Cyclohexanones ball milling

Ketone aJdehyde ligand benzoic acid 2 1 0.1 02mol, 25°C. Method A conventional magnetic stirring. Method B 4-nitrobenzaldehyde, catalyst, and benzoic acid were dissolved in THF and the solvent was evaporated prior to the addition of cyclohexanone. Method C. ball milling. 300rpm. Isolated products. 

In continuation of synthetic study, Juaristi and coworkers investigated the efficacy of the series of (5 )-proline-thioamide catalysts C4-C6 (Chart 2.1) [35]. When aldol reaction of 3-nitrobenzaldehyde with cyclohexanone was carried out, the best results were obtained when using 7 mol % of catalyst C4. On the other hand, in ball-milling conditions at -20°C the use of water and acidic additives was beneficial for the increase of diastereoselectivity in favor of the anfi-diastereomer however, the enantiomeric excess of the process was not improved. Thus, reactions between cyelic ketones and aromatic were carried out in conditions identical to these in Table 2.35 to afford aldol products in good isolated yields (70-89%) with high diastereo- (92 8 to >98 2 anti/syn) and enantioselectivities (82-96% ee) (Table 2.37). 

A more complex sulfur-proUne catalyst is sulfoimidamide of type 84 (Fig. 4.9). This catalyst, together with its diastereoisomer, have been tested in the aldol reaction between cyclohexanone (3b, 5 equiv.) and aromatic aldehydes to afford the corresponding aldol products, with best yields and selectivities being obtained using compound 84 (10 mol%) under ball-mill solvent-free conditions (22-84% yield, 84-92% de, 89-98% ee) [152]. 

Bolm [59-61] applied ball-milling to an asymmetric solvent-free aldol reaction catalyzed by L-proline (Scheme 21.27). Especially, reactions of cyclohexanone (1.1 equiv) and various crystalline aromatic aldehydes were studied under the ballmilling conditions (250-400 rpm) at room temperature. To evaluate the effect of the mechanochemical technique, comparative studies using conventional stirring were carried out for each reaction. 

Another proUne-based catalyst was also tested in solvent-free aldol reactions under baU-miUing conditions, for example, derivatives of l,T-binaphthyl-2,2 -diamine or proUne-based dipeptides. Nijera [62] and coworkers used a combination of (SJ-binam-bis-L-prolinamide and benzoic acid to catalyze a direct aldol reaction under solvent-free conditions using conventional magnetic stirring. In addition, comparative studies with ball milling (400 rpm) were carried out for the reaction of cyclohexanone and 4-nitrobenzaldehyde but no improvement was observed. After 1.5 h quantitative conversion and similar diastereoselectivity and enantioselectivity were obtained using these methods [62]. Moreover, a study... 

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