曼尼希型去芳构螺环化反应  

Mannich-type dearomative spiroannulation reaction

作　　者：郑华宇 葛怡聪 栾新军 ZHENG Hua-yu;GE Yi-cong;LUAN Xin-jun(College of Science,Chang’an University,Xi'an 710064,China;College of Chemistry and Materials Science,Northwest University,Xi'an 710127,China)

机构地区：[1]长安大学理学院,陕西西安710064 [2]西北大学化学与材料科学学院,陕西西安710127

出　　处：《分子科学学报》2021年第1期63-76,共14页Journal of Molecular Science

基　　金：国家自然科学基金资助项目(21925108);陕西省自然科学基金资助项目(2020JQ-348)。

摘　　要：以联芳基萘酚类化合物与价廉易得的甲醛作为原料,发展了一例分子间的曼尼希型去芳构螺环化反应.该反应无需金属参与,条件温和,且唯一副产物是水,具有较好的官能团兼容性,为含氮螺环骨架的快速构筑提供了一种新的方法.进一步研究表明,以手性磷酸作为催化剂,可初步取得该反应的不对称转化结果.A novel acid-catalyzed Mannich-type[4+1]dearomative spiroannulation of naphthol-based biaryls with formaldehyde has been developed for the one-step construction of spirocyclic frameworks,which are widely existing in natural products,functional molecules,and the ligands of metal catalysts.The reaction was initiated by in situ generated iminium through the condensation of aniline with formaldehyde,and followed by intramolecular dearomatization of naphthol,thus providing a series of azaspirocyclic molecules bearing an all-carbon quaternary stereocenter.Moreover,this approach is particularly attractive,since no metal was involved and water was the sole by-product under very mild conditions.The desired product was obtained in 98%yield by using TFA(5.0%)as Bronsted acid catalyst in CHCl3 at room temperature for 10 h.Control experiments revealed that the reaction performance was directly related with catalyst loading,and the product yield dramatically decreased in the presence of lower amount of TFA(1.0%,mole fraction).This phenomenon indicated that the rapid formation of key iminium intermediate was crucial for the[4+1]spiroannulation.Further studies disclosed that other Bronsted acid such as TfOH,HNTf2 or AcOH worked well for the process,but no better results were obtained compared to TFA.In addition,replacing TFA with Cu(OTf)2 led to a lower yield of the desired product.Furthermore,all the chlorinated solvents were suitable for the titled reaction,while ether solvents clearly decreased the yield of spirocyclic product.This reaction exhibited a broad substrate scope,and those spirocyclic product were efficiently synthesized in moderate to high yields(33%~98%).A series of different protecting groups for the aniline moiety were well tolerated in this process.Various substituents were found to be compatible,including electron-donating groups such as methyl,t Bu and electron-withdrawing groups such as fluoride,chloride,trifluoromethyl,ester and cyano groups.Moreover,sterically congested biaryl substrates were found to par

关 键 词：萘酚 曼尼希型反应 去芳构化 螺环己二烯酮 

分 类 号：O622[理学—有机化学]