Visible Light-induced DDQ-Catalyzed Fluorocarbamoylation Using Langlois Reagent = 랑글루아 시약을 사용한 가시광선 유도 DDQ 광촉매 플루오로카바모일화 반응 연구

다국어 초록 (Multilingual Abstract)

Fluorination has become an important reaction in medicinal chemistry because fluorine atom can
significantly influence drug metabolism and pharmacokinetics with increased lipophilicity,
metabolic stability, membrane permeability and bioavailability. In this study, the visible light
photocatalytic C-H trifluoromethylation of arenes and N-H fluorocarbamoylation of Nheterocycles
using sodium trifluoromethanesulfinate (CF3SO2Na), so called Langlois reagent, as a
source of fluorine, are described. The reactions of electron-rich aromatic compounds in the
presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a photoredox catalyst under
irradiation of visible light afforded the desired fluoroarenes in reasonable yields. Mechanistically,
the trifluoromethylation proceeded via addition of CF3 radical intermediate followed by hydrogen
abstraction. Alternatively, the CF3 radical, generated from visible light irradiation to Langlois
reagent, can be converted to CF3OO radical by aerobic oxidation, which would be rapidly
decomposed to generate carbonyl fluoride (F2C=O). This highly reactive species can be reacted
with various secondary amines to afford a wide range of carbamoyl fluorides in good to excellent
yield. Further transformation of carbamoyl fluorides to ureas or carbamates were also achieved
under mild reaction conditions.

목차 (Table of Contents)

• 1. Introduction . 1
• 1.1. Organofluorine compounds . 1
• 1.2. Carbamoyl fluoride 2
• 1.2.1. General synthesis method of carbamoyl fluorides 2
• 1.2.2. Carbamoyl fluoride applications . 3
• 1.3. Visible light-mediated radical fluoromethylation 5
• 1.3.1. Generation of trifluoromethyl radical using Langlois reagent 6
• 1.4. DDQ photocatalyst in organic synthesis . 8
• 1.5. Research objective and synthesis plans . 9
• 2. Result and discussion 10
• 2.1. Trifluoromethylation of Arenes 10
• 2.1.1. MS-EI study of trifluoromethylation 11
• 2.2. DDQ-catalyzed fluorocarbamoylation . 12
• 2.2.1. Reaction optimization . 13
• 2.2.2. Scope of DDQ-catalyzed fluorocarbamoylation . 15
• 2.2.3. DDQ-catalyzed fluorocarbamoylation under acidic condition . 18
• 2.2.4. Scope of TFA-supported DDQ-catalyzed fluorocarbamoylation 19
• 2.2.5. Mechanistic control experiments 21
• 2.2.6. Determination of reaction intermediates . 22
• 2.2.7. Proposed mechanism of fluorocarbonylation 24
• 2.2.8. Utilization of carbamoyl fluorides 25
• 3. Conclusion . 26
• 4. Experimental Section 27
• 4.1. Equipment and Reagent . 27
• 4.2. Reaction setup 28
• 4.3. Experiment for mechanistic study 28
• 4.4. Synthesis 30
• 4.4.1. Procedure for the preparation of substrates . 30
• 4.4.2. Procedure for photocatalytic fluorocarbamoylation 38
• 4.4.3. Procedure for the synthesis of ureas 51
• 5. Reference . 53
• Spectra data . 55
• 국문 요지 87