Investigation And Application Of Et₂Zn-Promoted β-Trans-Selective Hydroboration Of Ynamide

Background:The construction of carbon-heteroatom bonds plays an important role in medicinal chemistry,natural product synthesis,material chemistry and organic chemistry.Especially,the addition reactions of carbon-carbon unsaturated bonds has attracted great attention,because of its easy availability of starting materials,high atom economy,and high efficiency.Alkenyl borons are important intermediates in organic synthesis.They can undergo various chemical transformations.Ynamides are special alkynes in wihch a nitrogen atom attached to the carbon-carbon triple bond directly.It can be used as a synthetic building block for the synthesis of a variety of heteroatomic compounds.Objective:Development of ynamides trans-hydroboration reaction strategy to provide new construction methods and approaches for finding new heteroatom molecular skeletons with potential biological activity.Methods:A mixture of Acetylene amine（1 equiv）,NHC-borane（2 equiv）and Diethyl zinc（3 equiv）in n-hexane（1.0 mL）was stirred under N₂at 60 ^oC for 3 h.Then,saturated aqueous NH₄Cl was added.After being stirred for 20 min at room temperature,the aqueous layer was extracted with EtOAc,and the combined organic layers were washed with brine,dried over Na2SO4,filtered and concentrated.The residue was purified by flash column chromatography on silica gel.Results:The reaction leads to a stereoselective construction of alkenyl borons bearing a valuable boryl substituent.The substrate scope of reaction was explored.Both aromatic and aliphatic ynamides were applicable to the reaction.The method starts from simple raw material synthesis,occur under short reaction time and mild reaction conditions.The reaction features with good yield,high regioselectivity and good functional group tolerance.The reaction does not require high temperature and noble metal catalysts.Conclusion:We have developed an Et2Zn-promoted?-and trans-selective hydroboration of ynamides.Synthetic transformation of the C-B bond in the product via Suzuki-Miyaura coupling provides a simple and stereospecific route to multi-substituted enamides.The mechanism was discussed and a step-wise polar hydroboration pathway was suggested.