- Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients
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A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.
- Karasawa, Tomoya,Oriez, Rapha?l,Kumagai, Naoya,Shibasaki, Masakatsu
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p. 12290 - 12295
(2018/09/27)
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- New azole antifungals. 3. Synthesis and antifungal activity of 3- substituted-4(3H)-quinazolinones
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A series of azole antifungal agents featuring a quinazolinone nucleus have been subjected to studies of structure - activity relationships. In general, these compounds displayed higher in vitro activities against filamentous fungi and shorter half-lives t
- Bartroli, Javier,Turmo, Enric,Algueró, Mònica,Boncompte, Eulàlia,Vericat, Maria L.,Conte, Lourdes,Ramis, Joaquim,Merlos, Manuel,García-Rafanell, Julián,Forn, Javier
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p. 1869 - 1882
(2007/10/03)
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