School of Environmental Science and Engineering, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan.
Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-0871, Japan.
Org Biomol Chem. 2022 Mar 16;20(11):2282-2292. doi: 10.1039/d1ob02482e.
Diethyl mesoxalate (DEMO) exhibits high electrophilicity and accepts the nucleophilic addition of a less nucleophilic acid amide to afford ,-hemiacetal. However, our research showed that elimination of the amide moiety proceeded more easily than dehydration upon treatment with a base. This problem was overcome by reacting DEMO with an acid amide in the presence of acetic anhydride to efficiently obtain ,-acetal. Acetic acid was eliminated leading to the formation of -acylimine upon treatment with the base. -Acylimine is also electrophilic, accepting the second nucleophilic addition by pyrrole or indole to form α,α-disubstituted malonates. Subsequent hydrolysis followed by decarboxylation resulted in (α-indolyl-α-acylamino)acetic acid formation; homologs of tryptophan. Through this process, DEMO serves as a synthetic equivalent of α,α-dicationic acetic acid to facilitate nucleophilic introduction of the two substituents.
二乙基亚硝戊二酸酯（DEMO）具有高亲电性，可接受较少亲核性的酰胺酸的亲核加成，生成β-半缩醛。然而，我们的研究表明，与碱处理相比，酰胺部分的消除比脱水更容易进行。通过在醋酸酐存在下使 DEMO 与酸酰胺反应，可以有效地获得β-缩醛。乙酸消除，导致在碱处理下形成 -酰亚胺。-酰亚胺也是亲电性的，接受吡咯或吲哚的第二次亲核加成，形成α，α-二取代的丙二酸酯。随后的水解和脱羧导致（α-吲哚基-α-氨甲酰基）乙酸形成；色氨酸的同系物。通过这个过程，DEMO 充当α，α-二阳离子乙酸的合成等价物，促进两个取代基的亲核引入。
