Silyl-protected benzylic alcohol

Assuming that these reactions would proceed in the desired sense, the lingering question was how to induce this enyne macro-cyclization to occur atropselectively. The team s response was to append an extraneous silyl-protected benzylic alcohol to both cyclization precursors (12 and 15, Scheme 2) with the assumption that their presence could potentially govern which transition state would be adopted during the enyne-metathesis reaction. As shown in Scheme 4, if these benzylic groups existed as single enantiomers, they could then provide serious Aj steric interactions for... 

Triethylsilane can also facilitate the high yielding reductive formation of dialkyl ethers from carbonyls and silyl ethers. For example, the combination of 4-bromobenzaldehyde, trimethylsi-lyl protected benzyl alcohol, and EtsSiH in the presence of catalytic amounts of FeCls will result in the reduction and benzylation of the carbonyl group (eq 32). Similarly, Cu(OTf)2 has been shown to aid EtsSiH in the reductive etherification of variety of carbonyl compounds with w-octyl trimethylsilyl ether to give the alkyl ethers in moderate to good yields. Likewise, TMSOTf catalyzes the conversion of tetrahydrop)ranyl ethers to benzyl ethers with Ets SiH and benzaldehyde, and diphenylmethyl ethers with EtsSiH and diphenylmethyl formate. Symmetrical and unsymmetrical ethers are afforded in good yield from carbonyl compounds with silyl ethers (or alcohols) and EtsSiH catalyzed by bismuth trihalide salts. An intramolecular version of this procedure has been nicely applied to the construction of cA-2,6-di- and trisubstituted tetrahydropyrans. ... 

A similar behavior was observed in the synthesis of (5)-2-methylenecyclopropanemethanol (8). Cleavage of the j8-sulfonyl silyl group, together with removal of the tert-butyldimethyl-silyl protecting group from the alcohol, was accomplished in one step in 35% yield. With the alcohol protected as the benzyl ether and subsequently converted to a cyano group, however, elimination proceeded in 86% yield. 

Cyclohexylpropionic acid was deprotonated with 2.2 equivalent of lithium diisopropylamide and the resulting dianion was condensed with trifluoroacetaldehyde which was generated in situ from its ethyl hemiacetal. The P-hydroxy acid 1 was isolated as a racemic mixture of two diastereomers. Silylation with tert-butyldimethylsilyl triflate was followed by ester hydrolysis to give the acid 2. A Curtius rearrangement with diphenylphosphoryl azide in the presence of benzyl alcohol afforded the protected P-amino alcohol 3 which was used in the preparation of the trifluoromethyl alcohol I. Oxidation using the Dess-Martin periodinane reagent (9) yielded the trifluoromethyl ketone II as a mixture of diastereomers. The signal for the carbonyl carbon in the 13C-NMR spectrum of this ketone appeared at 94.5 ppm and this is consistent with the hydrated form of the trifluoromethyl ketone. 

Ultimately, it was determined that protected allyl alcohols, tetralkoxy silanes, and silyl ethers were the best substrates for these transformations. Alkyl or allyl silyl ethers (120) provided products such as 121 in >85% de and good 74-92% ee with Rh2(S-DOSP)4 as the catalyst (Scheme 27) [98], Extension of the reaction to alkoxysilanes, generated 122 in 88 to >94% de and 81-96% ee. Interestingly, this catalyst did not seem to be compatible with benzyl silyl ethers, and the products were formed with low selectivity (<40% ee). It was found that the use of either a chiral auxiliary or phthalimide Rh2(PTTL)4 resulted in improved results [31]. 

The diversity associated with silyl protecting groups as well as the chemical conditions available for their removal makes them attractive alternatives to benzyl protection of the hydroxy groups of either D- or L-tartaric acid derivatives. O-isopropylidene-L-threitol (37) is mono-protected with er -butyldimethylsilyl chloride to furnish 266, which is converted in three steps to the nitrile 267. Reduction with DIBAL and Wittig olefination followed by desilylation with fluoride and Swern oxidation of the resulting alcohol provides aldehyde 268, which reacts with methyl 10-(triphenylphosphorane)-9-oxo-decanoate (269) to afford enone 270. Reduction of 270 with subsequent preparative TLC and acetal hydrolysis furnishes (9R)-271 and (9 S)-272, both interesting unsaturated trihydroxy Cig fatty acid metabolites isolated from vegetables [91] (Scheme 62). 

A very effective and mild procedure for the silyl protection (using TBDMSCl and TBDPSCl) of a wide variety of OH-containing substrates (including primary, secondary, allyUc, propargylic, benzylic, hindered secondary, tertiary, add-sensitive and base-sensitive alcohols, and also hindered phenols) involves the use of lb as the catalyst, Eq. (23). The reactions are carried out in acetonitrile as a solvent from 24 to 40°C, and on rare occasions in DMF from 24 to SOX. 

The combination of TMSOTf and EtsN in dichloromethane (DCM) allows the direct conversion of p-methoxybenzyl ethers into silyl-protected alcohols, thus affording an expedient way to replace the benzyl ether-type protective group with the sUyl ether-type one (eq 35). ... 

The reaction of 5-acetoxy-5,6,7,8-tetrahydroisoquinoline 109 with Mel followed by reduction afforded the octahydroisoquinoline 110, which upon treatment with ethyl chloroformate followed by hydrolysis gave 111. The condensation of 111 with 2-bromoisovanillin afforded 112, which was reduced to give the benzyl alcohol intermediate 113. Heck reaction of 113 led to the formation of 0-ring affording 115. The yield of the above intramolecular cyclization was increased significantly via prior protection of the alcohol in 113 as silyl ether 114. Conversion of 115 to benzyl chloride 116 was achieved via the treatment with NCS and triphenylphosphine. Further, Heck reaction of 116 afforded the tertiary amine 117 via an intramolecular A -benzylation. The amine 117 was converted into the corresponding iV-methylammonium iodide 118, which was then subjected to Stevens rearrangement with PhLi to afford ( )-desoxycodeine 119 in 83 % yield. ... 

Protecting Group. Several new methods have been developed for using the reagent to protect primary and secondary alcohols as their TBDPS ethers. In the presence of ammonium nitrate or ammonium perchlorate, reaction between TBDPS-Cl and a primary alcohol, such as benzyl alcohol, in DMF provided excellent yields of the corresponding silyl ethers in just 15 min (eq 1). When silver nitrate was used as promoter, the reactions gave inferior yields under otherwise identical conditions. 

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