T-Butyldimethylsilyl ethers

SEM ethers are stable to the acidic conditions (AcOH, H2O, THE, 45°, 7 h) that are used to cleave tetrahydropyranyl and t-butyldimethylsilyl ethers. 

NaH, HMPA, 0°, 5 min H2O, 83-84% yield. These conditions selectively cleave a TBDPS ether in the presence of a t-butyldimethylsilyl ether. 

The same coordination is used to account for the observed anti preference in the allylation of (t-hydroxybutanal with allyl bromide/indium in water (Scheme 8.16). The intermediate leads to the anti product. In support of the intramolecular chelation model, it is found that if the hydroxy group is converted to the corresponding benzyl or t-butyldimethylsilyl ether, the reaction is not stereoselective at all and gives nearly equal amounts of syn and anti products. 

A nickel-chromium catalyst prepared from chromous chloride and (p-diphenylphos-phinopolystyrene)nickel dichloride mediates the ring-closure of the ene-allene 236 (R = H) to a mixture of 3.4 parts of 237 and 1 part of 238 (equation 120)121. An analogous reaction of the t-butyldimethylsilyl ether of 236 yields solely the (E)-isomer 237 (R = t-BuMeaSi). Cyclization of the ene-allene 239 affords the perhydroindane 240 in 72%... 

Reduction of benzyl ethers. Benzyl ethers are cleaved in high yield by calcium (2 equiv.) in liquid ammonia. By proper control of the amount of metal, selective reduction of benzyl ethers is possible in the presence of a triple bond or a t-butyldimethylsilyl ether group. However, there is little selectivity between benzyl ethers and thiophenyl, epoxide, or keto groups in this reduction. 

Regio- and stereoselective dihydroxylation of dienes functionalized at the allylic position with a benzene sulfone group has been reported42. Osmylation of dienic sulfones 33, a potential key synthon for forskolin, occurred exclusively on the A6-7 double bound and preferentially from the a-face of the traws-fused bicyclic molecule, presumably due to a combination of steric and electronic factors (equation 25). While the reaction of diene sulfones proceeded sluggishly under catalytic conditions, treatment of 33a with a stoichiometric amount of OSO4 resulted in quantitative yield of diastereomeric diols 34a and 35 in a 9 1 ratio, respectively. Protecting the hydroxy group of the dienol as its t-butyldimethylsilyl ether (33b) affords diol 34b exclusively. 

Altylic alcohols from epoxides. Reaction of T with epoxides and then DBN gives reasonable yields of allylic alcohols as the t-butyldimethylsilyl ether. 

Cleavage of t-butyldimethylsilyl ethers.1 The silyl ethers of primary and secondary steroidal alcohols arc converted to the alcohols by LiBF4 in CHjCN-CH2C12 (yields 70-85%). 

Diels-Alder cyclization of IfiAO-undecatrienals.5 These unsaturated aldehydes undergo intramolecular Diels-Alder cyclization, particularly under Lewis acid catalysis. The reaction is highly endo-selective. Silyl-protected alcohol groups at C4 and Q can be present, and t-butyldimethylsilyl ethers show a strong axial preference. 

In a related reaction, stereochemical control during epoxidation of A4- .v-l, 2-disubstituted cyclohexenes 141 with MCPBA depends upon the hydroxyl functionality195. A free alcohol (141a) or an acetate (141b) affords. vyw-cpoxides exclusively. Epoxidation of a t-butyldimethylsilyl ether (141c) gives predominantly the rmtf-cpoxide (54%). 

The t-butyldimethylsilyl ether (TMBS-ether), formed from the alcohol with t-butyldimethylsilyl chloride in the presence of imidazole in dimethylformamide solution,84 is more stable to hydrolysis than the TMS-ether (see also Section 4.2.66, p. 461). Deprotection is readily effected by treatment with 2-3 equivalents of tetrabutylammonium fluoride in tetrahydrofuran at 25 °C,84a or tetrabutyl-ammonium chloride and potassium fluoride dihydrate in acetonitrile.84b... 

Methyl-/V-fert(butyldimethylsilyl)trifluoroacetam-ide (MTBSTFA, CAS 77377-52-7) is another common silylation reagent used for CWC-related chemicals. BSTFA silylates aminoalcohols such as triethanolamine (CAS 102-71-6) give higher recoveries than MTBSTFA, but the te/T-butyldimethylsilyl ethers formed when MTBSTFA is used are more stable than the trimethylsilyl ethers formed with BSTFA. 

