Fluorinated Analogues of Amicetose and Rhodinose – Novel Racemic and Asymmetric Routes

Abstract

Trifluoroethanol was converted into difluorinated (racemic) analogues of amicetose and rhodinose by metallated difluoroenol acetal chemistry, protection, release of the latent difluoromethyl ketone, stereoselective reduction and ozonolysis in acidic methanol. A fortuitous separation of diastereoisomers allowed the diastereoisomeric pyranoses to be obtained cleanly. Though reductive defluorination allowed a facile entry to the route, the corresponding monofluoro sugar

Synthesis of Fluorine‐Containing Molecular Entities Through Fluoride Ring Opening of Oxiranes and Aziridines

“…The authors successfully applied the reaction to enantiomeric (–)‐99 too. Importantly, TBAF/3H 2 O is commercially available and not expensive …”

“…Compounds with acyl or alkoxycarbonyl protecting groups on the N‐atom favor conformation (±)‐101β or (±)‐104β because of allylic 1,3 strain, while in the case of PG = H conformation (±)‐101α or (±)‐104α is preferred (Scheme ). Initial condition screening with oxirane (±)‐101aa showed that the conditions of Percy et al were the most advantageous (Scheme ). Because purification of (±)‐101aa was problematic due to its high polarity and chemical instability, the use of Fmoc‐protected epoxypiperidines was attempted.…”

“…Hanamoto and co‐workers showed that ring opening of epoxy sulfide 110 with a catalytic amount of n Bu 4 N + H 2 F 3 – and excess KHF 2 is more effective in the presence of excess TBAF (Scheme ). These conditions are similar to the method of Percy et al but TBAF was used as its THF solution (which is also commercially available) instead of its hydrate. Note that in this system three fluoride sources are present instead of two.…”

Conformation-induced regioselective and divergent opening of epoxides by fluoride: facile access to hydroxylated fluoro-piperidines

“…4 The cheaper reagents TBAF/ KHF 2 were still more effective, affording the desired product in 60% yield as a single isomer (entry 6). 20 It was interesting to note that simply replacing KHF 2 with KF decreased the yield and selectivity significantly (entry 7). Further screening identified that 120 °C was the optimal temperature (entry 8), and that the molar excess of reagents could be decreased (entry 9).…”

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

“…Fluorination was attempted using a range of conditions. The solvent-free reaction developed within our laboratory using commercial TBAF and KHF 2 was not sufficiently effective for this substrate [ 13 , 19 ]. The yield of the product was moderate (37%), but the purification of the product was extremely difficult due to the complex mixture of products.…”