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The present review discusses reactions of unprotected and protected carbohydrates in hydrogen fluoride as well as the synthesis of fluorinated carbohydrates by use of anhydrous liquid hydrogen fluoride or Systems containing hydrogen fluoride (e.g. HF/pyridine, triethylamine trishydrofluoride). Our results concerning the stereo-selective synthesis of kinetically controlled glycosyl fluorides and the micellar aggregation of amphiphilic 3-0-(n-alkyl)-D-gluco-pyranose derivatives in HF are involved. The paper presents a brief introduction in a survey concerning the application of fluorinated carbohydrates. The literature published since the article of Lenard (1969) is summarized.

The dithionite-mediated addition of BrCF(2)Cl to 3,4-di-O-pivaloyl-D-xylal (1) generated preferably 1-CF(2)Cl-substituted products, that is, (2-bromo-2-deoxy-3,4-di-O-pivaloyl-beta-D-xylopyranosyl)-chlorodifluoromethane and (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane. Selected chlorodifluoromethyl-substituted monosaccharide derivatives were hydrodechlorinated or alkylated at the CF(2)Cl-group using tin reagents under radical reaction conditions. Thus, hydrodechlorinations of (2,3,4-tri-O-acetyl-6-deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane and of methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2,6-dideoxy-alpha/beta-L-glucopyranoside are reported using tri-n-butyltin hydride initiated by AIBN. UV-initiated allylations are reported for reactions of (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane, (2,3,4-tri-O-acetyl-6-deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha-D-glucopyranose, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha-D-mannopyranose and methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha/beta-D-rabinopyranoside with allyltri-n-butyltin.

Regioselective one-pot O-silylation reactions of 1,2-O-isopropylidene-α-D-glucofuranose and 1,2-0-isopropylidene-β-D-fructopyranose using bulky oligosilyl groups are described. Some new silylating reagents (oligosilyl bistriflates), which were generated in situ from readily available phenylsilanes, resulted in 5,6-O-(glucofuranose) and 4,5-0-bridged (fructopyranose) carbohydrates with favoured seven- and eight-membered rings. In these cyclic oligosilyl diethers, three and four ring atoms, respectively, are Si atoms. It is noteworthy, that the seven-membered ring of 5,6-O-[2,4-bis(trimethylsilyl)-1,1,1,3,3,5,5,5-octamethylpentasilan-2,4-diyl]-1,2-O-isopropylidene-a-D-glucofuranose was expanded to an eight-membered ring by regioselective insertion of aerial oxygen into one of the Si-Si bonds. X-ray analyses of some derivatives are presented.

A convenient two-step strategy is reported for the synthesis of fluorinated optically pure acyclo-C-nucleoside analogues starting from simple glycals. In the first step, benzyl- or p-methoxybenzyl-protected glycals are treated with trifluoroacetic anhydride, bromodifluoroacetyl chloride, trichloroacetyl chloride, and perfluorooctanoyl chloride, respectively, in the presence of Et3N. This one-pot procedure yields 1,2-unsaturated sugars (1,5-anhydro-3,4,6-tri-O-benzyl (or p-methoxybenzyl) 2-deoxy-2-perhalogenoacyl- d -arabino / lyxo-hex-1-enitols 4–9) acylated at C-2. In the second step, a selective ring transformation is induced by treatment of the C-acylated glycals with bis-nucleophiles (hydrazine, phenylhydrazine, o-phenylenediamine, hydroxylamine). In particular, 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-trifluoroacetyl- d -arabino-hex-1-enitol (4) and 1,5-anhydro-2-deoxy-2-trifluoroacetyl-3,4,6-tri-O-(p-methoxybenzyl)- d -arabino-hex-1-enitol (8) were reacted with these nucleophiles generating the final C-nucleoside analogues of pyrazole (10, 11, and 12), diazepine (13), and isoxazole (15), respectively, containing a carbohydrate side chain linked to the heterocyclic ring.

An efficient procedure was established to synthesize a thymidine analogue bearing an acylsilane function at the 5¢-posi- tion, starting from thymidine in four steps and 58% overall yield. This compound proved to be a valuable intermediate for the synthe- sis of various nucleoside analogues with a one-carbon chain elonga- tion at the 5¢-position and a useful compound towards the construction of modified oligonucleotides.

