Alcohols silylated homoallylic

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Silyl homoallylic alcohols are obtained with high y-regioselection and E-stereoselection on reaction of chiral alkoxy- and aminomethyl-substituted a -silylallyl carbanions with aldehydes factors which influence the diastereomeric excess have been identified. 

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. 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Carbonyl compound alkylations. Allylic alcohols and homoallylic silyl ethers are prepared from alkynes and dienes, respectively. 

Allylsilanes 190 were used as the precursors for the synthesis of y-silylallylborane 21 that on further reaction with aldehydes yields a n-a-silyl homoallylic alcohols. Tamao oxidation of the corresponding silyl group provides anh-diols 193 stereoselectively. Hence, this procedure is complimentary to alkoxyallylboration that typically provides syn diols (Scheme 25.29). 

Synthetic transformations of the products of the intramolecular bis-silylation have been examined. The five-membered ring products derived from homopropargylic alcohols were hydrogenated in a stereoselective manner (Scheme ll).90 Oxidation of the products under the Tamao oxidation conditions (H202/F /base)96 leads to the stereoselective synthesis of 1,2,4-triols. This method can be complementary to the one involving intramolecular bis-silylation of homoallylic alcohols (vide infra). 

Table 1 Intramolecular bis-silylation of disilanyl ethers of substituted homoallylic alcohols in the presence of a palladium/ f-OcNC catalyst... 

The tandem use of asymmetric allylboration to give enantiomerically pure ho-moallyHc alcohols followed by cross-metathesis of homoallylic silyl ethers with p-substituted styrenes has been reported [120] (Eq. 19). Exclusively trans cross-coupled products were formed in 50-75% yields. 

During the past 2 years several research groups have published research that either uses or expands upon Crowe s acyclic cross-metathesis chemistry. The first reported application of this chemistry was in the synthesis of frans-disubstitut-ed homoallylic alcohols [30]. Cross-metathesis of styrenes with homoallylic silyl ethers 15, prepared via asymmetric allylboration and subsequent alcohol protection, gave the desired trans cross-metathesis products in moderate to good yields (Eq. 15). 

Ab initio calculations also confirm that the use of an allyl magnesium alkoxide in place of the alcohol functionality will lead to high or complete stereoselectivity (138). When homoallylic alcohols are used, the Kanemasa protocol afforded the respective isoxazolines with poor stereoselectivity ( 55 45) in the case of terminal aUcenes, but with very high diastereoselectivity (up to 96 4) in the reaction of cis-1,2-disubstituted olefins (136). Extension of this concept to the reaction of a-silyl allyl alcohols also proved feasible and produced the syn (threo) adducts as nearly pure diastereomers (>94 6) (137). Thus, the normal stereoselectivity of the cycloaddition to the Morita-Baylis-Hillman adducts (anti > syn, see above) can be reversed by prior addition of a Grignard reagent (176,177). Both this reversal... 

The nature of the Lewis acid catalyst has been found to play a pivotal role in the chemo- and stereoselectivities of the Sakurai-Hosomi reaction. For example, the reaction of 33, which contains both allylsilane and allylstannane moieties, with benzaldehyde leads to the silyl-substituted homoallylic alcohol 34 in moderate yield when a mild Lewis acid such as Et3Al is used. On the other hand, when BF3 OEt2 or fluoride ion is employed,... 

Two recently developed coupling reactions of an alkene (R1CH2CH=CH2), an aldehyde (R2CHO), and a silyl triflate (R33SiOTf) yield an allylic (66) or homoallylic (67) alcohol (in protected form).188 Employing nickel-phosphine catalysts, either product can be selected by small changes in the phosphine component. A mechanism distinct from that of Lewis acid-catalysed carbonyl-ene reactions is proposed and discussed. 

In 1982, Sakurai [7] described a catalytic version of this reaction (Scheme 13.4). The addition of small quantities of fluoride anions to the allylsilane 1 generates the pentacoordinated silicon species 10, probably in equilibrium with the starting materials 1 and 11. This activated species can react with the carbonyl derivative 6 to yield the alkoxide 12 which is trapped by fluorotrimethylsilane. This last step not only furnishes the silylated compounds 13 but also regenerates the fluoride catalyst 11. Acidic work-up then leads to the desired homoallylic alcohol 7. 

