钯催化选择性构筑(Z)-[3]戟烯反应研究

Palladium-catalyzed Stereoselective Synthesis of(Z)-[3]Dendralenes

本工作发展了钯催化下芳甲醛对甲苯磺酰腙与膦酰基取代联烯的偶联反应,顺利地以中等至良好的收率及较高的立体选择性制备了一系列(Z)-[3]戟烯衍生物.不同于烷基取代的苯磺酰腙与烯烃的简单偶联,该反应使用芳甲醛对甲苯磺酰腙作为底物,经由1,3-钯迁移历程成功构筑了两个C=C双键.在最优反应条件下,该反应展示了较宽的底物适用范围和较高的立体选择性.最终以31个反应实例获得一系列(Z)-[3]戟烯衍生物,最高79%分离产率和>20∶1 Z/E选择性,为(Z)-[3]戟烯衍生物的合成应用提供了简便高效的方法.

In this work,coupling of allenylphosphine oxides with aromatic tosylhydrazones were successfully developed under palladium catalysis,delivering(Z)-[3]dendralene derivatives in medium to good yields with high stereoselectivity.Different from the simple coupling of alkyl substituted tosylhydrazones and alkenes,aromatic tosylhydrazones were used as substrate in this work,with which two C=C bonds were constructed simultaneously involving a 1,3-palladium migration process.Under the optimized reaction conditions using Pd(PPh)Clas catalyst,anhydrous methanol as solvent and 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU) as base,the reaction showed wide substrate scope and high stereoselectivity.31examples of(Z)-[3]dendralenes were obtained with up to 79% isolated yield and up to >20∶1 Z/E selectivity.The protocal provideds a simple and efficient method for the synthesis and application of(Z)-[3]dendralene derivatives.Further transformation of compound 3al was achieved to consturct the chromene skeleton which is widely occured in biologically active molecules and natural products.The general procedure is as following:to a Schlenk tube was added allenylphosphine oxide 1(0.3 mmol),aromatic tosylhydrazone 2(0.6 mmol),Pd(PPh)Cl(5 mol%,11 mg),and tBu COONa·HO(0.6 mmol,85 mg).The reaction flask was sealed,evacuated and back-filled with nitrogen for three times.Afterwards,anhydrous methanol solvent(3 mL) was added through a syringe and DBU(0.9 mmol) was injected slowly.The reaction was carried out at 85 ℃ for 2~3 h.Upon completion of the reaction,the solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel using petroleum ether/ethylacetate(V/V=1∶1~2∶1) to afford the target product 3.The general procedure for transformation of 3al is as following:to a 10 mL round-bottom flask containing 3al(0.3 mmol),3 mL of anhydrous dichloromethane was added under argon protection.After cooled to-78 ℃,boron tribromide was added dropwise and the mixture was sitrred for 20 min before moved to room temperature and stirred overnight.The reaction solution was quenched with ice water,extracted with dichloromethane and saturated brine,evaporated under reduced pressure,after which the crude product was separated by column chromatography using petroleum ether/ethylacetate(V/V=2∶1) to afford the target product.