Esters bromotrimethylsilane

Bromotrimethylsilane has proven to be useful for a wide variety of applications most of them being reviewed.5 8 Other recent applications are mild cleavage of oxiranes,9 the synthesis of glycosyl bromides,10 the selective cleavage of tetrahydro-2,5-dimethoxyfuran and tetrahydro-2,6-dimethoxy-pyran,11 the cleavage of esters and ethers,12 and the synthesis of benzyl bromides.13... 

Scheme 28 Selective Cleavage of a Phosphonate Methyl Ester with Bromotrimethylsilane 66 ...

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... 

Cleavage of lactones and carbonates. Lactones and carbonates react with bromotrimethylsilane to afford bromocarboxylic acid derivatives (equation I) and bromohydrin trimethylsilyl ethers (equation II), respectively acyclic, aliphatic esters do not react with bromotrimethylsilane. lodotrimethylsilane reacts in an analogous fashion with lactones, but in reaction with ethylene carbonate the main product is 1,2-diiodoethane (equation III). The >-bromocarboxylate derivatives are converted into acid chlorides by reaction with SOCL (equation I). 

Selective phosphonate ester dealkylation. Alkyl phosphonate esters are selectively and nearly quantitatively cleaved by bromotrimethylsilane in the presence of alkyl carboxylate esters, carbamates, acetylenes, ketones, and halides. Alkyl iodides do not exchange under the reaction conditions. The resulting bis(trimethylsilyl) phosphonates are hydrolyzed in acetone by a small excess of water. 

Alkyl bromides. Alcohols are converted into bromides by reaction with bromotrimethylsilane (1.5-4 equiv.) in CHCI3 at 25-50° (equation I). The reaction occurs with inversion. Tertiary and benzylic alcohols react more rapidly than primary or secondary alcohols. Bromides are not formed under the same conditions from Irimethylsilyl ethers of alcohols. However, trimethyl orthoformate is converted into methyl formate, HC(OCH3)3 —s HCOOCH3. Unlike iodotrimethylsUane, the bromosilane does not dealkylate esters, ethers, or carbamates. 

McKenna. C.E., and Schmidhauser, J., functional selectivity in phosphonate ester dealkylation with bromotrimethylsilane. J. Chem. Soc.. Chem. Commun.. 739. 1979. 

McKenna, C.E., Higa, M.T., Cheung. N.H., and McKenna, M.C., The facile dealkylation of phosphonic acid dialkyl esters by bromotrimethylsilane. Tetrahedron Lett., 18, 155, 1977. 

The 2, 3 -dideoxy-3 -C-(phosphonomethyl)nucleosides (38) of the five common nucleotide bases have been prepared by a condensation of the nucleobases with 1,2-di-O-acetyl-S-O-benzoyl-3-deoxy-3-(methoxyphosphorylmethyl)-6-D-ribofuranose (39). Conversion to the deoxyribose derivative was accomplished by reduction of the 2 -thionocarlKHUite and hydrolysis of the phosphonic ester groups using bromotrimethylsilane. 9-(l-Deoxy-l-phosphono-B-D-p(5CO-furanosyl)-l,9-dihydro-67f-purin-6-one (40, Scheme 4) has been prepared as a potential transition state inhibitor of purine nucleoside phosphorylase. The crucial step in the synthesis involved the carixm-phosphorus bond formation by reaction of the hemiacetal (41) with triethyl-phosphite. Nucleotide (40) proved to be very susceptible to hydrolysis of the glycosidic bond (half-life of thirty-nine minutes, pH 7), but showed weak inhibitory activity (K- = 26 /iM) against purine nucleoside phosphorylase. 

Halosilanes are very effective at cleaving MOM ethers in the presence of a range of polar functional groups. Thus, bromotrimethylsilane removes MOM ethers at -30 C in dichloromethane - — conditions that preserve TBDPS ethers, but TBS ethers may cleave to some extent whereas trityl ethers, tetrahy-dropyranyl ethers, and isopropylidene acetals seldom emerge unscathed. The method has been employed in syntheses of Nogalamycm" and Gilvocarcin without detriment to two phenolic methyl ethers, a lactone and four acetate esters [Scheme 4.243]. ... 

An elegant way for the synthesis of tertiary phosphine oxides comprises the catalytic rearrangement of phosphinous esters by bromotrimethylsilane (Scheme 1). ... 

The target polymer was prepared by bromotrimethylsilane-induced cleavage of the n-butyl phosphonate ester groups in neutral precursor polymer. After neutralisation of the reaction mixture with aqueous sodium hydroxide, the target polymer has exhibited good solubility in water. 

In recent years, phosphorus-based polymers have been widely studied as they exhibit very unusual and interesting properties/ Whereas the ester forms are the most available compounds, monoacids and diacids can be easily obtained under mild conditions with the use of bromotrimethylsilane, opening the way to a wide range of polymers showing different properties. The latter can be explained in part by the ionization potential of phosphonic acids, which is intermediate between that of sulfonic and carbojgrlic acids due to their intermediate p/fa-... 

Bromotrimethylsilane, a reagent similar to but not as powerful as lodotrimethylsilane, will cleave MOM ethers as well as acetonide, THP, trityl, and f-BuMe2Si groups, but the reagent will not cleave esters, methyl and benzyl ethers, f-butyl-diphenylsilyl ethers, and amides. One example is shown in eq 6. ... 

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