Mesylation of alcohol

Mesylation of alcohol 14 and hydrolysis of the acetal with oxalic acid leads to the key decalone 16 which cyclises in the presence of NaH in dioxane to afford twistanone 17 in quantitative yields. The elimination of the carbonyl group was carried out by an alternative method to the Wolff-Kishner reduction, which involves the thioacetalisation of the twistanone (18) with ethane-1,2-dithiol and removal of the resulting thioacetal by Raney nickel in boiling ethanol (62% yield). 

MeS02Cl, pyridine, 0°C, 65-83% yield." Although the yields are moderate compared to more conventional methods, this reaction is important in that these conditions are often used to prepare mesylates of alcohols which indicates that some caution must be exercised with free acids during reactions with alcohols. 

The use of enzyme technology has also been exemplified in a Chirotech process for the synthesis of both enantiomers of the hydrogenation catalyst DuPHOS (80) [2,86]. A hexanediol mixture consisting of 50% meso and 50% racemic diol 77 was acylated with the aid of immobilized CAL-B (Scheme 23). Only the (i )-configured alcohol was converted by the enzyme and led to the monobutyrate (RyS)-7S and the bisbutyrate RyR)-79. The unchanged (S,S)-diol 77 could be removed by extraction with water and was purified by crystallization from ethyl acetate, to reach an optical purity of 98% ee and 88% de. The mesylate of alcohol (RyS)-7S could be inverted with potassium acetate, and saponification of this acetate and of compound RyR)-79 followed by a crystallization step provided the enantiopure diol (RyR)-77 in 48% yield. Although this procedure was used to produce approximately 30 kg of DuPHOS, it has not been used further for commercial catalyst production. 

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)... 

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). 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

The cyclobutanone (255) reacted with acid to furnish the keto-acid (259). Upon esterification, ketalization and reduction, (259) was converted to the alcohol (260). Mesylation of the alcohol (260) and then treatment of the mesylate with NaN3 in DMSO provided the azide (261). The azide (261) was then transformed to the urethane (262) by reduction and ethyl chloroformate reaction. The urethane (262) was deketalized by acid, nitrosated by N204—NaOAc and decomposed by NaOEt—EtOH to give the ketone (263) 89). The ketone (263) served as a starting material for the synthesis of veatchine (264)90). 

In Ziegler and Kloek s synthesis of ( )-steviol methyl ester, irradiation of hydrin-denal 17 and 1,2-propadiene (1) afforded the photocycloadduct 18 in 45% yield as a 14 1 mixture of diastereomers (Scheme 19.4) [6]. The major cycloadduct was subsequently converted to ( )-steviol methyl ester via a reduction of the aldehyde, followed by mesylation of the resulting alcohol and treatment with aqueous acetone in 2,6-lutidine. Unfortunately, steviol methyl ester (19) was obtained in only 3% yield. 

Mesylation of the alcohol 65 followed by deprotonation afforded the sul-fone-stabilized carbanion 66 that underwent a macrocyclization to afford the artificial dolabellane 67 in moderate yield (Scheme 9). Hydrolytic cleavage of the ketal (67) followed by a base-mediated double bond isomerization (into conjugation) afforded an enone containing an exocyclic carbonyl group. Nucleophilic 1,2-addition of methyl lithium introduced the missing... 

Fig. 10.2. Reaction protocol for the transformation of alcohols to amines via mesylation and amine substitution, as shown in PGVL Flub.

Methyl (25, 3i )-2-(ferf-Butoxvcarbonylamino)-3-f(methylsulfonyl)oxy]-3-phenylpropanoate (99A) [13°1 To a soln of alcohol 98A (0.94 g, 3.18 mmol) and TEA (0.73 g, 7.18 mmol) at 0°C in CH2C12 was added MsCl (418 mg, 3.65 mmol). The mixture was stirred at 0°C for 45 min, and then quenched with aq dil HC1 and extracted with CH2C12. The organic layer was washed with aq NaHC03, followed by brine, and dried (Na2S04). The solvent was removed under reduced pressure to give the crude mesylate 99A as a foamy white solid that was used in the next step without further purification. 

SN2-Suhf.titutions. The configuration of secondary alcohols can be inverted by reaction of the mesylate with cesium propionate (65-100% yield). The reagent reacts with secondary alkyl halides to form the ester of the inverted alcohol (85 100% yield). Some elimination occurs in reaction of the mesylates of menthol and cholestanol. ... 

We have focussed on alkyl halides but tosylates from TsCl and mesylates from MsCl can be used too. The conversion of alcohols to chlorides and bromides is discussed earlier in this chapter and the combination of reagents used to make thiols is discussed in the next chapter. 

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