Diethylaminosulfur Trifluoride Research Articles

Stereoselective introduction of a trifluoromethyl allylic group

High regio- and stereo-selective introduction of a trifluoromethyl group in various unsaturatedsystems is described. The key step is the treatment of 1,1-difluoro-1-alken-3-olswith (diethylamino)sulphur trifluoride (DAST) to give 1,1,1-trifluoro-2-alkenes.

Synthesis of α,α-difluoronitriles from acyl cyanides

Aromatic α,α-difluoronitriles (aryl α,α-difluoroacetonitriles) have been synthesized by reaction of aroyl cyanides with diethylamino sulphur trifluoride. Some liquid crystalline difluoronitriles have been prepared by this method.

Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3-deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy- d-hexopyranoses

Treatment of benzyl 2-acetamido-4,6- O-benzylidene-2-deoxy-α- d-allopyranoside with diethylaminosulfur trifluoride or of the 3- O-mesyl derivative with tetrabutylammonium fluoride gave the 2,3-unsaturated compound instead of the expected 3-deoxy-3-fluoro derivative. The latter was obtained when benzyl 2-acetamido-4,6-di- O-benzyl-2-deoxy-3- O-mesyl-α- d-allopyranoside was treated with potassium fluoride. Methyl 2-azido-4,6- O-benzylidene-2-deoxy-α- d-altropyranoside was converted into the 2-acetamido- and 2-phthalimido-3- O-mesyl derivatives; when treated with fluoride nucleophile, these gave only the 2,3-aziridine derivative. However, treatment of the 2-azido-2-deoxy derivative with diethylaminosulfur trifluoride gave methyl 2-azido-2,3-dideoxy-3-fluoro-α- d-mannopyranoside which, after reduction, deprotection, and acetylation, gave the acetylated derivative of methyl 2-acetamido-2,3-dideoxy-3-fluoro-α- d-mannopyranoside in excellent yield. These acetylated 3-fluoro derivatives exhibited inhibition of cell growth of murine L1210 leukemia cells in culture at micromolar concentrations.

Some intramolecular rearrangements when pentofuranoses are treated with diethylaminosulphur trifluoride (DAST)

Treatment of methyl 2,3- O-isopropylidene-β- D-ribofuranoside with DAST gave a goodyield of 2,3- O-isopropylidene-5- O-methyl-β- D-ribofuranosyl fluoride in which the methoxygroup had migrated from C-1 → C-5 and been replaced with retention of configurationby fluorine. The corresponding aldehyde when treated under similar conditions underwenta similar migration to give 5-deoxy-5-fluoro-2,3- O-isopropylidene-5- O-methyl-β- D-ribofuranosylfluoride. A similar migration occurred with methyl 2′,3′-di- O-acetyl-β- D-ribofuranosideand with acetyl 2,3- O-isopropylidene - D-ribofuranose but not with 1,2,3-tri- O-acetyl- D-ribofuranose. Thus the migration depends upon the migratory aptitude of thesubstituent at C-1 and the conformation of the furanose ring. Two ribofuranosyl fluorideswere used as starting materials from which to make nucleosides by the method of Noyoriand Hayoshi.

Stereospecific syntheses of all four stereoisomers of 4-fluoroglutamic acid

(+)- L- threo-4-Fluoroglutamic acid [(+)-(2 S, 4 S)-fluoroglutamic acid] has been synthesizedstarting with the natural (−)-4- trans-hydroxy- L-proline. Its acetylation at nitrogen followedby esterification with diazomethane afforded methyl 1-acetyl- trans-4-hydroxy- L-prolinatewhich was converted to methyl 1-acetyl- cis-4-fluoro- L-prolinate by means of diethylaminosulfurtrifluoride (DAST) or 2-chloro-1,1,2-trifluorotriethylamine. The mixture wasoxidized by ruthenium tetroxide to methyl 1-acetyl- cis-4-fluoro- L-pyrrolidin-5-one-2-carboxylate,whose acid hydrolysis yielded the title compound. A similar sequence of reactionsconverted cis-4-hydroxy- D-proline to (−)- D- erythro-4-fluoroglutamic acid [(−)(2 R, 4 S)-fluoroglutamic acid]. (−)- D- threo-4-Fluoroglutamic acid [(−)-(2 R, 4 R)-floroglutamicacid] was prepared analogously from trans-4-hydroxy- D-proline, obtained from its diastereomerby inversion of configuration at carbon 4 of the pyrrolidine ring using thediethyl azodicarboxylate-triphenylphosphine procedure. cis-4-Hydroxy- L-proline, necessaryfor the synthesis of (+)- L- erythro-4-fluoroglutamic acid [(+)-(2 S, 4 R)-fluoroglutamicacid], was prepared from trans-4-hydroxy- L-proline by benzyloxycarbonylation at thenitrogen, oxidation of the 1-benzyloxycarbonyl- trans-4-hydroxy- L-proline to 1-benzyloxy-carbonyl-4-oxo- L-proline, its reduction to 1-benzyloxycarbonyl- cis-4-hydroxy- L-proline anddeprotection of the latter at the nitrogen. (−)- cis-4-Fluoro- L-proline and (+)- trans-4-fluoro- D-proline were isolated after the hydrolysis of incompletely oxidized methyl 1-acetyl- cis-4-fluoro- L-prolinate and methyl 1-acetyl- trans-4-fluoro- D-prolinate, respectively.

