Functional Group Transformations And Mechanisms

Front 1

EWG

Back 1

carbonyl, ester, nitro, nitriles, sulfoxide

Front 2

How can enolization process be catalysed?

Back 2

using base to form the enolate ion

Front 3

How is the enolate ion stabalized?

Back 3

By resonance

Front 4

What type of species are enolate ions?

Back 4

nucleophiles

Front 5

What types of enolates are there?

Back 5

singly stabilised and double stabilised

Front 6

single stabilised enolate + examples?

Back 6

stabilised by one EWG

e.g. aldehydes, ketones, esters, nitriles, nitros, sulfoxides (make sure you know all of these

Front 7

pka's of CH-C=O protons(singly stabalised)? and base required to remove?

Back 7

over 20

Strong base - lithium diisopropyl amide, BuLi, NaH, LDA

Front 8

Reaction conditions for irreversible deprotonation to enolate?

Back 8

low temp, no H⁺ source, strong base

Front 9

How to alkylate an enolate(or derivitive)?

Back 9

1) strong base (to make the enolate)

2) alkly halide that are Sn2 active

Front 10

What alkyl halides are Sn2 active?

Back 10

primary maybe secondary but not tertiary

Front 11

exceptions to alkylation of enolates?

Back 11

aldehydes

unsymmetrical ketones

Front 12

problem with alkylation of aldehydes?

Back 12

enolate reacts in competition with undeprotonated aldehyde

Front 13

How to alkylate aldehydes?

Back 13

use an enolate equivalent - enamines, silyl enol ethers, aza enolates

Front 14

making enamines as enolate equivalent?

Back 14

carbonyl + secondary amine + H⁺

Front 15

enamine back to carbonyl?

Back 15

add water

Front 16

What is enamines good for?

Back 16

react with very reactive alkylating agents (allyl or benzyl systems) selectively

Front 17

Making silyl enol ethers as enolate equivalent?

Back 17

carbonyl + trimethyl silyl chloride

Front 18

silyl enol ether back to carbonyl?

Back 18

acid or halogen compounds

Front 19

What are silyl enol ethers good for?

Back 19

less reactive than lithum enolates or enamines and will only react with strong electrophiles such as carbocation species formed from tertiary alkyl halides (Sn1 type alkylating reagents) and a lewis acid TiCl₄

Front 20

making aza-enolates as enolate equivalent?

Back 20

aldehydes + primary amines -> imine

imine + strong base -> aza-enolate

Front 21

aza-enolate to carbonyl?

Back 21

H⁺ + H₂O

Front 22

What are aza-enolates good for?

Back 22

best for reactions involving Sn2 type alkylating reagents

Front 23

problem with unsymmetrical ketons?

Back 23

may be more than one possible deprotonation route

Front 24

regioselective control?

Back 24

kinetic or thermodynamic

Front 25

Kinetic control for deprotonation of an unsymmetrical ketone

Back 25

large bulky strong bases like LDA will remove the least hindered H at low temperature

Front 26

Thermodynamic control for deprotonation of an unsymmetrical ketone?

Back 26

1) base at higher temperature and longer reaction times to allow the more stable enolate to form

2) silyl enol ethers at room temperature

Front 27

Summary of which enolate equivalent for aldehyde is best for which alkylating agent type?

Back 27

reactive alkylating agents - enamine

Sn1 type alkylating agents- silyl enol ether

Sn2 type alkylating agents - aza-enolates

Front 28

Doubly stabilised enolates? + examples?

Back 28

Two EWG are attached to a single carbon atom e.g. 1,3-Dicarbonyl

Front 29

pka of double stabilised enolate hydrogens? + bases required?

Back 29

10-15 ∴ only weak bases required e.g. K₂CO₃, NaOEt

Front 30

Dialkylation of doubly stabilized enolates?

Back 30

can occur when there are two hydrogens on appropriate carbon, useful when synthesising carbocyclic rings

Front 31

Diester decarboxylation?

Back 31

1)NaOH, H₂O -> carboxylate anion

2) HCl, Heat -> lose CO₂

Front 32

Further reactions of enolates?

