摘要
γ-亚烷基-丁烯酸内酯是许多具有重要生理活性天然产物的结构单元.本工作通过铱催化N,N-二甲基芳基甲酰胺与呋喃硅醚间的类插烯Aldol缩合反应,成功地实现了温和条件下γ-亚苄基-丁烯酸内酯的合成.反应对硝基、氰基、乙烯基、三氟甲基等吸电子基取代的苯甲酰胺底物有很好的适用性.γ-亚苄基-丁烯酸内酯经Pd/C氢化反应即可转化为作为众多活性天然产物的核心骨架的γ-苄基丁内酯.本工作还对Z型和E型γ-亚苄基-丁烯酸内酯的特征^(1)H NMR谱峰的化学位移分布规律进行总结比较,利用这些规律可以很方便地区分Z、E两种异构体.
γ-Alkylidenebutenolides[5-alkylidene-2(5H)-furanones]are present in many biologically important natural products.One of the most direct and effective approaches to construct such compounds is the strategy based on vinylogous aldol condensation.However,this typically involves 2~3 reaction steps or a one-pot reaction carried out at high temperature.Compared to imines/iminiums and aldehydes,inert feedstock amides are more stable and readily available starting materials.Benefiting from the significant development of direct transformations of amides over the past few decades,amides have been well served as the surrogate of imine/iminium and aldehyde.In this work,we report a facile and efficient synthesis of γ-benzylidenebutenolides under mild conditions through Ir-catalyzed vinylogous aldol-type condensation between N,N-dimethyl arylformamides and silyloxyfuran.Nineteen examples of amides were transformed and fourteen examples of γ-benzylidenebutenolides were obtained in up to 91%yields and up to 83∶17 Z/E ratio.Notably,this reaction is well compatible with benzamides bearing electron-withdrawing substituents such as halogen,nitro,cyano,vinyl,and CF_(3) groups,with yields from 67%to 91%and Z/E ratios from 55∶45 to 83∶17.The general procedure is described as following:to a dried 10-mL round-bottom flask containing IrCl(CO)(PPh_(3))_(2)(4 mg,0.50 mmol%)was added a tertiary amide(0.50 mmol)in toluene(2.5 mL)and 1,1,3,3-tetramethyldisiloxane(TMDS)(115µL,0.65 mmol)at room temperature.After being stirred for 30 min,the resulting mixture was cooled to 0℃.Then CF_(3)CO_(2)H(57µL,0.75 mmol)and tert-butyldimethylsilyloxyfuran(TBSOF)(248 mg,1.25 mmol)were added dropwise successively.The mixture was allowed warm to room temperature,reacted for ca.10 h.Upon completion of the reaction,the resulted mixture was concentrated under reduced pressure.The residue was purified by flash chromatography on silica gel to provide the corresponding γ-benzylidenebutenolide.Additionally,a summary of the chemical shift values for the
作者
何倩
李杰
喻思佳
吴东坪
叶剑良
黄培强
He Qian;Li Jie;Yu Sijia;Wu Dongping;Ye Jianliang;Huang Peiqiang(Fujian Provincial Key Laboratory of Chemical Biology,College of Chemistry and Chemical Engineering,Xiamen University,Xiamen 361005)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2023年第10期1265-1270,共6页
Acta Chimica Sinica
基金
国家自然科学基金(No.21931010)资助.
