アミン触媒による多置換アルデヒド・ケトンの選択的フッ素化反応

抄録

Organofluorine compound is one of the most important classes of organic compounds in medicinal chemistry, because fluorine has several effects for improving biological activity. In order to express these effects of fluorine as expected, fluorine has to be installed at a specific location in molecules with well-controlled stereoconfiguration; in the case of sp³ fluorinated carbon in a structure, an enantioselective fluorination is highly demanded. In this context, we have developed β,β-diaryl serine as a new primary amine catalyst, which has been found to be an efficient catalyst for enantioselective α-fluorination of α-branched β-dicarbonyl compounds, such as β-diketone, β-ketoester, and β-ketoamide with high enantioselectivity (≥90% ee). Moreover, the cinchona-alkaloid based primary amine was found as the effective catalyst for enantioselective α-fluorination of γ-enolizable α,β-unsaturated aldehydes (≥90% ee). On the other hand, α-regioselective difluorination of γ-enolizable α,β-unsaturated aldehydes was successfully carried out by L-proline as a catalyst with high stereoselectivity (E/Z=≥20/1).