From High-Throughput Catalyst Screening to Reaction Optimization: Detailed Investigation of Regioselective Suzuki Coupling of 1,6-Naphthyridone Dichloride

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• 作者：Chaoxian Cai ; John Y. L. Chung ; J. Christopher McWilliams ; Yongkui Sun ; C. Scott Shultz ; Michael Palucki
• 刊名：Organic Process Research & Development
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：11
• 期：3
• 页码：328 - 335
• 全文大小：200K
• 年卷期：v.11,no.3(May 2007)
• ISSN：1520-586X

文摘

Efficient catalyst systems and reaction protocols were discovered for the regioselective Suzuki coupling of 1,6-naphthyridonedichloride through high-throughput experimentation. With Pd₂(dba)₃·CHCl₃ as the precatalyst, either (2-MeO-Ph)₃P or IMes·HCl afforded greater than 95% conversion to the couplingproducts with up to 92% desired regioselectivity. DMF/K₃PO₄was found to be the most effective combination of solvent andbase. The concentration profiles of reactants and productsindicated that, with the regioselective catalyst, the first couplingstep at one of the two competitive reactive centers was 10 timesfaster than the second coupling step at the other reactive center,resulting in high regioselectivity of the desired monoadduct.