Synthesis of racemic 6-deoxy-6-fluoro- chiro-inositol 2,3,5-trisphosphate

The synthesis of (±)-6-deoxy-6-fluoro- chiro-inositol 2,3,5-trisphosphate ( 4) is reported, starting from cyclohexa-1,4-diene. A key step involved the stereospecific 1,4-addition of singlet oxygen to trans-1,2-di- O-(2-methoxyethoxymethyl)cyclohexa-3,5-diene-1,2-diol ( 7) to afford (±)-1,2,4/3-2,3-di- O-(2-methoxyethoxymethyl)cyclohex-5-ene-1,2,3,4-tetrol ( 9). Benzylation of 9 followed by osmylation and selective protection of the equatorial hydroxyl group gave (±)-1,4-di- O-benzyl-2,3,5-tri- O-(2-methoxyethoxymethyl)- chiro-inositol ( 12), which reacted with diethylaminosulphur trifluoride (DAST) with retention of configuration, to yield the 6-deoxy-6-fluoro derivative 13. Partial deprotection of 13, followed by phosphorylation and hydrogenolysis, gave 4.

Synthesis of Non-Ester Pyrethroids Having a 1-Fluoro-1-methylethyl Group Using 1,2-Migration of an Aryl Group

Abstract When 1,4-diaryl-4-methyl-1,3-pentanediol was treated with diethylaminosulfur trifluoride to introduce fluorine atoms into the central link, 1,2-aryl group migration products which have a 1-fluoro-1-methylethyl group were obtained as two diastereomers. Utilizing this migration, some non-ester pyrethroids possessing a 1-fluoro-1-methylethyl group were prepared. The reactivity of other fluorinating reagents is also discussed.

Selective fluorination of 1-fluoro-l-arylethanols by diethylaminosulfur trifluoride

Fluorinated aryl methyl ketones have been prepared using a Friedel-Crafts reation by treating fluorinated aromatic hydrocarbons with acetyl chloride in the presence of anhydrous aluminium chloride in dry carbon disulfide. Reduction of these fluorinated aryl methyl ketones with sodiumborohydride in dry isopropanol affords 1-fluoro-1-arylethanols, which on treatment with diethylaminosulfur trifluoride (DAST) yields 1-fluoro-1-arylethane (racemic product). Studies on enantioselective reduction, followed by fluorination of 2, are in progress. ▪

Reaction of acceptor-substituted carbonyl compounds with diethylamino sulfur trifluoride

The reaction of carbonyl compounds with SF 4 or its derivatives like diethylamine sulfur trifluoride (DAST) is a well-established method for the introduction of fluorine into organic systems. However, in contrast to ‘normal’ aldehydes and ketones (eqn. 1; R and AH, alkyl or aryl), compounds containing an electron-withdrawing group adjacent to the carbonyl group have been used rather infrequently in carbonyl-fluorination. (Reaction with DAST have been described only for few examples.) ▪ R = alkyl, aryl A = CO 2R′, CF 3, CF 2R″ We have found that various acceptor-substituted carbonyl compounds react very easily with DAST (faster than ‘normal’ aldehydes and ketones). This opens up a facile route to α, α-difluoro-substituted carboxylic esters as well as to compounds containing pentafluoroethyl groups or tetrafluoroethylene moieties (eqn. (1). The use of this method is demonstrated in the synthesis of new liquid crystalline materials [ DE Pats 4 002 374 and 4 101600 (Aug. 1, 1991), 4 015 681 (Nov. 21,1991)] to E. Bartmann, E. Poetsch, U. Finkenzeller and B. Rieger (for Merck-Patent GmbH).