Back 32

Michael addition reactions, aldol reactions, Claisen condensations

Front 33

Michael addition reactions?

Back 33

michael acceptors are good electrophiles for enolates in conjugate addition reactions

Front 34

What is a michael acceptor?

Back 34

α-β unsaturated carbonyl (carbonyl can be any EWG)

Front 35

Aldol reactions?

Back 35

reaction of an enolate anion with a further >C=O system, which can be with the same carbonyl starting material (self condensations) or with a differert carbonyl (crossed aldol reactions)

Front 36

E1cb elimination from aldol?

Back 36

if the aldol reaction is carried out in excess base, it can eliminate to give the unsaturated carbonyl deriviative

Front 37

How to make the correct aldol?

Back 37

-use pre-formed lithium enolates and enolate equivalents to control crossed condensations

-use one carbonyl that cannot enolize

Front 38

Claisen condensations?

Back 38

reactions between enolates and esters are claisen condensations, acid chlorides can be used instead of the ester

Front 39

When are claisen condensations most effective?

Back 39

when the ester electrophile cannot enolise allowing useful acetylation reactions to be carried ou

Front 40

Oxidation level of oxygen containing functional groups?

Back 40

alcohols - 1 bond

aldehydes, ketones - 2 bonds

acids, esters, acid chlorides, amides - 3 bonds

Front 41

Secondary alcohol to ketones?

Back 41

(Jones oxidation)
metal oxidants- sodium dichromate in acid, Pyridinium chlorochromate (PCC) -last is more soluble in organic solvents

Front 42

Primary alcohols to aldehydes?

Back 42

Need to prevent overoxidation

-TPAP, NMO

-swern oxidation

-TEMPO, NaOCl

Front 43

TPAP?

Back 43

Tetra-n-propylammonium perruthenate (TPAP) is used to oxidise primary alcohols to aldehydes. It is used catalytically alongside a cooxidant like NMO

Front 44

Swern oxidation?

Back 44

DMSO (dimethyl sulfoxide), oxalyl chloride and base (Et₃N) used to oxidise primary alcohols to aldehydes

Front 45

TEMPO?

Back 45

Tetramethylpiperidine oxide (TEMPO) used for the oxidation of primary alcohols to aldehydes - it is a stable radical species which catalyses the process and used a stoichiometrirc oxidant NaOCl

Front 46

What can NaBH₄ reduce?

Back 46

ketones and esters to alcohol

imine to amine

slowly reduces ester to alcohol

Front 47

What can NaCNBH₃ reduce?

Back 47

imine to amine

slowly reduces aldehydes and ketones to alcohol

Front 48

What can LiBH₄ reduce?

Back 48

imine to amine

aldehyde,ester and ketone to alcohol

Front 49

What can LiAlH₄ reduce?

Back 49

imine to amine

aldehyde, ester and ketone to alcohol

amide to amine

amide to aldehyde at 0⁰C

carboxylic acid slowly to alcohol

Front 50

What can BH₃ reduce?

Back 50

imine to amine

amide to amine

carboxylic acid to alcohol

aldehyde, ketone and ester slowly to alcohol

Front 51

Wolff-Kishner reaction?

Back 51

NH₂-NH₂/aq.KOH reduces >C=O to CH₂

Front 52

What do we use DIBAL for?

Back 52

ester -> aldehyde

Front 53

Summary reduction

1)Ketone -> secoundary alcohol

2)Ester -> aldehyde

3)Ester, amides -> primary alcohols

4)ketones to CH₂

Back 53

1)NaBH₄, LiAlH₄

2)DIBAL

3)LiAlH₄

4)NH₂NH₂ + KOH

Front 54

What can reductive hydrogenation reduce?

Back 54

C=C, C=N, C≡C, C≡N

Front 55

Why can't hydrogen reduce carbonys?

Back 55

it is not nucleophilic enough

Front 56

Hydrogenation catalysts?

Back 56

Pd, Pt

Front 57

catalytic reduction of alkenes?

