Aryl trifluoromethyl ketones reduction

Catalytic synthesis of aryl trifluoromethyl ketone via RC(0)-0Ar bond cleavage is also known. Combination of Pd(OAc)2 with 3 equiv of P Bu3 catalyzes the formation of aryl trifluoromethyl ketone from phenyl trilluoroacetate and arylbo-rane (Eq. 3.12) [69]. This reaction is interpreted by RC(0)-0Ph bond oxidative addition to give (acyl)(phenoxo)palladium(II) complex, followed by metathesis (transmetallation) of phenoxopalladium species with arylborane and reductive elimination of acyl and aryl carbons to form the product. 

Table 18. Asymmetric reduction of aryl trifluoromethyl ketones with PNAH and sodium borohydride.

Baba N, Matsumura Y, Sugimoto T (1978) Asymmetric reduction of aryl trifluoromethyl ketones with an achiral NADH model compound in a chiral hydrophobic binding site of sodium cholate micelle,... 

Reduction of Alkyl Fluoroalkyl Ketones. Since 1 reduces non-fluorinated aralkyl ketones in high ee, a better understanding of the effects of fluorine atom in asymmetric induction with this reagent was sought from the reduction of a series of alkyl a-fluoroalkyl ketones. The fact that unhindered prochiral dialkyl ketones are typically reduced by 1 in relatively poor ee added value to this proj t. DBP-CMoride reduced alkyl trifluoromethyl ketones at a rate faster dwn that of the aryl derivatives... 

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. 

Ru-Cataiyzed Transfer Hydrogenation of Ketones (Merck, Lanxess). Two Ru-catalyzed transfer hydrogenations have been developed and applied on a multi-10-kg scale. Two variants are applied, one based on Ru/amino alcohol complexes with iPrOH/base and the other based on Ru/Ts-dpen complexes with HCOOH/NEta as a reducing system, respectively. Generally, good enantioselectivities have been obtained for several aryl ketones but with lower activities than for comparable hydrogenation reactions described above (see, eg, the results for 3,5-bis-trifluoromethyl-acetophenone described above (72)). Merck (77) has developed a process for the reduction of 3,5-bis-trifluoromethyl-acetophenone, and Lanxess has applied Noyori s Ru/Ts-dpen system to reduction of aryl y3-keto esters on up to a ton scale (78). 

---