Trifluoromethylated Sugars

The trifluoromethyl group has been introduced on every position, except position 5 in the fiiranose series and position 6 in the pyranose series. These reactions can be performed through several pathways by nucleophilic trifluoromethylation with the 

Ruppert reagent (CF3TMS), by radical trifluoromethylation, and finally by total synthesis starting from alicyclic precursors. 

The addition of CF3TMS on a lactone group in position 1 allows introduction of CF3 on the anomeric position. Due to its electron-withdrawing effect, the CF3 group inhibits the possible formation of the oxocarbenium ion intermediate of the anomeric substitution. Consequently, the substiment introduced on the anomeric position (OAc, 

3 Synthesis from Non-Osidic Precursors Some total syntheses of trifluoromethylated sugars have been described, starting from non-acidic precursors, fluorinated or not. 

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Figure 6.38 Synthesis of trifluoromethyl sugars through trifluoromethylation of non-osidic...

Other cyclic ketene acetals have significant utility in the preparation of trifluoromethylated sugars, e.g. 28. ... 

Kawada, K. Kitagawa, O. Taguchi, T. Hanzawa, Y Kobayashi, Y litaka, Y. Studies on organic fluorine compounds XLII. synthesis of trifluoromethylated sugars through Aldol reaction of 2-trimethylsilyloxyM-trifluoromethylfuran. Chem. Pharm. Bull. 1985, 33, 4216 222. 

Kawada K, Kitagawa O, Taguchi T, Hanzawa Y, Kobayashi Y, litaka Y (1985) Studies on organic fluorine compounds. XLVII. Synthesis of trifluoromethylated sugars through the aldol reaction of 2-trimethylsilyloxy-4-trifluoromethylfuran. Chem Pharm BuU... 

In 1969, Adamson, Foster, and others - reported the synthesis of 2-deoxy-2-fluoro sugars by addition ofCFjOF (in CFCI3, — 80°) to 3,4,6-tri-O-acetyl-l,5-anhydro-2-deoxy-D-flra/)/>zo-hex-l-enitol (61 3,4,6-tri-O-acetyl-D-glucal). The reagent fluorinates 61 electrophilically - °° at C-2, to afford c/v-addition products trifluoromethyl 3,4,6-tri-C)-acetyl-2-deoxy-2-... 

Chemical Name l,l-dimethyl-3-(a,a,a-trifluoro-m-tolyl)urea N,N-dimethyl-N -[3-(trifluoromethyl)phenyl]urea Uses herbicide to control many annual broadleaf weeds in sugar cane and cotton. 

Another example of a trifluoromethyl heteroaryl-containing herbicide is di-thiopyr (Dimension ) [72], Structure-activity studies have demonstrated that a fluorinated alkyl group is required for optimum activity at the 2 and/or 6 positions of the pyridine ring [73], Thiazopyr (Mandate , Visor ), a herbicide related to dithiopyr, was introduced by Monsanto in 1992 and later sold to Rohm and Haas. It is used for the pre-emergence control of annual grass and a few broadleaf weeds in tree fruit, vines, sugar cane, and other crops. 

Several examples of the addition of trifluoromethyl hypofluorite to an unsaturated sugar have been reported. " " " Some of these examples are illustrated by the formation of... 

Trimethyl(trifluoromethyl)silanc reacts with the derivatives of four- and six valent sulfur-containing mobile halogen atoms to form the trifluoroniethyl deri vatives. Trifluoromethylation with trimethyl(trifluoromethyl)silane has also been used in the preparation of a trifluoro-methylatcd sugar derivative. 

M. G. Ambrose and R. W. Binkley, Synthesis of deoxyhalogeno sugars. Reactions of haUde ions with l,2,3,4-tetra-0-acetyl-6-0-[(trifluoromethyl)sulfonyl]-(3-D-glucopyranose, J. Org. Chem. 48 674 (1983). 

A number of nucleoside analogues, either used clinically as anticancer dmgs or evaluated in clinical studies, are of C-branched structures which can be prepared by introducing methyl [12], allyl [13], ethynyl [12a,14], trifluoromethyl [15], and the other groups [16] through addition of organometallics to sugar moieties. This will not be discussed in detail here. 

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