Concise Preparation of 2,2-Difluorohomopropargyl Carbonyl Derivatives. Application to the Synthesis of 4,4-Difluoroisoquinolinone Congeners

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• 作者：Satoru Arimitsu ; Bego&ntilde ; a Ferná ; ndez ; Carlos del Pozo ; Santos Fustero ; Gerald B. Hammond
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：April 4, 2008
• 年：2008
• 卷：73
• 期：7
• 页码：2656 - 2661
• 全文大小：132K
• 年卷期：v.73,no.7(April 4, 2008)
• ISSN：1520-6904

文摘

A scalable synthesis of 2,2-difluorohomopropargyl esters was achieved using a magnesium-promotedBarbier reaction of substituted difluoropropargyl bromides with alkyl chloroformates. These 2,2-difluorohomopropargyl esters were effective precursors in the synthesis of homopropargylic amides-byaminolysis using AlMe₃, as well as of ketones-through the reaction of the corresponding Weinreb amideswith Grignard reagents. Ring closing metathesis using difluorinated 1,7-enyne carbonyl compoundsfurnished six-membered diene products, which were used as susbstrates in a Diels-Alder reaction toafford 4,4-difluoroisoquinolin-3-ones. The [2 + 2 + 2] cycloaddition of alkynes with fluorinated 1,7-diyne amides gave 4,4-difluoro-1,4-dihydro-3(2H)-isoquinolinone derivatives regioselectively.