Ketones, hydroxy dihydroxylation

The oxidation of enol ethers and their derivatives is a useful method for the synthesis of a-hydroxy-ketones or their derivatives, which are versatile building blocks for organic synthesis. Since enol ethers and esters are types of olefin, some asymmetric epoxidation and dihydroxylation reactions have been applied to their oxidation. 

Important extensions of proline catalysis in direct aldol reactions were also reported. Pioneering work by List and co-workers demonstrated that hydroxy-acetone (24) effectively serves as a donor substrate to afford anfi-l,2-diol 25 with excellent enantioselectivity (Scheme 11) [24]. The method represents the first catalytic asymmetric synthesis of anf/-l,2-diols and complements the asymmetric dihydroxylation developed by Sharpless and other researchers (described in Chap. 20). Barbas utilized proline to catalyze asymmetric self-aldoli-zation of acetaldehyde [25]. Jorgensen reported the cross aldol reaction of aldehydes and activated ketones like diethyl ketomalonate, in which the aldehyde... 

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-... 

Since Hassner s initial report in 1975,7 oxidation of an enol silyl ether with peracid has been a reliable method for the preparation of a-siloxy and ot-hydroxy ketones. However, the submitters have found that, if the enol silyl ether possesses certain structural features, the reaction, with more than two equivalents of the oxidant, affords oc.a -dihydroxylated ketones (i.e., introduction of two oxygen atoms in a single-step) instead of the expected monohydroxylated compounds.8... 

Catalytic dihydroxylations can sometimes suffer from appreciable overoxidation, and the various co-oxidants can often give quite different results. For example, when /er/-butyl hydroperoxide is used as stoichiometric co-oxidant important amounts of a-hydroxy ketones are obtained. Such products are expected to derive from oxobis(l,2-diolato)osmate(VI) 7 oxidation and do not involve diol overoxidation44. Similar results are observed using peracetic acid as stochiometric co-oxidant45. 

An indirect route to a-hydroxy carbonyl compounds uses enol ethers as substrates for dihydroxylations (Scheme 8.24). The primary product is a vicinal hydroxy-hemiacetal which fragments to afford an a-hydroxyketone, rendering the overall route a two-step conversion of ketone to a-hydroxy ketone. The stereochemically important step can use a chiral auxiliary or enantioselective catalysis [64]. The sense of asymmetric induction found in Oppolzer s sulfonamide, shown in Scheme 8.24a... 

To investigate their possible occurrence in plants, we have developed convenient methods for the synthesis of 24-epiteasterone (71) and 24-epityphasterol (75) as well as their corresponding B-homo lactones 43 and 42, respectively (Scheme 9). For the synthesis of compound 71 the (24f )-3p-hydroxy-6-ketone 68 was used. Asymmetric catalytic dihydroxylation of the A22 double bond of 68 gave the (22/ ,23/f)-diol 71 as the main product, besides traces of its (22S,23S)-epimer. Baeyer-Villiger oxidation of 71 with CF3CO3H led to a 1 0.6 mixture of 2-deoxy-3,24-diepi brassinolide (43) and its 5a-oxa-6-oxo isomer 72, which were separated by preparative HPLC. 

Hydroxy-ketones have also been obtained very conveniently by epoxidation or dihydroxylation of silyl enol ethers (derived from ketones with either kinetic or thermodynamic control), for example with mCPBA or osmium tetroxide and N-methylmorpholine-A-oxide. Asymmetric dihydroxylation, for example with AD-mix-a or -(3 (see Section 5.3), can provide highly enantioenriched products (6.56). ... 

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). ... 

C-Glycosidation of enol silane 279 to lactol acetate 278, prepared from 277 in two steps, furiushed ynone 280 as a single isomer. Reduction of the ketone with L-selectride furnished alcohol 270 with poor selectivity, but the minor isomer can be converted into the desired isomer via the Mitsunobu protocol Dihydroxylation of the terminal alkene, reduction of alkyne, and oxidative cleavage of the resulting triol gave the intermediate hydroxy aldehyde, which was spontaneously transformed into macrolactol 281 as a single diastereomer. 

Scheme 5.125 Conversion of silyl enol ethers 506 and 509 into a-hydroxy ketones 508 and 510, respectively, by Sharpless asymmetric dihydroxylation.

The asymmetric oxidation of a variety of differently substituted, acyclic and cyclic enol phosphates using the Sharpless AD (asymmetric dihydroxylation)-reagents, AD-mix-a and AD-mix- 0, and a fructose-derived chiral ketone as a catalyst, with PMS was a terminal oxidant, afforded the corresponding a-hydroxy ketones in good yield and with high enantioselectivity. The influence of substrate steric and electronic factors on the facial stereoselectivity has been studied. Kinetic and activation parameters for copper(II)-catalysed and -uncatalysed oxidation of ornithine with PMS have been determined. Cyclic voltammetric and absorption studies confirmed the formation of a copper-ornithine-PMS complex and ESR spectral studies ruled out the participation of free radical intermediates. Kinetic and activation parameters for the oxidation of aspartic acid and nicotinic acid with PMS have been determined and plausible mechanisms have been proposed. 

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