The halogenated 1 H -1,2,4-triazole glycosides 6 – 10 were synthesized by BF 3 -activated glycosylation of 3(5)-chloro-1,2,4-triazole ( 2 ), 3,5-dichloro-1,2,4-triazole ( 3 ), 3,5-dibromo-1,2,4-triazole ( 4 ), and 3(5)-bromo-5(3)-chloro-1,2,4-triazole ( 5 ) with 1,2,3,4-tetra- O -pivaloyl-β- d -xylopyranose ( 1 ). The β-anomeric major products 3-chloro-1-(2,3,4-tri- O -pivaloyl-β- d -xylopyranosyl)-1,2,4-triazole ( 6 β ), 3,5-dichloro-1-(2,3,4-tri- O -pivaloyl-β- d -xylopyranosyl)-1,2,4-triazole ( 7 β ), and 3,5-dibromo-1-(2,3,4-tri- O -pivaloyl-β- d -xylopyranosyl)-1,2,4-triazole ( 8 β ) were used as starting materials for transition metal catalyzed C–C-coupling reactions. Arylations of the triazole ring of 7 β , and 8 β were successful in 5-position with phenylboronic acid, 4-vinylphenylboronic acid, and 4-methoxyphenylboronic acid, respectively, under Suzuki cross-coupling conditions (products 11 – 17 ). Moreover, a Cu-catalyzed perfluoroalkylation of 8 β is reported with 1-iodo-perfluorohexane yielding 3-perfluorohexyl-1-(2,3,4-tri- O -pivaloyl-β- d -xylopyranosyl)-1,2,4-triazole ( 18 ). Compound 18 was depivaloylated to the trihydroxy derivative 19 . The copper-mediated reaction of 8 β with Rupert's reagent gave the bis(3-bromo-1-(2,3,4-tri- O -pivaloyl-β- d -xylopyranosyl)-1,2,4-triazol-5-yl) ( 20 ).

1.2.4-Triazole nucleoside analogues bonded at N-1 of the base were synthesized by addition of N-halo-3,5-dibromo-1,2,4-triazoles to 1,2-unsaturated carbohydrate derivatives (glycals). Examples are given for l,5-anhydro-3,4,6-tri-O-acetyl-2-deoxy-D-arabino-hex-1-enitol (tri-O-acetyl-D-glucal), and 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-D-arabino-hex- -enitol (tri-O-benzyl-D-glucal), respectively. The graduated reactivity of the three halogens [C-5 (triazole) > C-2 (sugar) > C-3 (triazole)] in the addition products allows subsequent regioselective replacement and deprotection reactions like hydrodehalogenations, nucleophilic substitutions (by methoxide, hydrazine, benzylamine, thiophenolate), deacetylations, and debenzylations, respectively. Thus, the paper opens a new synthetic approach to triazole nucleoside analogues of 2-deoxy-sugars. X-ray analyses support the structures of nine products.

The dithionite-mediated chlorodifluoromethylations of 3,4-di-O-acetyl-1,5-anhydro-2,6-dideoxy-L-arabino-hex-1-enitol (1), 1,5-anhydro-2,3,4-tri-O-pivaloyl-D-erythro-pent-1-enitol (13), 2,3,4-tri-O-acetyl-1,5-anhydro-6-deoxy-L-lyxo-hex-1-enitol (15), and 2.3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enitol (18) with CBrClF 2 in acetonitrile-water and methanol, respectively, are described. Sodium dithionite serves as radical initiator and reducing reagent. Whereas, starting with 1, the chlorodifluoromethyl group was predominantly introduced into position 2, the 1-chlorodifluoromethyl substituted C-glycosides l,5-anhydro-1-(S)-chlorodifluoromethyl-2,3,4-tri-O-pivaloy]-D-ribitol (14), 2,3,4-tri-O-acety]-1,5-anhydro-1-(R)-chlorodifluoromethyl-6-deoxy-L-galactitol (16), and 2,3,4,6-tetra-O-acety]-1,5-anhydro-1-(S)-chlorodifluoromethyl-D-glucitol (19) could be synthesized in moderate to good yields from 13, 15, and 18, respectively. X-ray analyses are given for the products 3,4-di-O-acetyl-1,5-anhydro-2-chlorodifluoromethyl-2,6-dideoxy-L-glucitol, 1,3,4-tri-O-acetyl-2-chlorodifluoromethyl-2,6-dideoxy-α-L-mannopyranose, 1,5-anhydro-1-(S)-chlorodifluoromethyl-2,3,4-tri-O-pivaloyl-D-ribitol, and 2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(S)-chlorodifluoromethyl-D-glucitol.

Starting with 3,4‐O‐[(R)‐2,2,2‐trichloroethylidene]‐1,2‐O‐isopropylidene‐β‐D‐tagatopyranose 2 obtained from 1,2‐O‐isopropylidene‐β‐D‐fructopyranose 1 by a non‐classical one‐step acetalization with chloral/DCC, the fluoroalkylated glycosyl donors 15 and 17 were synthesised in 3–4 steps. By this sequence, one stereogenic center was inverted, one new chiral center was introduced, and one stereogenic center, for the time being eliminated, was later re‐introduced. The glycals 11 and 12, key intermediates of the synthesis sequence, were accessible from triflate precursors (e.g., 10) by treatment with DBU. Corresponding halogeno‐(6, 7), tosyl‐(5, 8), or mesyl‐(9) precursors were unsuitable. The stereoselective introduction of a chlorodifluoromethyl group was realised by dithionite‐mediated CF2ClBr‐addition to the glycal double bond. Subsequently, either the chlorodifluoromethylated glycosyl bromide (13) or the corresponding pyranoses (14 and 16) were isolated. The latter were still acetylated to the 1‐O...

