97674-02-7Relevant articles and documents
Catalytic Enantioselective Direct Aldol Addition of Aryl Ketones to α-Fluorinated Ketones
Barber, David M.,Dixon, Darren J.,Thomson, Connor J.
supporting information, p. 5359 - 5364 (2020/02/28)
The catalytic enantioselective synthesis of α-fluorinated chiral tertiary alcohols from (hetero)aryl methyl ketones is described. The use of a bifunctional iminophosphorane (BIMP) superbase was found to facilitate direct aldol addition by providing the strong Br?nsted basicity required for rapid aryl enolate formation. The new synthetic protocol is easy to perform and tolerates a broad range of functionalities and heterocycles with high enantioselectivity (up to >99:1 e.r.). Multi-gram scalability has been demonstrated along with catalyst recovery and recycling. 1H NMR studies identified a 1400-fold rate enhancement under BIMP catalysis, compared to the prior state-of-the-art catalytic system. The utility of the aldol products has been highlighted with the synthesis of various enantioenriched building blocks and heterocycles, including 1,3-aminoalcohol, 1,3-diol, oxetane, and isoxazoline derivatives.
A one-pot diazotation-fluorodediazoniation reaction and fluorine gas for the production of fluoronaphthyridines
Abele, Stefan,Schmidt, Gunther,Fleming, Matthew J.,Steiner, Heinz
, p. 993 - 1001 (2014/10/15)
Several synthetic routes to 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine (1) are presented, and their suitability for scale-up is discussed. The way of introducing the fluorine atom is crucial. Early routes start from commercially available fluorinated building blocks or employ F+ reagents like SelectFluor and delivered up to 70 kg of 7-fluoro-2-methoxy-1,5-naphthyridine (18). To prepare for larger scales, the focus turned to the use of HF or elemental fluorine, both one of the cheapest sources of fluorine. The first method, a one-pot diazotation-fluorodediazoniation with 6-methoxy-1,5- naphthyridin-3-amine (9) in HF gave the fluorinated naphthyridine 18 in high yield and purity without isolation of the unstable diazonium salt, the latter being a severe drawback of the related Balz-Schiemann protocol. The second method relies on the use of fluorine gas for a surprisingly selective ortho-fluorination of 6-methoxy-1,5-naphthyridin-4-ol (10).
