development of methods for regioselective …...ジフルオロカルベンを用いる...
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ジフルオロカルベンを用いる
位置選択的ジフルオロメチレンユニット導入法の開発
発表者 高山 亮
指導教員 市川 淳士
Development of Methods for Regioselective
Introduction of Difluoromethylene Unit Using
Difluorocarbene
Bioactive Compounds Bearing the CF Unit2
Fluorine Atom
Introduction
Electrophilic
Introduction
Nucleophilic
Introduction
Synthesis of CF Compounds2
Building Block
Introduction
Fluorine Atom
Introduction
Electrophilic
Introduction
Nucleophilic
Introduction
Synthesis of CF Compounds2
Building Block
Introduction
Synthesis of CF Compounds2
Fluorinated One-Carbon Unit: Difluorocarbene
Difluorocarbene
Severe Conditions
Problems in Generation of Difluorocarbene (1)
Recent Difluorocarbene Source: TFDA
Overreaction
Problems in Generation of Difluorocarbene (2)
Dimerization
Controlled Generation of :CF by Organocatalysts2
Table of Contents
Chapter 1. General Introduction
Chapter 2. Introduction of Difluoromethylene Unit into
Thiocarbonyl Compounds
Chapter 3. Introduction of Difluoromethylene Unit into
Dienol Silyl Ethers
Chapter 4. Conclusions
Chapter 2
2-1. S-Selective Difluoromethylation of Thiocarbonyl Compounds
2-2. Difluoromethylidenation of Dithioesters
S-Selective Difluoromethylation of Thioamides
Bioactive Compounds
2-1. S-Selective Difluoromethylation of Thiocarbonyl Compounds
S-Selective Difluoromethylation of Thioamides
O-Selective Difluoromethylation of Amides
2-1. S-Selective Difluoromethylation of Thiocarbonyl Compounds
Optimization of TFDA Activator
Role of Proton Sponge: Nucleophile
Role of Proton Sponge: Base
Role of Proton Sponge: Base
Proposed Reaction Mechanism
S-Selective Difluoromethylation of Thioamides
S,N-Selectivity
Chapter 2
2-1. S-Selective Difluoromethylation of Thiocarbonyl Compounds
2-2. Difluoromethylidenation of Dithioesters
Difluoromethylidenation of Dithioesters
2-2. Difluoromethylidenation of Dithioesters
Bioactive Compounds
Difluoromethylidenation of Dithioesters
Nucleophilic (Wittig-type) Difluoromethylidenation
Electrophilic (Barton–Kellogg-type) Difluoromethylidenation
Difluoromethylidenation of Dithioesters
Table of Contents
Chapter 1. General Introduction
Chapter 2. Introduction of Difluoromethylene Unit into
Thiocarbonyl Compounds
Chapter 3. Introduction of Difluoromethylene Unit into
Dienol Silyl Ethers
Chapter 4. Conclusions
Chapter 3
3-1. Regioselective Difluorocyclopropanation of Dienol Silyl Ethers
Difluorocyclopropanation of Dienol Silyl Ethers
Regioselective Difluorocyclopropanation
Chapter 3
Applications of Difluoro(vinyl)cyclopropanes3-2.
3-3.
Metal-Free Synthesis of Cyclic Enol Silyl Ethers
Metal-Free Synthesis of Cyclic Enol Silyl Ethers
Advantage of the Metal-Free Synthesis
Chapter 3
Applications of Difluoro(vinyl)cyclopropanes3-2.
3-3.
Regioselective Synthesis of Fluorinated Cyclopentenones
Regioselective Synthesis of Fluorinated Cyclopentenones
Nazarov Cyclization
Regioselective Synthesis of Fluorinated Cyclopentenones
Fluorine-Directed and -Activated Nazarov Cyclization
Preparation of Nazarov Precursors
Regioselective Nazarov Cyclization
Effect of Fluorine Substituent: Activation
Effect of Fluorine Substituent: Direction
Effect of Fluorine Substituent: Direction
Non-fluorinated Cyclopentenones
Conclusion
Conclusion
Chapter 1. General Introduction
TFDA の合成法
1.窒素求核剤
Chapter 2. Difluoromethylation of Thioamides
2.炭素求核剤
Chapter 2. Difluoromethylation of Thioamides
→ 1,8-ビス（ジメチルアミノ）ナフタレンが塩基として働いた可能性を示唆
Chapter 2. Difluoromethylation of Thioamides3.塩基
Chapter 2. Difluoromethylation of Thioamides
異性化の確認
Chapter 2. Difluoromethylation of Thioamides
他のカルベン源との比較
Chapter 2. Difluoromethylidenation of Dithioesters
脱硫過程の推定機構
1. ジフルオロカルベンによる脱硫
2. チイランからの自発的な脱硫
Chapter 3. Regioselective Difluorocyclopropanation
Chapter 3. Regioselective Difluorocyclopropanation
Chapter 3. Regioselective Difluorocyclopropanation
Chapter 3. Regioselective Difluorocyclopropanation
Chapter 3. Regioselective Difluorocyclopropanation
Chapter 3. Regioselective Nazarov Cyclization
ルイス酸の最適化
Chapter 3. Regioselective Nazarov Cyclization
フッ素による位置選択性の発現
Chapter 3. Regioselective Nazarov Cyclization
Chapter 3. Regioselective Nazarov Cyclization
フッ素無置換の基質
Chapter 3. Regioselective Nazarov Cyclization
フッ素が置換した基質