New perfluoroalkylated amphiphiles based on carbohydrates (D-xylose, D-ribose, D-glucose) and on myo-inositol were synthesized and their thermotropic liquid crystalline behaviour was investigated. The introduction of perfluoroalkyl groups was carried out by radical addition of 1-iodoperfluoroalkanes to O- and C-allyl-substituted sugar and inositol derivatives.

The review summarizes the results of our research group in the field of fluorinated sugar and inositol derivatives using direct fluorination methods and using fluorinated “building blocks”. Contributions of other German working groups are included, as far as the synthesis of fluorinated carbohydrates was target of these reports.

Two competitive regio- and stereoselective epimerization reactions were investigated in four cyclitols characterized by four contiguous OH groups with a cis-trans-trans sequence and by varied substituents (OMe, OBz, F, H) adjacent to this tetrol unit. The starting materials were synthesized from L-quebrachitol (compounds 5−7) and myo-inositol (compound 8). Their acetalization with the chloral/DCC reagent system gave cyclic acetals with one epimerized chiral ring atom and also with two epimerized chiral centres. The single epimerization takes place exclusively at the middle C-atom of the cis-trans triol unit in the tetrol sequence (products 15, 17, 19/20 and 24−27), whereas the double epimerization occurs at both of the "centrally located" C-atoms in the cis-trans-trans tetrol unit (products 16, 18, 21 and 28). The product ratios of singly to doubly inverted compounds change as follows: the lower the electron-withdrawing effect of the substituents adjacent to the tetrol unit, the higher the percentage of the corresponding doubly inverted product. However, the singly inverted products remain the major products in all cases. X-ray analyses are given for the starting material 1-fluoro-2-O-(methyl)cyclohexane-2,3,4,5,6-pentol (5) and for the products 1-O-cyclohexylcarbamoyl-2,3-O-(2,2,2-trichloroethylidene)5-O-(methyl)cyclohexane-1,2,3,4,5-pentol (17), 3-O-acetyl-1-O-benzoyl-6-O-cyclohexylcarbamoyl-2-O-methyl-4,5-O-(2,2,2-trichloroethylidene)-muco-inositol (22) and 2,3-di-O-ethylidene)-(+/-)-chiro-inositol (24). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Starting with 1,2,4,6-tetra-O-acetyl-3-O-dodecyl-β- d -glucose (1), mixed alkyl-perfluoroalkyl substituted sugar derivatives with an anomeric perfluoroalkylthio group and an O-alkyl group in the 3 position were synthesized via 2,4,6-tri-O-acetyl-3-O-dodecyl-1-thio-β- d -glucose (4). The latter was S-perfluorohexylated with 1-iodoperfluorohexane in a dithionite initiated reaction yielding perfluorohexyl 2,4,6-tri-O-acetyl-3-O-dodecyl-1-thio-β- d -glucopyranoside (5). Experiments with the aim compound 5 completely to deacetylate ended in surprising results. Thus, methanolic methanolate solution produced the orthoester 7 as the result of α-fluoride replacement by methoxy groups as well as the methyl glucoside 8 as the result of a transglycosylation reaction. Alumina supported cesium fluoride cleaved regioselectively the two acetyl groups in the 4- and 6-position yielding perfluorohexyl 2-O-acetyl-3-O-dodecyl-1-thio-β- d -glucopyranoside (10). A complete deacetylation of 5 to amphiphile 11 succeeded only with methanolic tert-butanolate. However, the products 8 and 10 were likewise formed.

This mini‐review summarizes the knowledge about the scope and pathway of a novel non‐conventional tandem procedure of acetalization which allows a simultaneous epimerization of cyclic polyols with three or four contiguous hydroxyl groups. Such triols and tetrols, e.g., pyranosides or inositols, form acetols on heating with highly active aldehydes or ketones in the presence of a carbodiimide, provided that their OH‐groups show a cis/trans or cis/trans/trans sequence. The inversion of one chiral center (triols) and of one or two chiral centers (tetrols) was achieved. The stepwise removing of the protecting groups is reported. †Dedicated to Prof. Dr. Gerard Descotes on the occasion of his 70th birthday.

The perfluorohexyl-aryl-thioethers 3 and 4, building blocks for the synthesis of the chiral target mesogens 12–15, were prepared by dithionite-mediated S-perfluoroalkylation of the p-substituted thiophenols 1 and 2. The phenolic HO group of 3 was O-glucosylated with pentaacetyl- d -glucopyranose to 5 followed by deacetylation forming the tetrol 6 and by acetalizing with 4-(4-perfluorohexylsulfanyl-benzoyloxy)-benzaldehyde-dimethylacetal (8) generating the dihydroxy-intermediate 9. The latter contains two perfluorohexylthio chains. Alternatively, the dimethylacetal 8 was linked to p-octylphenyl-β- d -glucopyranoside (10) giving the mixed octyl/perfluorohexyl substituted p-octylphenyl-4,6-O-[4′-(4″-perfluorohexylsulfanyl)-benzoyloxy]-benzylidene-β- d -glucopyranoside (11). Compound 8 was obtained via esterification of 4 with p-hydroxy-benzaldehyde to 4-(4-perfluorohexylsulfanyl-benzoyloxy)-benzaldehyde (7). Finally, the diols 9 and 11 were dehydroxylated to 12 and 13 followed by hydrogenation yielding 14 and 15, respectively. Tetrol 6, diols 9, 11 and the non-amphiphilic compounds 7, 12–15 are thermotropic liquid crystals.

