Of-Hydroxyketones

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of / -hydroxyketones from /J-sulfinylhydrazones 166211-214, of /3, /l -dihydroxyketones from 3-(p-tolylsulfinyl-methyl)-A2-methylisoxalinones 167215, of /1-hydroxyacids from 2-(p-tolylsulfinylmethyl)oxazolines 168216 and of /J-hydroxyesters from ethyl-p-tolylsulfinyl-W-methoxyacetamide 169217. 

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of -hydroxyketones from -sulfinylhydrazones of -dihydroxyketones from 3-(p-tolylsulfmyl-... 

Reaction of hydroxyketone 308 with Lawesson s reagent afforded dithiaphos-pholane 309 as a single P-diastereomer in 52% yield after HPLC purification (Scheme 73) [110]. 

Another recent example is the asymmetric Mannich-type reaction of hydroxyketones using a ZnEt2-BINOL complex as a catalyst.429 The complex provided superior enantioselectivity and had a very high turnover number. 

In practice (Scheme 13.3.3), the reduction of hydroxyketone 4 with either metal hydrides or sodium in wet ether gave only one compound to which the structure 3b (X = OH) was assigned (attack on the convex face of the tricyclic system). 

Iron(III) complexation by 5-nitrotropolone follows the usual mechanistic pattern, 4 at Fe +, at FeOH +aq. Dinuclear Fe2(OH)2 aq, like FeOH +aq, reacts by an mechanism. Curcumin (232) and its diacetyl derivative form complexes with Fe + whose stabilities approach that of Fe -desferrioxamine, hence their suggested use for treatment of iron overload—a topic which dominates the following section devoted to two specific classes of hydroxyketones, viz hydroxypyranones and hydroxypyridinones. ... 

An alternate, shorter route was also developed which involved reaction of the alcohol derived from 27 with 3-4 equivalents of hthium r-butyl acetate to afford an excellent 75-80% yield of hydroxyketone 31 without the need for pnor protection of the alcohol and with no detectable reaction with the nitrile (Scheme 7). Although these routes still involved a low-temperature reduction, both could be scaled to kilogram... 

The proportion of the acyclic form also increases with increasing temperature this is true for aldoses and ketoses,16,31 as well as for simple hydroxyketones.74 This would be expected from considerations of entropy, as the acyclic form has a greater degree of freedom, but studies on y- and d-hydroxyketones show that change in enthalpy contributes even more to the changing position of the equilibrium with increasing temperature. Evidently, cyclization of hydroxyketones is exothermic, and is favored by lower temperatures.74... 

This carbocylization method has been used successfully with a range of hex-5-enopyranose derivatives, and good yields of hydroxyketones of various configurations have been recorded [4]. It is less satisfactory with the 6-deoxy-5-ene derived from l,2 3,4-di-0-isopropylidene-a-D-galactose, giving only 40% of compound 51 [26], but good yields of the cyclohexanones have been obtained from substituted methyl galactopyranosides [25]. The reaction does not afford cyclopentanones when applied to 5-deoxy-4-enofuranose derivatives [27]. 

In the template reactions, acetone can be replaced by the preformed aldol, diacetone alcohol, and also the a, P-unsaturated ketone mesityl oxide.90-93 The use of hydroxyketones can be extended to include benzoins, provided that the l,3-diaminopropanenickel(II) complex is used (equation 13).91... 

In 1976, Ueno and Okawara highlighted the fact that no oxidation of primary saturated alcohols to aldehydes via tin alkoxides had been reported in the literature and published a procedure for the selective oxidation of secondary alcohols.25 Interestingly, rather than performing the oxidation on pre-formed tin alkoxides, these researchers subjected a mixture of the diol and (Bu3Sn)20 in CH2C12 to the action of Br2. Regardless of the fact that no complete formation of tin alkoxides is secured and no HBr quencher is added, this method may provide useful yields of hydroxyketones during the selective oxidation of diols.26... 

The selective oxidation of the secondary alcohol is performed by dropping a bromine solution on a mixture of (Bu3Sn)20 and the diol in CH2CI2. Although, no complete formation of bis-tin alkoxide is secured and the generated HBr—that may cause the hydrolysis of tin alkoxides—is not quenched, a useful yield of hydroxyketone is obtained. 

A very good yield of hydroxyketone results from the regioselective oxidation of a secondary alcohol using hydrogen peroxide in the presence of catalytic peroxotungstophosphate. 

Acid-catalysed hydration of 2-norbornen-5-one (27) in aqueous HCIO4 results in the formation of hydroxyketone 28 and lactone 29 as the major products. Kinetic measurements suggest complex rearrangement pathways60. 

This analysis was confirmed by the cyclization studies of hydroxyketone thiols 69 and 72. Compound 69 gave on cyclization the isomer 70 rather than the isomer 71 which has an equatorial oxygen. Similarly, cyclization of 72 gave 73 only the isomer 74 was not observed. It was further shown that compounds 70 and 73 exist in a conformation equivalent to 68A, which has two anomeric effects. 

Matsunaga S, Kumagai N, Harada S, Shibasaki M (2003) anti-Selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing beta-amino alcohols. J Am Chem Soc 125 4712—4713 Mayer S, List B (2006) Asymmetric counteranion-directed catalysis. 

