones with peroxy acidsgives esters by a novel rearrangement.gives esters by a novel rearrangement.
Dr. Wolf's CHM 201 & 202 17- 25
R"COR"COOOHH
OO
RRCCR'R'
OO
++ R"COHR"COH
OO
++
KetoneKetone EsterEster
RROOCCR'R'
OO
GeneralGeneral
Dr. Wolf's CHM 201 & 202 17- 26
CC66HH55COCOOOHH
OO
(67%)(67%)
Oxygen insertion occurs between carbonyl Oxygen insertion occurs between carbonyl carbon and larger group.carbon and larger group.
Methyl ketones give acetate esters.Methyl ketones give acetate esters.
CHClCHCl33
ExampleExample
CCHCCH33
OO
OOCCHCCH33
OO
Dr. Wolf's CHM 201 & 202 17- 27
CC66HH55COCOOOHH
OO
(66%)(66%)
Reaction is stereospecific.Reaction is stereospecific.
Oxygen insertion occurs with retention ofOxygen insertion occurs with retention ofconfiguration.configuration.
CHClCHCl33
StereochemistryStereochemistry
OO
CCHCCH33HH33CC
HH HH
OOCCHCCH33
OO
HH33CC
HH HH
Dr. Wolf's CHM 201 & 202 17- 28
R"COR"COOOHH
OO
RRCCR'R'
OO
++ RROOCCR'R'
OO
R"COHR"COH
OO
++
First step is nucleophilicFirst step is nucleophilicaddition of peroxy acidaddition of peroxy acidto the carbonyl group of to the carbonyl group of the ketone. the ketone.
OO
OO
CC
OO HH
RR R'R'
OCR"OCR"
MechanismMechanism
Dr. Wolf's CHM 201 & 202 17- 29
R"COR"COOOHH
OO
RRCCR'R'
OO
++ RROOCCR'R'
OO
R"COHR"COH
OO
++
OO
OO
CC
OO HH
RR R'R'
OCR"OCR"
Second step is migrationSecond step is migrationof group of group RR from carbon from carbonto oxygen. The weakto oxygen. The weakOO—O —O bond breaks in thisbond breaks in thisstep. step.
MechanismMechanism
Dr. Wolf's CHM 201 & 202 17- 30
Certain bacteria use hydrocarbons as a Certain bacteria use hydrocarbons as a source of carbon. Oxidation proceeds via source of carbon. Oxidation proceeds via ketones, which then undergo oxidation of the ketones, which then undergo oxidation of the Baeyer-Villiger type.Baeyer-Villiger type.
Biological Baeyer-Villliger OxidationBiological Baeyer-Villliger Oxidation OObacterialbacterial
oxidationoxidation
OO
OO
OO22..
cyclohexanonecyclohexanone
monooxygenase,monooxygenase,
coenzymescoenzymes
Dr. Wolf's CHM 201 & 202 17- 31
Section 17.17Section 17.17Spectroscopic Analysis ofSpectroscopic Analysis of
Aldehydes and KetonesAldehydes and Ketones
Dr. Wolf's CHM 201 & 202 17- 32
Presence of a C=O group is readily Presence of a C=O group is readily apparentapparentin infrared spectrumin infrared spectrum
C=O stretching gives an intense absorptionC=O stretching gives an intense absorptionat 1710-1750 cm-1at 1710-1750 cm-1
In addition to peak for C=O, aldehydes giveIn addition to peak for C=O, aldehydes givetwo weak peaks near 2720 and 2820 nm two weak peaks near 2720 and 2820 nm for H—C=Ofor H—C=O
Infrared SpectroscopyInfrared Spectroscopy
Dr. Wolf's CHM 201 & 202 17- 33Francis A. Carey, Organic Chemistry, Fifth Edition. Copyright © 2003 The McGraw-Hill Companies, Inc. All rights reserved.
2000200035003500 30003000 25002500 1000100015001500 500500
Wave number, cmWave number, cm-1-1
Figure 17.16 Infrared Spectrum of ButanalFigure 17.16 Infrared Spectrum of ButanalFigure 17.16 Infrared Spectrum of ButanalFigure 17.16 Infrared Spectrum of Butanal
C=OC=O
CHCH33CHCH22CHCH22CH=OCH=O
H—C=OH—C=O
2720 cm2720 cm-1-1
2820 cm2820 cm-1-1
1720 cm1720 cm-1-1
Dr. Wolf's CHM 201 & 202 17- 34
Aldehydes: H—C=O proton is at very low fieldAldehydes: H—C=O proton is at very low field(( 9-10 ppm). 9-10 ppm).
Methyl ketones: CHMethyl ketones: CH33 singlet near singlet near 2 ppm. 2 ppm.
11H NMRH NMR
Dr. Wolf's CHM 201 & 202 17- 35
01.02.03.04.05.06.07.08.09.010.0
Chemical shift (Chemical shift (, ppm), ppm)
HH CC
OO
CH(CHCH(CH33))22
Dr. Wolf's CHM 201 & 202 17- 36
01.02.03.04.05.06.07.08.09.010.0
Chemical shift (Chemical shift (, ppm), ppm)
CHCH33CC
OO
CHCH33CHCH22
Dr. Wolf's CHM 201 & 202 17- 37
1313C NMRC NMR
Carbonyl carbon is at extremely low field-near Carbonyl carbon is at extremely low field-near 200 ppm 200 ppm
Intensity of carbonyl carbon is usually weakIntensity of carbonyl carbon is usually weak
Dr. Wolf's CHM 201 & 202 17- 38Chemical shift (Chemical shift (, ppm), ppm)
020406080100120140160180200
CHCH33CHCH22CCCHCH22CHCH22CHCH22CHCH33
OO
Dr. Wolf's CHM 201 & 202 17- 39
UV-VISUV-VIS
Aldehydes and ketones have two bands in the Aldehydes and ketones have two bands in the
UV region:UV region:
* * andand nn**
*: excitation of a bonding *: excitation of a bonding electron to electron to
an antibonding an antibonding * orbital * orbital
*: excitation of a nonbonding electron on *: excitation of a nonbonding electron on
oxygen to an antibonding oxygen to an antibonding * orbital * orbital
Dr. Wolf's CHM 201 & 202 17- 40
UV-VISUV-VIS
HH33CC
HH33CC
CC OO•••• ••
••* * maxmax 187 nm 187 nm
nn* * maxmax 270 nm 270 nm
Dr. Wolf's CHM 201 & 202 17- 41
Molecular ion fragments to give an acyl cationMolecular ion fragments to give an acyl cation
m/z m/z 8686
++
m/z m/z 5757
Mass SpectrometryMass Spectrometry
CHCH22CHCH33••
CHCH33CHCH22CCCHCH22CHCH33
••++OO ••
••
CHCH33CHCH22CC OO ••••
++