Chlorodifluoromethyl groups were introduced into the 2-position of the glycals 1, 5, 8, and 11 by dithionite-mediated addition of CF 2 ClBr. The reaction proceeded stereoselectively, i.e. the CF 2 Cl-group is always found trans to the neighbouring substituent at C-3 in the products. Because the primarily formed glycosyl bromides hydrolyse easily, the corresponding 2-chlorodifluoromethyl-2-deoxypyranoses 3, 6, 9, and 12 were isolated. Only 3,4,6-tri-O-acetyl-2-chlorodifluoromethyl-2-deoxy-D-glucopyranosyl bromide (2) was stable enough for chromatographic separation. The unprotected anomeric pyranoses 3, 6, 9, and 12 were acetylated by acetic anhydride/pyridine yielding the 1-O-acetyl derivatives 4, 7, 10, and 13. These compounds are suitable glycosyl donors, just as the anomeric phenyl thioglycosides 16 and 17 generated from 1,3,4-tri-O-acetyl-2-chlorodifluoromethyl-2-deoxy-D-arabinopyranside (7) and thiophenol (BF 3 -catalysis). Furthermore, the reactivity of glucosyl bromide 2, 6-deoxy-L-glucose derivative 13 and thioglycosides 16, 17 was investigated. On treatment of glucosyl bromide 2 with pyridine, the 2-chlorodifluoromethyl substituted glycal 14 is formed as the result of HBr elimination. Furthermore, the chlorodifluoromethyl group of compounds 14 and 16 was converted into a methoxycarbonyl group by refluxing in methanolic sodium methoxide (products 15 and 19, respectively). Finally, the thioglycosides 16 and 17 were subsequently deacetylated by CsF on alumina (yielding the dihydroxy derivatives 18 and 20) and acetalized with chloral/DCC (18 forming acetal 21 and carbonate 22) and acetone (20 forming acetal 23), respectively. X-ray analyses are given for the 1-O-acetate 4 and the thioglycosides 21 and 24.

Reversed nucleosides, i.e., fluoroalkyl-substituted 1,2,3-triazoles linked to the C-atom 6 of d -galactose and d -altrose were synthesised by 1,3-dipolar cycloadditions using the monosaccharide azides 8, 11 and the perfluoroalkyl substituted phenyl vinyl sulfones 5–7. The starting material 11, methyl 6-azido-3,4-O-(trichloroethylidene)-2-O-cyclohexylcarbamoyl-6-deoxy-α- d -altropyranoside, was synthesized from methyl 2-O-cyclohexylcarbamoyl-3,4-O-(2,2,2-trichloroethylidene)-α- d -altropyranoside (9), via its 6-iododeoxy derivative 10. The homologous dipolarophiles 5–7, (E)-1-perfluoroalkyl-2-phenylsulfonyl-ethenes with a CF3 (5), n-C4F9 (6), and n-C6F13 (7) group, respectively, were obtained by Wittig–Horner olefination from phosphonate 4 and the corresponding perfluoroalkanals 1–3. Cycloaddition of 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-α- d -galactose (8) with the dipolarophiles 5–7 yielded the reversed nucleosides 12–14; altrose azide 11 gave the reversed nucleosides 15 and 16. The products of cycloaddition were deprotected using usual techniques. Thus, the 1-(6-deoxy-1,2:3,4-di-O-isopropylidene-α- d -galactopyranoso-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 13 and 14 were deacetalated by treatment with aqueous trifluoroacetic acid yielding the corresponding 1-(6-deoxy-α- d -galactopyranoso-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 17 and 18. The deprotection of the 1-[methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-α- d -altropyranosido-6-yl]-4-perfluoroalkyl-1,2,3-triazoles 15 and 16 was made stepwise (hydrodechlorination→deacetalation→decarbamoylation), i.e., the 1-(methyl 6-deoxy- d -altropyranosido-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 23 and 24 were synthesised via the ethylidene acetals 19, 20 and the 1-(methyl 2-O-cyclohexylcarbamoyl-6-deoxy-α- d -altropyranosido-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 21 and 22. For the methyl 6-azido-2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-α- d -altropyranoside (11) an X-ray structure is given.

