Enolsilanes, Rubottom oxidation

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... 

Indirect evidence for silyloxyoxirane intermediates was also provided by Hassner, who described the isolation of 14lc in the Rubottom oxidation of 12. This product could potentially derive from the silyloxyoxirane 13 via an acid-mediated SN1 or Sn2 mechanism.10 The possible formation of silyloxyoxirane intermediates analogous to 4 in Rubottom oxidations of enolsilanes derived from ketones has also been discussed.6... 

Many variations of the Rubottom oxidation employ oxidants other than m-CPBA in order to execute the transformation under mild conditions or to allow for enantioselective synthesis. Use of dimethyl dioxirane (DMDO) for the oxidation of enolsilanes has become a popular alternative to traditional conditions for Rubottom oxidations. This mild oxidant has been used to facilitate the isolation of 2-silyloxyoxiranes, which are stable under the essentially neutral reaction conditions." For example, treatment of 26 with DMDO at -40 °C afforded 27 in 99% yield.1 Ib These compounds can subsequently be converted to 2-hydroxyketones, as described above, or can be used in other transformations.12 Chiral dioxiranes generated in situ from chiral ketones and oxone have also been employed in enantioselective Rubottom oxidations developed independently by Shil3a and Adam.13b As shown above, enolsilane 28 was transformed to a-hydroxyketone 29 in 80% yield and 90% ee.l3a... 

Rubottom oxidation reactions have been conducted on enolsilanes derived from a number of different carbonyl derivatives including carboxylic acids and esters.15 For example, the Rubottom oxidation of bis(trimethylsilyl)ketene acetal 30 provided a-hydroxy carboxylic acid 31 in 81% yield. Use of alkyl trimethylsilyl ketene acetal substrates generates a-hydroxy esters, as seen in the conversion of 32 to 33.16 The synthesis of 3-hydroxy-a-ketoesters (e.g., 36) has been accomplished via Rubottom oxidation of enolsilanes such as 35 that are prepared via Homer-Wadsworth-Emmons reactions of aldehydes and ketones with 2-silyloxy phosphonoacetate reagent 34.17 The a-hydroxylation of enolsilanes derived from P-dicarbonyl compounds has also been described, although in some cases direct oxidation of the P-dicarbonyl compound is feasible without enolsilane formation.18... 

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 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. 

The Rubottom oxidation1 is the peracid-mediated oxidation of trimethylsilyl enol ethers to afford a-silyloxy- or a-hydroxy aldehydes or ketones.2,3 Use of an aqueous workup generally affords the hydroxy compounds, whereas nonaqueous workups provide the silyloxy derivatives. For example, the enolsilane 1 derived from cycloheptanone was converted to 2 in 77% yield by treatment with /w-CPBA followed by workup with 10% aqueous sodium hydroxide. Omission of the aqueous workup afforded 3 in 85% isolated yield,1 ... 

The first examples of enolsilane oxidations were described independently by Brook,lb Hassner,lc and Rubottom in late 1974-early 1975. Brook reported that oxidation of enolsilanes derived from cyclic and acyclic ketones with w-CPBA affords a-silyloxy ketones in good yields subsequent hydrolysis of these products provided the corresponding alcohols. Rubottom noted that either a-silyloxy ketones or a-hydroxy ketones could be obtained depending on the nature of the workup (nonaqueous vs. aqueous). Hassner observed that enolsilanes derived from both aldehydes and ketones are suitable substrates for these transformations. Subsequent studies by Rubottom and others led to significant expansions of this methodology along with a more complete understanding of the mechanism of these reactions.2,3... 

The oxidation of dienyl enolsilanes to the corresponding a-hydroxy ketones has also been developed and explored by Rubottom.19 For example, diene 37 was cleanly converted to ketone 38 under standard conditions. As expected, high selectivity for oxidation of the more electron-rich double bond was observed. As illustrated by the conversion of 37 to 39, acylation of the crude alcohols was achieved in high yields after removal of w-chlorobenzoic acid and the hexane solvent employed for the oxidation. 

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