Synthesis and characterization of highly substituted deoxyfluorocellulose acetate

Deoxyfluorocellulose acetates were prepared from cellulose acetate (CA, degree of substitution by acetyl groups: 2.2 and 1.7) by using diethylaminosulfur trifluoride (DAST) in 1,4-dioxane or diglyme. The maximum degree of substitution of fluorine of the products was ∼ 0.60, and depolymerization was not significant during fluorination. The replacement of hydroxyl groups by fluorine atoms occurred exclusively at C-6, as confirmed by carbon-13 NMR spectroscopy. In the presence of pyridine, an N-pyridinium derivative of CA was obtained instead of a deoxyfluoro derivative of cellulose.

Two Methyl Tri-O-benzoyl-hex-enopyranosides Are Amongst the Products of the Reaction of Methyl 2,3,6-Tri-O-benzoyl-β-D-galactopyranoside with Dimethylaminosulfur Trifluoride (DAST)

Abstract In the past, we have used deoxyfluoro sugars as probes for studies of ligand-anti-body interactions.1–3 Investigations of the putative role of hydrogen bonding in the binding process involving antibodies that show specificity for epitopes containing β-D-glucopyranose required hitherto unknown methyl 4-deoxy-4-fluoro-β-D-glucopyranoside (5). For the synthesis of 5, we have chosen the readily available4 methyl 2,3,6-tri-O-benzoyl-β-D-galactopyranoside (1) as the starting material, and diethylaminosulfur trifluoride DAST) as the fluorinating reagent. Although DAST has been frequently used to produce fluorinated carbohydrates in high yields, the outcome of the reaction is somewhat unpredictable. Treatment of carbohydrates with the reagent has occasionally resulted in the formation of unexpected side products.5–9 and no specific rules exist regarding the application of DAST for the preparation of fluorosugars. In fact, high yields of the desired products of the substitution with fluoride ion have been sometimes obtained when DAST was applied under conditions generally known to favor elimination over substitution, e.g. in the presence of a base.10–13 Olefinic products resulting from treatments of carbohydrates with DAST have been sporadically isolated and characterized. Here we describe the title reaction which we believe is unique in that two products of elimination have been formed, as a consequence of attacks of the proton-abstracting species at different sites in the molecule.

Synthesis, resolution and biological activity of 7′,7′-difluoroabscisic acid

7′,7′-Difluoroabscisic acid was synthesized in seven steps from the known ketoaldehyde 4,4-ethylenedioxy-2-formal-6,6-dimethylcyclohex-2-en-1-one. Fluorination with diethylaminosulphur trifluoride afforded the key intermediate 2-difluoromethyl-4,4-ethylenedioxy-6,6-dimethyleyclohex-2-en-1-one which was further transformed to 7′,7′-difluoroabscisic acid. The racemic mixture and the individual optical isomers, obtained by resolution of the methyl esters by HPLC, displayed activity similar to the optical isomers of ABA in assays for germination in cress and freezing tolerance in bromegrass cell suspension culture.

An unusual twist in the synthesis and hydrolysis of the 23,24-epoxide of 22,23-dihydroavermectin B 1a

Treatment of 4″,5-di-O-tert-butyldimethylsilyl(or phenoxyacetyl)-7-O-trimethylsilyl-avermectin B 2a ( 1a,b) with diethylaminosulfur trifluoride (DAST) at 20ÁC in dichloromethane resulted in net elimination of water to yield 65% of the 23,24-olefin ( 2a,b), 5–10% 23-fluoroavermectin derivative ( 3a,b), and 20–25% of two rearranged products ( 4a,b:5a,b in a 2:1 ratio). The trisubstituted 23,24-olefin ( 2a,b) was selectively epoxidized with m-chloroperbenzoic acid to give a mixture of alpha ( 6a,b major) and beta ( 7a,b minor) 23,24-epoxides in 64% yield. The acid catalyzed hydrolysis of epoxide 6a,b unexpectedly afforded hemiketal 9a,b as the major product (60%) and the usual 23,24-diol 10a,b as the minor product (6%). Subsequent Ley perruthenate oxidation of 9b produced lactone 13b in 15% yield. Lead tetracetate oxidation of 10a produced the desired cleavage product 14a in 40–50% yield.

A facile regioselective aromatic fluorination of N-aryl-N-hydroxyamides with diethylaminosulfur trifluoride (DAST)

Treatment of N-aryl-N-hydroxyamides with diethylaminosulfur trifluoride (DAST) under conventional reaction conditions results in removal of the hydroxy function and introduction of a fluorine atom at the para position of the aromatic ring, in high yield.