The title compounds were synthesized by 1,3-dipolar cycloaddition of 3,3,3-trifluoropropinyl benzene (2) to the azido sugars 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl azide (1), 6-O-acetyl-4-O-cyclohexylcarbamoyl-2,3-O-(2,2,2-trichloroethylidene)-β-D-gulopyranosyl azide (6), 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (12), and methyl 6-azido-4-O-cyclohexylcarbamoyl-6-deoxy-2,3-O-(2,2,2-trichloroethylidene)-β-D-gulopyranoside (16), respectively. Because of the dissymmetry of the dipolarophile 2, always two regioisomeric products were obtained, the nucleoside-analogous compounds 3/4 (from 1) and 7/8 (from 6), respectively, and the reversed nucleosides 13/14 (from 12) and 17/18 (from 16), respectively. Protecting group chemistry like transesterification, deacetalation, hydrodechlorination is demonstrated in some cases. Thus, the trichloroethylidene derivatives 7, 8, 17, and 18 were converted into the corresponding ethylidene derivatives (9, 10, 19, 20) by treatment with tributylstannane/AIBN. An X-ray analysis is given for the 1-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-4-trifluoromethyl-5-phenyl-1,2,3-triazole (4) and for the 1-[6-O-acetyl-4-O-cyclohexylcarbamoyl-2,3-O-(2,2,2-trichloroethylidene)-β-D-gulopyranosyl]-4-trifluoromethyl-5-phenyl-1,2,3-triazole (7).

(4′R)-4,6-Di-O-acetyl-1,2,3-trideoxy-3-iodo-4′-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononyl)-2′,3′,4′,5′-tetrahydro-α-D-glucopyranoso[1,2-b]furan (2) and its (4′S) diastereomer (3) were prepared by dithionite-mediated addition of 1-iodoperfluorooctane to allyl 4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranoside (radical “domino reaction”). Subsequently, the major product [(4′R) form] was deprotected via 4 to the hexahydrofuro[2,3-b]pyran derivative 5, which was used as a fluorinated building block to prepare the nonamphiphilic chiral mesogens 6–8 by “Mitsunobu” etherification and 9 by esterification. The reagents used to transform 5 to 6–9 were 4-cyanophenol, 4-(4-cyanophenyl)phenol, 4-(4-heptyloxybenzoyloxy)phenol, and 4-heptyloxybenzoyl chloride.

Allyl 2,3,4,6-tetra-O-acetyl-β- d -glucoside (1), 2,3,4,6-tetra-O-acetyl-1-thio- d -glucopyranose (6), and 2,3,4,6-tetra-O-acetyl-1-thio- d -galactopyranose (9) were alkylated with 1-iodo-perfluoroalkanes (C4F9I, C6F13I, C8F17I, C10F21I) giving the corresponding (2-iodo-3-perfluoroalkyl-propyl) glucosides 2a–d, perfluoroalkyl s- d -thioglucosides 7b,c, and perfluoroalkyl s- d -thiogalactosides 10a-c, respectively. From these compounds the amphiphilic sugars 4a–d, 8b,c, and 11b,c were synthesized. The deacetylation of 3a–d, 7b,c, and 10b,c was carried out by treatment with alumina-supported CsF. Finally, 4c was converted to 5 by a regioselective 6-O-decanoylation. The “single tailed” amphiphiles 4a–d, 8b,c, and 11b,c are liquid crystals (SA-type), whereas compound 5, which contains a lipophilic as well as a fluorophilic chain, forms a columnar mesophase.

1,2 -O- Isopropylidene-β- d -fructopyranose was directly converted into 5 -O- cyclohexylcarbamoyl-1,2 -O- isopropylidene-3,4 -O- (2,2,2-trichloroethylidene)-β- d -tagatopyranose by treatment with chloral/ N , N ′-dicyclohexylcarbodiimide. Subsequent acid-catalysed cleavage of the isopropylidene protecting group followed by acetylation afforded, exclusively, 1,2-di -O- acetyl-5 -O- cyclohexylcarbamoyl-3,4 -O- (2,2,2-trichloroethylidene)-α- d -tagatopyranose. This product was simultaneously dehydrochlorinated and decarbamoylated to 1,2-di -O- acetyl-3,4 -O- ethylidene-α- d -tagatopyranose using Bu 3 SnH/AIBN.

Twisting the silicon backbone conformation in oxygen containing oligosilanes towards dihedral angles of 120-130 degrees either by intramolecular hydrogen bonding or incorporation into a covalently bonded ring system effectively extends the delocalization of electrons in these sigma-n mixed conjugated systems.

In a convenient one-pot acetalation procedure using chloral/DCC, methyl (-)-quinate and methyl (-)-shikimate were converted into their 4- epi -derivatives containing a carbamoyl function in 3-position and the trichloroethylidene acetal group in 4,5-position. Additionally, an spiro-byproduct, 1 R, 3 R, 4 R, 5 R)- 3 ′-N- cyclohexyl - 3 -O-( cyclohexylcarbomyl )- 4,5 -O-( 2,2,2-trichloroethylidene)spiro[[cyclohexane-3,4,5-triol-1,5′-[1,3]oxazolidine]]-2′,4′-dione , was formed from methyl (-)-quinate in 10% yield. Decarbamoylation of the compounds is possible by heating in methanolic sodium methoxide.

The mesogenic fluoroalkyl β-d-glucopyranosides 5a-d (smectic A) were generated via a dithionite initiated addition of the homologous 1-iodo-perfluoroalkanes 1a-d to allyl 2,3,4,6-tetra-O-acetyl-β-d-glucopyranoside (2) forming 3a-d followed by hydrodeiodination to 4a-d and deacetylation.

