Silylations alcohols

Under carefully controlled conditions, TBAF and aqueous HF selectively deprotect phenolic and alcoholic silyl ethers respectively. An excess of either reagent will, of course, ultimately result in complete deprotection. 

Alcohol Silyl chloride Yield (%) of silyl ether... 

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],... 

Catalyhc systems based on the commonly used iridium precursor [ Ir(g-Cl)(cod) 2] and diferrocenyl dihalcogenides of L4 and L5 type were also studied in the asymmetric hydrosilylahon of acetophenone, giving a relahvely high yield of sec-phenetyl alcohol silyl ether (I) and a moderate ee of one stereoisomer [49]. 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

Alkynyl alcohols, silylative lactonization, 11, 493 Alkynyl aldehydes, in [5+2+l]-cycloadditions, 10, 632 Alkynyl alkali metal derivatives, characteristics, 2, 17 Alkynyl amides, in [5+2+l]-cycloadditions, 10, 632... 

Silyl ether Alcohols Silyl-type linkers [16, 17]... 

Hydrosilylation of acetophenone to give silyl ether (M R = Me) can also be achieved using copper(I) complexes with the chiral phosphine ligands (-)-DIOP (87) or (+)-NORPHOS (88). The enantioselectiv-ity is rather low, but a nonphosphine auxiliary, PYTHIA (89) with a Rh(COD)Ch catalyst using neat diphenylsilane reduces aryl ketones to (R)-l-phenylethyl alcohol silyl ethers in high yield and with high enantiomeric excess (Scheme 18). " ... 

Treatment of 462 with iodine and pyridine leads to a-iodination [208]. Successive reduction under Luche conditions, alcohol silylation, carbonylation of the iodoalkene, reduction of the obtained enal and alcohol silylation leads to 463. Ozonolysis of 463 gives the corresponding keto-aldehyde, which is then transformed into 464 via reductive amination with high diastereoselectivity syn anti> Deprotection delivers (-f)-465 (Scheme 13.107). 

Phenylalanine-derived oxazolidinone has heen used in O Scheme 52 as a chiral auxiliary for as)rmmetric cross-aldolization (Evans-aldol reactions [277,278,279,280,281,282,283,284, 285]). The 6-deoxy-L-glucose derivative 155 has heen prepared by Crimmins and Long [286] starting with the condensation of acetaldehyde with the chlorotitanium enolate of O-methyl glycolyloxazohdinethione 150. A 5 1 mixture is obtained from which pure 151 is isolated by a single crystallization. After alcohol silylation and subsequent reductive removal of the amide, alcohol 152 is obtained. Swem oxidation of 152 and subsequent Homer-Wadsworth-Emmons olefination provides ene-ester 153. Sharpless asymmetric dihydroxylation provides diol 154 which was then converted into 155 (O Scheme 60) (see also [287]). 

The first synthesis of vermiculine by Corey, outlined in Scheme 4.14, employed an isopropenyl group as a protected version of the acetone sidechain. Aldehyde 57, the Dibal reduction product of readily available dimethyl 2,2-dimethoxyglutarate, was condensed with dimethallyl cadmium and the resulting alcohol silylated to produce 58 (70%). Reduction of ester 58 to the aldehyde followed by two-carbon homologation afforded a 94% yield of a,P unsaturated ester 59. Hydrolysis of 59 to the to the acid and conversion to the 2-thiopyridyl ester (77%) set the stage for double lactonization. This transformation was accomplished by thermolysis of a diluted solution of the thioester, affording a 30% yield of the diasteromeric diolides 60a and 60b (1 1). The former was then converted by oxidation into the synthetic 56 and the latter into the meso isomer 61, both in 70% yield. 

In the total synthesis of talaromycin A, silylmethyl radical cyclization serves as a method for the stereoselective introduction of the 1,3-diol unit64. Starting from the corresponding alcohol, silylation, radical cyclization of the (bromomeihyl)dimethylsilyl eLher 4 and subsequent oxidative cleavage gives the desired product in 78% overall yield. 

The /-butyldimethylsilyl group introduced by TBDMIM has a number of advantages in protecting alcohols (6). The silylated alcohol hydrolyzes more slowly than an alcohol silylated with TMS by a factor of 104. The silyl ether is also stable to powerful oxidizing and reducing agents, but it can easily be removed by aqueous acetic acid or tetrabutylammonium fluoride in tetrahydrofuran. 

Alternatively, the diastereomeric mixture of aldol adducts undergoes lithium aluminum hydride reduction, primary alcohol silylation, and chromatographic separation to afford 291. Subsequent Mitsunobu inversion at C-3 to furnish the j -alcohol 292 followed by a depro-tective sequence and ring closure provides (+ )-castanospermine (293). This poly-hydroxylated indolizidine alkaloid isolated from Castanospermum australe and Alexa leipetala is a potent inhibitor of various a- and j8-glucosidases [98] (Scheme 68). 

By using cyanoformate esters as electrophiles, Johnson and coworkers were able to employ catalytic amounts of the cyanide initiator in reactions with acyl silanes. This process led to carbon-carbon bond formation via C-acylation. For example, acyl silane 61 and ethylcyanoformate combined under these conditions to provide the tertiary alcohol silyl ether 62 in nearly quantitative yield. Johnson s group has also developed an asymmetric version of this process, utilizing the Jacobsen (salen)aluminum system as a chiral carrier for the cyanide anion. ... 

We mentioned that by mixing vinyl epoxides and zerovalent palladium, the alcoholate formed was usually sufficiently basic to deprotonate the pronucleophile entity. In some cases, especially with ketones, low reactivity and yields were reported (Table To overcome the problem of the weak basicity of the alcoholate, silyl enol ethers, keto adds, or preformed lithium enolates have successfully been employed.f f" f f /3-Keto acids are masked enolates via the decarboxylation of the intermediary Tr-allylpalladium ]3-ketocarboxylate complexes. The main limitation of the use of keto adds as pronucleophiles seems to be their low reactivity toward the hindered cyclic vinyl epoxides. In these cases, the cationic n-allylpalladium complex undergoes ]S-elimination. Indeed, the reaction between benzoyl acetic acid and cyclobutadiene monoxide in the presence of Pd(PPh3>4 gives only the corresponding cyclopentanone and acetophenone as the... 

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