3,3 -Dihydroxy ketones

A useful protocol for effecting the stereoselective synthesis of masked 3,3 -dihydroxy ketones and compounds derived therefrom has recently been developed (Schemes 17 and 18). The process features the metallation of enantiomerically pure 3-p-tolylsulfinylmethyl-4,5-dihydroisoxazoles such as (36), followed by reaction with an aldehyde to give the intermediate adducts (37). The diastereomeric ratio of the... 

The adducts obtained upon reaction of enantiomerically pure, metallated sulfinyl-4,5-dihydroisoxa-zoles with aldehydes can be converted into (3,(3 -dihydroxy ketones in what is the equivalent of a regio-specific double aldol condensation of a ketone with two different aldehydes (Scheme 18). For example, metallation of (41) with r-butylmagnesium bromide followed by quenching the intermediate anion with... 

A solution of 0.25 g sodium borohydride in 140 ml of ethanol is added to a stirred solution of 0.56 g of calcium chloride in 60 ml of ethanol at —25°. The vigorously stirred mixture is treated dropwise at —25° over 5 min with 4.87 g of 1 la-hydroxy-5/S-pregnane-3,20-dione in 100 ml of ethanol. After a further 3 hr at —20°, 10 ml of 40% aqueous acetic acid is added and the mixture is evaporated to dryness under vacuum. The residue is dissolved in 150 ml of ether and the ethereal solution is washed with 30 ml of 2 A hydrochloric acid and twice with 30 ml of water and dried over Na2S04. Removal of the solvent gives 4.6 g of crystals, which are recrystallized from 20 ml of ether to yield 2.9 g (60%) of the dihydroxy ketone, mp 182-184° [aj 110° (ethanol). 

Hydrogenolytic cleavage of isoxazolines has also proved useful in preparation of -dihydroxy ketones and -hydroxy carboxylic acids (47). The isoxazolines were prepared by a [3 -1- 2] cycloaddition. 

The aldol adducts 17 can be transformed by desulfurization with sodium amalgam to the substituted dihydroisoxazoles 20, or directly to /f/T-dihydroxy ketones by hydrogenolysis24. In general, chromatographic separation of the sulfmyldihydroisoxazoles 17 and/or their desulfurization products is possible and allows isolation of the enantio- and diastereomerically pure compounds24. 

In 1997, Laux and Krause showed that ruthenium(III) chloride can catalyze the oxidation of allenes 48 to a,a -dihydroxy ketones 49 [17]. They used sodium periodate as a stoichiometric oxidant and obtained the products in moderate to good yields, probably owing to overoxidation (Scheme 17.16). The dihydroxy compound was formed with high diastereomeric excess in one example when a chiral allene was oxidized. 

Bpgevig, A., Sund, H. and Cordova, A. Direct Catalytic Enantioselective a-Aminoxylation of Ketones A Stereoselective Synthesis of a-Hydroxy and a,a -Dihydroxy Ketones. Angew. Chem. Int. Ed. 2004, 43, 1109-1111. 

Asymmetric, osmium-catalysed dihydroxylation of 1,1-disubstituted and 1,3-disub stituted allenes has been employed to synthesize chiral a-hydroxy ketones, a,a - (g) Dihydroxy ketones were obtained from 1,3-disubstituted allenes with high enantio-... 

These dianions react with ketones to give p,(3 -dihydroxy ketones in 55-95% yield.4... 

The cydization of the dihydroxy ketone to the acetal is very favorable because it is intramolecular and occurred spontaneously under the reaction conditions of the hydrolysis. Brevicomin was produced in 91% yield from the epoxide. 

Bpgevig A, Sundeen H, Cordova A (2004) Direct catalytic enantioselective alpha-aminoxylation of ketones a stereoselective synthesis of alpha-hydroxy and alpha,alpha -dihydroxy ketones. Angew Chem Int Ed Engl 43 1109-1112... 

A highly useful twofold reaction of silyl dithioacetals with epoxides was described by Tietze and coworkers (Scheme 2.107) [249]. Treatment of 2.2equiv. of enan-tiopure epoxides 2-463 with lithiated silyldithiane 2-458b in the presence of a crown ether led to 2-467 after aqueous work-up. It can be assumed that by attack of the lithium compound 2-462 at the sterically less-hindered side of the epoxide 2-463, the alkoxide 2-464 is formed which in a subsequent Brook rearrangement produces the lithium dithioacetal 2-465. This reacts again with an epoxide to give 2-466 and furthermore 2-467. Treatment with NaF then leads to the diol 2-468 which can be converted into the dihydroxy ketones 2-469 and the corresponding 1,3,5-triols, respectively. 

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