Application of P,N ligands in the asymmetric alkynylation of quinolone Dáiríne Morgan, Cian Reid, Patrick J. Guiry UCD Centre for Synthesis and Chemical Biology, University College Dublin, Ireland P,N ligands are a privileged class of ligands that have shown proficiency in a wide variety of metal catalysed reactions, including Cu-catalysed A3 coupling reactions, Pd-catalysed allylic alkylations and Ir-catalysed hydrogenations. 1–3 In 2017 Guiry and co-workers reported the synthesis of ( S,S,Ra )-UCD-Phim an axially chiral ligand bearing an imidazoline backbone which showed proficiency in enantioselective A3 coupling reactions achieving high yields and ee’s under low catalyst loadings and mild conditions. 4
In 2022 Harutyunyan and co-workers developed the Cu(I)-catalysed alkynylation of quinolones. 5 In this work we expand upon this initial methodology by applying UCD-Phim to the synthesis of alkynylated quinolones. To date 22 alkynylated products have been synthesised with variation to both the alkyne, and quinolone backbone obtaining yields of up to 92% and enantioselectivities of up to 97%. The utility of the methodology has further been expanded upon by application to the synthesis of the natural products (+)-Cuspareine and (+)-Galipinine in high enantioselectivities.
References 1. Koradin, C.; Polborn, K.; Knochel, P. Chemie - Int. Ed . 2002 , 41 (14), 2535–2538. 2. Brown, J. M.; Hulmes, D. I.; Guiry, P. J. Tetrahedron 1994 , 50 (15), 4493–4506. 3. Li, S.; Zhu, S.-F.; Zhang, C.-M.; Song, S.; Zhou, Q.-L. I Am. Chem. Soc . 2008 , 130, 8584–8585. 4. Rokade, B. V.; Guiry, P. J. ACS Catal . 2017 , 7 (4), 2334–2338. 5. Maestro, A.; Lemaire, S.; Harutyunyan, S. R. Lett . 2022 , 24, 5, 1228–1231
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