A wide variety of silyl ethers can be employed, leading to functionalized homo-allylic alcohols or ethers. This three-component coupling reaction, which generates in a single operation a range of homoallylic ethers, does not require the initial and independent synthesis of the acetal (or ketal) derived from 6. 

Ketones were also reacted under these conditions, leading to tertiary ethers. Thus, by mixing equimolar quantities of a carbonyl (aldehyde or ketone), allyl-silane and a silylated alcohol, followed by the addition of a catalytic amount of TMSOTf, homoallylic ethers can be obtain in good yields via a three-component coupling reaction (Scheme 13.22). 

Ni alkoxide as a stoichiometric reaction. However, in this reaction the silylnickel alkoxide 76 is formed, and its reductive elimination affords silyl ethers 77 and 78. At the same time, Ni(0) is regenerated to make the reaction catalytic. The formal total synthesis of elaeokanine C (79) was carried out by this reaction [25], Homoallylic alcohol 81 is obtained by the intermolecular reaction of benzaldehyde with the diene 80 and hydrosilane in high regio- and stereoselective manner [26],... 

Silaboration of diene with the silylborane 209 is also catalysed by Pt complexes to give the 1,4-adduct 211 as an E/Z mixture which reacts with benzaldehyde to afford the homoallyl alcohol 212 having a silyl group [91], However, the silaborative... 

The C—Si bond formed by the hydrosilation of alkene is a stable bond. Although it is difficult to convert the C—Si bond to other functional groups, it can be converted to alcohols by oxidation with MCPBA or H2O2. This reaction enhances the usefulness of hydrosilylation of alkenes [219], Combination of intramolecular hydrosilylation of allylic or homoallylic alcohols and the oxidation offers regio- and stereoselective preparation of diols [220], Internal alkenes are difficult to hydrosilylate without isomerization to terminal alkenes. However, intramolecular hydrosilation of internal alkenes can be carried out without isomerization. Intramolecular hydrosilylation of the silyl ether 572 of the homoallylic alcohol 571 afforded 573 regio- and stereoselectively, and the Prelog-Djerassi lactone 574 was prepared by applying this method. 

Homoallylic alcohols with a silyl group attached to the terminal alkene carbon were cyclised to oxetanes in high yields by reaction with bis(.sy z-collidine)bromine(l) hexafluoroantimonate (e.g., Equation 31) <2001TL2481>. This reaction exclusively gave the four-membered cyclic ether, with the silyl group directing formation of the electrophilic intermediate for the subsequent 4-fvo-/rrg -cyclization. When the carbon /3 to the silyl group on the double bond was unsubstituted, the reaction was diastereospecific. 

The accelerated rate for alcoholysis with le, which was observed for the 10 % Pd/C catalytic system, was also seen with the Mn(CO)sBr catalyst. Reactions of le with primary, secondary or tertiary alcohols resulted in moderate yields of the corresponding silyl ketals after 2 h (Table 8 and 9). When mono-alkoxy silane from 3-hydroxy butyrate (lg) was treated with homoallyl alcohol in the presence of Mn(CO)sBr as the catalyst under the standard conditions, 76 % of the silyl ketal was obtained. These silyl ethers possess neighboring carbonyl groups that can participate in the reaction by forming a more reactive pentacoordinated silicon center upon addition of the silane to the metal center.. 

Indium-mediated allylation of trialkyl(difluoroacetyl)silane 70 in aqueous media gives homoallylic alcohol 71 exclusively (Scheme 60). Both water and THF are essential for the allylation reaction. It is worth noting that homoallylic alcohol 71 is formed exclusively under these reaction conditions. On the contrary, enol silyl ether 72 is a major product of the fluorinated acylsilanes reaction with other organometallic compounds than indium via a Brook rearrangement and defluorination. Indium-mediated allylsilylation of carbonyl compounds provides a facile route to 2-(hydroxyethyl)allylsilanes. The allene homologs are similarly prepared (Scheme 61).244,244a... 

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