Acetalations of methyl α- d -mannopyranoside (1), methyl 6-O-trityl-α- d -mannopyranoside (5), benzyl α- d -mannopyranoside (14), and methyl β- d -galactopyranoside (17) with perfluoroaldehydes (C4F9CH=O, C6F13CH=O, and C8F17CH=O) in the presence of dicyclohexylcarbodiimide (DCC) lead, under epimerization at the C-atom 3 of the corresponding pyranose moiety, to perfluoroalkylidene derivatives of α- d -altrosides (2–4, 6/7, 15) and of β- d -gulosides (18–20), respectively. After partial deprotection of 3 (or 15) and 18–20, respectively, the liquid crystalline, amphiphilic 3,4-O-perfluorohexylidene- d -altropyranoside (13) and 2,3-O-perfiuoroalkylidene- d -gulopyranosides 24–26 were obtained.

The thermal properties of twelve 'single-tailed' carbohydrate-based liquid crystal materials which have a perfluoroalkyl chain (n-C4F9, n-C6F13, n-C8F17) linked to the polar sugar head group are described. All reported amphiphiles, the 6-deoxy-6-C-perfluorohexyl-L-altrose 1, the (5R)-xylopentoses 2, 3 and 4, the 5,6-dideoxy-6-C-perfluoroalkyl-D-glucofuranoses 5 and 6, the 2,3-O-perfluoroalkylidene-D-gulopyranoses 7, 8 and 9 and the 3,4-O-perfluoroalkylidene- D-altropyranoses 10 and 11 form mesophases of the smectic A type. Even a C4F9-chain (compounds 2, 7, and 10) is long enough to cause liquid crystalline behaviour.

The perfluoroalkyl chains (−C4F9, −C6F13, −C8F17) were terminally connected to the 5-enopyranose 1, and the 5-enofuranoses 8 and 23 by addition, in the presence of sodium dithionite, of the corresponding homologous perfluoroalkyl iodides to the double bond. Up to six products were separated from each reaction mixture and then fully characterised. The 5-iodo derivatives 9, 10 (prepared from 8), 24, 25, and 26 (prepared from 23) were diastereomeric mixtures (5R-5S). Compounds 9, 10, and 25 were hydrodeiodinated to the methylene derivatives 17, 18, and 27, respectively. Complete deprotection of the perfluoroalkyl-substituted pyranose 3 (prepared from 1), and of the furanoses 17 and 18 led to the carbohydrate-based amphiphilic mesogens 29/30, 21, and 22, respectively, with a perfluoroalkyl tail. These formed mesophases of the smectic A type.

The homologous 1-iodo-perfluoroalkanes 1a-1c and α,ω-dibromo-perfluoroalkanes 4a, 4b were carbonylated with DMF in the presence of Al/SnCl 2 Al/PbBr 2 under sonication in a short reaction time. The hydrated aldehydes 2a-2c and 5a, 5b respectively were obtained in good yields allowing dehydration to 3a-3c and 6a, 6b . Some of the fluorinated aldehydes were selected as substrates in a Wittig-Horner olefination assisted by ultrasound and in non-conventional acetalations of methyl α- l -rhamnopyranoside ( 9 ). Thus, ( E )-1-perfluorooctyl-2-phenylsulphonyl-ethene ( 8 ) was prepared from 3c and the phosphonate 7 by Wittig-Horner synthesis. Acetalations of 9 were carried out with the aldehydes ( 3a, 3b, 6a ), hydrated aldehydes ( 2a, 2b ), and the aldehyde hemiacetal 12 respectively, in the presence of dicyclohexylcarbodiimide (DCC). In all cases, a selective epimerization was observed at the C-atom 3 of the monosaccharide, i.e. polyfluoroalkylidenated 6-deoxy-α- l -altropyranosides 10,11,13 , and 14 were obtained.

Chiral 12-crown-4 ethers (13–16) and 18-crown-6 ethers (21–24) containing two and three ethylene-bridged D-glucopyranose moieties, respectively, have been synthesized. 2-O-(Acetoxyethyl)-3,4,6-tri-O-benzoyl-α-D-glucopyranosyl fluoride (5), generated by treatment of 2,3,4-tri-O-benzoyl-1,2-O-ethylene-β-D-glucose (4) with HF/nitromethane/acetic anhydride was the key building block. It was used as a glycosyl donor and/or – after modification – as an acceptor component in head-to-tail-type glycosylations. Thus, the openchain precursors 9/11, 10/12, 17/18 and 19/20 of the crown ethers were prepared from reaction of 5 with 7, 11 and 12, respectively, in BF3-catalyzed glycosylations. The stereoselectivity of the glycosylations could be influenced by the use of different solvents. α-Selective syntheses of the crown ethers 14 (from the thioglycoside 11) and 23 (from the thioglycoside 20) were achieved in dichloromethane using NIS/trifluoromethanesulfonic acid for activation. In acetonitrile, the thioglycoside 11 yielded predominantly the 12-crown-4 ether 13, while thioglycoside 18 formed a mixture of the α-and β-anomers 21 and 22 under the same activation conditions.

