Synthesis of Fluorinated Amides Starting from Carbohydrates Based on the Claisen Rearrangement

Abstract

The search for new methods for installation of fluorine atoms into organic molecules is still a widely studied issue. In this work, an efficient synthetic protocol for the synthesis of fluorine‐containing amides derived from sugar has been presented. This approach involved the Claisen rearrangement of previously obtained fluorinated vinyl ethers. The three fluorinated olefins: 1,1,3,3,3‐pentafluoroprop‐1‐ene (2H‐PFP), 1,2,3,3,3‐pentafluoroprop‐1‐ene (1H‐PFP) and hexafluoroprop‐1‐ene (HFP) were used as a source of fluorine. New compounds were characterized by 1H, 19F and 13C NMR spectroscopy and high resolution mass spectrometry. The X‐ray crystal structures of some fluorinated derivatives were obtained confirming structure, geometry and absolute configuration. The resulting molecules, due to possibility of further transformation of their functional groups, can be valuable fluorinated scaffolds for the synthesis of subsequent chemical compounds.

Design and Synthesis of New α-hydroxy β-fluoro/β-trifluoromethyl and Unsaturated Phosphonates from Carbohydrate-Derived Building Blocks via Pudovik and Horner–Wadsworth–Emmons Reactions

“…In the present work we show a second class of molecules that we functionalized- these are the previously obtained by Claisen rearrangement α -fluoro- α -trifluoromethyl- γ , δ -unsaturated 18a/18a′ (1:0.65 ratio) and α -trifluoromethyl- γ , δ -unsaturated 18b/18b′ (1:1 ratio) alcohols [ 46 ]. These compounds were oxidized with quantitative yields to the corresponding aldehydes 19a/19a′ and 19b/19b′ using Dess-Martin reagent.…”

“…1,2;5,6-Di- O -isopropylidene- α - d -mannitol 9 was used as a starting material and successfully converted into 14–15 , 20–21 via 12 and 18 ( Scheme 2 ). Fluorinated ethers 11 and 12 were prepared using a strategy previously developed in our research group [ 46 , 48 ].…”

“…An efficient approach towards the synthesis of fluoro-containing compounds is through modular assembly using fluorinated building blocks. In the recent study we investigated application of the Claisen rearrangement reaction for construction of fluorine-containing scaffolds [ 46 ]. Carbohydrates were used as starting compounds, which are a very valuable source of building blocks, as well as chiral auxiliaries [ 47 , 48 , 49 , 50 , 51 , 52 ].…”

New trifluoromethylated sesquiterpenoids: synthesis, rearrangement, and biological activity

“…[5][6][7][8] To date, there have been many methods reported to synthesize fluorine-containing compounds. [9][10][11][12] For this purpose, F-olefins (e.g., 1H-PFP, HFP), 13 hexafluoroacetone 14,15 and trifluoroacetophenone, 14 methyl trifluoropyruvate (MTFP), 16 Umemoto's reagents 17,18 and other reagents are used. [19][20][21][22][23][24][25][26] CF 3 TMS, the Ruppert-Prakash reagent, is frequently used for introducing a CF 3 group into carbonyl substrates.…”

“…Compound 20a was isolated as a mixture (60%, w/w) together with the substrate 4 in a ratio 20 : 1 according to the NMR data. In the 13 C NMR spectrum of the major compound 20a, the signals of a CF 3 group and the quaternary carbon atom bonded to it were detected in the form of quartets at 128.3 and 79.2 ppm, respectively. The CF 3 group in 20a spatially affects the bridging C 12 H 2 group, as evidenced by its upfield signal shift in the 13 C NMR spectrum to 39.6 ppm compared to the signal of ketone 4 at 49.2 ppm.…”