A-Hydroxyketones, cyclic

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

Cyclic thiourea derivatives like l,3,4,5-tetramethylimidazole-2(3H)-thione— prepared by condensation of substituted thioureas with a-hydroxyketones—can be converted into the corresponding imidazolin-2-ylidene by desulfurization with sodium or potassium [Eq. (23)]. This method was used to prepare and isolate l,3-bis-neo-pentylbenzimidazolin-2-ylidene with Na/K. With LDA as the base it is also possible to generate free benzimidazolin-2-ylidenes in solution. ... 

TS-1 zeolites have been used in the presence of H2O2 to perform the BV reaction on cyclic and aromatic ketones . Cyclohexanone and acetophenone can be oxidized at 80 °C with selectivities lower that 60%, due to the formation of a-hydroxyketones and other undesired products. The observed modest results seem to be associated with the poor selectivity of the active Ti-peroxo species. In this respect, Corma and coworkers developed new Sn-based heterogeneous catalysts able to selectively activate the ketone instead of 11202 . Cyclic ketones are transformed into the corresponding lactones and unsaturated cyclic ketones like 110 are oxidized to unsaturated lactones in very high chemoselectivitjf , unusual for other oxidizing systems (equation 75). As expected, the authors failed to detect the presence of metal-peroxo derivatives in their systems . ... 

Terashima et al. 231) reported an asymmetric halolactonization reaction. This highly stereoselective reaction permits the synthesis of intermediates for the preparation of chiral a,a-disubstituted a-hydroxycarboxylic acids (227)231c), a-hydroxyketones (228) 231c), functionalized epoxides (229) 231d,e) and natural products 231h,j). Only amino acids have so far been used as a source of the chiral information in the asymmetric halolactonization reaction. Again, the best results have been obtained by using cyclic imino acid enantiomers, namely proline. 

In 1974, David18 reported that cyclic stannylenes (97), formed by reaction of 1,2-diols (96) with dibutyltin oxide— -Bu2SnO—in refluxing benzene with azeotropic elimination of water, reacted with Br2 in solution at room temperature at titrating speed, leading to a-hydroxyketones (98). 

Acetates can be used instead of alkenes. Cyclic ketones undergo ring expansion to give a-hydroxyketone precursors. Oxiranes ring-open with siloxymethylation at ambient temperature and CO pressure. ... 

Cyclic enol ethers are also good substrates for the Sharpless AD reaction with ee being dependant on the chain length of the enol ether side chain. Thus, while the pentyl enol ether (5.32) is converted into a-hydroxyketone (5.36) with 94% ee, the corresponding methyl enol ether is oxidised with only 83% ee. 

The asymmetric Michael addition of nonstabilised ketone enolates has proved difficult, with most success achieved using 1,3-dicarbonyls as donors. However, Shibasaki and coworkers have achieved high ees in the addition of a-hydroxyketones with both aromatic Michael acceptors such as (11.32) and also cyclic enones and alkyl vinyl ketones, using bifiinctional zinc catalysts prepared from linked BINOL (11.33). These catalysts are also effective in the asymmetric aldol reaction (see Section 7.1) and incorporate two zinc atoms, one of which activates the acceptor carbonyl group and the other forms a zinc enolate with the donor. In addition, catalysts of this type have been used to good effect in the addition of P-ketoesters to cyclic enones. 

Lactones from cyclic a-hydroxyketones Stereospecific rearrangement... 

The aldol reaction of cyclic ketones and acetone with aromatic aldehydes were carried out in combination with triflic acid in water at 25°C [250]. Other chiral primary-tertiary diamine catalyst such as compound 167 (20 mol%) was used in combination with solid polyoxometalate acid support (6.67% mol) in the aldol reaction between dihydroxyacetone (149a) and aromatic aldehydes in NMP as solvent at 25°C to afford mainly iyn-aldol products in good yields (59-97%) and high diastereo- and enantioselectivities (78-99% de, 84-99% ee). The combination of catalyst 167 with triflic acid was used in the reaction of acyclic ketones and a-hydroxyketones 8 with aromatic aldehydes also with good results [251]. Simple chiral diamine 168 (10 mol%) in the presence of Iriflic acid (20 mol%) was applied as catalyst in the reaction between acetone and cyclohexanone with aromatic aldehydes in water at 25°C, giving aldol adducts 4 in low yields (15-58%) and moderate diastereo- and enantioselectivities (50-98% de, 45-93% ee) [252]. 

Ketocarboxylic acids from cyclic glycols or a-hydroxyketones G... 

E)-4-hydroxyenestannanes, with 2 extra C-atoms 44, 850 a-hydroxyketones 43,1 P-hydroxyketones 44,627 hydroxynitriles, synthesis 43, 558 2-hydroxythioethers 43,450 rran5-l,2-iodohydrins 44 922 ketene acetals, cyclic 44, 575... 

Sodium hydroxide I chiral quaternary ammonium salts triethyl phosphite Cyclic a-hydroxyketones from ketones Asym. autoxidation under phase transfer catalysis... 

A soln. of startg. ketone in toluene, triethyl phosphite (for in situ reduction of labile hydroperoxide intermediates), and 5 mol% of the chiral cinchonine catalyst added successively to 50% aq. NaOH, and the mixture stirred vigorously at room temp, with 02-bubbling for 5 h - (S)-product. Y 95% (e.e. 79%). F.e. and cyclic p,y-ethylene-a-hydroxyketones from a,P-ethyleneketones s. M. Masui et al., Tetrahedron Letters 29, 2835-8 (1988). 

A new synthesis of furans from a-hydroxyketones has been reported, e.g. (326) was prepared from sebacoin. Treatment of phenyl hydrazones of cyclic ketones with arsenic trichloride gave arsadiazoles, e.g. (327) was obtained from cycloheptanone. Novel 1,5-benzodiazepines, e.g. (328), were obtained when cyclic ketones were condensed with o-phenylenediamine or its 4-chloro-derivative in the presence of boron trifluoride etherate. "... 

An investigation has been reported of the enediol anions and products of jS-elimination of cyclic a-hydroxyketones,- the observations were correlated with n.m.r, results. 

Similarly, diesters form cyclic a-hydroxyketones (acyloins) (Equation 9.90),... 

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