Reduction of fluoroketones

Many synthetically valuable reactions involving reductions of fluoroketones have been reported as shown in Fig. 15-30 i176 1781. Various monofluoroketones are reduced with yeast some of them proceeded with high diastereoselectivity. 

Photochemically induced reduction of alkyl perfluoro carboxylates in hexa-methylphosphoramide (FfMPA) can replace one, two, or (in the case of tn-fluoroacetate) three a-fluonne atoms with hydrogen [7, S] (equation 5) Chlorine-containing fluorocarboxylates preferentially lose a-chlorme and may even lose P-chlorinc in preference to a fluonne [9] (equation 6) Cyclic a-fluoroketones are also defluonnated photochemically [10] (equation 7)... 

The synthesis of the fluoroketone that combines the retroamide type bond (76) is shown in Scheme 5. The 2,2-difluoro-3-hydroxyester 11 from a Reformatsky reaction was converted to the primary amide 12 by treatment with ammonia in diethyl ether. Reduction of the amide with borane dimethyl sulfide and protection of the resulting amine gave the protected intermediate 13. For the preparation of peptides XIV and XV, the hydroxy function was oxidized to the corresponding ketone using pyridinium dichromate. 

The regioselectivity in oxetane formation is probably determined primarily by the orientation of the CT complexes. Additions of a-fluoroketones, which have such low reduction potentials as to be particularly hot 132> and therefore potentially unselective acceptors, do proceed with negligible regioselectivity 126>. The actual product ratio is quite complex kinetically because of all the various competing reactions of four separate intermediates. 

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