Back 57

hydrogens mainly go on the same face

Front 58

catalytic reduction of alkynes

Back 58

can be reduced all the way to saturated, or selectively reducet to cis-alkenes using Lindlar's catalyst, (Pd, CaCO₃ and Pb(OAc)₂)

Front 59

Dissolving metal reductions?

Back 59

as sodium and lithium metals release electrons in liquid ammonia the electrons can be trapped by either C≡C or aromatic systems in Birch reduction reactions

Front 60

Birch reduction of alkynes?

Back 60

Na dissolving in NH₃, forms the more thermodynamically stable E-configuration (trans)

Front 61

Birch reduction of aromatics ?

Back 61

Li, NH₃(l), EtOH, Et₂O
gives dienes, different substituents gives different products

Front 62

electron withdrawing group on aromatic birch reduction? + examples of electron withdrawing groups?

Back 62

para-reduction (non-conjuated diene)

EWG = CO₂h, CO₂Me, CF₃, etc

Front 63

electron donating groups effect on aromatic birch reduction? + examples of electron donating groups?

Back 63

ortho/meta reduction
EDG = CH₃, OMe, NH₂ etc

Front 64

anilines birch reduction?

Back 64

gives conjugated dienamine

Front 65

Three types of elimination reaction?

Back 65

E1, E1cb, E2

Front 66

E1 elimination?

Back 66

Front 67

E2 elimination?

Back 67

Front 68

E1cb elimination?

Back 68

reverse of E1, base is deprotonated first, then leaving group leaves

Front 69

Julia Olefination reation?

Back 69

Forms E-configuration by connection of two molecular fragments and a one electron reduction

Front 70

Mechanism of Julia Olefination reaction?

Back 70

Front 71

Modified one-step Julia Olefination reaction?

Back 71

Front 72

Peterson Reaction?

Back 72

gives mainly Z-alkenes

Front 73

Peterson Mechanism?

Back 73

Front 74

problem with peterson mechanism?

Back 74

difficult to synthesise the diastereomer starting material

Front 75

Wittig Reaction(+reagents)?

Back 75

most useful for making alkenes, reaction of phosphonium ylid with a carbonyl derivative

1)alkyl halide + Ph₃P + BuLi

2) + carbonyl

Front 76

Making the phosphonium ylid?

Back 76

Front 77

carbonyl + phosphonium ylid mechanism?

Back 77

Front 78

Stabilised ylids?

Back 78

systems bearing EWG give predominantly E-alkenes (reasoning why is still debated)

Front 79

unstabilised ylids?

Back 79

systems bearing EDG give predominantly z-alkenes

Front 80

Making Z-alkenes?

Back 80

wittig-unstabilised ylids

peterson base induced elimination

Reduction of alkynes using Lindlar's catalyst

Front 81

Making E-alkenes?

Back 81

wittig- stabilised ylids

julia and one-step julia reaction

reduction of alkynes by dissolving metal reactions

Front 82

Monohydroxylation reactions?

Back 82

oxymercuration process

hydroborylation

Front 83

Oxymercuration process?

Back 83

1)Hg(OAc)₂ + H₂O

2)NaBH₄

Forms the most substituted alcohol

Front 84

Oxymercuration process mechanism?

Back 84

Front 85

Hydroborylation?

Back 85

1)BH₃

2) H₂O₂, NaOH

gives primary alcohols

Front 86

Dihydroxylation of alkenes?

Back 86

OsO₄ or KMnO₄

mCPBA

Front 87

making cis diol from alkenes?(mechanism)

Back 87

Front 88

making trans-diols from alkenes?

Back 88

meta-chloro-perbenzoic acid(mCPBA) followed by base induced ring opening

Front 89

Trans-diols from alkenes mechanism?

Back 89

Front 90

ozonolysis?

Back 90

C=C cleavage using O₃ giving a range of products depending on the secound reagent added

Front 91

different reagents that can follow ozonolysis and their products?

Back 91

Me₂S -> RCHO + R'CHO

NaBH₄ - > RCH₂OH + R'CH₂OH

H₂O₂ -> RCO₂H + R'CO₂H