Allylic alcohol, silyl ethers formation

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

Dianion formation from 2-methyl-2-propen-l-ol seems to be highly dependent on reaction conditions. Silylation of the dianion generated using a previously reported method was unsuccessful in our hands. The procedure described here for the metalation of the allylic alcohol is a modification of the one reported for formation of the dianion of 3-methyl-3-buten-l-ol The critical variant appears to be the polarity of the reaction medium. In solvents such as ether and hexane, substantial amounts (15-50%) of the vinyl-silane 3 are observed. Very poor yields of the desired product were obtained in dirnethoxyethane and hexamethylphosphoric triamide, presumably because of the decomposition of these solvents under these conditions. Empirically, the optimal solvent seems to be a mixture of ether and tetrahydrofuran in a ratio (v/v) varying from 1.4 to 2.2 in this case 3 becomes a very minor component. 

The formation of ethers such as 1806 by EtsSiH 84b can also be catalyzed by trityl perchlorate to convert, e.g., benzaldehyde in 84% yield into dibenzyl ether 1817 [48]. The combination of methyl phenethyl ketone 1813 with O-silylated 3-phenyl-n-pro-panol 1818, in the presence of trityl perchlorate, leads to the mixed ether 1819 in 68% yield [48] (Scheme 12.15). Instead of trityl perchlorate, the combination of trityl chloride with MesSiH 84a or EtsSiH 84b and sodium tetrakis[3,5-bis-(trifluoro-methyl)phenyl]borane as catalyst reduces carbonyl groups to ethers or olefins [49]. Employing TMSOTf 20 as catalyst gives very high yields of ethers. Thus benzaldehyde reacts with O-silylated allyl alcohol or O-silylated cyclohexanol to give the... 

The transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Unfortunately, attempts to perform this substitution reaction on cyclohexenol and geraniol led to the exclusive formation of the corresponding silyl ethers. It thus would seem that one requirement for effective carbon-carbon bond formation is that allylic alcohols be secondary and have possess y,y-disubstitution. Pearson, however, discovered a method with less restriction on the natiue of the substrate he used allylic acetates with y-mono-substitution or primary alcohols [96]. Not only ketene silyl acetals but also a diverse set of nucleophiles including aUyl silane, indoles, MOM vinyl ether, trimethylsilyl azide, trimethylsilyl cyanide, and propargyl silane participate in the substitution of y-aryl allylic alcohol 90 to give allylated 91 (Sch. 45). Further experimental evidence suggests that these reactions proceed via ionization to allylic carboca-tions—alcohols 90 and 92 both afforded the identical product 93. 

In addition to the formation of silyl enol ethers, isomerization of epoxides to allylic alcohols is another highly typical transformation performed by combination of a silicon Lewis acid with a tertiary amine. Reaction with la was examined, and its scope and limitation reported, by Noyori [61]. Epoxide 44 can be successfully converted into the corresponding allyl silyl ether 45 (Sch. 34). 

The direct transformation of silyl ethers into esters can also be performed by reaction with an acid chloride in CH2CI2 (0 °C to room temperature) in the presence of FeCls (1.5 equiv.) [18]. The formation of allyl ethers from allylic alcohols and methanol is catalyzed by RUCI3 [19]. The reaction is likely to occur via a jr-allyl Ru intermediate. Allylic rearrangements and racemization of optically active allylic alcohols take place. 

The remaining segment, C-3 to C-8, was constructed by a similar route. Optically active allylic alcohol 229, produced from lithio ethylacetate and methacrolein followed by a second Sharpless kinetic resolution, was hydrolized to the corresponding hydroxy acid. Neutralization followed by iodolactonization then gave 230 in 85% yield. This highly stereoselective cyclization produced a cis-trans ratio of 20 1 via a one-pot procedure. Deprotonation and methylation afforded the expected anti a-methyl compound, contaminated with about 10% of the syn compound but none of the methyl ether. Formation of the silyl ether then produced 231 in 66% yield. Dibal reduction to the aldehyde concomitant... 

Jig (19) Octalin kebil (163) is converted to kete dithioacetal (164) by die cleavage of ketal function and cmdensation with caibon disulfide and methyl iodide. Subjection of (164) t the action of dimethylsulfonium methylide and acid hydrolysis leads to the formation of unsaturated lactone (165).Its fiiian silyl ether derivative is caused to undergo Diels-Alder reaction with methyl acrylate to obtain salicyclic ester (166) which is converted by standard organic reactions to abietane ether (167). It is converted to allylic alcohol (168) by epoxidation and elimination. Alcohol (169) obtained fiom (168) yields orthoamiite which undergoes transformation to amide (170). Its conversion to the previously reported intermediate has been achieved by epoxidation, elimination and hydrolysis. 

The Rubottom oxidation of enolsilane 49 was achieved in the presence of neighboring diene and allylic ether functionality to provide 51, an intermediate in Crimmins s synthesis of (+)-milbemycin D.23 The primary silyl ether product 50 was sufficiently labile that deprotection occurred upon slow chromatography on silica gel to yield 51. Similarly, Danishefsky noted that electron-poor diene functionality was well tolerated in the stereoselective Rubottom oxidation of ketone 52.24 Enolsilane formation followed by DMDO expoxidation, rearrangement, and acylation afforded keto-alcohol 53 in 82-90% yield. This compound was subsequently converted to the natural product guanacastepene A. 

Admixture of alkynylstannanes, aldehydes, trimethylsilyl chloride, and InClj in acetonitrile at room temperature results in the formation of propargyl silyl ethers. In the synthesis of homoallylic alcohols, simple allylic halides can be used to form the tin halides in situ in water. ... 

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