Tert-butyldimethylsilyl ethers

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

Aliphatic and aromatic carboxamides, with the exception of p-nitrobenzamide, are dehydrated in this way in high yield. Acid-labile protective groups such as tetra-hydropyranyl and tert-butyldimethylsilyl ether and base-sensitive compounds are not attacked. A,A -Sulfinyldi-1,2,4-triazole, easily prepared from thionylchloride and triazole [THF, (C2H5)3N, 0 °C, 1 h] in 85-95% yield, was used without further purification. 

Trost et al 1 have observed product distribution to be dependent in part on the steric and electronic properties of the substrate. For example, linear enyne 48 (Equation (30)) cyclized exclusively to the Alder-ene product 49, whereas branching at the allylic position led to the formation of 1,3-diene 50 (Equation (31)) under similar conditions. Allylic ethers also give 1,3-dienes this effect was determined not to be the result of chelation, as methyl ethers and tert-butyldimethylsilyl ethers both gave dialkylidene cyclopentanes despite the large difference in coordinating ability. 

The steric bulk which accounts for the relative stability of tert-butyldimethylsilyl ethers also hinders their formation and so the reaction between tot-butyldimethylsilyl chloride and hydroxy groups in the presence of pyridine is very slow. In the presence of catalytic amounts of imidazole, however, the reaction proceeds rapidly and in high yield as shown in Equation Si2.3. 

MeO /MeOH cleavage of trimethylsilyl ethers occurs much more rapidly (by a factor of approximately 104) than the corresponding cleavage of tert-butyldimethylsilyl ethers. Both types of ether, however, are very rapidly cleaved by F. ... 

While the cyclization of the tert-butyldimethylsilyl ether 73 furnished the spirocyclohexadienone 74 directly as reaction product, the iminium hydroiodide 75 was isolated as intermediate from the reaction of azide 76 (Scheme 28) [136]. Subsequent aqueous hydrolysis of 75 under acidic conditions led to the spirocyclohexadienone 77. 

N,Ai-Dialkylaminoethyl tert-butyldimethylsilyl ether 2.B.12 2-iV,iV-Dialkylaminoethyl trimethylsilyl sulfide... 

An asymmetric synthesis of aminocyclopentitols 134-137 has been used in the synthesis of trehazolin via free-radical cycloisomerization of enantiomerically pure, alkyne-tethered oxime ethers derived from D-mannose (Scheme 17).84 Treatment of 2,3 5,6-di-(9-isopropylidene-D-mannofuranose (128)85 with ethynylmagnesium bromide gave compound 129, which underwent sequential one-pot acid hydrolysis plus diol cleavage to give 130, oximation of which afforded the radical precursor 131, in 41% overall yield from 129. The free hydroxyl group of 131 was protected as acetate 132 and tert-butyldimethylsilyl ether 133, which were isolated as inseparable... 

Lewis acids can also be exploited for the cleavage of isopropylidene derivatives. One of the mildest examples comes from a synthesis of Lankacidin in which cleavage of an isopropylidene acetal without harm to a p-methoxybenzyl ether was effected with copper(Il) chloride dihydrate in methanol at reflux [Scheme 3.11].13 Alternatively, zinc(II) nitrate hexahydrate in acetonitrile at 50 DC can be used in which case even a primary tert-butyldimethylsilyl ether survives [Scheme 3.12].14 During a synthesis of Quinocarin, Katoh and co-workerscleaved an isopropylidene group using iron(IIT) chloride adsorbed onto silica gel [Scheme 3.13]. 

Potassium carbonate in methanol or HOAc-H20-THF (3 1 1) at room temperature is sufficient to cleave even terr-butyldimethylsilyl esters. The esters cleave faster than the corresponding ethers [Scheme 6.105].235 Their high base lability allows removal of rerr-butyldimethylsilyl esters in the presence of tert-butyldimethylsilyl ethers [Scheme 6,106].236 The dwerf-butylmethylsilyl group is sufficiently stable to allow selective removal of a tetrahydropyranyl group using pyridinium p-toluenesulfonate in warm ethanol.237... 

Hydroxy-3a-[(2-nitrophenyl) selenoj-4-androstene 17-tert-Butyldimethylsilyl Ether ... 

A small effect by the oxygen substitution on the distribution of the Diels-Alder adducts is observed. The stereochemical preference observed with the free hydroxy compound is reversed when the hydroxy group is protected either as the acetate or as the tert-butyldimethylsilyl ether. The roughly 60 40 distribution of adducts at 80 °C indicates that any differences in the two transition states must amount to less than 1 kcal/mole. The stereochemical preferences observed are the result of a kinetically controlled cycloaddition, rather than equilibration after an initial, fast cycloaddition process. 

Many functional groups are stable under conditions for the alkylation of pseudoephedrine glycinamide enolates, including aryl benzenesulfonate esters (eq 18), rert-butyl carbamate and rerf-butyl carbonate groups (eq 19), tert-butyldimethylsilyl ethers, benzyl ethers, ferf-butyl ethers, methoxymethyl ethers, and alkyl chlorides. The stereochemistry of the alkylation reactions of pseudoephedrine glycinamide and pseudoephedrine sarcosinamide is the same as that observed in alkylations of simple A(-acyl derivatives of pseudoephedrine. 

A common OH protecting group is a silyl ether. A silyl ether has a new O-Si bond in place of the O-H bond of the alcohol. The most widely used silyl ether protecting group is the tert-butyldimethylsilyl ether. 

The use of a tert-butyldimethylsilyl ether as a protecting group makes possible the synthesis of 4-methyl-1,4-pentanediol by a three-step sequence. 

Step [1] Protect the OH group as a tert-butyldimethylsilyl ether by reaction with tert-butyldimethylsilyl chloride and imidazole. 

The exceptional bulkiness of 2,6-di-tert-butyl-4-broniophenoxy ligands in MABR is essential here for the smooth rearrangement of epoxy silyl ethers, and the less bulky methylaluminum bis(4-bromo-2,6-diisopropylphenoxide) (MAIP) was found to be totally ineffective in the rearrangement of the tert-butyldimethylsilyl ether of epoxy-geraniol (139). BF3-OEt2 as an ordinary Lewis acid gave fluorohydrin 140 as sole isol-able product (Sch. 114). 

This strategy was followed in the example shown in Scheme 5.5, Scheme 5.6 and Scheme 5.7 using the tert-butyldimethylsilyl ether as the temporary protecting group. Silyl ethers, allyl, p-methoxyphenyl and 2-(trimethylsilyl)ethyl groups are all commonly used for temporary protection of the anomeric position. 

A method to prepare 1,2-amino alcohols through the dihydroxylation of an enol ether has been reported by Merck (Scheme 3.25) [330]. The ee was reported to diminish if shorter chain alcohols were used although the TBDMS enol ether was used successfully in a structurally related system [331]. Indeed, early work by Sharpless with acyclic methyl and tert-butyldimethylsilyl ethers showed high en-antioselectivities in AD reactions (cf. Table 3.2) [332]. 

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