Nickel-Catalyzed 1,4-Carbofluoroalkylation Of 1,3-Enynes

The increasing demand for fluorine-containing molecules in the field of pharmaceuticals,agrochemicals,and functional materials has triggered extensive attention in the establishment of novel synthetic methods to build fluorinated compounds from organic chemists.As key structural motifs,allenes are used as key intermediates for diverse organic transformations.As a result,to meet the great demand of drugs and new materials development,developing efficient methods for facile synthesis of structurally diverse fluoroalkylated allenes is highly desirable.With the combination of nickel-catalyzed fluoroalkylations and radical-involved difunctionalizations,this dissertation described a radical relay strategy that different types of coupling reagents could capture the in-situ generated fluoroalkylated allenyl radical,affording the allenes with fluorine-containing groups.The dissertation includes 4 parts:Chapter 1:Research backgroundWe described the application of fluorine-containing compounds and allenes.Then we reviewed the progress of difunctionalization reactions involving fluoroalkyl radicals and the synthesis of allenes from 1,3-enynes utilizing 1,4-functionalizations systematically.Chapter 2:Nickel-catalyzed arylfluoroalkylation of 1,3-enynesWe have developed a nickel-catalyzed 1,4-arylfluoroalkylation of 1,3-enynes to access structurally diverse fluoroalkylated allenes,with the use of aryl boronic acids as necleophiles and readily available fluoroalkyl halides as radical sources.This method demonstrated high catalytic reactivity,mild reaction conditions,and excellent functional group tolerance.This strategy realized facile synthesis of structurally diverse multi-substituted fluoroalkylated allenes.Further transformations of fluoroalkylated allenes can construct various fluorine-containing frameworks,providing an approach for the study of flurorinated drug’s structure-activity relationship.Chapter 3:Nickel-catalyzed alkylfluoroalkylation of 1,3-enynesWith the use of alkylzinc reagents as necleophiles,we developed a nickel-catalyzed 1,4-alkylfluoroalkylation of 1,3-enynes through a radical relay strategy.This method demonstrated high catalytic reactivity,realizing the synthesis of diverse fluoroalkylated allenes under room temperature.The asymmetric version of this transformation is currently under investigation.Chapter 4:Nickel-catalyzed reductive arylfluoroalkylation of 1,3-enynesWe developed a nickel-catalyzed reductive 1,4-arylfluoroalkylation of 1,3-enynes using aryl halides and fluoroalkyl bromides as electrophiles via reductive coupling and radical relay strategy.This methodology avoids the use of organometallic reagents,demonstrating excellent broad scope and functional group tolerance under mild conditions,unactivated difluoroalkyl bromides and bromodifluoromethane were well tolerated in the transformation.