17.12The Wittig Reaction

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

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

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.

Phosphorus ylidesPhosphorus ylides

R is usually CR is usually C66HH55 (phenyl) (phenyl)

key point is that carbon is negatively polarized key point is that carbon is negatively polarized

and nucleophilicand nucleophilic

(C(C66HH55))33PP CC++

AA

BB

••••––

(C(C66HH55))33PP CC

AA

BB

Figure 17.9 Charge distribution in a ylide

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'

••••

••••

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

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

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++

17.13Planning an Alkene Synthesis via

the Wittig Reaction

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

Retrosynthetic Analysis of StyreneRetrosynthetic Analysis of Styrene

CC66HH55CHCH CHCH22

CC66HH55CHCH

OO

++ (C(C66HH55))33PP CHCH22

++ ––

••••

Retrosynthetic Analysis of StyreneRetrosynthetic Analysis of Styrene

CC66HH55CHCH CHCH22

HCHHCH

OO

++(C(C66HH55))33PP CHCCHC66HH55

++ ––

••••

Retrosynthetic AnalysisRetrosynthetic Analysis

Both of the routes are acceptable.Both of the routes are acceptable.

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.

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––

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.

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

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