Monoalkylations of different nucleophilic azoles were investigated with the electron-deficient trans-3,3,3-trifluoro-1-nitropropene (1) as alkylating reagent without addition of any catalyst. In each case, the bonding of the alkene at the azole occurs regioselectively at the trifluoromethyl-substituted C atom of the alkene, whereas the azoles react at different positions depending on the electron density of the heterocycles. Thus, 1-methyl-pyrrole (2) reacted with 1 under C-C bond formation giving the two regioisomers 2-(1-trifluoromethyl-2-nitroethyl)-1-methyl-pyrrole (3) (major product) and 3-(1-trifluoromethyl-2-nitroethyl)-1-methyl-pyrrole (4). The less nucleophilic pyrazole (5), 1,2,4-triazole (7), 3-bromo-1,2,4-triazole (9), and 3,5-dibromo-1,2,4-triazole (12) gave exclusively the corresponding N-alkyl azoles 1- (1-trifluoromethyl-2-nitroethyl )-pyrazole (6), 1-(1-trifluoromethyl-2-nitroethyl) -1,2,4-triazole (8), 3-bromo-1- (1-trifluoromethyl-2-nitroethyl)-1,2,4-triazole (10)/5-bromo-1-(1-trifluoromethyl-2-nitroethyl)-1,2,4-triazole (11), and 3,5-dibromo-1-(1-trifluoromethyl-2-nitroethyl)-1,2,4-triazole (13), respectively. The enantiomeric pairs of the chiral monoalkyl-azoles could not be separated. Moreover, we used trans-3,3,3-trifluoro-1-nitropropene (1) as a dienophile in Diels-Alder cycloadditions with cyclopentadiene (14), cyclohexa-1,3-diene (16), and furan (18). Two diastereomeric products (15A/15B, 17A/17B, and 19A/19B), which could not be separated by column chromatography, are formed from each diene. All compounds were characterized by 1H, 13C, and 19F NMR data.

The homologous series of the amphiphilic alkyl 2-deoxy-2-fluoro-1-thio-α-D-glucopyranosides 5a–e and alkyl 2-deoxy-2-fluoro-1-thio-α-D-mannopyranosides 9a–e were prepared from the 2-deoxy-2-fluoro-D-glycosyl fluorides 1 and 6, respectively. Their liquid crystalline properties were investigated by polarising microscopy, DSC measurements, and X-ray measurements. The fluorine-containing thioglycosides 5a–e as well as 9a–e form enantiotropic mesophases of the type smectic A. The effects of F for OH and S for O substitution are discussed with reference to the homologous alkyl-1-thio-α-D-glucopyranosides 10 and alkyl 2-deoxy-2-fluoro-α-D-glucopyranosides 11.

Accidents with hydrogen fluoride are causes of the most hazardous injuries in laboratories. The effects of HF on human tissues are substantially different from those of ordinary acids. Therefore, the paper deals with the symptoms, first-aid and medical treatment of lesions caused by skin contact, inhalation or ingestion of HF. Furthermore, selected cases of accidents with hydrogen fluoride are reported to exemplify the unique dangers of such events. Some proper protection measures are also described.

This paper focuses on the use of ultrasound in the synthesis of organofluorine compounds by introduction of fluorine atoms or fluorine containing moieties. After a short introduction about sonochemical effects, reactions involving trifluoromethyl and higher perfluoroalkyl derivatives are described. Furthermore, the preparation of monofluorinated molecules is reported.

Methyl β-D-arabinopyranoside (1), phenyl 1-thio-β-D-galactopyranoside (3), methyl β-L-fucopyranoside (7), methyl β-L-fucopyranoside (9), 1,6-anhydro-β-D-galactopyranoside (D-galactosan; 11), and 1,6-anhydro-β-D-mannopyranoside (D-mannosan; 14) were stereospecifically converted in moderate up to good yields into methyl 4-O-cyclohexylcarbamoyl-2,3-O-(2,2,2-trichloroethylidene)-β-D-lyxopyranoside (2), phenyl 4-(9-cyclohexyIcarbamoyl-6-O-formyl-2,3-O-(2,2,2-trichloroethylidene)-1-thio-β-D-gulopyranoside (4) / phenyl 4-O-cyclohexylcarbamoyl-2,3-O-(2,2,2-trichloroethylidene)-1-thio-β-D-gulopyraoside (5), methyl 4-O-cyclohexylcarbamoyl-2,3-O-(2,2,2-trichloroethylidene)-6-deoxy-α-L-gulopyranoside (8), methyl 2,3-O-(2,2,2-trichloroethylidene)-4-O-cyclohexylcarbamoyl-6-deoxy-β-L-gulopyranoside (10), 1,6-anhydro-4-O-cyclohexyl-carbamoyl-2,3-O-(2,2,2-trichloroethylidene)-β-D-gulopyranoside (12), and 1,6-anhydro-2-O-cyclohexylcarbamoyl-3,4-O-(2,2,2-trichloroethylidene)-β-D-altropyranoside (15), respectively, ...