Ring contraction in the fluorination of methyl 2-O-benzyl-3,6-dideoxy- and methyl 2,3-di-O-benzyl-6-deoxy-.ALPHA.-D-hexopyranosides with diethylaminosulfur trifluoride(DAST).

Fluorination of methyl 2-O-benzyl-3, 6-dideoxy-α-D-ribo- and α-D-arabino-hexo-pyranosides (1 and 4) with diethylaminosulfur trifluoride (DAST) yielded methyl 2-O-benzyl-3, 5, 6-trideoxy-5-fluoro-β-L-arabino- and β-L-ribo-hexofuranosides (3 and 6), respectively, along with the corresponding 4-deoxy-4-fluoro-α-D-hexopyranosides with retained configuration at C-4. The reaction of methyl 2, 3-di-O-benzyl-6-deoxy-α-D-glucopyranoside (7) with DAST predominatly afforded methyl 2, 3-di-O-benzyl-5, 6-di-deoxy-5-fluoro-β-L-altrofuranoside (9).

Synthesis of Fluorinated Pyrethroids: Conversion of Pyrethroid Metabolites into Some Insecticidal Fluorinated Derivatives

New fluorinated pyrethroids were designed to block microsomal oxidation at the C-10 methyl group of biophenothrin and at the C-7′ methylene of bioallethrin. By using diethylaminosulfur trifluoride and/or hexafluoropropene diethylamine, 10,10-difluorobiophenothrin and 7′-fluorobioallethrin were synthesized from the oxidized derivatives of the parent insecticides, which have been recognized as microsomal metabolites. While 10-hydroxybiophenothrin was not successfully converted into the corresponding 10-fluoro derivative by either fluorination reagent, other monofluorinated compounds were formed and their structures were elucidated.

An Unprecedented Reaction of Diethylaminosulfur Trifluoride with Furanones

Reaction of diethylaminosulfur trifluoride (DAST) with furanones did not provide the expected gem-difluoro compounds instead the methylene hydrogens of furanones were replaced by a fluorine and sulfinyl group

Regio- and chemoselective fluorination of biodynamic molecules

The chemistry of biodynamic fluorine containing indole and allied derivatives has aroused great interest in the field of medicine and biochemistry. 2-(Fluoroaryl)-indoles have been prepared by Fischer indole synthesis. Treatment of 2-(Fluoroaryl)-indoles with oxalyl chloride in dry ether at O°C afforded 3-indolyl glyoxalyl chlorides, which in turn with secondary amine gave 3-indolyl glyoxamides. Treatment of 3-indolyl glyoxamides with diethylaminosulphur trifluoride (DAST) in chloroform at 0°C for 24–30 hours gave 3-indolyl-β,β-difluoroethanamides, while after prolonged reaction time (25–30 days) furnished 3-indolyl-α,α,β,β-tetrafluorotryptamines in good yield. ▪

Synthesis of potential inhibitors of the biosynthesis of the sex pheromone of Spodoptera littoralis. Part I: Monofluorinated fatty acids

Several monofluorinated fatty acids, structurally related to palmitic acid, have been synthesized and fully characterized for the first time and assayed as inhibitors of the β-oxidation step, in the proposed biosynthesis of the sex pheromone of the Egyptian armyworm Spodoptera littoralis. Silver fluoride, diethylaminosulfur trifluoride (DAST) and dichlorofluoromethane were used as fluorination agents in the synthesis of 2-fluoropalmitic acid. 3- and 4-fluoropalmitic acid and ( Z)-5-fluoro-4-hexadecenoic acid, respectively. Stereoselective 1,4-reduction of the conjugated fluorodienic ester with sodium dithionite has been utilized to prepare the required fluorinated intermediate ester for the synthesis of ( Z)-5-fluoro-4-hexadecenoic acid. A preliminary account of the biological activity of the synthetic compounds along with 2-bromopalmitic acid is also reported.

Observation of a stable orthoacyl fluoride in the reaction of a reducing sugar with diethylaminosulfur trifluoride

The use of pyranosyl fluorides as glycosylating agents has gained wide popularity, in part due to their enhanched stability over the corresponding bromides or chlorides’,2. Many methods are available for their preparation*5. One of the most direct methods is the reaction of reducing sugars with diethylaminosulfur trifluoride (DAST), but the yields of glycosyl fluorides are variable and solvent dependenP’.