aza-Morita-Baylis-Hillman反应二次串联构建氨基衍生的1,6-二烯化合物

Double aza-Morita-Baylis-Hillman Domino Reaction to Access Amino Derived 1,6-Dienes

aza-Morita-Baylis-Hillman反应是一类非常重要的构建C—C键的人名反应,被广泛应用于合成化学和药物化学领域.报道了一类新颖的1,4-二氮杂二环[2.2.2]辛烷(DABCO)介导的二次aza-Morita-Baylis-Hillman串联反应.该反应利用伯胺与甲醛能原位生成亚胺正离子的特征,在甲苯与水的混合溶剂中,实现了DABCO诱导的缺电子烯烃与亚胺正离子间的二次Mannich反应,最终以中等到良好的产率获得了一系列氨基衍生的1,6-二烯化合物.实验结果显示该三组分反应体系适用于一系列的苄胺、烷基胺和芳基胺底物,有效避免了传统aza-Morita-Baylis-Hillman反应对底物胺的束缚,为多样性1,6-二烯类化合物的合成提供了更加简洁的方法.

Aza-Morita-Baylis-Hillman reaction plays specific roles in the construction of C—C bond,and their applications in synthetic chemistry and pharmaceutical chemistry have also been well-documented.Herein,a novel 1,4-diazabicyclo-[2.2.2]octane(DABCO)mediated double aza-Morita-Baylis-Hillman cascade strategy toward synthetically important aza-MBH adducts is reported.Complementary to classical aza-MBH reaction,this protocol employs a wide variety of primary amines including benzyl,alkyl and aryl moieties as the reaction partners,giving an efficient alternative to produce amino derived 1,6-dienes in moderate to high yields in the presence of formaldehyde andα,β-unsaturated carbonyl compounds.Rather surprisingly,using an aqueous medium has proven to be successful in promoting the reaction efficiency and achieving a higher yield of target products.One-pot operation,high chemoselectivity,short reaction time,and broad substrate scope of primary amines exemplified the significant advances and practicability of this protocol.