Rubottom epoxidation

The authors used (5)-carvotanacetone (dihydrocarvone) as starting material (Scheme 34). To prepare the linearly conjugated sUylenol ether, they used the Kharash protocol and attained y-alkylation by Mukaiyama aldol reaction with trimethylorthoformate (195). The ketoacetal 295 was a-hydroxylated according to Rubottom by silylenol ether formation followed by epoxidation and silyl migration. Acid treatment transformed 296 to the epimeric cyclic acetals 297 and 298. endo-Aceta 297 was equilibrated thereby increasing the amount of exo-acetal 298. The necessary unsaturated side chain for the prospected radical cyclization was introduced by 1,4-addition of a (trimethylsilyl)butynylcopper compound. 

Hegedus and co-workers isolated a cyclobutane-fused epoxide intermediate in the Rubottom oxidation of silyl enol ether 17 (Scheme 9) <1998JOC4691>. 

Related reactions Jacobsen-Katsuki epoxidation, Prilezhaev oxidation, Rubottom oxidation, Sharpless asymmetric epoxidation, Shi... 

Highly acid sensitive a-siloxy epoxides (108 R1 = R2 = Me) are available in good to excellent yields through the epoxidation of silyl enols ethers (107) with jV-sulfonyloxaziridine (63b) <87JOC954>. Hydrolysis of (108) gave the a-hydroxy carbonyl compound (109) in good-to-excellent yield (55-95%) and represents an alternative to peracids usually used to effect this transformation known as the Rubottom reaction. With chiral nonracemic TV-sulfonyloxaziridines the ees of (109) were low (7-11% ee) because of the poor facial discrimination between the re and si faces of the silyl enol ether (Scheme 20). 

Unique successful hydroxylations with ozone and mCPBA First Successful Method Epoxidation of Silyl Enol Ethers (Rubottom Oxidation) Method, mechanism, and isolation of intermediates Chemo- regio- and stereoselectivity synthesis of fused y-laclones Hydroxylation of Amino-ketones via Silyl Enol Ethers Synthesis of vinca alkaloids and model compounds... 

First Successful Method Epoxidation of Silyl Enol Ethers (Rubottom Oxidation)... 

In 1958, Rubottom and co-workers introduced an oxidative methodology, which first requires the conversion of a carbonyl compound to either an enol silane or silyl enol ether. As generated, the enol silane 3, for example, is then treated with m-chloroperbenzoic acid (m-CPBA) to form the a-hydroxy carbonyl compound 4 following epoxidation and desilylation.3... 

The mechanism initially proposed for the Rubottom oxidation involved epoxidation of the enolsilane to afford intermediate silyloxyoxirane 4. It was suggested that this intermediate undergoes acid-mediated cleavage to afford stabilized carbocation 5, which is transformed to the a-silyloxy ketone 6 via 1,4-silicon migration. Hydrolysis of 6 by aqueous acid in a subsequent step generates the a-hydroxy ketone 7.lb 15 Attempts to provide support for this mechanism via isolation of intermediate silyloxyoxiranes derived from simple ketones proved difficult due to the lability of these compounds. However, Brook demonstrated that the related heterocyclic silyloxyoxirane 8 was isolable and was transformed to ketone 9 upon treatment with /j-TsOH. 

Further support for the mechanism described above was obtained in subsequent studies by several groups. Direct evidence for the initial epoxidation event in the Rubottom oxidation of an acyclic enolsilane was first obtained by Weinreb, who described the isolation of silyloxyoxirane 10 and demonstrated its conversion to a-silyloxy ketone 11 upon treatment with PPTS.4 The isolation of a macrocyclic bis(silyloxyoxirane) has also been reported.5... 

The stereochemical outcome of the Rubottom oxidation reaction is generally believed to be controlled by the stereoselectivity of the epoxidation step, with the subsequent rearrangement to the a-hydroxy ketone occurring with retention of configuration at the a-stereocenter.2,8 This issue was addressed further in an elegant study recently disclosed by Danishefsky.9... 

A double hydroxylation of enolsilanes under modified Rubottom oxidation conditions has been developed by Nakamura and Kuwajima.20 As shown below, treatment of enolsilane 40 with w-CPBA in the presence of excess KHCO3 generates doubly oxidized product 41 in 72% yield. The mechanism of these transformations is believed to involve elimination/epoxide opening of the intermediate silyloxyoxirane 42 followed by a second oxidation of the resulting enolsilane 43. 

The Rubottom oxidation has found widespread application in organic synthesis. A few recent examples of the use of this methodology for the construction of complex molecules are described below. As noted above, the stereoselectivity in these reactions is usually controlled by steric effects, which dictate the face-selectivity of the epoxidation step. The chemoselectivity is generally controlled by electronic effects, as the electrophilic oxidants react more rapidly with the electron-rich enol ether than with other double bonds in the substrate. 

This reaction was first reported by Rubottom and Brook et al. concurrently in 1974. It is the transformation of a ketone into the corresponding a-hydroxyketone by means of the epoxidation or dihydroxylation of a silyl enolate of the ketone with wi-chloroperbenzoic acid (m-CPBA) or dimethyldioxirane (DMDO). Therefore, this reaction is generally known as the Rubottom reaction or Rubottom oxidation. Under certain conditions, the Rubottom oxidation can establish a hydroxyl group enantioselectively, such as in the introduction of cw-hydroxyl group with respect to the isopropyl group in 8Q ,llj0-dimethyl-13)3-hydroxy-12/3-isopropyl-5/3,15-isopropylidenedioxy-14-keto-(A , A " )-tricycle. The silyl group can be cleaved by means of tetra-A-butylammonium fluoride (TBAF). ... 

The straightforward reaction of carbonyls with an oxidant is a very well-known route towards the widely present a-hydro>y-carbonyl structural motive and several types of organometallic or organocatalytic asymmetric protocols have been developed. The reaction is generally accepted as a variant of Rubottom oxidation (oxidation with peracids), with a mechanism proceeding via an epoxide intermediate obtained from an enol. The first catal5Aic asymmetric reaction was developed in 1988 using a quaternised Cinchona alkaloid. (See Chapter 16). 

An olefinic bond in the acyl side chain presents a site for undesired reaction during two steps in the above procedure. First is the potential for epoxidation during the introduction of the oxygen by m-chloroperbenzoic acid of the Rubottom hydroxylation. Second is e likelihood of hydrogenation during the catalytic r uction of the N-O bond of 9. 

Silyl enol ethers are a class of electron-rich, nonaromatic compounds that easily form reactive radical cations on one electron oxidation. The silyl enol ether functional group is closely related to the carbonyl function and consequently, syntheses of silyl enol ethers generally make use of enolates. In addition, silyl enol ethers can be described as masked enols or enolates since their reactions often yield ketones. A number of oxidation reactions of silyl enol ethers making use of oxygen or oxygen-containing reagents such as peroxides, peracids (known as Rubottom oxidation), dioxirane, osmium tetraoxide, or triphenyl phosphite ozonide have been described in the literature. In all cases either a-hydroxy-ketones or the silyl enol ether epoxides are formed. 

---