Chapter 17: Carbonyl Compounds II
Learning Objectives:
1.
2.
3.
4.
5.
6.
7.
Recognize and assign names to aldehydes and ketones.
Write the mechanism for nucleophilic addition and nucleophilic addition-elimination reactions
of aldehydes and ketones, and be able to predict the products of such reactions.
Be able to explain the relative reactivity of carbonyl compounds toward nucleophilic addition.
Be able to describe the concept of employing protecting groups.
Predict the products of the reactions of carbonyl compounds with Grignard reagents, hydride ion
donors, sulfur nucleophiles, and with phosphonium ylides (the Wittig reaction).
Be able to recognize Re and Si faces of carbonyl compounds, and the stereochemistry outcomes
from a nucleophilic addition.
Predict the products of addition reactions to  -unsaturated carbonyl compounds.
Sections:
17.1
17.2
17.3
17.4
17.5
17.6
17.7
17.8
17.9
17.10
17.11
17.12
17.13
17.14
17.15
17.16
17.17
17.18
Nomenclature of Aldehydes and Ketones
Relative Reactivities of Carbonyl Compounds*
How Aldehydes and Ketones React*
Reaction of Carbonyl Compounds with Grignard Reagents*
Reaction of Carbonyl Compounds with Acetylide Inos
Reaction of Carbonyl Compounds with Hydride Ion*
Reaction of Aldehydes and Ketones with Hydrogen Cyanide
Reaction of Aldehydes and Ketones with Amines and Derivatives of Amines*
Reaction of Aldehydes and Ketones with Water
Reaction of Aldehydes and Ketones with Alcohol*
Protecting Groups*
Addition of Sulfur Nucleophiles
The Wittig Reaction Forms an Alkene*
Stereochemistry of Nucleophilic Addition Reactions: Re and Si Faces#
Designing a Synthesis VI: Disconnections, Synthones, and Synthetic Equivalents
Nucleophilic Addition to -Unsaturated Aldehydes and Ketones*
Nucleophilic Addition to -Unsaturated Carboxylic Acid Derivatives
Enzyme-catalyzed Additions to -Unsaturated Carbonyl Compounds#
* Sections that will be focused
#
Sections that will be skipped
Recommended additional problems
17.45 – 17.65, 17.67 – 17.70, 17.73 – 17.77, 17.79 – 17.82, 17.84
1
Class Note
17.1
Nomenclature of Aldehydes and Ketones
O
O
H
H
O
O
H
H
O
H
H
HO
O
H
O
H
O
Cl
H
OCH2CH3
O
OCH2CH3
O
CHO
2
O
H
H
O
O
O
O
O
O
O
O
O
O
O
CH3
3
17.2
Relative Reactivities of Carbonyl Compounds*
Nucleophilic addition
17.3
How Aldehydes and Ketones React*
A. In basic condition
O
O
R
H (R)
Nu
R
H(R)
tetrahedral
intermediate
Nu (
Z)
4
O
H
R
Nu
H(R)
B. In acidic condition
H
B +
B
H
O
R
O
H (R)
H
R
H (R)
5
O
H
R
B
H(R)
17.4
Reaction of Carbonyl Compounds with Grignard Reagents*
A. Carbon nucleophile (basic or acidic?)
B. Reaction of aldehydes and ketones with Grignard reagent
6
C. Reactions of ester and carboxylic acid with Grignard reagent
7
17.5
Reaction of Carbonyl Compounds with Acetylide Inos
(i) pKa of
R
CH2
CH2
H
R
CH
CH
(ii) Mechanism
8
H
R
C
C
H
17.7
Reaction of Aldehydes and Ketones with Hydrogen Cyanide
(i) pKa of H-CN
(ii) Mechanism
(iii) Synthesis of -hydroxy carboxylic acid
9
17.6
Reaction of Carbonyl Compounds with Hydride Ion*
A. Source of hydride
B. Reduction of aldehydes and ketones
10
C. Reduction of esters
11
D. Reduction of carboxylic acids
12
E. Reduction of amides
13
17.8
Reaction of Aldehydes and Ketones with Amines and Derivatives of Amines*
A. pKa of amines
B. Addition of primary amines
14
C. Addition of secondary amines
D. Addition of hydrazine, hydroxyamine
15
E. Mechanism of Wolff-Kishner reduction
16
17.9
Reaction of Aldehydes and Ketones with Water
A. Addition of water (formation of hydrate, gem-diol, geminal diol)
O
HO
R
OH
H (R)
R
H2O
(i) Consideration of pKa
(ii) Stability consideration
17
H(R)
17.10
Reaction of Aldehydes and Ketones with Alcohol*
A. Addition of alcohol (formation of hemiacetal, acetal, hemiketal, and ketal)
O
R'O
R'O
R
OR'
OH
H
R
R
H
H
HOR'
(2 equivalents)
H2O
O
R'O
R'O
R
OR'
OH
R
R
R
R
R
HOR'
(2 equivalents)
H2O
18
C. Mechanism
19
17.11
Protecting Groups*
A. Stability of acetals and ketals
B. Example
O
O
+
O
+
HOCH2CH2OH
H2O
(i)
O
O
O
?
OCH3
OH
20
C. More examples
(i)
NH2
NH2
?
NO2
(ii)
NH2
NH2
?
CO2H
21
17.12
Addition of Sulfur Nucleophiles
17.13
The Wittig Reaction Forms an Alkene*
A. Wittig reagents
(C6H5)3P
CH2
(C6H5)3P
phosphonium ylide
B. Formation of Wittig reagents
22
CH2
C. Reactions
(i) Synthesis of
(ii) Synthesis of
23
D. Stereoselectivity (E vs. Z)
E. Arbuzov (Perkow) reaction and Horner-Emmons reaction
(i) Horner-Emmons reaction
24
(ii) Arbuzov (Perkow) reaction
25
17.15
Designing a Synthesis VI: Disconnections, Synthones, and Synthetic Equivalents
A. Retrosynthetic analysis
Example
OH
synthesis of
26
OH
from
17.16
Nucleophilic Addition to -Unsaturated Aldehydes and Ketones*
A. Analysis of  -unsaturated aldehydes and ketones
O


R
B. Direct addition (1,2-addition) and conjugate addition (1,4-addition)
27
C. Examples
(i)
O
1) CN
2) HCl
(ii)
O
+
HSCH3
(iii)
O
+
(CH3)2NH
CH3
28
(iv)
O
1) NaBH4, CeCl3
2) H2O, H+
(v)
1) CH3MgBr
2) H2O, H+
O
H
(vi)
O
1) CH3MgBr
2) H2O, H+
29
(vii)
O
17.17
1) (CH3)2CuLi
2) H2O, H+
Nucleophilic Addition to -Unsaturated Carboxylic Acid Derivatives
O
Cl
+
HOCH3
O
NHCH3
+
O
HOCH3
1) LiAlH4
2) H2O, H+
OCH3
O
+
NH3 (excess)
Cl
30