Selective cleavage of t-butyldimethylsilyl ethers. This reagent cleaves r-butyldimethylsilyl ethers at 22-55° in 80-92% yield in the presence of r-butyl-diphenylsilyl ethers. 

Cleavage of tetrahydropyranyl ethers. Tetrahydropyranyl ethers are cleaved to the alcohol by dimethylaluminum chloride or methylaluminum dichloride in high yield at temperatures of -25 to 25°, conditions that do not affect t-butyldimethylsilyl ethers. MOM and MEM ethers are converted into ethyl ethers by a methyl transfer reaction. 

UButylmethoxyphenylsilyl ethers (r-BMPSi ethers). In DMF in the presence of NfCjHj), this bromosilane reacts with primary, secondary, and tertiary alcohols to form silyl ethers in good yield, and also with some enolizable ketones to form enol silyl acetals. Selective silylation of primary alcohols is possible by use of CHjClj as solvent. The hydrolytic stability of these ethers is intermediate between that of t-butyldimethylsilyl ethers and that of t-butyidiphenylsilyl ethers. The most useful feature of this new protecting group is the selective cleavage by fluoride ion in the presence of other silyl ethers. 

Cleavage of t-butyldimethylsilyl ethers. These ethers can be cleaved by KO2 and 18-crown-6 in DMSO. In the case of t-butyldimethylsilyl 4-phenylbutyl ether the reaction proceeds in quantitative yield in 10 minutes with 3 equiv. of KO2. This unexpected reaction was first noted in a total synthesis of, 11 -epi- PGF2. accompanying the inversion shown in equation (I). ... 

Tiitylation silylation. This amine is an efficient catalyst for tritylation of hydroxyl groups with trityl chloride and triethylamine. The method permits use of solvents other than pyridine, such as DMF or CHjClj. The same conditions can be used to prepare t-butyldimethylsilyl ethers. Yields are comparable to those obtained with imidazole (4, 57-58). A further advantage is that the selectivity for reaction with a primary hydroxyl group is enhanced in this new procedure. ... 

Detritylation Trityl ethers are cleaved by reaction with formic acid in ether in high yield in 7-45 minutes. Under these conditions isopropylidene and benzyl-idene acetals and t-butyldimethylsilyl ethers are not affected, but tetrahydropyranyl ethers are partially cleaved. 

DesUyiation. t-Butyldimethylsilyl ethers of primary allylic homoallylic, benzylic alcohols and phenols are cleaved by DMSO-HjO at 90° (10 examples, 79-87%) those other primary and secondary alcohols remain unaffected. 

Transsilylation. Several reagents have been recommended for preparation of t-butyldimethylsilyl ethers by transsilylation. These include allyl-r-butyldimethyl-silane and r-butyldimethylsilyl enol ethers of pentane-2,4-dione and methyl aceto-acetate,2 both prepared with r-butyldimethylchlorosilane and imidazole. Unlike the reaction of f-butyldimethylchlorosilane with alcohols, which requires a base catalyst, these new reagents convert alcohols to silyl ethers under slightly acidic conditions (TsOH) in good yield. The trimethylsilyl ethers of pentane-2,4-dione and methyl acetoacetate convert alcohols to trimethylsilyl ethers at room temperature even with no catalyst. The former reagent is also useful for silylation of nucleotides.3... 

The selective formation of t-butyldimethylsilyl ethers, which is often possible with bifunctional steroids, facilitates n.m.r. study with the use of lanthanide shift reagents by blocking co-ordination at the derivatized position. The assignment of configurations to substituents at both C-16 and C-17 by n.m.r. can be unreliable unless all four isomers are available for comparison. Data are presented for Jie.n in 16,17-disubstituted 3-methoxyoestra-l,3,5(10)-trienes, for chemical shifts of the 13/3-methyl protons, and for C-17 protons in 17-hydroxy-derivatives, including acylation shifts. 

Reductive cleavage of t-butyldimethylsilyl ethers,5 /-Butyldimethylsilyl ethers arc generally cleaved by fluoride ion, but they can also be reductively cleaved by DIBAH in CH2CI2 at 23° in 1-2 hours to yield the corresponding alcohols in 84-91% yield. 

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