Hydroxy-ketones, saturated

Stork s elegant use of a protected cyanohydrin function in the synthesis of PGF2a (2) is also noteworthy. The electron-withdrawing cyano substituent in intermediate 21 (Scheme 7) confers nucleophilic potential to C-9 and permits the construction of the saturated cyclopentane nucleus of PGF2a (2) through intramolecular alkylation. In addition, the C-9 cyanohydrin function contained within 40 is stable under the acidic conditions used to accomplish the conversion of 39 to 40 (see Scheme 7), and it thus provides suitable protection for an otherwise labile /J-hydroxy ketone. 

Hydroxy ketones and hydroxy-a,/3-unsaturated ketones in the steroids such as estrone and testosterone, respectively, can be reduced to diols biochemically. Estrone acetate gave 68% yield of a-estradiol on incubation with baker s yeast at room temperature after five days [909]. Testosterone was reduced by bacteria to the saturated hydroxy ketones, etiocholan-17-ol-3-one and androstan-17-ol-3-one, and further to the diols, ep/-etiocholane-3,17-diol and the epimeric isoandrostane-3,17-diol, both in low yields [329]. 

The initial experiments discussed in this section were performed without oxygen in the gas phase. Figures la and lb show conversion of i and selectivity towards 2 and 3 as a function of time, respectively. Initially, the conversion (65%) as well as the selectivity were stable. However, after 6 hours on stream the catalyst started to be deactivated. The decrease in conversion was accompanied by a decrease in selectivity towards the unsaturated diketone 2 and an increase in that for the saturated diketone 3. The ratio of the hydroxy ketone isomers 1 and 4 was not influenced by the deactivation. 

Reduction.1 a, 3-Epoxy ketones are selectively reduced to (3-hydroxy ketones, even when the substrate (2) also contains an enone group. Reduction of 2 with Zn/Cu also results in the same product (3), but in low yield as well as a number of products including the fully saturated ketone 4. 

Noyori and colleagues investigated the ring opening of unsaturated mono- and bicyclic endoperoxides catalyzed by 5-10 mol% of Pd(PPh3)4 [226, 227]. Similarly to the cobalt-catalyzed reactions, (Z)-4-hydroxy enones resulted as the main products, which were accompanied by (Z)-2-ene-l, 4-diols and diepoxides. The latter are formed as the major products under either ruthenium or cobalt catalysis (see Part 2, Sects. 3.5 and 5.8). Both two-electron and radical mechanisms were considered for this transformation. Saturated bicyclic endoperoxides gave mixtures of cyclic 4-hydroxy ketones and 1,4-diols and their formation may be a result of a radical process [227, 228]. 

Where the dienol form of an a,3-unsaturated ketone is availalde, autoxidadon giving the a -hydroxy ketone through the a -hydroperoxide is possible, as seen for saturated ketones (see Section 2.3.2.l.l.iii). Benzeneseleninic anhydride (see Section 2.3.2.l.l.iv) effects a -hydroxylation at tertiary centers, e.g. (118) to (119), again in the same manner as for saturated ketones. ... 

Hydrated ruthenium dioxide will act as a catalyst for the oxidation of primary allylic alcohols (equations 8 and 9) in an oxygen atmosphere (a trace of the antioxidant 2,6-di-r-butyl-4-methylphenol is required to prevent autoxidation of the aldehyde to the acid). The oxidation is not accompanied by any loss in double bond stereochemistry, secondary allylic alcohols are oxidized but at a decreased rate, and saturated alcohols are scarcely oxidized at all. However, a-hydroxy ketones and a-hydroxylactones will oxidize under forcing conditions, so there is clearly likely to some degree of substrate dependence. ... 

Primary benzylic alcohols (equation 10) can be oxidized in the presence of saturated primary alcohtris using a catalyst derived from ammonium cerium(IV) nitrate supported on charcoal with air as the cooxidant (under these conditions a-hydroxy ketones are oxidized to a-diketones). ... 

The lithium salts of aldehyde t-butylhydiazones react with electrophiles (aldehydes, ketones, alkyl halides) to form C-trapped t-butylazo compounds isomerization and hydrolysis give a-hydroxy ketones or ketones in good yields, thereby providing a convenient path via a new acyl anion equivalent (Scheme 6). Reaction of th lithium salts with aldehydes and ketones, followed by elimination, provides a new route to azaalkenes, whereas homolytic decomposition of C-tnq>ped azo compounds of trityl and diphe-nyl-4-pyridylmethylhydrazones lead to the formation of alkanes, alkenes, alcohols or saturated esters. ... 