The bicyclohexenone-dienone isomerization 33a - -34a + 35a (Chart 5) has also been observed in the dark by acetic and formic acid catalysis and clearly involves the cationic intermediate 110 (Chart 16)." Further, under more drastic acidic nonphotolytic conditions, photoketones of the general formula 111 (R = H or alkyl) give hydroxy-ketones 113 (R = alkyl) and 114 (R = H), respectively. In these transformations, cationic intermediates of type 112 are obviously formed. Mixtures of hydroxyketones such as 113 and 114 are also produced upon irradiating the corresponding dienones (cf. Chart 7) in aqueous acetic acid. Av, is, 27,30 Here, participation of intermediates that are either identical with or structurally related to the ground-state species 112 seems indicated Ai Both intermediates, 112 and 110, represent conjugate acids of the proposed mesoionic intermediates (general formula 102 and 106, respectively) in the photoisomerizations. 

The generation of hydroxyketones by the brominolysiS of staimylenes has been used several times in total synthesis. Experiment G [see Eq. (IS)] describes a key step in the total synthesis of the antibiotic (+)-spectinomycin [12,13]. It is remarkable that the two oxygen atoms bound to the tin atom originate from hydroxyl groups, which are part of different fimctions, a hemiketal and a secondary alcohol. The oxidation is selective for one alccdiolic function out of three. The same product was obtained by A(-bromosuccinimide oxidation of the tributylstannyl ether. 

Similarly, the Felkin-Anh products are formed when chelation is prevented by the formation of r-BuMe2Si ethers of -hydroxyketones 3.118 and 3.119. This allows access to syn,anti or antUanti a-alkylated diols, depending on the configura-... 

An interesting end product, tetramethylpyrazine was also presented in the reaction mixture (27.3% of peak area of the total volatiles). Previous study of the model reaction of 2,3-butanedione and ammonium acetate did not yield any tetramethylpyrazine. It is probably due to the reducing environment provided by H2S which reduced 2,3-butanedione to 3-hydroxy-2-butanone. This explained that both 3-hydroxy-2-butanone and 3-mercapto-2-butanone were found in the reaction mixture. This study also supported the mechanism proposed by Elmore and Mottram 10) who observed that, during the reactions of hydroxyketones with aldehydes and ammonium sulfide, the formation of thiazoles was discouraged due to reducing environment provided by H2S derived from ammonium sulfide. It is also interesting to note that con aring to previous a-hydroxyketone series tetramethylpyrazine was present at trace levels whereas in the a-dicarbonyl series it was the major product under comparable tenq)erature conditions. The reason for this observed phenomenon is not obvious. It is possible that in the reaction system of acetoin and ammonium sulfide, the... 

In this contribution we have presented the synthesis of the new photoreactive thiol MUAP bearing a photoreactive phenyl ester. This molecule is well suited for the preparation of SAMs on gold substrates and can be photochemically modified by UV-illumination due to the photo-Fries rearrangement leading to the formation of hydroxyketones. By a subsequent post-modification reaction with a fluorinated compound low-energy surfaces are attainable. 

Two distinct effects, namely initial rs and the increase of rs at high conversion levels of reactant due to kinetic resolution of 1-OH and 2-OH, should not be confused when elucidating the rs in the reaction system under consideration. The reaction is consecutive (dione -> hydroxyketone -> diol (Figure 1)) and the products giving rise to regioselectivity are the intermediates, 1-OH and 2-OH, which react further to diols. They react, however, with a much lower rate than the reactant hydrogenates to hydroxyketones. The rs is thus controlled at low reactant conversion by the production of hydroxyketones from the reactant and at high... 

Application of the Abramov reaction has received little more attention, but it has been used in conjunction with toluenesulphonyl derivatives of hydroxyketones in the presence of dbu (Scheme 28) when acted upon by thiourea in MeOH at room temperature, the oxi-ranes 344 (R = Me or Et, R = Me or Cy) are converted into the corresponding thiiranes 345 ". The reaction between the protected oxoacetal 346 with methyl phenylphosphinate in the presence of dbu provides the epoxide 347 as a mixture of the diastereoisomeric 4RS and 4SR pairs in the ratio 7 3. Reduction of the product with H2 and Raney nickel yields the linear phosphinate ester 348 Similarly, the reactions between the ketose 349 (R = Me or CH2Ph) with either dialkyl hydrogenphosphonate or alkyl phenylphosphinate, again in the presence of dbu, gave the epoxides 350 (R = Me or CH2Ph R = R = MeO R = Ph,... 

A variation of the pinacol reaction has been applied to esters for the preparation of hydroxyketones (acyloins). A simple example is the reaction of 257 with sodium metal (Na°) in refluxing xylene, which gave a good yield of 2-hydroxy cycloheptanone (258) after hydrolysis.203 The condensation of an a,(o-diester to an... 

Treatment of ) -hydroxyketones or j8-trimethylsilyloxyketones with trimethylsilyldiazomethyl-lithium yields 2,3-dihydrof urans, which can be dehydrogenated to furans with mangenese dioxide (Scheme 18) <94SL46i>. Obviously a carbene is an intermediate in the first step of the reaction. 

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