Silyl epoxy alcohols

Vinylsilanes — silyl epoxy alcohols. Photooxygenation of vinylsilancs in the presence of Ti(0-(-Pr)4 affords silyl epoxy alcohols with high regio- and diastcreosclcctivity. The conversion involves as the first step an enc reaction with O2 to provide a /3-silyl allylic alcohol, which then undergoes epoxidation. 

The 6-endo activated epoxy alcohol cyclization process was also expected to play a central role in the annulation of pyran ring G of the natural product (see Scheme 22). Silylation of the free secondary hydroxyl group in compound 131 furnishes, after hydrobora-tion/oxidation of the double bond, compound 132. Swern oxidation of alcohol 132 produces an aldehyde which reacts efficiently with (ethoxycarbonylethylidene)triphenylphosphorane in the presence of a catalytic amount of benzoic acid in benzene at 50 °C, furnishing... 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

P-Hydroxy ketones can be prepared by treating the silyl ethers (53) of a,p-epoxy alcohols with TiCU- ... 

Epoxidation of / - or y-trimethylsilyloxy allylic alcohols. The stereoselectivity of cpoxidation of these allylic alcohols (followed by desilylation) can be controlled by substitution with a trimethylsilyl group. A /i-silyl substituted allylic alcohol is converted mainly into an erythro-epoxy alcohol, whereas a y-silyl substituent favors formation of a threo-epoxy alcohol. The stereoselectivity is usually the opposite to that obtained with m-chloroperbenzoic acid.1 Example ... 

Reaction with silyl ketene acetals epoxy alcohols. C6H5SC1 reacts with silyl ketene acetals to give a-sulfenyl-p-hydroxy esters (2) with anti-selectivity. The... 

The epoxy alcohol (97), a key intermediate in the synthesis of maytansine, has been prepared through Ti-catalyzed epoxidation of (95 equation 56). The alcohol (95) exists predominantly in conformation (162), with the allylic hydrogen at C-4 and the ir-bond very nearly eclipsed. The oxygens of the alcohol and silyl ether which are located below the plane of the ir-bond complex with Ti this complex blocks the approach of the epoxidizing reagent from the a-face and hence the p-epoxide is formed. It is of interest to note that the ir-facial selectivity resulting from this route is the opposite of the ir-facial selectivity observed in MCPBA epoxidation (see equation 33). 

Very interesting results were obtained during studies on the epoxidation of /f-hydroxy enones 8. Attempts at selective epoxidation under typical basic conditions failed and 2 3 mixtures of syn- and anf/-epoxides 9 were obtained. Surprisingly, epoxidation using Sharpless conditions, titanium tetraisopropoxide/tm-butyl hydroperoxide or vanadyl acetylacetonate/rm-butyl hydroperoxide, which are normally unreactive towards simple enones, proceeded smoothly, yielding exclusively syn-epoxy alcohols syn-9. No epoxidation took place for the corresponding nitrile or when the hydroxy function was blocked as a silyl ether32. 

Photooxygenation of vinylsilanes affords, after reduction, /3-silyl allylic alcohols regioselective-ly in good yields i4a c. Moreover, because of the steric demand of the silyl group, the titanium-catalyzed oxyfunctionalization described leads in high yield to (R, S )-epoxy alcohols80. 

In fact, allyl alcohol 13 was not used at the start of this synthesis because low ees result if there is no substituent on the alkene trans to the alcohol (R2 in the mnemonic should be something other than H). It is much better here to add a removable group and so the silyl alkene 14 was used instead of 13. The silyl group allowed the isolation of the epoxy alcohol 15 in a much higher yield than was possible using allyl alcohol itself and the ee of 15 was >95%. The alcohol was converted to a mesylate 16. 

P-Siloxyaldehydes. Chiral epoxy alcohols are readily available (e.g., by Sharpless epoxidation of allylic alcohols). Their transformation via a stereoselective rearrangement-silylation induced by the silyl triflate and i-Pr2NEt opens a new way to protected aldols. 

The synthetic utility of (i )-enoate 392 is illustrated in the stereoselective synthesis of the bengamide E derivative 399 (Scheme 88). Silyl protection of 392, reduction with DIBAL, and Sharpless epoxidation of the resulting allylic alcohol furnishes epoxy alcohol 396 as a 95 5 anti syn mixture. Conversion of the primary hydroxyl group of 396 to an iodide under neutral conditions followed by a metallation-elimination and subsequent in situ methylation provides the ether 397. Ozonolysis, desilylation with aqueous acetic acid, and a Dess-Martin oxidation supplies the a,jS-dialkoxy aldehyde 398. This, utilizing stannane Se addition, is then converted to 399 [135]. 

Schaumann and coworkers have also examined the addition of l,3-bis(silyl)allyl anions to epoxides followed by epoxidation. The first addition of the bis(silyl) anion to the epoxide gave a 3 1 mixture of diastereomers differing at the stereocenter a to the silyl moiety, while the subsequent epoxidation gave the product as a single diastereomer albeit in low yield (31%). Treatment of the resulting epoxy alcohol with a Lewis acid then yielded 0-Me 3-lactol regioselectively in a moderate 48% yield (eq 10). ... 

From the chiral epoxide 56, the TMM cycloaddition precursor 55 for construction of the tetraquinane stmcture was prepared in a straightforward manner. Oxidation of epoxy alcohol 56 by the Swem protocol followed by treatment with Bestmann-Ohira reagent (E) produced alkyne 70. Iron-catalyzed Sisr2 -type reaction of 70 afforded an allene moiety as a diastereo-meric mixture in a 1 1 ratio and this mixture was used in the next step without the separation of isomers. Allenyl alcohol 71 was protected as a TBDPS ether to give 0-silylated allene 72. Deprotection of the acetal of 72 was delicate as the allenyl moiety was not stable under acidic condition. Fortunately, treatment of 72 with p-toluenesulfonic acid monohydrate in presence of formaldehyde afforded aldehyde 73, and subsequent treatment with p-toluene sulfonyUiyrazide furnished the precursor 55 for the tandem cycloaddition reaction (Scheme 21). 

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