C–H Arylation of Heterocyclic N-Oxides Through in Situ Diazotisation Of Anilines without Added Promoters: A Green And Selective Coupling Process

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• 作者：Aymeric P. Colleville ; Richard A. J. Horan ; Sandrine Olazabal ; Nicholas C. O. Tomkinson
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：July 15, 2016
• 年：2016
• 卷：20
• 期：7
• 页码：1283-1296
• 全文大小：901K
• 年卷期：0
• ISSN：1520-586X

文摘

A green and selective method for the generation of biaryl compounds through C–H arylation of heterocyclic N-oxides, in which the addition of ascorbic acid as a promoter is not required for either the generation of an aryldiazonium species or the subsequent arylation, is presented. Reaction conditions were optimized through multivariate data analysis, including orthogonal projections to latent structures (OPLS) and design of experiments (DoE) methodologies, resulting in further sustainability improvements, and were then applied to a range of substrates to establish the scope and limitations of the process. The reaction was studied using in situ infrared spectroscopy and a mechanism is presented that accounts for the available data from this and previous studies. The reaction was also performed on a multigram scale, with calorimetry studies to support further scale-up of this promoter-free transformation.