Tosyl fluoride

Allylic and benzylic alcohols have been converted into the corresponding fluorides in a one-pot reaction via in situ tosylation with tosyl fluoride and fluorination with lithium fluoride or in situ mesylation with mesyl fluoride and fluorination with cesium fluoride in the presence of crown ethers, respectively. 

To a solution of isopropylaminc (1.1 mmol). Et3N (1.0 mmol), and a catalytic amount of TBAF (10 mol%, 0.1 mL of a 1.0 M THF solution) in MeCN (1 mL) was added a solution of sulfonate 49 (1.0 mmol) in MeCN (2 mL) at 0 C. The mixture was stirred at rt for 3 h and then quenched with brine. The organics were then extracted with CH2C12, dried (Na2S04), and concentrated under vacuum. The resultant residue was chromatographed (silica gel, EtOAc) to yield analytically pure 50 (R1 = H, R2 = i-Pr) yield 86% along with tosyl fluoride. 

If a C-substituted derivative of TOSMIC is used in the reaction, the product is a 1,4,5-trisubstitutcd imidazole. Such substituted isocyanidcs can be made either by dehydration of the iV-(a-tosylalkyl)formamide, or by alkylation of an appropriate isocyanide followed by reaction with tosyl fluoride. It is also possible to alkylate TOSMIC directly using phase transfer conditions 13], Such alkylations work best with primary alkyl halides (75-95%), with the isopropyl (40%), allyl (75%) and benzyl (80%) derivatives proving quite accessible. 

Sulfonyl fluorides have so far been reported to react at only two amino acid residues, cysteine and serine. The chemical evidence for the reaction of phenylmethylsulfonyl fluoride at the reactive cysteine of papain is indirect (Whitaker and Perez-Villasenor 1968). However, the strong chemical evidence for the attack of phenylmethane sulfonyl fluoride at the serine of chymotrypsin (Gold and Fahrney 1964) has been confirmed by the X-ray crystallographic structure of tosyl-chymotrypsin (Matthews et al. 1967) which had been prepared from tosyl fluoride (Sigler et al. 1966). 

One such example is shown in Scheme 9, where intermediate 20 was swiftiy taken to 37 in a one-pot deprotection-tosylation-intramolecular y-alkylation mechanism utilizing tosyl fluoride. The resulting terminal olefin, when subject to Tsuji-Wacker oxidation conditions, furnished methyl ketone 38, which when exposed to strongly basic conditions triggered the Robinson annulation sequence, providing us with a cyclopentenone annulated analog 39. 

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

From 1,2-0-isopropylidene-3,5-di-0-tosyl-/ -d-xylofuranose (21) (29). Treating 29 with silver fluoride in pyridine and isolating as described above for the l-arabino isomer gave a 40% yield of 32 after a reaction time of 48 hours. The product had [ ]D25 — 14.9° and had an infrared spectrum identical with material prepared as above. 

From 5-deoxy-5-iodo-1,2-0-isopropylidene- -d-xylofuranose (30). A solution of 1.14 grams of 30 in pyridine (8.0 ml.) was shaken at room temperature with silver fluoride (2.0 grams). The reaction was slower than with the corresponding 5-tosylate (22) and was complete after 72 hours. The reaction mixture was processed as described above to give a pale yellow sirup which contained, in addition to 28, three minor components. Distillation afforded pure material (0.4 grams, 75%) identical with material prepared as above. 

The reaction can be done intramolecularly. N-Benzyl pent-4-ynamide reacted with tetrabutylammonium fluoride to an alkylidene lactam. Similar addition of a tosylamide-alkene, with a palladium catalyst, led to a vinyl Al-tosyl pyrrolidine. Similar cyclization reactions occur with tosylamide-alkynes. ... 

The preparation of glycosyl fluorides is described next. Aiming to have a convenient glycosyl donor convertible into 1,2-CM-furanosides, Mukaiyama and coworkers prepared 2,3,5-tri-O-benzyl-yS-D-ribofuranosyl fluoride (36y3) by treatment of a protected D-ribofuranose (35) with 2-fluoro-1 -meth-ylpyridinium tosylate (FMPTs) the total yield was raised by anomerizing the simultaneously produced a-1-fluoride (36a, 7, p 66, 72.f 24 Hz) to 36 (7, F 63.5 Hz, 72,F very small ) by treatment with BF3-OEt2. 

Abbreviations IMP, 2,4,6-trimethylpyridinium fluoride FMPTs, 2-fluoro-l-methylpyridinium tosylate Ishikawa, Ishikawa reagent (Ref. 74) Mitsunobu, through Mitsunobu reaction (Ref. 80) NBS, A-bromosuccinimide Piv, pivaloyl and Py, pyridine. 

Deoxy-5 -fluorothymidine (838) was prepared by Langen and Kowol-jj. 796,797 fpQjyj 5 -0-tosyl precursor by treatment with fluoride. Compound 838 cannot be phosphorylated enzymically owing to the lack of OH-5, but it inhibits the growth of carcinoma cells. This was explained as follows the thymidine 5 -monophosphate (thymidylate) kinase in carcinoma cells, catalyzing the transformation of thymidine 5 -monophosphate into the diphosphate, is inhibited by 838, thus preventing the synthesis of... 

Deoxy-5 -fluoroadenosine (911) and the analogs 910, 912, 913 were prepared by coupling of 5-deoxy-5-fluoro-D-ribofuranose and 6-chloro-purine. 2, 5 -Dideoxy-5 -fluoroadenosine (914) was prepared through a displacement reaction of the corresponding 5 -0-tosyl precursor with fluoride (BU4NF in DMF). The carbocyclic nucleosides 915 and 916 have been prepared and their antiviral activities evaluated. 

Especially for large-scale work, esters may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents45 or with crown ether catalysts.46 The reactivity order for carboxylate salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due to both high solubility and minimal ion pairing with the anion 47 Acetone is a good solvent for reaction of carboxylate anions with alkyl iodides48 Cesium fluoride in DMF is another useful... 

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