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 ••••

++