Mesyl with fluoride

The hydroxyl group was mesylated and displaced with 1-naphthoxide and, after treatment with fluoride to remove the silicon, the epoxide was opened with isopropylamine. 

The hydroxy part of a hydroxy acid can also be activated for macrolactonization. Vedejs et al. [60] applied such a strategy to the synthesis of the macrocychc pyrrolizidine alkaloid monocrotaline 108). Thus, the seco acid derivative 106 was first mesylated with MsCl/EtjN in dichloromethane, and the crude product was added over 3 h to an excess of tetrabutylammonium fluoride trihydrate in acetonitrile at 34 °C to effect ring carboxy deprotection and ring closure to give 107 in 71% yield (Scheme 36). It has been noted that the active intermediate of this kind of lactonization may be an allylic chloride rather than a mesylate [61a], In addition, an intramolecular nucleophilic displacement process of chloride from an a-chloro ketone moiety by a remote carboxylate has been recently reported as an efficient approach to macrocychc keto lactones [61 bj. 

Due to the relatively forcing reaction conditions, i.e. severe heating in strongly polar media, that are usually applied in potassium fluoride fluorinations. several attempts have been made to find mild and efficient methods to fluorinate with metal fluorides. l-(Mesyloxy)octane is converted into 1-fluorooetane in high yield with aqueous potassium fluoride in the presence of catalytic amounts of tributyldecylphosphonium bromide. Similarly, (m-fluoropropoxy)ni-trobenzenes are obtained in good yield from the corresponding mesylates with potassium fluo-... 

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. 

Table 14.4 Reactions of alkyl halide mesylates with [18F]fluoride ion in protic solvent systems...

On the other hand, removal of the silyl group in 22 with fluoride ion and subsequent mesylation afforded 25. Hydrogenation of 25 followed by cychzation in the presence of sodium acetate and subsequent protection of the amino group with Cbz, treatment with ethanethiol in aqueous TFA, followed by dibenzylation, mercuric chloride catalyzed hydrolysis, sodium borohydride reduction and mesylation afforded 26. Selective hydrogenolysis of the carbamate group in 26 followed by intramolecular cyclization afforded the 3,5-di-O-benzyl ether of quinuclidinediol. Removal of the benzyl groups afforded 2. 

Unfortunately, the obvious starting material, allyl alcohol itself, gives an epoxide that is hard to handle, so Sharpless, who carried out this synthesis of propranolol, used this silicon-substituted allylic alcohol instead. The hydroxyl group was mesylated and displaced with 1-naphthoxide and, after treatment with fluoride to remove the silicon, the epoxide was opened with isopropylamine. 

Reactions of ar>l or alkyl bis(siloxy)isopropyl ethers with tetrabutyl-ammoninm fluoride-mesyl fluoride reagent lead to replacement of one siloxy group by fluorine and dehydrosiloxylation, providing an efficient access to fluoroisopropenyl ethers, which are useful as specific building blocks in drug design The reactions proceed via the intermediate allyl methanesulfonates [30, 31] (equation 23)... 

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)... 

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

Condensation of sodium phenoxide witli 2,2,2-trifluoroethyl iodide gives a product of direct substitution in a low yield, several other ethers are formed by eliminatton-addition reactions [7] Use of mesylate as a leaving group and hex amethyl phosphoramide (HMPA) as a solvent increases the yield of the substitution [S] Even chlorine can be replaced when the condensation is performed with potassium fluoride and acetic acid at a high temperature [9] (equations 6-8)... 

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 ... 

Deoxy-3 -fluorothymidine (813), a selective inhibitor of DNA synthesis, was prepared " in moderate yields from 3 -0-mesyl- or 3, 5 -di-O-mesyl-thymidine, through 2,3 -anhydro-1 -(2-deoxy- -D-t/2reopentofur-anosyl)thymine (808), by treatment with hydrogen fluoride (0.1% HF in l,4-dioxane-AlF3, 3.764 hf in DMF-AlFj, or 10% HF in DMF ),... 

The almost instantaneous intramolecular ether formation by reaction of phenoxy anions, generated from the silyl ethers with a stoichiometric amount of tetra-n-butylammonium fluoride, on mesylate esters has been used to synthesize labile benzo-0-2-isocephams (>90%) [20]. 

Optically pure alcohols are converted via their mesylates into the corresponding chiral haloalkanes with the opposite configuration (>70% with an optical purity 90%) by a liquiddiquid phase-transfer catalysed SN2 reaction (2.1.5) with the appropriate potassium halide [7]. The preparation of chiral fluorides normally requires more vigorous conditions (160°C, 14 h in an autoclave). By-products of the reaction are the alcohol and alkene. 

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