Tosyl ester reduction

Under appropriate conditions, Raney nickel can also cause reductive desulfonylation (compare, p. 156). Two procedures284 have been worked out, both involving, for tosyl esters, the over-all reaction ... 

In addition to the methyl ethers of dextro-, levo-, and myo-inositol which have been discussed in the preceding paragraphs, methyl ethers of most of the other inositols are now known. These compounds have been incidentally obtained in the course of other investigations—by the reduction of inososes formed from known ethers, by the inversion of tosyl esters of known ethers, and by opening the epoxide rings of anhydroinositols with methoxide ion. The individual compounds are listed in Tables II-X, pp. 192-203. 

Methylene-xylitol has been obtained also by periodate oxidation of 3,5-methylene-gluco-j/uZo-heptitol (XVI) and reduction of the 2,4-methylene-xyfo-trihydroxyglutardialdehyde thus produced.68 Benzyli-denation of 2,4-methylene-xylitol affords a mixed acetal, 2,4-methylene-3,5-benzylidene-D,L-xylitol, the structure of which was established by conversion of its tosyl ester into 1-desoxy-compounds.28... 

In the absence of protons the deprotection is complicated by nucleophilic attack of RO on the tosylate ester with formation of the ether, ROR [Eq. (60)]. This side reaction can be suppressed on addition of a proton donor, such as acetic acid. In that case aromatic radical anions cannot be used as catalyst and Ni(acacen) was used. The difference in yield of deprotected alcohol from direct and indirect reduction was insignificant [249]. 

LiAlH4 reduction of the tosyl ester of dihydroparavallaridine (55) gives 16)5,18-oxido-derivatives (56). The corresponding 17)5-dimethylamino-derivative has... 

The indirect reduction of tosyl esters can be performed7 in non-aqueous solutions. Thus, for example, the anthracene anion radical formed by cathodic reduction in DMF/TBAB (tetrabutylammonium bromide) electrolyte may reduce tosylates in solution. Similarly, the pyrene anion radical was shown8 (Figure 1) to react also with ethyl tosylate. The redox catalysis general scheme (indirect reduction by a redox P/Q couple) where P is a reducible species and Q its stable reduced form can be written as below ... 

The indirect reduction of tosyl esters by reduced forms of organic mediators may lead15 in certain cases to chemiluminescence and then help to determine the mode of cleavage of the S—O bond and the nature of the free radical present. 

Reduction of the nitro group and halides. Amines are obtained in good yields. The reduction can also be performed by a reagent generated from borohydride resin. The latter reagent converts alkyl bromides and iodides to the hydrocarbons, whereas chlorides, tosylates, esters, and nitriles are not affected. 

The reductive ring opening of 330a with sodium cyanoborohydride/titanium tetrachloride in acetonitrile occurs with no ester reduction whatsoever to provide 421 in 83% yield. Subsequent conversion to the tosylate followed by reduction with lithium borohydride/lithium triethylborohydride affords in 61% yield the crystalline diol 422. Lithium aluminum hydride or sodium borohydride reduction of the tosylate of 421 fails to produce clean reductions to 422. Epoxide ring closure of 422 is achieved with two equivalents of sodium hydroxide in methanol to fiimish in 93% yield (2 S, 3i )-2-benzyloxy-3,4-epoxybutan-l-ol (423) [140] (Scheme 94). 

The known 7-e carboxylic acid 506, obtained by the condensation of acrylic acid with furan, was used as a substrate for synthesis of validamine, (510) a component of validamycin antibiotics. The treatment of 506 with hydrogen peroxide in formic acid gave the tricyclic compound 507, which after reduction and hydrolysis afforded cyclitol. Treatment of 508 with 2,2-dimethoxy-propane in the presence of an acid gave a mixture of diisopropylidene derivatives in which compound 509 was predominant. Introduction of an amino group, by way of a tosyl ester and azide displacement, followed by hydrogenation and hydrolysis, completed the synthesis of DL-val-... 

Deoxy-, 6-deoxy- and 4,6-dideoxy-D-mannose derivatives have been prepared by sodium borohydride reduction of the relevant tosyl esters and/or Barton deoxygenation at C-4 of compound 11, followed by deprotection. One-pot dideoxygenation of the fully protected -pentenyl 3,6-di-O-thionocarbonyl 3-d-galactopyranoside 12 to give the 3,6-dideoxy-sugar 13 (a derivative of n-pentyl... 

The simplest conversion of the tosyl ester to the deoxysugar is by reductive cleavage. Although reduction with sodium amalgam or Raney nickel regenerates the primary hydroxyl group, the use of lithium aluminum hy-... 

Several reducing agents have been utilized to remove tosylate esters of sugars and other polyols. In particular, lithium aluminum hydride and lithium triethylborohydride have been most extensively used [20-23]. When secondary alcohol tosylates are used, epoxide intermediates are frequently involved. Reduction is observed to occur through either C-0 or O-S bond cleavage [24]. In this chapter, we discuss our results from the reduction of 6-0-tosylates of D-glucal and D-galactal with lithium aluminum hydride in THF. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Dialkylation of an amine or sulfonamide with a 1,3-dihalide provides a further route to azetidines <79CRV33l, 64HC( 19-2)88 5). Examples of this approach are the formation of N-tosylazetidine from tosylamide and l-bromo-3-chloropropane and the formation of N-alkylazetidinyl esters (36). The latter reaction works well except for R=Me the former provides a useful route to azetidine since the tosyl group can be removed by reductive methods. 

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