Alcohols, secondary, conversion into preparative procedures

Vedejs and Chen [39] described an efficient non-enzymatic system able to approach the efficiency of some of the lipase methods in enantioselectivity. The reaction was carried out in a 2 1 ratio racemic secondary alcohol acylating agent, in contrast to Evans procedure. The pyridinium salt 8 was prepared by reaction of the chiral 4-dimethylaminopyridine (DMAP) 6 with the commercially available chloroformate 7. This pyridinium salt proved to be unreactive to secondary alcohols. The reactivity was found only upon strict experimental conditions addition of a Lewis acid, then the racemic alcohol, followed by addition of a tertiary amine gave the carbonate 9. Under these conditions (using MgBr2 and triethylamine), (2-naphthyl)- -ethanol was converted (room temperature, 20 h and 54% conversion) into the (S)-carbonate (82% ee). The recovered alcohol showed 83% ee, revealing a stereoselectivity s=39 for the process. A number of 1-arylalkanols have been resolved by this procedure in 20-44% yield (based on the racemic material) and 80-94% ee. For the use of this system in enantiodivergent reactions, see Schemes 6.1 and 6.32. 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

For example, the acetate prepared from l,l,l-trifluoro-2-octanol was transformed into (.R)-l,l,l-trifluoro-2-octanol in 96% when hydrolyzed with lipase MY at 40% conversion. Other, trifluoromethylated chiral secondary alcohols shown in Table 2 were prepared by the same procedure. The corresponding alcohols were converted to their acetate, followed by asymmetric hydrolysis to attain the higher enantiomeric excess [28]. 

An excellent method for the conversion of ether-soluble secondary alcohols to the corresponding ketones is by chromic acid oxidation in a two-phase ether-water system. The reaction is carried out at 25-30 °C with the stoichiometric quantity of chromic acid calculated on the basis of the above equation, and is exemplified by the preparation of octan-2-one and cyclohexanone (Expt 5.86). The success of this procedure is evidently due to the rapid formation of the chromate ester of the alcohol, which is then extracted into the aqueous phase, followed by formation of the ketone which is then extracted back into the ether phase and is thus protected from undesirable side reactions. 

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