School of Engineering Science, Kochi University of Technology, Tosayamada, Kami 782-8502, Kochi, Japan.
Research Center for Molecular Design, Kochi University of Technology, Tosayamada, Kami 782-8502, Kochi, Japan.
J Org Chem. 2023 Feb 17;88(4):2207-2213. doi: 10.1021/acs.joc.2c02647. Epub 2023 Feb 6.
The central carbonyl group of diethyl mesoxalate (DEMO) exhibits high electrophilicity that allows it to be attacked by versatile nucleophiles. Even a less nucleophilic acid amide serves as a nucleophile to produce ,-acetal upon treatment with DEMO in the presence of acetic anhydride. When the obtained ,-acetal was treated with a base, the elimination of acetic acid generated -acylimine in situ. -Acylimine is also highly electrophilic, allowing it to accept the second nucleophilic addition by an amine, resulting in α,α-bis(functionalized) aminals. This protocol facilitates the modification of the two different amino groups by altering nucleophiles, resulting in the production of tetra-functionalized methane derivatives on demand. The ring closure between the amide moiety and the amino group was achieved using the structural features to form a six-membered ring.
草酸二乙酯（DEMO）的中心羰基具有高亲电性，可被各种亲核试剂攻击。即使是亲核性较弱的酰胺也能作为亲核试剂，在醋酸酐存在下与 DEMO 反应生成β-缩醛。当所得β-缩醛用碱处理时，通过消除乙酸，原位生成α-酰亚胺。α-酰亚胺也是高亲电性的，它可以接受第二个胺的亲核加成，生成α,α-双（官能化）亚胺。该方案通过改变亲核试剂，使α,α-双（官能化）亚胺的两个不同氨基基团发生修饰，从而按需生成四官能化甲烷衍生物。酰胺部分和氨基之间的环合是利用结构特征形成六元环来实现的。
