Polar Reaction Under Basic Conditions - PowerPoint Presentation

Slide1

Polar Reaction Under Basic ConditionsSubstitution and Elimination at C(sp3)-X σ bondsAddition of Nuclephiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements

Chapter

Two

Slide2

Nuclephility and BasicityGood nuclephiles and good basesUnhindered RO-, R2N-, R3N, RC≡C-, Cl-Good nuclephiles and poor basesBr-, I-, R2S, RS-, R3P, malonate anion, R2CuLiPoor

nuclephiles

and

good bases (bulky)t-BuO-, i-Pr2NLi(LDA), R3N, (TMS)2NK, i-Pr2NEt, t-BuLi

R

-

Nu

-

B

-

S

N

2

S

N1

E2

E1

TMS:

T

rimethylsilane

S

N

2, E2: basic condition

S

N1, E1: acidic condition

Slide3

Substitution by the SN2 Mechanismsa. Back attackb. Sterospecificc. Only 1o and 2o C(sp3) undergo SN2SR

S

N

Ar

How to retent the configuration?

S

S

SP

2

C and 3

o C can’t undergo S

N2

Solvent: Polar Aprotic

DMSO, DMF, Acetone, THF,

MeCN

, EA…Polar solvent can stabilize the intermediate.

Aprotic solvent can avoid H+ react with Nu-.

Slide4

Loss Configurational Purity by Nuclephilic SubstitutionSubstituted group is good nuclephile, also good leaving group.The leaving group is α or

β

to a carbonyl group

.

Slide5

Elimination by the E2 Mechanismsβ hydrogen, Good base, 3o CPlease draw the structure of product.Stereochemistry of E2

E2

a.

b

.

E2

c

.

Sawhore

projection

Newman projection

d.

Slide6

Syn EliminationIf the base were part to the substrate, the acidic hydrogen be removed in an intramolecular reaction(syn elimination).Syn elimination

Hofmann Elimination

major

Slide7

E1cb and 1,3-EliminationE1cb: β hydrogen is particularly acidic(carbonyl) and leaving group is poor(-OH, -OR)hemiacetalcarbonyl1,3-Elimination(decarboxylation)

CH

2

COOH

Slide8

Substitution by the Elimination-Addition ReactionNu: -OMeE+: carbonyl group, BrNo SN2 due to the steric hindrance.Leaving group: Br, β hydrogenElimination-Addition Reaction

better electrophile than carbonyl group(steric)

Please draw the reasonable mechanisms

of this reaction

Slide9

ExercisesPlease draw the mechanisms of following reactiona.b

.

c

.d.e.

CO2CO2

Slide10

α-Elimination: Generation of CarbeneDefination: A carbene is a divalent carbon species link to two adjacent groups by covalent bonds, possessing two nonbonded electrons and six valence electrons.Preparation of carbenes

a.

b

.

c.

d.

-

+

Slide11

Reaction of Carbene

Slide12

ExercisesPlease draw the mechanisms of following reaction

a.

b.

c.d.

e.

Slide13

Polar Reaction Under Basic ConditionsSubstitution and Elimination at C(sp3)-X σ bondsAddition of Nuclepphiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements

Slide14

Carbonyl GroupUnder basic conditions, carbonyl compounds are electrophilic at carbonyl C and nuclephilic at α C’s.Arrange the stabilities and reactivities of carbonyl compounds as follow.R is donating groupStabilize the carbocation

d

ecrease the reactivity

Slide15

Carbonyl Group As Electrophilea. M-Nu (R-MgBr, NaBH4, LiAlH4, R2CuLi)b. Amines as nuclephiles (Please draw the mechanism)

c. Water and alcohols as

nuclephiles

under basic conditions.

base

Slide16

Carbonyl Group As Nuclephiles (Aldol Reaction)Aldol reaction: Enolates react with ketones and aldehydes.Draw mechanisms for the following aldol reactions

Slide17

Michael AdditionMichael addition: The 1,4-(conjugated) addition of a carbon nuclephile to an α, β-unsaturated carbonyl system is referred to as Michael addition.Draw mechanisms for the following reactions

a.

b

.

c

.

d

.

e.

Slide18

Baylis-Hillman reaction: An acrylate ester reacts with an aldehyde in the presence of an amine or phosphine catalyst.b. Robinson annulationBaylis-Hillman Reaction and Robinson Annulation

Slide19

Polar Reaction Under Basic ConditionsSubstitution and Elimination at C(sp3)-X σ bondsAddition of Nuclephiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bonds

Base-promoted Rearrangements

Slide20

Substitution at Carbonyl CDraw mechanisms for the following reaction and explain why carbonyl acid can’t undergo similar reaction Reduction of aldehyde, ketone or ester.

Organometallic reagents as Nu

-

(RMgBr, R2CuLi…)

Slide21

Claisen condensation: An ester enolate is condensed with a ketone, aldehyde, or ester.Dieckmann condensation: An intramolecuar version of the Claisen condensationSubstitution at Carbonyl CDraw mechanisms for the following reactions

Slide22

Substitution at Alkenyl C and Aryl C(SNAr)α, β-Unsaturated carbonyl compounds with a leaving group in the β position are susceptible to addition-elimination reactions.SNAr: Aromatic compounds that are substituted with electron-withdrawing groups undergo nuclephilic

aromatic substitution.

Favor

Unfavor

Slide23

Nuclephilic Aromatic Substitution(SNAr)AB

A

B

Explain the results which was showed below

Draw mechanisms for the following reaction

Slide24

Substitution at Aryl C(SNAr)Aryl halides undergo substitution reactions with very strong base such as –NH2, terbutyl lithium.Why alkenyl halides such as CH3CBr=ChCH3 don’t undergo substitution upon treatment with a strong base(-NH2)? Ans

: ring strain.

Sandmeyer

reaction

Nu:

CuX

, H

2

O, X

-, CN-

, H3PO2

Ex

Slide25

Polar Reaction Under Basic ConditionsSubstitution and Elimination at C(sp3)-X σ bondsAddition of Nuclepphiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements

Slide26

Migration from C to CFavorskii rearrangemetDiazomethane(CH2N2) reacts with ketones(R2C=O) to insert CH2 unit between C=O and R

Wolf rearrangement

Please draw the mechanisms

Please draw the mechanisms

Baeyer-

Villiger

rearrangement

Slide27

Curtius rearrangement (acyl chloride to amine)Hofmann rearrangement (amide to amine)Migration from C to O or NBaeyer-Villiger rearrangement

base

Please draw the mechanisms of Hofmann rearrangement

Slide28

The Swern OxidationMechanism1o alcohol to aldehyde; 2o alcohol to ketone

Slide29

The Mitsunobu ReactionA 2o alcohol and a carboxylic acid are converted to an ester. A poor leaving group is converted to an excellent leaving group.MechanismSR

Slide30

Draw mechanisms for the following reactions

a.

b.

c.d.e.

B

Slide31

Draw mechanisms for the following reactions

a.

b.

c.

d.

e.

f.

g.

h.

i

.

Slide32

Thanks For Your Attention

Slide33