Butyldimethylsilyl TBS Ethers

The solvent dependence of the rate of solvolysis of TBS ethers has useful implications for selective deprotection of acetal-type protecting groups. Thus, dilute 

Cleavage of /erT-butyldimetfaylsUyl ethers by complexes of HF with amines 

Deprotection of TBS ethers is not limited to acidic reagents fluoride is also effective and the most popular reagent is tetrabutylammonium fluoride (TBAF). which is available commercially as the trihydrate (mp 62-63 ). Benzyltri-methylammonium fluoride has also been recommended in cases where TBAF has failed. The solid hydrate is highly hygroscopic and so it is usually dispensed as a 1.0 M solution in THE The presence of water diminishes the effectiveness of TBAF owing to the tenacious hydration of fluoride ion however, the water cannot be completely removed — nor should it — because anhydrous TBAF is 

EtaNHHF (4 equiv) MeCN, reflux. 12 h 89% (0.5 mmol scale) 

The electron withdrawing effect of the phenyl substituents enhances the electro-philicity of the silicon atom in TBDPS groups and thereby enhances their susceptibility towards nucleophiles including fluoride ions For this reason, it is 

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The C.115 amino group was protected as a trimethylsilylethyl carbamate (Me3SiCH2CH20C0NHR), a group that was stable to the synthesis conditions and cleaved by the conditions used to remove the t-butyldimethylsilyl (TBS) ethers. 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

As depicted in Fig. 6, syntheses of enantiomerically pure 116 and 117 have been carried out [236]. Lipase AK-catalysed asymmetric acetylation of meso-2,4-dimethyl-1,5-pentanediol A yielded (2R,4S)-5-acetoxy-2,4-dimethylpen-tanol B. Protection of the free hydroxy group as the terf-butyldimethylsilyl (TBS) ether, saponification of the acetate, and oxidation furnished the aldehyde C. Reaction of C with ethylmagnesium bromide gave a diastereomeric mixture of the corresponding secondary alcohols which could be resolved by asym-... 

Such is the lability of TMS ethers, that they can usually be removed selectively in the presence of other members of the silyi ether family. For example, in Car-reira s synthesis of Zaragozic Acid C,5 a tertiary TMS ether was removed in the presence of a primary fetf-butyldimethylsilyl (TBS) ether with chloroacetic acid in methanol [Scheme 4.2] moreover, tertiary TMS ethers can be removed in the presence of primary triisopropyl (TIPS) ethers using pyridinium /Moluene-sulfonate in methanol [Scheme 4.3).6... 

Finally, the / er butyldimethylsilyl (TBS) ether is cleaved with tetra- -butylammonium fluoride (TBAF) to provide alcohol 22. TBAF is suitable for this deprotection step because silicon has a high affinity for fluorine. Thus, fluoride attacks a d-orbital of the silicon atom in 46 providing the negatively charged pentacoordinate intermediate 47, which then breaks down with loss of the alkoxide 49 to give 48. 

The synthesis of segment C.77-C.115 from segments C.77-C.84 and C.85-C.115 involved the liberation of an aldehyde at C.85 from its protected form as a dithioac-etal, RCH(SEt)2, by mild oxidative deblocking (H/NaHCOs, acetone, water) and the use of the p-methoxyphenyldiphenylmethyl (MMTr) group to protect the hydroxyl group at C.77. The C.77 MMTr ether was subsequently converted to a primary alcohol (PPTS/MeOH-CH2Cl2, rt) without affecting the 19 t-butyldimethylsilyl (TBS) ethers or the cyclic acetonide at C.lOO-C.lOl. 

The synthesis of fragment B will be done according to Scheme 3. The known hexacarbonyldicobalt complexed alkyne (12) will be prepared according to the work done by Krafft and co workers. First, 3-butyn-l-ol (13) will be converted to its rerr-butyldimethylsilyl (TBS) ether by treating a mixture of (13) with TBS-Cl in triethylamine and DMAP. Treatment of the protected alkynol with 5ec-butyl lithium in THF followed by low temperature quench with ethyl chloroformate yields the alkynoate (14). The alkynoate is then complexed with dicobaltoctacarbonyl in petroleum ether to yield (12) in excellent yield. 

STRATEGY AND ANSWER First protect the —OH group by converting it to a rerf-butyldimethylsilyl (TBS) ether (Section 11.1 lE), then treat the product with ethyl magnesium bromide followed by dilute acid. Then remove the protecting group. 

Silyl ethers, including tert-butyldimethylsilyl (TBS) ethers (Section 11.HE) and phenyl-substituted ethers, are also used as protecting groups in carbohydrate synthesis. tert-Butyldiphenylsilyl (TBDPS) ethers show excellent regioselectivity for primary hydroxyl groups in sugars, such as at C6 in a hexopyranose. 

It is also of interest that the palladium-catalyzed cross-coupling between lithium alkynylzincates and chiral enantiopure l,2-(Z)-vinyHc teUurides that are generated in situ by the regioselective hydrotelluration of the corresponding propargyHc tert-butyldimethylsilyl (TBS) ethers, can be achieved [223]. The reaction is carried out in the presence of 10mol% of Pd(PPh3)4 and Cul, as a catalyst, in a mixture of THF and DMF at rt. Under these conditions, Z-enynes such as 308 are obtained stereoselectively (Scheme 4.70). 

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