氮杂环卡宾/二氯化钯催化1,3-二亚烷基-1,3-二氢异苯并呋喃的合成

N-heterocyclic Carbene/Palladium Chloride-catalyzed Synthesis of 1,3-Dialkylidene-1,3-dihydroisobenzofuran

由于1,3-二氢异苯并呋喃类化合物在医药和合成方面有着越来越重要的作用,本文探讨了噻唑卡宾与二氯化钯接力催化邻炔基苯甲醛与N-酰基亚胺生成1,3-二亚烷基-1,3-二氢异苯并呋喃的新方法。反应经历了卡宾催化的氮杂苯偶姻反应和钯催化的5-exo-dig环化的历程。通过筛选得到了氮杂苯偶姻反应优化的条件为:30%(物质的量分数,下同)噻唑卡宾为催化剂、原料1与化合物2a的物质的量之比为1.5∶1.0、三乙胺为碱、乙腈为溶剂、反应温度为50℃、反应时间为12 h;环化的优化条件为:PdCl_(2)为催化剂、乙腈为溶剂、反应温度为25~30℃和反应时间为12 h。通过底物拓展,合成了中间产物α-酰胺基芳酮(4a和4b),产率为90%~96%;目标产物1,3-二亚烷基-1,3-二氢异苯并呋喃(5a和5b),产率为91%~94%,并对产物结构进行了^(1)H NMR确证。

Given the increasingly importance of 1,3-dihydroisobenzofuran compounds in medicine and synthesis,we reported a novel approach for the construction of 1,3-dialkylidene-1,3-dihydroisobenzofurans from o-alkynylbenzaldehyde and N-acylimine relay-catalyzed by thiazole carbene and palladium chloride.The reaction underwent a process of thiazole carbene-catalyzed azabenzoin reaction and palladium-catalyzed 5-exo-dig cyclization.The optimized conditions of azabenzoin reaction as follows:30%(mole fraction,the same below)thiazole carbene as catalyst,the substrate ratio to 1∶2a=1.5∶1.0,Et 3 N as base,acetonitrile as solvent,reaction at 50℃for 12 h.The optimized conditions were chosen as the conducting the cyclization catalyzed by PdCl_(2),in acetonitrile at 25~30℃for 12 h.Through surveying substrate scope,the intermediate productsα-amido aromatic ketones(4a and 4b)were synthesized in 90%~96%yields,and the target products 1,3-dialkylidene-1,3-dihydroisobenzofurans(5a and 5b)were synthesized in 91%~94%yields.The structures of the products were confirmed by^(1)H NMR.