Kinds of Carbanion
1. Simple ionic
2. Resonance-stabilised carbanions
3. Resonance-stabilised carbanions containing heteroatoms
4. Carbanion with some Covalent Character
3
Simple ion Alkynides
Recall that acetylenic hydrogens have a pKa of about 25
and are much more acidic than most other C-H bonds
The relative acidity of acetylenic hydrogens in solution is:
Acetylenic hydrogens can be deprotonated with relatively
strong bases (sodium amide is typical)
The products are called alkynides
4
Bond Lengths of Ethyne, Ethene and Ethane
The carbon-carbon bond length is shorter as more bonds hold the
carbons together
With more electron density between the carbons, there is more “glue” to hold
the nuclei of the carbons together
The carbon-hydrogen bond lengths also get shorter with more s
character of the bond
2s orbitals are held more closely to the nucleus than 2p orbitals
A hybridized orbital with more percent s character is held more closely to the
nucleus than an orbital with less s character
The sp orbital of ethyne has 50% s character and its C-H bond is shorter
The sp3 orbital of ethane has only 25% s character and its C-H bond is longer
Resonance-stabilised carbanions
containing heteroatoms
The Acidity of the a Hydrogens of Carbonyl Compounds:
Enolate Anions
Hydrogens on carbons a to carbonyls are unusually acidic
The resulting anion is stabilized by resonance to the carbonyl
7
The enolate anion can be protonated at the carbon
or the oxygen
The resultant enol and keto forms of the carbonyl are
formed reversibly and are interconvertible
8
Keto and Enol Tautomers
Enol-keto tautomers are constitutional isomers that are easily
interconverted by a trace of acid or base
Most aldehydes and ketones exist primarily in the keto form because of
the greater strength of the carbon-oxygen double bond relative to the
carbon-carbon double bond
9
b-Dicarbonyl compounds exist primarily in the enol form
The enol is more stable because it has a conjugated p system and
because of stabilization of the enol through hydrogen bonding
Chapter 16 10
Reaction of triphenylphosphine with a primary or
secondary alkyl halide produces a phosphonium salt
The phosphonium salt is deprotonated by a strong base to
form the ylide
Several other groups can increase the acidity of –
hidrogen.
pKa Comparation pKa
CH3CN 25 HCCH 25
CH3NO2 10 Ph-OH 10
CH2(NO2)2 3,6 CH3COOH 4,8
CH(CN)3 < 1
REACTION OF CARBANIONS
(A) AS A BASES:
R- + H-A → R-H + A-
(B) AS NUCLEOPHILES
(I) AT A SATURATED CARBON
(II) AT A CARBONYL GROUP
(III) AT AN α,β-UNSATURATED CARBONYL GROUP
15
Replacement of the Acetylenic Hydrogen Atom of
Terminal Alkynes
Sodium alkynides can be used as nucleophiles in SN2
reactions
New carbon-carbon bonds are the result
Only primary alkyl halides can be used or else elimination
reactions predominate
Chapter 16 16
Addition of the ylide to the carbonyl leads to
formation of a four-membered ring oxaphosphetane
The oxaphophetane rearranges to the alkene and
triphenylphosphine oxide
The driving force for the last reaction is formation of the
very strong phosphorus-oxygen double bond in
triphenylphosphine oxide
Chapter 16 19
The Horner-Wadsworth-Emmons reaction employs a
phosphonate ester and generally leads to formation of
an (E)-alkene
Chapter 16 20
The Addition of Organometallic Reagents: The
Reformatsky Reaction
The Reformatsky reaction involves addition of an
organozinc reagent to an aldehyde or ketone
The organozinc reagent is made from an a-bromo ester;
the reaction gives a b-hydroxy ester
The b-hydroxyester is easily dehydrated to an a,b-
unsaturated ester
Chapter 12 21
Organometallic Compounds
Carbon-metal bonds vary widely in character from
mostly covalent to mostly ionic depending on the metal
The greater the ionic character of the bond, the more
reactive the compound
Organopotassium compounds react explosively with water
and burst into flame when exposed to air
Chapter 12 22
Preparation of Organolithium and Organo-
magnesium Compounds
Organolithium Compounds
Organolithium compounds can be prepared by
reaction of an alkyl halide with lithium metal in an
ether solvent
The order of reactivity of halides is R-I > R-Br > R-Cl (R-F
is seldom used)
Chapter 12 23
Grignard Reagents
Grignard reagents are prepared by the reaction of
organic halides with magnesium turnings
An ether solvent is used because it forms a complex with
the Grignard reagent which stabilizes it
Chapter 12 24
Reactions of Organolithium and Organo-magnesium
Compounds
Reactions with Compounds Containing Acidic Hydrogen Atoms
Organolithium and Grignard reagents behave as if they were
carbanions and they are therefore very strong bases