Thermotropic Liquid Crystals Based on Amphiphilic Carbohydrates The paper gives an advanced report (related to the reviews of Jeffrey) on thermotropic mesogens based on carbohydrate amphiphiles. The different influences being responsible for the formation, stabilization, and for the type of the mesophases, such as the hydrogen bond network, the van der Waals interactions of the lipophilic chains, the regio- and stereochemical arrangements, and the molecular geometry are discussed more in detail. Furthermore, fluorinated sugars and selected inositol derivatives are involved in order to discuss the liquid crystalline behaviour of amphiphilic sugar mesogens.

The review focuses on the use on ultrasound in the synthesis of organofluorine compounds by direct introduction of fluorine atoms or fluorine containing moieties. After a short introduction about sonochemical effects reactions involving difluoromethyl, trifluoromethyl and higher perfluoroalkyl derivatives are described. Furthermore, the preparation of monofluorinated molecules from alkenes, alcohols, epoxides and aryl halides is reported.

The liquid crystalline 6-O-alkyl-α-D-galactopyranosyl fluorides (3a–f) and the mesogenic 6-O-dodecyl-α-D-glucopyranosyl fluoride (7) were prepared from the homologous 6-O-alkyl-1,2:3,4-di-O-isopropylidene-α-D-galactopyranosides (1a–f) and from the methyl 2,3,4-tri-O-benzyl-glucopyranoside (4), respectively, in two and three steps. The fluorinations of 1a–f to the α-fluorides 2a–f and of 5 to the α-fluoride 6 were carried out with the reagent system HF/nitromethane/acetic anhydride, which simultaneously effects the complete exchange of the isopropylidene groups (1a-f) and of the benzyl groups (5) for acetyl functions in the non-glycosidic positions. Moreover, the 6-O-dodecyl-2,3,4-tri-O-acetyl-α-D-galactopyranosyl fluoride (11) was prepared in three steps from the 6-O-dodecylgalactopyranose (8). The stereoselective introduction of the fluoride into the β-anomeric position (10 11) was achieved by bromide-fluoride exchange with the two-phase system triethylamine-trishydrofluoride/petroleum ether. Dodecyl 6-deoxy-6-fluoro-α-D-glucopyranoside (13), prepared from the glucoside 12 with the fluorinating agent DAST, shows a narrow monotropic SA-phase and lyotropic liquid crystalline behaviour in contact with water. Dodecyl 6-deoxy-6-fluoro-β-D-galactopyranoside (17), prepared in three steps from the acetal 14, does not form mesophases. The liquid crystalline behaviour of the amphiphilic glycosyl fluorides 3a–f, 7, and of the 6-deoxy-6-fluoro derivative 13 is described.

Regio- and stereoselective acetalizations of methyl α-D-lyxopyranoside (1), methyl β-L-arabinopyranoside (6), methyl α-D-galactopyranoside (11), and methyl β-D-galactopyranoside (13) with chloral, including an inversion of the configuration at C-3, were achieved with dicyclohexylcarbodiimide as a coagent. Additionally, the formed methyl 3,4-O-(2,2,2-trichloroethylidene)-α-D-arabinopyranoside 2, methyl 2,3-O-(2,2,2-trichloroethylidene)-β-L-lyxopyranoside 7, methyl 2,3-O-(2,2,2-trichloroethylidene)-α-D-gulopyranoside 12, and methyl 2,3-O-(2,2,2-trichloroethylidene)-β-D-gulopyranosides 14 and 15 contain an N-cyclohexylcarbamoyl group vicinal to the chloral acetal moiety; the compounds 12 and 15, moreover, a formyl group in 6-position. The formyl and carbamoyl functions may be cleaved stepwise with methanolic sodium methoxide. Deformylation of the 6-O-formyl derivative 15 affords the urethane 16 with simultaneous migration of the carbamoyl group from the 4- to the 6-position. The fluorination of 3 and 8 with anhydrous hydrogen fluoride/nitromethane/acetic anhydride, giving the glycosyl fluorides 4 and 9 without any cleavage of the cyclic chloral acetal functions, is described. BF3-catalyzed glycosylations of chloro-ethanol with the fluorides 4 and 9α/β yield the α-glycoside 5 and the anomeric mixture 10α/β, respectively, showing that neither a cyclic chloral acetal function in 3,4-O-nor in 2,3-O-position affects such reactions.

The reactions of dioxolanylium and oxazolinium ions, formed in anhydrous HF from N-acylated 2-amino-2-deoxy-D-glucoses and one equivalent of carboxylic acid anhydride or chloride, were investigated by treatment of their HF solutions with triethylamine/alkane or triethylamine/ether systems. Thus, the 2-acylamido-2-deoxy-D-glucoses 1 and 2 react with acetic anhydride, dodecanoic anhydride or pivaloyl chloride in anhydrous HF at −30°C to give 5,6-dioxolanylium ions. On treatment with formic acid at room temperature they undergo further reaction to yield the thermodynamically favored 3,6-anhydro derivatives. The glucofurano-oxazolines 3–5, containing an orthoester substructure, as well as the 3,6-anhydro-D-glucofuranose derivatives 6 and 7 can be isolated after treatment of the HF solutions with triethylamine. The oxazoline derivative 4 was used as glycosyl donor for methanol giving the methyl glycoside 8 without cleavage of the orthoester moiety.