A six-membered chelate model, as depicted in A, is proposed for the reduction of /1-hydroxy ketones, that leads predominantly to the corresponding r/treo-products138. Workup of the Mcerwein-Ponndorf Verley reaction involves addition of a saturated tartrate solution to chelate the aluminum (see ref 5). 

Other authors95 have reported that Aspergillus niger JTS 191 converted 4-oxoisophorone into five different saturated products. In addition to the diketone (9) four types of hydroxy ketones (including 10) were produced after prolonged incubation (120 144 h). 

Another saturated hydroxy ketone derivative 12 can be prepared from 3-caren-2,5-dione (11) using a Rhoclotomla strain106. 

More general routes to rings containing one double bond utilize elimination of an alcohol from a 2-alkoxy derivative of the saturated ring system or elimination of water, which frequently occurs under cyclization conditions. Thus, acid-catalyzed reactions of a-hydroxy ketones with ethylene glycol, 2-thiolethanol, and 1,2-ethanedithiol furnish, in most cases, the corresponding dihydro-... 

Introduction of asymmetry into a homodimer was demonstrated [9] by Winterfeldt and coworkers at Hannover (Scheme 5). Commercially available hecogenin acetate was transformed [10] to 5 and dimerized to symmetrical diketone 6. The two carbonyls could be statistically differentiated by controlled reduction or trapping of the dienolate to yield hydroxy ketone 7. Compounds 6 and 7 were evaluated at the NCI. The symmetrical 6 affects 32 of the 58 cell lines tested, while a saturated version lacking the D ring alkene shows weak activity. Meanwhile, unsymmetrical 7 is significantly cytotoxic against all 58 cell lines, being approximately 4,000 times weaker than cephalostatin 1. 

Reaction of a-hydroxy-ketones (e.g. 275) with the Simmons-Smith reagent replaces the carbonyl group by a methylene (276) or ethano-group (277), depending upon the conditions employed. Bromomethyl-lithium in THF reacts with saturated aldehydes and ketones to give epoxides. Several steroid examples are given. 

In the second synthesis, 8a-methyltestosterone (I48b) was prepared from the previously reported 8a-methyl-5a-pregn-9(l l)-ene-3)3.20-diol (149). Catalytic hydrogenation of (149) gave the saturated diol, which was successively oxidized to the diketone, selectively protected as the C-3 dimethyl ketal, reduced at C-20, and hydrolysed to the hydroxy-ketone (150). This in turn was transformed into the 8 -methylprogesterone (151), 8a-methyltestosterone (I48b), and 8a-methyl-oestradiol (152) analogues by conventional methods. ... 

Bode and Carreira recently reported a method for the selective reduction of conjugated isoxazolines 253 to the corresponding unsatmated 8-hydroxy ketones 254 (Scheme 60) [161]. This involves selective reduction of N-0 bond in 253 by Smb and subsequent hydrolysis of the imine imder mild acidic conditions (boric acid). While Mo(CO)6 provided a mixture of the imsatur-ated hydroxy ketone 254 and its saturated analog 255, Ra-Ni and Sml2 in the absence of B(OH)3 provided only the saturated analog 255. 

The Pd(Quinox)Cl2, (Quinox = 2-(2-quinolyl)-4,5-dihydrooxazole) catalysed Wacker-type oxidation of olefins bearing homoallylic alcohols by TBHP led to the corresponding /3-hydroxy ketones in good yields. Since the oxidation was catalyst controlled, it was significantly faster than the substrate-controlled Tsuji-Wacker oxidation. The bis- and fra-homoallylic alcohols were oxidized to cyclic peroxyketals, presumably via nucleophilic attack of the methyl ketone. Kinetics of the Wacker-type oxidation of olefins by TBHP in the presence of Quinox (ligand), and (54) as the catalyst reveal first-order dependence on ligand and olefin, and rate saturation in TBHP, as expected of the proposed mechanism (Scheme 9)... 

Methyl vinyl ketone can be produced by the reactions of acetone and formaldehyde to form 4-hydroxy-2-butanone, followed by dehydration to the product (267,268). Methyl vinyl ketone can also be produced by the Mannich reaction of acetone, formaldehyde, and diethylamine (269). Preparation via the oxidation of saturated alcohols or ketones such as 2-butanol and methyl ethyl ketone is also known (270), and older patents report the synthesis of methyl vinyl ketone by the hydration of vinylacetylene (271,272). 

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