Hydroxyketones acetals

On treatment with phenyhodine(III) diacetate and potassium hydroxide in methanol [80[, tetralone 56 gave the hydroxyketone acetal 59 (Scheme 13). Trans-ketalization of 59 with (2S,3S)-l,4-dimethoxybutane-2,3-diol (60), followed by oxidation with pyridiniiun dichromate (PDC) [80[, yielded oxoketal 61 [76[. 

The formation of acyloins (a-hydroxyketones of the general formula RCH(OH)COR, where R is an aliphatic residue) proceeds best by reaction between finely-divided sodium (2 atoms) and esters of aliphatic acids (1 mol) in anhydrous ether or in anhydrous benzene with exclusion of oxygen salts of enediols are produced, which are converted by hydrolysis into acyloins. The yield of acetoin from ethyl acetate is low (ca. 23 per cent, in ether) owing to the accompanying acetoacetic ester condensation the latter reaction is favoured when the ester is used as the solvent. Ethyl propionate and ethyl ji-butyrate give yields of 52 per cent, of propionoin and 72 per cent, of butyroin respectively in ether. 

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

Most diaziridines are not sensitive towards alkali. As an exception, diaziridines derived from 2-hydroxyketones are quickly decomposed by heating with aqueous alkali. Acetaldehyde, acetic acid and ammonia are formed from (162). This reaction is not a simple N—N cleavage effected intramolecularly by a deprotonated hydroxy group, since highly purified hydroxydiaziridine (162) is quite stable towards alkali. Addition of small amounts of hydroxybutanone results in fast decomposition. An assumed reaction path — Grob fragmentation of a hydroxyketone-diaziridine adduct (163) — is in accord with these observations (B-67MI50800). 

Cyclodecanedione has also been prepared by oxidation of sebacoin with chromium trioxide in acetic acid, - Cupric acetate in acetic acid has been used for oxidation of an a-hydroxyketone by Ruggli and Zeller. ... 

A closely related oxygenated heterocyclic system devoid of acidic groups interestingly shows quite different biological activity. Thus, condensation of the benzofuran hydroxyketone 66 with ethyl thiomethyl acetate (67) probably proceeds initially by formation of the acylation product 68. Intramolecular dehydration leads to formation of a pyran ring. There is thus obtained the hypo-cholesterolemic agent timefurone (69) [14],... 

Trisubstituted imidazoles have been synthesized from 1,2-diketones or a-hydroxyketones with ammonium acetate in very short reaction times with excellent yields in the presence of l,l,3,3-VAr V ,(V -tetramethylguanidinium trifluoroacetate as an ionic liquid <06SC65>. Iodine acted as an efficient catalyst in the synthesis of 1,2,4,5-tetraarylimidazoles 93 using benzoin 91,... 

Synthesis of 31 by Method I (107,108) and its conversion to the related anti and syn diol epoxide derivatives (32,33) has been reported (108). The isomeric trans-1,lOb-dihydrodiot 37) and the corresponding anti and syn diol epoxide isomers (38,39) have also been prepared (108) (Figure 19). Synthesis of 37 from 2,3-dihydro-fluoranthene (109) could not be accomplished by Prevost oxidation. An alternative route involving conversion of 2,3-dihydrofluoranthene to the i8-tetrahydrodiol (3-J) with OsO followed by dehydration, silylation, and oxidation with peracid gave the Ot-hydroxyketone 35. The trimethylsilyl ether derivative of the latter underwent stereoselective phenylselenylation to yield 36. Reduction of 3 with LiAlH, followed by oxidative elimination of the selenide function afforded 3J. Epoxidation of 37 with t-BuOOH/VO(acac) and de-silylation gave 38, while epoxidation of the acetate of JJ and deacetylation furnished 39. 

In contrast with all the other species of Crematogaster studied till now, the venom of C. sp. 2 from Papua New Guinea did not contain mixtures of homologous compounds. Two derivatives, 136 and 137, characterized by the presence of a conjugated triene on one end of the chain, and by a 1,3-hydroxyketone at the other end, were isolated from this species (Fig. 23). These structures could constitute biosynthetic intermediates en route to the cross-conjugated dienone system. The venom of C. sp. 3 contained 4-oxo-2,5-dienyl acetates similar to... 

A related sequence was used by Kozikowski and Park (74) to prepare the ring skeleton of streptazolin (200), a compound that exhibits antibacterial and antifungal effects. In this approach, the tricyclic isoxazoline intermediate 198 was formed in the key cycloaddition step (Scheme 6.86). Thus, the reaction of oxime 197 (obtained from 4-piperidone) with sodium hypochlorite-triethylamine afforded tricyclic isoxazoline 198 in very good yield. This cycloadduct was converted to p-hydroxyketone 199 by reduction/hydrolysis using Raney Ni in the presence of acetic acid. Racemic streptazolin (200) was obtained from 199 in several additional steps (74). 

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... 

In addition to the examples of coumarin syntheses given in the reviews mentioned above and in the treatise on heterocyclic compounds (B-51MI22400), more recent studies have made use of the Perkin synthesis. These include the use of substituted phenoxyacetic acids to prepare 3-phenoxycoumarins (78CI(L)628> and the synthesis of chlorocoumarins from chlorosalicylaldehydes (81T2613). The use of DBU in place of sodium acetate was necessary to effect the ring closure of a number of o-hydroxyketones (78BCJ1907). 

Approximately 1.05 3a equivalents of sodium hypochlorite (MW = 74.44) in an aqueous ca. 1.8 M b solution are slowly added over 15-30 min.c to a ca. 0.6 1.4 M stirred solution of the diol in acetic acid. When most of the starting alcohol is consumed,d a saturated NaHCCF aqueous solution is added and the resulting mixture is extracted with an organic solvent such as ether or CH2C12. The organic phase is washed with water, dried (MgS04) and concentrated, providing a hydroxyketone that may need further purification. 

Oxidation of the a-hydroxyketone with concentrated nitric acid, or by catalytic amounts of copper(n) salts in acetic acid solution which are regenerated continuously by ammonium nitrate, yields the diketone (e.g. benzil and furil, Expt 6.143). 

X. Kong and T. B. Grindley, An improved method for the regioselective oxidation of stannylene acetals and dimerization of the a-hydroxyketone products, J. Carbohydr. Chem., 12 (1993) 557-571. 

Dibutylstannylene acetals of diols (such as 11) were found to be oxidized regiospecifically by NBS to a-hydroxyketones (12)45 (Scheme 6). 

Finally, it should be noted that achiral dioxiranes can be used to generate chiral hydroxyketones from enantiomerically pure diols or acetals [140, 141]. 

Acetals such as C are referred to as spiroketals because their acetal carbon is a spiro atom. (In a spiro compound two rings are connected by a single common atom that is called a spiro atom ). The intermediates in this acetalization are lactols B. They resemble those lac-tols whose rapid formation from y- or 5-hydroxyketones was shown in Figure 9.4. Note that because of the unfavorable reaction entropy, there is often no path hack from spiroketals to the open-chain form Usually, spiroketals cannot be hydrolyzed completely. 

Enolizable ketones were converted directly into their a-hydroxy dimethyl acetals upon reaction with DIB and methanolic potassium hydroxide at room temperature. If, during work up, there was acid treatment, then a-hydroxyketones were directly obtained. Numerous examples are known for such transformation, e.g. with 3-pentanone, acetophenones, 2,6-diacetylpyridine [16], tropan-3-one [17], -amino-ketones of great structural variety [18], etc. even a free radical reacted successfully in this way [19]. This conversion for an acetyl-oxazole served for the preparation of pyrimidine derivatives. 

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