2,2,2-Trifluoroacetophenone asymmetric reduction

Fukuzumi S, Kondo Y, Tanaka T (1983c) Evidence for a single electron transfer activation in the hydride transfer from an NADH model compound to tetracyanoethylene. Chem Lett 751-754 Fushimi M, Baba N, Oda J, Inouye Y (1980) Asymmetric reduction of a-keto-esters and trifluoroacetophenone with N-anionized Hantzsch ester. Bull Inst Chem Res Kyoto Univ 58 357-365 Gase RA, Boxhoorn G, Pandit UK (1976) Metal-complex mediated catalysis of reduction of 2-benzoylpyridine by an NADH-model. 

Ohnishi Y, Numakunai T, Ohno A (1975b) Reduction by a model of NAD(P)H. Contribution of metal ion to asymmetric reduction of trifluoroacetophenone. Tetrahedron Lett 3813-3814 Ohnishi Y, Kagami M, Ohno A (1975c) Reduction by a model of NAD(P)H. Reduction of a-diketones and a-keto alcohols by 1-benzyl-1,4-dihydronicotinamide. Tetrahedron Lett 2437-2440 Ohnishi Y, Kagami M, Numakunai T, Ohno A (1976a) Reduction by a model of NAD(P)H. VIII. Effects of metal ion on the course and stereochemistry of the biomimetic reduction of olefin. Chem Lett 915-916... 

We developed fi-chlorodiisopinocamphOTlborane (Aldrich DIP-Chloride , 1) as an excellent leagrat for the asymmetric reduction of aiall l and a-hindeied ketones (JO). Examination of the reduction of 2,2,2-trifluoroacetophenone with (-)-l exhibited... 

Figure 1. Comparison of asymmetric reduction of acetophenone, pivalophenone, and 2,2,2-trifluoroacetophenone with DIP-Chloride ...

A catalytic asymmetric in situ reduction of N-H imines has been achieved in a sequence in which trifluoroacetophenones, ArCOCF3, are first converted to silylimines [using LiN(SiMe3)2], and then on to give trifluoromethylated amine salts, Ar-C(CF3)-NH2.HC1, in good to excellent yield and ee.5s The intermediate N-H imines can be isolated via methanolysis of the N-Si bond, while the enantioselective reduction can be carried out using a chiral borane auxiliary. 

In the reduction of co.a+a+trifluoroacetophenone with (S)-2-phenyl-l,l,2-trideuteroethylmag-nesium bromide, deuterium transfer shows a higher asymmetric induction than hydrogen transfer (RD = 54.4% ee. SH = 47.1 % ee), although the hydrogen exceeds the deuterium transfer (H/D = 1.6)123. The result is rationalized in terms of a transition state A (preferred over B) in which the two phenyl groups are facing each other. 

---