22.7: A, B-Unsaturated Carbonyl Compounds

Front 1

B-keto esters like malonic esters

Back 1

more acidic than ordinary esters, completely ionized by alkoxide bases

Front 2

enolate ions derived from b-keto esters like malonate ester derivatives

Back 2

can be alkylated by primary / unbranched secondary alkyl halides or sulfonate esters

Front 3

Dialkylation of B-keto esters also possible

Back 3

Front 4

Alkylation of Dieckmann cond prod is same type of rxn

Back 4

Front 5

Like esters of sub malonic acids, alkylated derivatives of ethyl acetoacetate can be

Back 5

hydrolyzed & decarboxylated to give ketones

Front 6

Ester saponification & protonation gives

Back 6

substituted B-keto acid

Front 7

B-keto acids spont decarboxylate @

Back 7

room temp

Front 8

alkylation of ethyl acetoacetate followed by saponification, protonation, decarboxylation to give a ketone

Back 8

acetoacetic ester synth

Front 9

whether a target ketone can be prepared by acetoacetic ester synth can be determined by

Back 9

mentally reversing synth

Front 10

replace a-H of target ketone w

Back 10

-CO2Et group- unveils B-keto ester required for synth

Front 11

B-keto ester can be prepared by Claisen cond or

Back 11

from other B-keto esters by alkylation or dialkylation w appropriate alkyl halides

Front 12

conj arrangement of C=C & C=O bonds endows a,b unsat carbonyl groups w unique reactivity

Back 12

Front 13

Back 13

Front 14

nuc add to db in a,b-unsat carbonyl cmpd occurs bc

Back 14

gives resonance-stabilized enolate ion intermediate

Front 15

enolate ion can be protonated on O or C

Back 15

either way, carbonyl group eventually regen bc enols spont form carbonyl cmpds - overall result of rxn is net add to db

Front 16

nuc add to C-C db of a,b-unsat aldehydes, ketones, esters & nitriles

Back 16

general reaction can be observed w variety nucs

Front 17

Back 17

Front 18

Back 18

addition of cyanide forms new C-C bond, nitrile then converted into CA group by hydrolysis

Front 19

cyanoethylation

Back 19

add of nuc to acrylonitrile

Front 20

Back 20

driven to completion by enolization of ketone in brackets to phenol, which is aromatic

Front 21

Back 21

basic site of a,b-unsat carbonyl cmpd not db but carbonyl O

Front 22

Protonation on carbonyl O folloewd by

Back 22

rxn w halide ion

Front 23

Electrophilic O can accept e as result of nuc rxn of halide ion @ carbonyl C or bc of conj arrangement of pi bonds at

Back 23

b-C

Front 24

reaction of Br- @ carbonyl C yields

Back 24

relatively unstable tetrahedral addition intermediate

Front 25

rxn at B-C yields

Back 25

enol which rapidly reverts to observed carbonyl prod

Front 26

addition to db of a,b-unsat carbonyl cmpd is example of

Back 26

conj addition

Front 27

DMech of conj add of HBr similar to

Back 27

conj addition of HBr to 1,3-butadiene (involve carbocation intermediates)

Front 28

nucleophilic conj addition such as addition of cyanide

Back 28

has no parallel in rxns of simple conj dienes

Front 29

any conjugate addition rxn competes w

Back 29

carbonyl group rxn

Front 30

in case of aldehydes & ketones, conj addition competes w

Back 30

addition to carbonyl group

Front 31

In case of estres, conj add competes w

Back 31

nuc acyl sub

Front 32

Relatively weak b that give reversible carbonyl-add rxns w ordinary aldehydes & ketones tend to give

Back 32

conj add w a,b-unsat aldehydes & ketones

Front 33

Among relatively weak bases are

Back 33

cyanide ion, amines, thiolate ions, enolate ions derived from B-dicarbonyl cmpds

Front 34

Conj add observed w these nucs bc

Back 34

conj add prod are more stable than carbonyl add products

Front 35

If carbonyl add is reversible (even if it occurs more rapidly)

Back 35

conj addition can drain the carbonyl cmpd from addition equil & conj add prod is formed ultimately

Front 36

Conj add prod is

Back 36

thermodynamic (more stable) prod of rxn

Front 37

Greater stability of conj add prod

Back 37

conj add retains C-C db @ expense of carbonyl group - C=O bond is considerably stronger than C=C bond

Front 38

Carbonyl addition

Back 38

kinetically favored process (faster than conj addition)

