In this overview, recent trends and developments for the selective hydrogenation of multifunctional molecules are discussed and assessed from the point of view of fine chemicals synthesis. In a first part, the design and preparation of catalysts and ligands with interesting properties are summarized, particularly meant for the catalysis specialist. The following topics are described in some detail: How enantioselective homogeneous catalysts are designed and tested; new effective chiral monodentate phosphines; successful bidentate phosphines ligand families (with axially chiral biaryl-and ferrocenyl-based backbones, new phospholanes and with stereogenic phosphorus); novel bidentate ligand families with P-O and P-N bonds; and oxazoline-based ligands. A short overview on immobilized chiral complexes and of the toolbox of heterogeneous catalysis (bimetallic, colloidal and modified catalysts) concludes this chapter. In a second part, progress for selected catalytic transformations and generic selectivity problems is described, intended mainly for the organic chemist who has to solve specific synthetic problems. Emphasis is on the following topics: The enantioselective hydrogenation of olefins with various substitution patterns; the chemo-and enantioselective hydrogenation of ketones; the diastereo-and enantioselective hydrogenation of C N functions; the stereoselective hydrogenation of aromatic rings; chemoselectivity and hydroxylamine accumulation in the reduction of functionalized nitroarenes; chemoselectivity and new protecting groups for catalytic debenzylation; the mild hydrogenation of carboxylic acid derivatives; and the chemoselective hydrogenation of nitriles. In the last parts of the review, transfer hydrogenation and mechanistic issues are discussed, followed by a short conclusions and outlook paragraph.
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).
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