Highly Efficient Hydroxylation of Carbonyl Compounds with Dimethyldioxirane

Abstract

The enolates and/or enols of ketones, esters, P-diketones, P0x0 esters, and p-0x0 lactones were transformed by dimethyldioxirane (isolated in acetone solution or generated in situ)into their a-hydroxy compounds in good to excellent yields. The direct hydroxylation of the enols was significantly enhanced by the use of fluoride ion. For the enolate of camphor the exolendo diastereoselectivity depended significantly on the metal ligand; the highest exo/endo ratio (93:7) was observed for the enol trimethylsilyl ether of camphor.Since our review') on the synthetic utility of dimethyldioxirane in oxidation chemistry, we have demonstrated*) that it is unquestionably the most convenient and versatile epoxidant to date. Especially advantageous is the isolated dimethyldioxirane (in a~etone)~), which allows preparing hydrolytically and thermally labile epoxides, most of which were prior to our efforts not accessible. The related oxaziridines4), which are considerably less reactive than dioxiranes in transferring an oxygen atom, have recently been extensively used in the a-hydroxylation of electron-rich enolates. Similary, dioxiranes should serve this purpose and, indeed, it was recently reported5) that isolated dimethyldioxirane is a useful oxidant to convert enolates into a-hydroxy carbonyl products. The latter preliminary communication urges us to disclose our own results in this area. Herein we show, that also enols derived from 1,3-dicarbonyl compounds can directly be a-hydroxylated by dimethyldioxirane, provided elevated temperatures, longer reaction times, and a larger excess of oxidant are employed. Results and DiscussionThe carbonyl compounds 1 a -i were transformed into their a-hydroxy derivatives 2 a -i by dimethyldioxirane, the latter either isolated (as acetone solution) or generated in situ. The results are summarized in Table 1, in which the three different Methods A, B, and C, reaction conditions and yields are stated. In Method A the carbonyl compounds 1 a -e were transformed by sodium disilazane into their enolates (Scheme 1) and subsequently the enolate solution was added rapidly to the dioxirane (in acetone). After aqueous workup, the a-hydroxy derivatives 2a -e were isolated in good yields. This inverse addition proved to be the best method and resulted in the highest yields.In comparison to the corresponding lithium enolates, generated from 1 by lithium diisopropylamide, the sodium enolates employed here offer several advantages. For the sodium enolates, prepared by using sodium disilazane as base (Method A), the yields of the acyloins were usually (except for 2d) up to 30% higher. This trend was also observed in the hydroxylation of enolates by ~xaziridines~~."). Presumably, the more dissociated sodium enolates react more eficiently with dioxirane than the more aggregated lithium enolates, so that for the latter deprotonation of the acetone (the solvent for the dioxirane) competes more effectively to regenerate 1.

Preparation of Acyloins by Cerium‐Catalyzed, Direct Hydroxylation of β‐Dicarbonyl Compounds with Molecular Oxygen

“…α‐Acetyl‐α‐hydroxy‐γ‐butyrolactone (5g): According to the General Procedure, 4g (208 mg, 1.62 mmol) and CeCl 3 ·7 H 2 O (30 mg, 0.081 mmol) in i PrOH (0.5 mL) were converted to yield 5g after Workup B (PE/EA, 1:1, R f = 0.26) as a yellow oil (183 mg, 1.27 mmol, 78%). All data are in accordance with the literature 12…”

“…Since acetone is the only by‐product formed in these DMD oxidations,11 this method may be viewed as environmentally sound “green chemistry”. The yields can be improved by the application of either KF (supposedly stabilizing the enol tautomer by H‐bonding)12 or catalytic amounts of [Ni(acac) 2 ] 13. However, with regard to economical and ecological considerations molecular oxygen represents the optimal oxidizing reagent, an issue that has received continuous attention 14.…”

Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A

“…To achieve facially selective α-hydroxylation, bislactone 15 was treated with LiHMDS in the presence of LiCl 28 at −78 °C in THF. The resulting enolate complex was subsequently oxidized with MoOPH 29 to afford a secondary alcohol, which was then treated with BnBr/Ag 2 O 30 to give bislactone 16 in 88% overall yield as a single diastereoisomer.…”

Synthesis of Naturally Occurring Diosphenols and Hydroxydiosphenols

“…6-Hydroxy-c-diosphenol (6). Diosphenol (3) (1.0 g, 5.95 mmol) in dry THF (5 cm 3 ) was added dropwise during 5 min to a stirred suspension of oil-free sodium hydride (0.16 g, 6.66 mmol) in THF (5 cm 3 ) at 0 C. Stirring was continued for an additional 90 min at 0 C and 15 min at room temp., the resulting grey enolate suspension was cooled to À78 C and rapidly added to 0.043 M dimethyl dioxirane in acetone 8,9 (166.5 cm 3 , 7.14 mmol) at À78 C. The reaction mixture was worked up and extracted as in 3 to afford an oily residue which was crystallized from hexane to give white, crystalline 6-hydroxy-c-diosphenol (6) (0.71 g, 65%), m.p.…”