They react readily with hydrogen atoms attached to oxygen, nitrogen or
sulfur, in addition to other acidic hydrogens (water and alcohol solvents
cannot be used)
Chapter 12 25
Organolithium and Grignard reagents can be used to
form alkynides by acid-base reactions
Alkynylmagnesium halides and alkynyllithium reagents are
useful nucleophiles for C-C bond synthesis
Chapter 12 26
Reactions of Grignard Reagents with Oxiranes (Epoxides)
Grignard reagents are very powerful nucleophiles and can react
with the d+ carbons of oxiranes
The reaction results in ring opening and formation of an alcohol product
Reaction occurs at the least-substituted ring carbon of the oxirane
The net result is carbon-carbon bond formation two carbons away from
the alcohol
Chapter 12 27
Reaction of Grignard Reagents with Carbonyl Compounds
Nucleophilic attack of Grignard reagents at carbonyl carbons is
the most important reaction of Grignard reagents
Reaction of Grignard reagents with aldehydes and ketones yields a new
carbon-carbon bond and an alcohol
Chapter 12 28
Alcohols from Grignard Reagents
Aldehydes and ketones react with Grignard reagents
to yield different classes of alcohols depending on the
starting carbonyl compound
Chapter 12 29
Esters react with two molar equivalents of a Grignard
reagent to yield a tertiary alcohol
A ketone is formed by the first molar equivalent of
Grignard reagent and this immediately reacts with a
second equivalent to produce the alcohol
The final product contains two identical groups at the
alcohol carbon that are both derived from the Grignard
reagent
Chapter 12 31
Planning a Grignard Synthesis
Example : Synthesis of 3-phenyl-3-pentanol
The starting material may be a ketone or an ester
There are two routes that start with ketones (one is shown)
Chapter 12 32
Solved Problem: Synthesize the following compound
using an alcohol of not more than 4 carbons as the only
organic starting material
33
Restrictions on the Use of Grignard Reagents
Grignard reagents are very powerful nucleophiles and bases
They react as if they were carbanions
Grignard reagents cannot be made from halides which contain acidic
groups or electrophilic sites elsewhere in the molecule
The substrate for reaction with the Grignard reagent cannot contain any
acidic hydrogen atoms
The acidic hydrogens will react first and will quench the Grignard reagent
Two equivalents of Grignard reagent could be used, so that the first equivalent is
consumed by the acid-base reaction while the second equivalent accomplishes
carbon-carbon bond formation
Chapter 17 34
The Acidity of the a Hydrogens of Carbonyl Compounds:
Enolate Anions
Hydrogens on carbons a to carbonyls are unusually acidic
The resulting anion is stabilized by resonance to the carbonyl
Chapter 17 35
The enolate anion can be protonated at the carbon
or the oxygen
The resultant enol and keto forms of the carbonyl are
formed reversibly and are interconvertible
Chapter 17 36
Keto and Enol Tautomers
Enol-keto tautomers are constitutional isomers that are easily
interconverted by a trace of acid or base
Most aldehydes and ketones exist primarily in the keto form because of
the greater strength of the carbon-oxygen double bond relative to the
carbon-carbon double bond
Chapter 17 37
b-Dicarbonyl compounds exist primarily in the enol
form
The enol is more stable because it has a conjugated p
system and because of stabilization of the enol through
hydrogen bonding
Chapter 17 38
Reactions via Enols and Enolate Anions
Racemization
An optically active aldehyde or ketone with a
stereocenter at the a-carbon can racemize in the
presence of catalytic acid or base
The intermediate enol or enolate has no stereocenter at the
a position
Chapter 17 40
Halogenation of Ketones
Ketones can be halogenated at the a position in the
presence of acid or base and X2
Base-promoted halogenation occurs via an enolate
Chapter 17 42
Haloform Reaction
Reaction of methyl ketones with X2 in the presence of
base results in multiple halogenation at the methyl
carbon
Insert mechanism page 777
Chapter 17 43
When methyl ketones react with X2 in aqueous
hydroxide the reaction gives a carboxylate anion and
a haloform (CX3H)
The trihalomethyl anion is a relatively good leaving group
because the negative charge is stabilized by the three
halogen atoms
Chapter 17 44
The Aldol Reaction: The Addition of Enolate
Anions to Aldehydes and Ketones
Acetaldehyde dimerizes in the presence of dilute
sodium hydroxide at room temperature
The product is called an aldol because it is both an
aldehyde and an alcohol
Chapter 17 46
Dehydration of the Aldol Product
