A Convenient Synthesis of 1-Alkoxy-2-alkyl-1,2-dihydroisoquinoline-3,4-diones Utilizing the Reaction of 2-(Dialkoxymethyl)phenyllithiums with Dimethyl Oxalate

作者：Kobayashi Kazuhiro; Honda Yuuya; Kuroda Minami

来源：Helvetica Chimica Acta, 2016, 99(2): 125-129.

DOI：10.1002/hlca.201500254

• 1
• 2-Dihydroisoquinoline-3
• 4-diones
• 2-(Dialkoxymethyl)phenyllithiums
• Bromine
• lithium exchange
• Dimethyl oxalate
• Isoquinoline-1
• 3
• 4(2H)-triones

A new and convenient method for the preparation of 1,2-dihydroisoquinoline-3,4-diones with alkoxy and alkyl groups at the 4- and 3-positions, respectively, using an easily operated three-step sequence starting from 2-(dialkoxymethyl)phenyl bromides has been developed. Thus, the starting materials are treated with BuLi to generate 2-(dialkoxymethyl)phenyllithiums, which are allowed to react with (COOMe)(2) to give methyl 2-(dialkoxymethyl)phenyl-2-oxoacetates. These are then transformed into the corresponding secondary amides by the reaction with primary amines. Treatment of these keto amides with a catalytic amount of TsOHH2O affords the desired products. In order to demonstrate the synthetic utility of these products, transformation of one of them into the corresponding isoquinoline-1,3,4(2H)-trione derivative by the oxidation with PCC was achieved.

• 出版日期2016-2