Alcohol mesylation

Chemical Properties of 1,2,5-Thiadiazoles. Lithiation and carbonylation of one methyl of 3,4-dimethyl-1,2,5-thiadiazole were described, followed by subsequent transformation into alcohol, mesylate, and vinyl derivatives. The reaction of 2,5-dicyclohexyl-l,2,5-thiadiazole-3,4-dione with RC6H4-SO2N3 gave the compounds (294 R = 4-MeO or 3-O2N). ... 

In this process (Fig. 22), ketone 61 underwent reduction with an over-stoichiometric amount of borane in THF in the presence of 5 mol % of the proline-derived Corey s oxa-zaborolidine 62 to afford alcohol 63 in 100% yield and 92% e.e. SN2 displacement carried out on the alcohol mesylate with a higher-order cuprate gave adduct 64, that was transformed first into tetralone 65 by a triflic acid-promoted Friedel-Crafts-type reaction, and then into sertraline 66 (86% e.e.) by imine formation and borohydride reduction. 

Olefin 104 was then subjected to a Sharpless asymmetric dihydroxylation which proceeded with moderate diastereoselectivity, leading to an inseparable mixture of the diols 105a and 105b (d.r. 71 29) (Scheme 29). Fortunately, when the mixture of 105a and 105b was submitted to the following three-step sequence, for example, selective protection of primary alcohol, mesylation, and then cyclization, the major isomer 106a could be isolated in pure form. Two further deprotection steps were necessary to provide the hyacinthacine Bi 3 in 45.5% overall yield and 13 steps from lactam 101. In paraUel,... 

Primary tosylates are more prone than bromides to form f-butyl ethers by Sn2 displacement by the f-butoxide anion in DMSO. Sulfonate esters of flexible cyclic and secondary acyclic alcohols give predominately alkenes in the presence of f-BuOK/DMSO. With sulfonate esters of 3-hydroxy steroids, there is competition between /S-elimination and attack of the f-butoxide ion on sulfur to form alcohols mesylates are more prone to this reaction than tosylates. Sulfonate esters of 3a-acetoxy-12a-hydroxycholanate undergo mainly /3-elimination with f-BuOK/DMSO (eq 4). In this case, substitution of various other aprotic solvents for DMSO and DMSO Na+ for f-BuOK was not as effective. Treatment of both the mesylate and the tosylate of cholesterol with f-BuOK/ DMSO gives the conjugated diene, 3,5-cholestadiene, in high yield. ... 

Quaternary ammonium ion-exchange resins in the fluoride form, used in non-polar solvents, provide naked fluoride ion that produces alkyl fluorides from alcohol mesylates. Residual water in the resin enhances the undesired basic nature of naked F but careful dehydration of the resin ensures clean Sn2 substitution. 

Scheme 50). ° A further three steps afforded ketone (+)-365, reductive amination of which produced a mixture of the two diastereomeric indolizidines (—)-366 and (—)-367 in ratios ofbetween 76 24 and 84 16. The orientation of the new stereocenter was confirmed by NOESY studies. An alternative cyclization by reducing the ketone of 365 to the alcohol, mesyl-ation and cyclization was less favorable, giving approximately equal amounts of the isomers. Hydrogenolysis of 366 and 367 completed the syntheses of (+)-steviamine ent-352) and the aforementioned diastereomer (—)-361, respectively. The weak inhibitory activity of natural (—)-steviamine toward various P-glucosidases and its stronger inhibition of p-galactosidase was estabhshed in this work, while weak inhibition of a-L-rhamnosidase by the (+)-enantiomer and by 361 was also demonstrated. 

It is used as a catalyst in esterification, dehydration, polymerization and alkylation reactions. Converted by e.g., ihionyl chloride, to melhanesulphonyl chloride (mesyl chloride) which is useful for characterizing alcohols, amines, etc. as melhanesulphonyl (mesyl) derivatives. 

Replacement of a primary or secondary hydroxyl function with deuterium is usually carried out by first converting the alcohol into a mesylate or tosylate ester, which can then be displaced by treatment with lithium aluminum deuteride. The... 

The use of mesyl chloride for the dehydration of C-11 alcohols has already been mentioned, and mesylates can certainly be intermediates at least in the a-series. The preference for a coplanar trans arrangement is demonstrated by the well-known elimination reactions of tosylates of epimeric 20-alcohols (ref. 185, p. 616), although this does not restrict the usefulness of the reaction, and in some cases (sulfonates of 1 la-alcohols, for example) cw-elimination occurs (ref. 216, p. 293 ref. 224, 225, 226). 