Front 39

When nuc used that undergo irreversible carbonyl add

Back 39

carbonyl add prod observed rather than conj add prod

Front 40

LiAlH4 & organolithium reagents add irreversibly to carbonyl groups

Back 40

form carbonyl addition prod whether reactant carbonyl cmpd is a,b-unsat or not

Front 41

many of same nuc that undergo conj add w aldehydes & ketones also undergo

Back 41

conj add w esters

Front 42

stronger b that react irreversibly @ carbonyl C react w esters to give

Back 42

nuc acyl sub prod

Front 43

Hydroxide ion reacts w a,b-unsat ester to give

Back 43

prod of saponification, a nuc acyl sub rxn, bc saponification is not reversible

Front 44

LiAlH4 reduces a,b-unsat esters @ carbonyl group bc

Back 44

rxn of hydride ion @ carbonyl group is irreversible

Front 45

conj addition usually occurs w nuc that are relatively

Back 45

weak bases

Front 46

stronger bases give

Back 46

irreversible carbonyl addition or nuc acyl sub rxns

Front 47

enolate ions, esp derived from malonic ester derivatives, b-keto esters & like

Back 47

undergo conj add rxns w a,b-unsat carbonyl cmpds

Front 48

mech follows same pattern for other nuc conj add

Back 48

nuc is enolate ion formed in rxn of ethoxide w diethyl malonate

Front 49

In contrast to Claisen ester cond

Back 49

rxn requires only cat amt base

Front 50

rxn does not rely on ionization of prod

Back 50

to drive to completion - goes bc c-c pi bond in starting a,b-unsat carbonyl cmpd is replaced by stronger c-c sigma bond

Front 51

Michael additions

Back 51

conj add of carbanions to a,b-unsat carbonyl cmpds

Front 52

Product of a given Michael addition might originate from

Back 52

2 diff pairs of reactants

Front 53

Weaker bases tend to give

Back 53

conj add

Front 54

Stronger bases tend to give

Back 54

carbonyl group rxns

Front 55

To maximize conjugate add

Back 55

choose pair of reactants w less basic enolate ion

Front 56

Robinson annulation

Back 56

immediate prod of add subjected to aldol cond that closes a ring

Front 57

carbonyl group of a,b-unsat aldehyde or ketone like ordinary aldehyde or ketone

Back 57

reduced to ROH w LiAlH4 - involves nuc rxn of hydride @ carbonyl C (is therefore carbonyl addition)

Front 58

Why is carbonyl add rather than conj add observed?

Back 58

Carbonyl add is faster than conj add & irreversible bc hydride is a poor LG

Front 59

reduction of carbonyl group w LiAlH4 is

Back 59

kinetically controlled

Front 60

many a,b-unsat carbonyl cmpds are reduced by

Back 60

NaBH4 to give mix of both carbonyl add prod & conj add prod

Front 61

why isn't NaBH4 reduction of a,b-unsat ketones useful?

Back 61

mixtures obtained

Front 62

Although some cases of conj addition w LiAlH4 known

Back 62

reagent usually reduces carbonyl groups, including carbonyl groups of esters w/o affecting db

Front 63

c-c db of a,b-unsat carbonyl cmpd can in most cased be reduced selectively by

Back 63

cat. hydrogenation

Front 64

organolithium reagents react w a,b-unsat carbonyl cmpds to yield

Back 64

prod of carbonyl addition

Front 65

why does carbonyl add occur rather than conj addition?

Back 65

carbonyl add is more rapid than conj add & irreversible

Front 66

lithium dialkylcuprate reagents

Back 66

give exclusively prod of conj add when react w a,b-unsat esters & ketones

Front 67

even a,b-unsat aldehydes, normally very reactive @ carbonyl group

Back 67

give all/mostly prod of conja dd, esp at low temp

Front 68

grignard reagents often

Back 68

give mixtures of conj add & carbonyl add

Front 69

bc both types add occur w grignard reagents

Back 69

organolithium reagents used w a,b-unsat carbonyl cmpds when only carbonyl add is desired rxn

Front 70

conj add of lithium dialkylcuprate reagents proceed by special mech promoted by presence of

Back 70

Cu, which is esp favorable for conj add, but can be considered similar to other conj add

Front 71

nuc rxn of an anion @ db gives

Back 71

resonance-stabilized enolate ion

Front 72

when h2o added to rxn mix

Back 72

protonation of enolate ion gives conj add prod

Front 73

grignard reagents react w a,b-unsat carbonyl cmpds to give mix of

Back 73

carbonyl add & conj add prod

Front 74

conj add prod due to

Back 74

small amts transition metals known to be present in commercial magnesium

Front 75

certain transition metals known to

Back 75

promote conj add of grignard reagents

Front 76

If a grignard reagent is treated w CuCl

Back 76

magnesium organocuprate reagents are formed & give exclusively conj add like lithium counterparts

Front 77

to carry out carbonyl add rxn w organometallic reagent

Back 77

use organolithium reagent

Front 78

to carry out conj add rxn

Back 78

use lithium organocuprate

Front 79

when is conj add rxn useful in organic synth?

Back 79

any group @ b-position of carbonyl cmpd (or nitrile) can in principle be delivered as nuc in conj add

Front 80

conj add can be

Back 80

mentally reversed by subtracting nuc group from b-position of target mlc & pos fragment (usually proton) from a-position