CHAPTER 8 – INTRODUCTION TO CARBONYL REDUCTION OF ALDEHYDES AND KETONES

CHEMISTRY & ORGANOMETALLIC

REAGENTS  Metal hydride reagents are used for reducing
aldehyde and ketones.
GENERAL REACTIONS OF CARBONYL  Source of Hydride anion.
COMPOUNDS

 A carbonyl group is a chemically organic

functional group composed of a carbon atom
double-bonded to an oxygen atom-->[C=O]
 Two broad classes of compounds contain the
carbonyl group:
 Aldehydes produce primary alcohols, while
[1] Aldehydes and ketones ketones produce secondary alcohols.
[2] Carboxylic acid derivatives

 C=O is prone to additions and nucleophilic

attack because of carbon's positive charge and
oxygen's negative charge
 Note: Just a reminder, the nucleophile is a good
acid therefore "likes protons" so it will attack
the side with a positive charge.
 Carbonyl carbons: sp2 hybridized, trigonal Mechanism of Hydride Reduction
planar, have C=O and polar, and has 2 resonance
structure. Step 1. Nucleophilic attack by the Hydride ion.
 Aldehydes and ketones undergo nucleophilic
addition.
 Carbonyl compounds that contain leaving
groups undergo nucleophilic substitution.
Notes:
Why can’t aldehydes and ketones undergo nucleophilic
Step 2. Protonation of the alkoxide.
substitution?

 Once a tetrahedral intermediate is formed,

aldehydes and ketones cannot reform their
carbonyls. Because of this, aldehydes and
ketones typically undergo nucleophilic additions
and not substitutions.
The more electronegative leaving groups withdraw Note: Catalytic hydrogenation also reduces aldehydes to
electron density from the carbonyl, thereby increasing its primary alcohols and ketones to secondary alcohols.
electrophilicity.
 REDUCTION OF CARBOXYLIC ACIDS AND
THEIR DERIVATIVES

 Metal hydride reagents are the most useful

reducing reagents.
 Lithium aluminum hydride is a strong reducing
agent that reacts with all carboxylic acid
derivatives.
Two other related but milder reducing agents are
Examples:
also used:

 Diisobutylaluminum hydride, [(CH3)2CHCH2]2AlH,

abbreviated as DIBAL-H
 Lithium tri tert butoxyaluminum hydride, LiAlH
[OC(CH3)3]3
Reduction of Acid Chlorides and Esters

 Acid chlorides and esters can be reduced to

THE STEREOCHEMISTRY OF CARBONYL either aldehydes or primary alcohols, depending
REDUCTION on the reagent.

OXIDATION OF ALDEHYDES

 Most common oxidation reaction of carbonyl

compounds is the oxidation of aldehydes to
 sp2 to sp3 hybridized.
carboxylic acids.
 Formation of a new stereogenic center.
 Oxidizing agents – Chromate reagents.
ENANTIOSELECTIVE CARBONYL  Aldehydes are oxidized selectively in the presence
REDUCTIONS of other functional groups using silver(I) oxide in
aqueous ammonium hydroxide This is called
 One enantiomer can be formed selectively from Tollens reagent.
the reduction of a carbonyl group, provided a  Oxidation with Tollens reagent provides a distinct
chiral reducing agent is used. A reduction that color change because the Ag+ reagent is reduced to
forms one enantiomer predominantly or silver metal (which precipitates out of solution).
exclusively is an enantioselective or asymmetric
reduction.
 Example: One such reagent, formed by reacting
borane with a heterocycle called an
oxazaborolidine has one stereogenic center (and
thus two enantiomers).

ORGANOMETALLIC REAGENTS
Organometallic Reagents contain a carbon atom bonded
to a metal.

 R = carbon skeleton
 M = Li or Mg, sp hybridized
 Because metals are more electropositive (less
electronegative) than carbon, they donate electron
density towards carbon, so that carbon bears a
partial negative charge.
 The more polar the carbon metal bond, the more
reactive the organometallic reagent
 Organolithium reagents RLi and Organomagnesium
reagents RMgX contain very polar carbon metal
bonds and are therefore very reactive reagents.
 Organocopper reagents (R2CuLi) contain less polar
carbon metal bond and therefore, less reactive.
 contain two alkyl group bonded to copper
but only one R is utilized in a reaction.
 Organometallic reagents are useful synthetically
because they react as if they were free carbanions
that is, carbon bears a partial negative charge, so the
reagents react as bases and nucleophiles.
REACTION OF ORGANOMETALLIC
REAGENTS WITH ALDEHYDES AND KETONES
 The reaction of an aldehyde (RCHO) or ketone with
an organometallic reagent forms an alcohol
(RCH2OH, R2CHOH or R3COH).
RETROSYNTHETIC ANALYSIS OF GRIGNARD
PRODUCTS
• Retrosynthesis is the reverse synthesis to determine
the start materials used in a reaction to form a
particular product.
• We have two terms for this which is GAKA and
GEEK.
• GAKA is Grignard + Aldehyde or Ketone =
Alcohol.
• GEEK is Grignard + Ester = Ketone.
Protecting Groups
 A protecting group (PG) is a molecular framework
that is introduced onto a specific functional group
(FG) in a poly functional molecule to block its
reactivity under reaction conditions needed to make
modifications elsewhere in the molecule.
 Protecting groups are used in synthesis to
temporarily mask the characteristic chemistry of a
functional group because it interferes with another
reaction.
 One of the major problems in organic synthesis is
the suppression of unwanted side reactions
Frequently, the desired reaction is accompanied by
reaction at other parts of the molecule, especially
when more than one functional group is present.
 Functional groups usually are the most reactive
sites in the molecule, and it may be difficult or
even impossible to insulate one functional group
from a reaction occurring at another.
Reaction of Organometallic Reagents with
Carboxylic Acid Derivatives
 Addition of Grignard reagents convert esters to
tertiary alcohols.
 When reacting with esters, the Grignard
reagent adds twice the first addition forms a
ketone, but Grignard reagents are strong
enough nucleophiles to add to ketones as well
Therefore, the reaction continues to the tertiary
alcohol.
Reaction of Organometallic Reagents with Other
Compounds
 Organometallic reagents can react with many other
electrophiles in addition to carbonyl groups since
they are strong nucleophiles.
 These reactions lead to the formation of new
carbon-carbon bonds they are valuable in organic
synthesis.
Reaction of RMgX with epoxide

α, β-Unsaturated Carbonyl Compound

 α, β-Unsaturated carbonyl compounds are

conjugated molecules containing a carbonyl group
and a carbon-carbon double bond, separated by a
single σ bond.
 Functional groups of α, β unsaturated carbonyl
compounds have π bonds but individually, they
react with very different kinds of reagents.
 Carbon-carbon double bonds react with
electrophiles.
 Carbonyl groups react with nucleophiles.

 The electron density in an α, β unsaturated

carbonyl compound is delocalized over four
atoms.
 Three resonance structures show that the carbonyl
carbon and the β carbon bear a partial positive
charge.
 α, β unsaturated carbonyl compounds can react
with nucleophiles at two different sites.
Summary of Reactions involving Grignard
reagents