Alcohols silyl-protected

The ability to convert a protective group to another functional group directly without first performing a deprotection is a potentially valuable transformation. Silyl-protected alcohols have been converted directly to aldehydes, ketones, bro-mides, acetates, and ethers without first liberating the alcohol in a prior deprotection step. 

The hydrosilylation of carbonyl compounds by EtjSiH catalysed by the copper NHC complexes 65 and 66-67 constitutes a convenient method for the direct synthesis of silyl-protected alcohols (silyl ethers). The catalysts can be generated in situ from the corresponding imidazolium salts, base and CuCl or [Cu(MeCN) ]X", respectively. The catalytic reactions usually occur at room tanperature in THE with very good conversions and exhibit good functional group tolerance. Complex 66, which is more active than 65, allows the reactions to be run under lower silane loadings and is preferred for the hydrosilylation of hindered ketones. The wide scope of application of the copper catalyst [dialkyl-, arylalkyl-ketones, aldehydes (even enoUsable) and esters] is evident from some examples compiled in Table 2.3 [51-53],... 

A silyl-protected alcohol can be converted into the corresponding sulfonate by treating with p-toluenesulfonylimidazole and tetrabutylammonium fluoride 165... 

Similarly, enolsilanes 44 and 45 are afforded when silyl-protected alcohols and alkynes are reacted with ruthenium catalyst 41 (Equation (27)).40 The linear to branched ratio typically ranged from 2-4 1, except when the alkyne terminus was substituted with a TMS group. These internal alkynes afforded only the branched products. 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

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. 

At the exotic end of the Lewis acid scale is tetrafluorosilane (mp -90 5C, bp -86 UC) first proposed by Corey and Yi as a mild and selective reagent for the cleavage of silyl-protected alcohols with the reactivity order being EtiSi > f-Bu-Me2Si f-BuPhiSi/ 1 The substrate in dichloromethane or acetonitrile, is stirred at room temperature under an atmosphere of excess tetrafluorosilane provided by a gas-filled balloon. The reaction is slow in dichloromethane but quite fast (ca. 15 min) in acetonitrile. In the final step of Yamamoto s synthesis of the Hemibrevetoxin B [Scheme 4.40]61 the secondary TIPS and TBS ethers were removed from 40.1 with tetrafluorosilane. Identical conditions were used by Nicolaou et al to remove two TBS ethers in the final step of their synthesis of Hemibrevetoxin B.62 In the example shown in Scheme 4,41, deprotection with fluoride (basic) or cerium(lV) ammonium nitrate (CAN) in methanol (neutral) isomerised the angelate to the more thermodynamically stable tiglate.63 However, with tetrafluorosilane, no isomerisation occurred during the deprotection step. 

This fluorinating reagent is compatible with a wide range of functionalities (Table 3, entries 2-4) only silyl-protected alcohols arc removed by the reagent under the reaction conditions. Reactions take place under mild conditions (McCN, 80 C. 15 30 min). In addition, F-Tcda BK4 has the advantage of being commercially available, inexpensive and safe. 

The soluble PEG-DCT reagent was utilized to scavenge alcohols in the synthesis of esters and silyl-protected alcohols as well as acetals, and thiols in the synthesis... 

Waymouth has polymerized silyl protected alcohols and amines, and non conjugated diene monomers, with cationic Group IV metallocene single site-catalysts. He has found that chiral [(EBTHI)ZrMc] X catalysts, where EBTHI = ethylene-1,2 bis(Ti -4,5,6,7-tetrahydro-l-indenyl), are more easily poisoned by silyl ethers than are [CP2 ZrMe] ] catalysts. Also [(EBTHI)ZrMe] X catalysts are inactive for the polymerization of 4-TMSO-l,6 heptadiene but readily polymerize with the more sterically hindered TBDMS protect monomer. 

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 third and fourth examples involve intramolecular oxidation of olefins with a protected alcohol and with a carboxylic acid. Cleavage of a silyl protected alcohol, followed by oxidative C-0 bond formation at the p-position of an acrylate group was conducted at the late stage of the synthesis of the alkaloid alstophylline. Intramolecular 1,4-oxidations of dienes have been used in the synthesis of a number of natural products. For example, the intramolecular oxidation shown in Scheme 16.30 led to the precursor to Paeonilactone... 

---