Selective C-H Alkynylation Of Benzylamines And Aldehydes Catalyzed By Ir(Ⅲ)

Objective:Benzylamines,aliphatic aldehydes and alkynes are important components in many bioactive molecules,natural products,drugs and functional materials.The development of an efficient strategy for the synthsis of these compounds has attracted wide attention from chemists.With the development of transition metal catalysis,the C–H alkynylation by transition metal has become an important means of introducing alkyne functional groups.Directing groups（DG）are frequently employed to achieve a site-selective C–H bond functionalization.Therefore,this thesis aims to develop a directing group-assisted Ir（III）catalyzed C–H alkynylation reaction,affording an efficient method for the construction of a series of alkynylated benzylamines and alkynylated aliphatic aldehydes.Methods:As model reactions,we firstly examined the reactions of（E）-N-benzyl-2,2-dimethylpropan-1-imine 1a and（Z）-2,2-dimethyl-N-phenylpropan-1-imine 2a with（bromoethynyl）triisopropylsilane 3a by using various catalyst under different reaction conditions,respectively.The scope of the substrates was then investigated under the optimal conditions.The further transformations of the final alkylation products were also conducted.Finally,mechanistic studies including H/D exchange experiment,deuterium labeling experiment,competitive experiment and free radical trapping experiment were carried out to explore the mechanism of the reaction.Results:The optimal reaction conditions were determined as following:Under nitrogen atmosphere,imines（0.2 mmol）,（bromoethynyl）triisopropylsilane（0.3mmol）,[Cp*Ir Cl₂]₂（5 mol%）,Ag NTf₂（20 mol%）and Ag OAc（1.5 equiv）were mixed with DCE（1 m L）.The reaction was then stirred at 70°C for 12 h.The 41examples of alkynylation products of benzylamine were obtained in 45-85%yield,and 13 examples of alkynylation products of aliphatic aldehydes were obtained in 30-85%yield.The mechanistic studies indicated that the C-H activation is irreversible and proceeds through a concerted metalation deprotonation（CMD）mechanism.The single electron transfer pathway was excluded in this reaction.Conclusion:We have developed an iridium-catalyzed regioselective C–H alkynylation reaction of benzylamines and aliphatic aldehydes with（bromoethynyl）triisopropylsilane using an in situ-installed directing group.This reaction offers an efficient protocol for the synthesis of a series of alkynylated benzylamines and alkynylated aliphatic aldehydes in good yields and high regioselectivity,featuring broad substrate scopes and good functional group compatibility and a gram-scale synthesis.