nitrogen based carbonyl reactions. some reactions of aldehydes and ketones progress beyond the...
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Nitrogen Based Carbonyl Reactions
Some reactions of aldehydes and ketones progressSome reactions of aldehydes and ketones progressbeyond the nucleophilic addition stagebeyond the nucleophilic addition stage
Acetal formationAcetal formation
IminesImines
Compounds related to iminesCompounds related to imines
EnaminesEnamines
The Wittig reactionThe Wittig reaction
Enamine from 2Enamine from 2oo amines amines
Question
• The compound below is best classified as a(n)
(CH3)3CCH2CH=NCH3
• A) carbinolamine.• B) enamine.• C) hydrazone.• D) imine.
Question
• Identify the product isolated when cyclopentanone reacts with dimethyl amine.
• A) B)
• C) D)
The 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.
(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.
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++
Alkene Synthesis viathe 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
HCHHCH
OO
++(C(C66HH55))33PP CHCCHC66HH55
++ ––
••••
CC66HH55CHCH
OO
++ (C(C66HH55))33PP CHCH22
++ ––
••••
Both routesBoth routesare acceptable.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.
(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.
(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
Question
• Select the product isolated when butanal reacts with the slide shown below.
• A) B)
• C) D)
QuestionWhat is the product of the reaction sequence below?
A. 2-methyl-1-hexene B. 2,3-dimethyl-2-pentene C. 2-methyl-2-hexene D. 3-methyl-1-hexene
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.
20%20%
ExampleExample CHCH33HH33CC
OO
80%80%
OOHH
HH
CHCH33HH33CC
OOHH
HH
CHCH33HH33CCNaBHNaBH44
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
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
Figure 1Figure 1
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.
Figure 2Figure 2
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.
Oxidation of AldehydesOxidation of Aldehydes
KK22CrCr22OO77
HH22SOSO44
HH22OO
OO
OO
CHCH
OO
OO
COHCOH
(75%)(75%)
ExampleExample
Baeyer-Villiger OxidationBaeyer-Villiger Oxidation
of Ketonesof Ketones
Oxidation of ketones with peroxy acidsOxidation of ketones with peroxy acids
gives esters by a novel rearrangement.gives esters by a novel rearrangement.
R"COR"COOOHH
OO
RRCCR'R'
OO
++ R"COHR"COH
OO
++
KetoneKetone EsterEster
RROOCCR'R'
OO
GeneralGeneral
CC66HH55COCOOOHH
OO
(67%)(67%)
Oxygen insertion occurs between carbonyl Oxygen insertion occurs between carbonyl carbon and more substituted group.carbon and more substituted group.
Methyl ketones give acetate esters.Methyl ketones give acetate esters.
CHClCHCl33
ExampleExample
CCHCCH33
OO
OOCCHCCH33
OO
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
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
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
Certain bacteria use hydrocarbons as a source of Certain bacteria use hydrocarbons as a source of carbon. Oxidation proceeds via ketones, which then carbon. Oxidation proceeds via ketones, which then undergo oxidation of the Baeyer-Villiger type.undergo oxidation of the Baeyer-Villiger type.
Biological Baeyer-Villiger OxidationBiological Baeyer-Villiger Oxidation
OO
bacterialbacterial
oxidationoxidation
OO
OO
OO22..
cyclohexanonecyclohexanone
monooxygenase,monooxygenase,
coenzymescoenzymes
Question• What is the product of the following Baeyer-Villiger oxidation reaction?