Dimethyl sulfoxide (DMSO) has been used to effect the elimination of sulfonates at elevated temperatures (see, for example, ref. 237). Benzene-sulfonates are recommended. The elimination of a variety of sulfonates proceeds readily in this medium in the presence of potassium /-butoxide. A -Compounds have been formed at 100°, but heating is not necessary. The effects of temperature change, orientation of the hydroxy group and changes in the sulfonate employed have been examined. The principal side reaction appears to be formation of the original alcohol (uninverted), particularly with equatorial mesylates at low temperatures it is minimized with axial tosylates. 

The azido alcohol is dissolved in a minimal amount of dry pyridine and cooled in an ice bath. Methanesulfonyl chloride (1 ml/g of azido alcohol) is added to the cold solution. The reaction mixture is allowed to stand at 0° for 24 to 72 hr. The reaction mixture is processed by pouring into ice water and either filtering the product, if possible, or by extraction with an organic solvent. Methanol or methanol-ether have been used to recrystallize the crude azido mesylates. 

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)... 

Mesylates and tosylates may be used as variants of the 0-sulfate ester. For instance, 55% of aziridine 7 was obtained from base-mediated cyclization of amino mesylate 6. In comparison, the classic Wenker protocol only gave 3% of 7. In another instance, A-tosyl amino alcohol 8 was tosylated to give 9, which was transformed to aziridine 10 in 64% yield, along with 29% of the P-elimination product due to the presence of the ester moiety. Likewise, aziridine 12 was assembled from tosylate 11 in two steps and 60% yield. ... 

Activity is also retained when the hydroxyl group at the 21 position is replaced by chlorine. Reaction of corticoid 44 with methanesulfonyl chloride proceeds preferentially at the 21-hydroxyl (45) due to the hindered nature of the 11-alcohol. Replacement of the mesylate by means of lithium chloride in DMF affords clobetasol propionate (46) a similar sequence starting with the 17- butyrate ester 47, via mesylate 48, should give clobetasone butyrate, (49) [11]. 

In a similar vein, acylation of the corticoid 50 with furoyl chloride gives the diacyl derivative 51. Reduction with sodium borohydride serves to convert the 11-ketone to the alcohol 52. Hydrolysis under mild acid conditions preferentially removes the acyl group at the less hindered 21 position. The hydroxyl group in that derivative (53) is then converted to the mesylate 54. Replacement by chlorine affords mometasone (55) [12]. 

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 ... 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

The present route to (terminal alkynes reported by a group from the Chemical Process Department at the DuPont Pharmaceutical Company.2 This alcohol serves as a convenient starting material for the preparation of 1-acyloxy 4-mesylates 10 (eq 1). 

These mesylates, in turn, can be converted to enantioenriched allenyltin, zinc, and indium reagents which add to aldehydes with excellent diastereo-and enantioselectivity to afford either syn- or anti-homopropargylic alcohols or allenylcarbinols (eq 2, 3, and 4).3 4 Adducts of this type serve as useful intermediates for the synthesis of polyketide and hydrofuran natural products.5... 

Transformation of bromocriptine free base 2 into water soluble salt -mesylate, is the only way to obtain a suitable therapeutical form. Crystallization of mesylate using alcohol as a solvent in the presence of excess of strong acid, e.g. methanesulphonic acid can induce formation of 12 -0-alkyl-derivative 2. Until now this derivatisation of ergot molecule has been practically unknown. In continuation we developed the preparative method for obtaining these compounds, (using tetrafluoroboric acid as a catalyst) (ref. 20). 

Although halides are common leaving groups in nucleophilic substitution for synthetic purposes, it is often more convenient to use alcohols. Since OH does not leave from ordinary alcohols, it must be converted to a group that does leave. One way is protonation, mentioned above. Another is conversion to a reactive ester, most commonly a sulfonic ester. The sulfonic ester groups tosylate, brosylate, nosylate, and mesylate are better leaving groups than... 

Quenching of the same lithiated species with CO2, followed by reduction of the carboxyUc acid functionality obtained with BH3-THF complex, yielded the next higher analogues 78 to these alcohols [94]. Subsequent treatment of the depro-tonated alcohols with TsCl or MsCl afforded (l )-l-boranato[alkyl(methyl)plios-phino] ethanol-2-tosylates or the mesylate phosphine-boranes in over 90% ee and excellent overall yields. 

---