Reductive Dehalogenation Enabled By NaH And CaH₂

This thesis focuses on palladium-catalyzed reduction of halogen by NaH and CaH2 as reducing agent.Many natural products contain halogens and show different biological activities.Some of them have medicinal properties.It can be used as a lead compound and further optimized to obtain clinical drugs.Some halogens are introduced in organic synthesis.For example,the halogen on the aromatic ring can be used as a"position-blocking group" in organic synthesis,which needs to be removed after fulfilling its task.It is also one of the key functional groups for building carbon-carbon bonds and carbon-hetero bonds.At present,the most commonly used methods for removing halogen are transition-metal catalytic hydrogenation reactions,metal hydride mediated reductions,and metal reduction.NaH and CaH2 are usually used as a base and rarely as a reducing agent.In this thesis,we use Pd as a catalyst to activate the reducing properties of NaH and CaH2 for the reduction of halogens.This method features simple operation,mild reaction conditions,and atom economy.A wide range of functional groups,such as acid,alcohol,ester,aniline,nitro,cyano and heterocyclic compounds,were all tolerated to the reaction conditions.Both C-Br and C-Cl bonds were smoothly reduced by NaH/Pd or CaH2/Pd in good to excellent yields.Polyhalide substrates could also be chemoselectively reduced.The reaction could be carried out in gram-scale without reducing the efficiency.Our method is mild and reliable,which is of great significance for the synthesis of complex drug molecules.This thesis includes two sections:The first section describes palladium-catalyzed reduction of aryl halide by NaH and CaH2 as reducing agent.The second section describes palladium-catalyzed reduction of alkyl halide by NaH and CaH2 as reducing agent.