Post on 09-Jun-2018
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Chapter 18: Carbonyl Compounds II
Learning Objectives:
1. Recognize and assign names to aldehydes and ketones.
2. 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.
3. Be able to explain the relative reactivity of carbonyl compounds toward nucleophilic addition.
4. Be able to describe the concept of employing protecting groups.
5. Predict the products of the reactions of carbonyl compounds with Grignard reagents, hydride ion
donors, sulfur nucleophiles, and with phosphonium ylides (the Wittig reaction).
6. Be able to recognize Re and Si faces of carbonyl compounds, and the stereochemistry outcomes
from a nucleophilic addition.
7. Predict the products of addition reactions to α,β-unsaturated carbonyl compounds.
Sections:
18.1 Nomenclature
18.2 Relative Reactivities of Carbonyl Compounds*
18.3 How Aldehydes and Ketones React*
18.4 Reaction of Carbonyl Compounds with Carbon Nucleophiles*
18.5 Reaction of Carbonyl Compounds with Hydride Ion*
18.6 Reaction of Aldehydes and Ketones with Nitrogen Nucleophiles*
18.7 Reaction of Aldehydes and Ketones with Oxygen Nucleophiles*
18.8 Protecting Groups*
18.9 Addition of Sulfur Nucleophiles
18.10 The Wittig Reaction*
18.11 Stereochemistry of Nucleophilic Addition Reactions: Re and Si Faces#
18.12 Designing a Synthesis V: Disconnections, Synthones, and Synthetic Equivalents
18.13 Nucleophilic Addition to α,β-Unsaturated Aldehydes and Ketones*
18.14 Nucleophilic Addition to α,β-Unsaturated Carboxylic Acid Derivatives
18.15 Enzyme-catalyzed Additions to α,β-Unsaturated Carbonyl Compounds#
* Sections that will be focused # Sections that will be skipped
Recommended additional problems
8.40 – 8.55, 8.58 – 8.61, 8.63 – 8.67, 8.69 – 8.72, 8.74
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Class Note
18.1 Nomenclature
O
H
O
H
O
H
O
H
H H
O O
O
H
O
H
HO
H OCH2CH3
O O
OCH2CH3
CHO O
Cl
3
H
O O
H
O O
O O OO
O
CH3
O O
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18.2 Relative Reactivities of Carbonyl Compounds
Nucleophilic addition
18.3 How Aldehydes and Ketones React
A. In basic condition
R H (R)
O
R H(R)
O Nu
Nu ( Z)
tetrahedral intermediate
R H(R)
O NuH
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B. In acidic condition
H B B + H
R H (R)
O
R H(R)
O BH
R H (R)
OH
6
18.4 Reaction of Carbonyl Compounds with Carbon Nucleophiles
A. Carbon nucleophile (basic or acidic?)
B. Reaction of aldehydes and ketones with Grignard reagent
7
C. Reactions of ester and carboxylic acid with Grignard reagent
8
D. Reactions of aldehydes and ketones with acetylide ions
(i) pKa of
CH2 CH2 HR CH CH HR C C HR
(ii) Mechanism
9
E. Reactions of aldehydes and ketones with hydrogen cyanide
(i) pKa of H-CN
(ii) Mechanism
(iii) Synthesis of α-hydroxy carboxylic acid
10
18.5 Reaction of Carbonyl Compounds with Hydride Ion
A. Source of hydride
B. Reduction of aldehydes and ketones
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C. Reduction of esters
12
D. Reduction of carboxylic acids
13
E. Reduction of amides
14
18.6 Reaction of Aldehydes and Ketones with Nitrogen Nucleophiles
A. pKa of amines
B. Addition of primary amines
15
C. Addition of secondary amines
D. Addition of hydrazine, hydroxyamine
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E. Mechanism of Wolff-Kishner reduction
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18.7 Reaction of Aldehydes and Ketones with Oxygen Nucleophiles
A. Addition of water (formation of hydrate, gem-diol, geminal diol)
R H (R)
O
R H(R)
HO OH
H2O
(i) Consideration of pKa
(ii) Stability consideration
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B. Addition of alcohol (formation of hemiacetal, acetal, hemiketal, and ketal)
R H
O
R H
R'O OR'
HOR'
R H
R'O OH
(2 equivalents)
H2O
R R
O
R R
R'O OR'
HOR'
R R
R'O OH
(2 equivalents)
H2O
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C. Mechanism
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18.8 Protecting Groups
A. Stability of acetals and ketals
B. Example
O
HOCH2CH2OH+
OO
+ H2O
(i)
O
OCH3
O
?O
OH
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C. More examples
(i)
NH2?
NH2
NO2
(ii)
NH2?
NH2
CO2H
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18.9 Addition of Sulfur Nucleophiles
18.10 The Wittig Reaction
A. Wittig reagents
(C6H5)3P CH2
phosphonium ylide
(C6H5)3P CH2
B. Formation of Wittig reagents
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C. Reactions
(i) Synthesis of
(ii) Synthesis of
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D. Stereoselectivity (E vs. Z)
E. Arbuzov (Perkow) reaction and Horner-Emmons reaction
(i) Horner-Emmons reaction
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(ii) Arbuzov (Perkow) reaction
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18.12 Designing a Synthesis V: Disconnections, Synthones, and Synthetic Equivalents
A. Retrosynthetic analysis
Example
OHOH
synthesis of from
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18.13 Nucleophilic Addition to α,β-Unsaturated Aldehydes and Ketones
A. Analysis of α,β-unsaturated aldehydes and ketones
R
O
α
β
B. Direct addition (1,2-addition) and conjugate addition (1,4-addition)
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C. Examples
(i)
O1) CN2) HCl
(ii)
O
+ HSCH3
(iii)
CH3
O
+ (CH3)2NH
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(iv)
O1) NaBH4, CeCl32) H2O, H
+
(v)
H
O 1) CH3MgBr2) H2O, H
+
(vi)
O1) CH3MgBr2) H2O, H
+
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(vii)
1) (CH3)2CuLi2) H2O, H
+
O
18.14 Nucleophilic Addition to α,β-Unsaturated Carboxylic Acid Derivatives
Cl
O
HOCH3+
NHCH3
O
HOCH3+
OCH3
O 1) LiAlH42) H2O, H
+
Cl
O
NH3 (excess)+