Trifluoroacetic acid, ether cleavage with

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [11L1, Scheme 3.111 j as the butane-2,3-diace-tal 111 2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase.205 Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111 1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase206 and influenza neuraminadase207-208 as well as shikimic add derivatives.209 210... 

Abresoline (66) was prepared recently by Quick and Ramachandra by transesterification of MB-methoxyethoxymethyl (MEM) ether of methyl ferulate with MEM derivative of quinolizidol (63a) and cleavage of protective groups with trifluoroacetic acid (103). 

The disilyl derivative of all-cix-1,2-epoxycyclopentane-3,5-diol 5 7 was treated with diethyloctynylalane to afford after cleavage of the silylether function the triol 58. This triol was convered via the acetonide to the benzyl ether 59. Hydrolysis with aqueous trifluoroacetic acid yielded the diol benzylether 60 which could be prepared by an alternative route as well. This route proceeds via the monotrityl epoxide 61 and benzylation to the trityl benzylether 62 and then reaction with diethyl octynyl alane to the diolbenzylether 60 and the isomeric 1,3-diol. 

Sodium borohydride and trifluoroacetic acid (TFA) reduce 2-aryl-l,3-dioxoIanes to hydroxy ethers. Zinc borohydride, with TMS-Cl as its acidic partner, has proven to be effective in the reductive cleavage of a variety of acetals. MOM ethers are reduced to methyl ethers in good yield (equation 13). Cyclohexene is hydroborated under these conditions, indicating that diborane may be present. 

Also the trityl group was applied for the masking of SH functions. The sulfides were prepared by the reaction of the thiol with trityl chloride (75% yield) or from trityl alcohol and the thiol in the presence of anhydrous TFA (85-90% yield). The cleavage of this group can be carried out under several conditions (Scheme 58). It is sensitive to acids (e.g. trifluoroacetic acid/ethanethiol 1 1) and to heavy metals. Thiocyanogen (SCN)2 oxidizes 5-trityl ethers to the disulfides and iodine converts 5-tritylcy -teine derivatives to cystine structures. 

With strong protic acids, the regiochemistry of the reductive cleavage reverses to give the benzyl ether of the less hindered alcohol. One of the few metal hydrides that can withstand the harshly acidic conditions of the reaction is sodium cyanoborohydride. When used in large excess, it will reduce benzylidene acetals in the presence of anhydrous HG [Scheme 3.61] -or trifluoro-methanesulfonic acid. The excess is required because the sodium cyanoborohydride is consumed under the reaction conditions at an appreciable rate. More convenient reaction conditions were described by DeNinno and co-workers in which the benzylidene acetal is reductively cleaved using triethylsilane in the presence of trifluoroacetic acid [Scheme 3.62]. ... 

The acid-sensitive hydroxyl group was protected as an O-thiocarbamate, and treatment of the resulting vinyloxirane 49 with catalytic amounts of trifluoroacetic acid (TFA) afforded the substituted-dihydrofuran derivative 50 in high yield. Free-radical deoxygenation followed by the cleavage of the methyl ethers conpleted the synthesis. 

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