If the aldol reaction mixture is heated, dehydration to an a,b-
unsaturated carbonyl compound takes place
Dehydration is favorable because the product is stabilized by conjugation of
the alkene with the carbonyl group
In some aldol reactions, the aldol product cannot be isolated because it
is rapidly dehydrated to the a,b-unsaturated compound
Chapter 17 47
Synthetic Applications
The aldol reaction links two smaller molecules and
creates a new carbon-carbon bond
Chapter 17 48
Aldol reactions with ketones are generally unfavorable
because the equilibrium favors the starting ketone
The use of a special apparatus which removes product
from the reaction mixture allows isolation of a good yield
of the aldol product of acetone
The Reversibility of Aldol Additions
Aldol addition products undergo retro-aldol reactions in
the presence of strong base
Chapter 17 49
Acid-Catalyzed Aldol Condensation
This reaction generally leads directly to the
dehydration product
Chapter 17 50
Crossed Aldol Reactions
Crossed aldol reactions (aldol reactions involving two
different aldehydes) are of little use when they lead to
a mixture of products
Chapter 17 51
Practical Crossed Aldol Reactions
Crossed aldol reactions give one predictable product when one of
the reaction partners has no a hydrogens
The carbonyl compound without any a hydrogens is put in basic solution,
and the carbonyl with one or two a hydrogens is added slowly
Dehydration usually occurs immediately, especially if an extended
conjugated system results
Chapter 17 52
Claisen-Schmidt Reactions
Crossed-aldol reactions in which one partner is a
ketone are called Claisen-Schmidt reactions
The product of ketone self-condensation is not obtained
because the equilibrium is not favorable
Chapter 17 54
Cyclization via Aldol Condensations
Intramolecular reaction of dicarbonyl compounds proceeds to form
five- and six-membered rings preferentially
In the following reaction the aldehyde carbonyl carbon is attacked
preferentially because an aldehyde is less sterically hindered and more
electrophilic than a ketone
Chapter 17 55
Lithium Enolates
In the presence of a very strong base such as lithium
diisopropyl amide (LDA), enolate formation is greatly
favored
Weak bases such as sodium hydroxide produce only a
small amount of the enolate
Chapter 17 56
Regioselective Formation of Enolate Anions
Unsymmetrical ketones can form two different enolates
The thermodynamic enolate is the most stable enolate i.e. the
one with the more highly substituted double bond
A weak base favors the thermodynamic enolate because an
equilibrium between the enolates is estabilished
The kinetic enolate is the enolate formed fastest and it
usually is the enolate with the least substituted double bond
A strong, sterically hindered base such as lithium diisopropyl
amide favors formation of the kinetic enolate
Chapter 17 57
Lithium Enolates in Directed Aldol Reactions
Crossed aldol reactions proceed effectively when a
ketone is first deprotonated with a strong base such as
LDA and the aldehyde is added slowly to the enolate
Chapter 17 58
An unsymmetrical ketone can be selectively
deprotonated with LDA to form the kinetic enolate and
this will react with an aldehyde to give primarily one
product
Chapter 17 59
Direct Alkylation of Ketones via Lithium Enolates
Enolates can also be alkylated with primary alkyl
halides via an SN2 reaction
Unsymmetrical ketones can be alkylated at the least
substituted position if LDA is used to form the kinetic
enolate
Chapter 17 60
a-Selenation: A Synthesis of a,b-Unsaturated
Carbonyl Compounds
A lithium enolate can be selenated with benzeneselenyl
bromide
Chapter 17 61
The a-selenyl ketone is converted to the a,b-
unsaturated carbonyl compound by reaction with
hydrogen peroxide
Elimination of the selenoxide produces the unsaturated
carbonyl
Chapter 17 62
Additions to a,b-Unsaturated Aldehydes and
Ketones
a,b-Unsaturated aldehydes and ketones can react by
simple (1,2) or conjugate (1,4) addition
Both the carbonyl carbon and the b carbon are
electrophilic and can react with nucleophiles
Chapter 17 63
Stronger nucleophiles such as Grignard reagents favor
1,2 addition whereas weaker nucleophiles such as
cyanide or amines favor 1,4 addition
Chapter 17 65
Michael Additions
Addition of an enolate to an a,b-unsaturated carbonyl
compound usually occurs by conjugate addition
This reaction is called a Michael addition
Chapter 17 66
A Robinson annulation can be used to build a new six-
membered ring on an existing ring
Robinson annulation involves a Michael addition followed
by an aldol condensation to close the ring