Similarity trifluoromethyl aryl ketones

The approach using cyclodextrin as a binding site has also been developed. Cyclodextrins are widely utilized in biomimetic chemistry as simple models for an enzyme because they have the ability to form inclusion complexes with a variety of molecules and because they have catalytic activity toward some reactions. Kojima et al. (1980, 1981) reported the acceleration in the reduction of ninhydrin and some dyes by a 1,4-dihydronicotinamide attached to 3 Cyclodextrin. Saturation kinetics similar to enzymatic reactions were observed here, which indicates that the reduction proceeds through a complex. Since the cavity of the cyclodextrin molecule has a chiral environment due to the asymmetry of D-glucose units, these chiralities are expected to be effective for the induction of asymmetry into the substrate. Asymmetric reduction with NAD(P)H models of this type, however, has not been reported. Asymmetric reduction by a 1,4-dihydronicotinamide derivative took place in an aqueous solution of cyclodextrin (Baba et al. 1978), although the optical yield from the reduction was quite low. Trifluoromethyl aryl ketones were reduced by PNAH in 1.1 to 5.8 % e.e. in the presence of 3-cyclodextrin. Sodium borohydride works as well (Table 18). In addition to cyclodextrin, Baba et al. also found that the asymmetric reductions can be accomplished in the presence of bovine serum albumin (BSA) which is a carrier protein in plasma. 

As shown in Table 18, trifluoromethyl aryl ketones were reduced in 22.3-46.6 % e.e. by PNAH and 15.6-38.8 % e.e. by sodium borohydride in 1.5-1.7 mM solution of BSA. The degree of asymmetric induction was rather high in comparison with those from the reactions with cyclodextrin, which suggests the possibility that such a simple protein as BSA can provide a chiral reaction field, as an enzyme does. As already mentioned some proteins have a similar (or sometimes greater) affinity toward a molecule in the ground state in comparison with an enzyme. The difference between these two proteins in different classes is the affinity toward a transition state. The enzyme has to bind the transition state more strongly than the ground state. 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

This result is not surprising since it was shown earlier that trichloromethyl ketones react more rapidly with methanol (alcohols) than with water under alkaline conditions.29 The ethanolic cleavage of a trichloromethyl ketone has been used to prepare ethyl 3,3-diethoxypropanoate,30 and aryl trifluoromethyl ketones can be cleaved to give carboxylic acids or esters.31 A similar reaction of 3-trifluoroacetylindole (19) with lithium dialkylamides affords good yields of the corresponding indole-3-carboxamides (20).3... 

The case of 2,4,6-tris(trifluoromethyl)acetophenone has been discussed in some detail in order to demonstrate that sometimes Rp chemistry can be quite different from that of less sterically hindered aromatic compounds. Similar problems as in the case of RfC(0)CH3 were encountered in an attempted preparation of a related aryl vinyl ketone, RfC(0)CH=CH2 (28), When RfLI was reacted with acryloyl chloride, CH2=CH-C0C1, a mixture of two ketones was obtained. One of them seemed to be RfC 0)CH=CH2, The other ketone, RfC(0)CH2CH2Rf, resulted from a Michael addition between RfC(0)CH=CH2 and the strong nucleophile RfLI (Equation 3),... 

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