LiAlH4, reaction with tosylates

The subsequently applied synthetic scheme was analogous to the one for the corresponding racemic compounds (see 2.2.2.I., 3.2.3. and 3.2.4.). Treatment of the (—)-alcohol 379 with iodine in chloroform yielded the (-)-10° -iodide 383 as sole product. Its reaction with silver tosylate in acetonitrile led to a mixture of 10°(7).tosyloxy-isotwistane 384 and -twistane 386, which was directly treated with LiAlH4 in refluxing dioxane to give a mixture, easily separable by vpc., of (—)-2,7-dioxa-isotwistane 385 [oc]d = —23.3 0.7°) and (-)-2,7-dioxa-twistane 387, see Table 8). The absolute configuration of 387 [(—)-( R, 3R, 6R, 8R), right-handed helix (P)] and of all other compounds involved in its synthesis was determined by chemical correlation with (—)-(2S)-malic acid (559). As relais compounds served the endo-2-hydroxy-9-oxabicyclo[3.3.1]nonanes +)-390 and (—)-J97, (-t)-5-hydroxy-cyclooct-l-ene [ +)-392] and the 4-methoxy-suberic acid dimethylester —) 393 and +)-394. 

Tosylation of beta-CD-crown ether was carried out with tosyl chloride in pyridine. Reduction of the produced tosylate with LiAlH4 afforded a completely apolar crown ether-like compound the structure of which is being investigated (Fig. 7). Studies in similar reaction sequence with alfa- and gamma-cyclodextrins is now in progress. 

The cathodic cleavage of CX- to CH-bonds can be achieved with a variety of substituents X, such as Hal, NR3+, PR3+, OTos, or epoxides. Generally, good yields, a high potential selectivity, and often good stereoselectivities are encountered (see also Chapters) [117-123]. Chemical reactions for similar conversions, which are well worked out, especially with regard to yield and selectivity, are the reduction of tosylates with LiAlH4 and halides with... 

N-Tosylated p-hydroxy alkylamines (which can be easily hydrolyzed to f -hydroxyamines79h) can be prepared797 by treatment of alkenes with the trihydrate of Chloramine-T637 and a catalytic amount of 0s04. In some cases yields can be improved by the use of phase-transfer catalysis.798 The reaction has been carried out enantioselectively.799 In another procedure, certain p-hydroxy secondary alkylamines can be prepared by treatment of alkenes with the osmium compounds /-Bu—N=0s03, followed by reductive cleavage with LiAlH4 of the... 

When steric hindrance in substrates is increased, and when the leaving anion group in substrates is iodide, SET reaction is much induced (Cl < Br < I). This reason comes from the fact that steric hindrance retards the direct nucleophilic reduction of substrates by a hydride species, and the a energy level of C-I bond in substrates is lower than that of C-Br or C-Cl bond. Therefore, metal hydride reduction of alkyl chlorides, bromides, and tosylates generally proceeds mainly via a polar pathway, i.e. SN2. Since LUMO energy level in aromatic halides is lower than that of aliphatic halides, SET reaction in aromatic halides is induced not only in aromatic iodides but also in aromatic bromides. Eq. 9.2 shows reductive cyclization of o-bromophenyl allyl ether (4) via an sp2 carbon-centered radical with LiAlH4. 

A large number of aza crowns are made by these routes. Stepwise addition of CH2CH2NHTs groups occurs readily by reaction of the appropriate tolu-enesulfonamide with 2-bromoacetamide followed by borane reduction and A-tosylation. If a trimethylene spacer is desired, then reaction of the tosyla-mide with acrylonitrile followed by reduction and tosylation gives good yields of the desired product (Scheme 1.2). An example of such a sequence is provided by the synthesis of the symmetrical [24]-N6 cycle, 4 (Scheme 1.3).9 In this particular case, introduction of the desired C3 spacer was undertaken on the. electrophilic component by conjugate addition of the tosylamide with methyl acrylate followed by reduction with LiAlH4 and mesylation. 

As mentioned, LiAlH4 in refluxing THF was the initial system introduced to reduce preformed tosyl-hydrazones to hydrocarbons and a number of successful conversions have been reported, representative examples of which are presented in Table 5. Alkene side products often accompany the hydrocarbon products,a result attributed to proton abstraction from the a-carbon of intermediate (59), leading to a vinyldiimide anion (64), followed by N2 expulsion and protonation during work-up (Scheme 3). With certain ketones, including 17-keto steroids, alkenes are the major s or sole product (entries 7-9, Table 5). This side reaction mimics the elimination obtained upon treatment of to-sylhydrazones with other strong bases (i.e. alkyllithiums, the Shapiro reaction 29). Note that use of LiAlD4 introduces one deuterium (with H2O work-up) or two deuteriums (with D2O work-up entries 5 and 6, Table 5, respectively). 

Primary tosylates are reduced by LiAlH4. The diacetal of D-fucose 5.39, an enantiomer of L-fucose, is thus prepared by reduction of tosylate 5.38 derived from the diacetal of D-galactose 5.11. A hydroxyl group can also be replaced by a halogen (Cl, Br, I) at any position of a protected sugar. The halide is easily reduced by a radical mechanism with tributylstannane, Bu3SnH (reaction 5.19). 

Base-hydrolysis of the 10° -acetoxy-isotwistane 310 (3.4.3.) gave the alcohol 333, which was also obtained as sole product in a 99% yield by L1A1H4-reduction of the ketone 331. LiAlH4-treatment of the tosylate 334, prepared from the alcohol 310, yielded only alcohol 310 again and no unsubstituted 2,7-dioxa-isotwistane 128). Obviously the cleavage of the bond between 0-C(10)° and S—OC(10)° is preferred over the formation of an oxonium ion G 59. This result, compared with the exclusive formation of an oxonium ion G 46 (no reaction to the alcohol 137) in the analogous treatment of the 10° -tosylate 267 (3.2.3.), is a qualitative measure for the differences of the tendencies for the formation of the oxonium ions G 46 and G 59, starting from C(10)° - and C( 10)° -substituted isotwistanes ... 

Preparative Method the title compound with 5-configuration can be made from (5)-mandelic acid following a four-step reaction sequence reduction (LiAlH4), selective tosylation (TsCl/Bu2SnO/Et3N), displacement (NaSPh), and acetylation (Ac20/pyridine). The racemic isomer can be prepared by electrophilic addition to st3rene. ... 

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