Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

• Valter E. Murie^a
• Paula V. Nicolino^a
• Thiago dos Santos^a
• Guido Gambacorta^b
• Rodolfo H. V. Nishimura^a
• Icaro S. Perovani^c
• Luciana C. Furtado^d
• Leticia V. Costa-Lotufo^d
• Anderson Moraes de Oliveira^c
• Ricardo Vessecchi^c
• Ian R. Baxendale^b
• Giuliano C. Clososki^{b, c}

• ^aDepartamento de Ciências BioMoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café S/N, Ribeirão Preto 14040-903, Brazil
• ^bDepartment of Chemistry, Durham University, South Road, Durham DH1 3LE, United Kingdom
• ^cDepartamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto 14040-901, Brazil
• ^dDepartamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives.

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