Oxidation using fluoroketones

Synthesis of the perfluoroalkyl P-amino alcohol 5 (70) required for the preparation of the perfluoroalkyl ketone VI as shown in Scheme 2 is illustrative of the method used to prepare analogous compounds. Tm-butyloxycarbonyl-L-cyclohexylalaninal 4 was condensed with perfluoroethyl or perfluoropropyl lithium which was generated in situ by the addition of methyllithium-lithium bromide complex to the corresponding perfluoroalkyl iodide. The alcohol 5 was isolated as an epimeric mixture which was used in the preparation of peptide IV. Oxidation using the Dess-Martin periodinane reagent (9) yielded the fluoroketone VI. 

Fluorinated alcohols, and in particular HFIP, have also proven beneficial for epoxidations of alkenes using persulfate (Oxone) as the terminal oxidant and fluoroketones as catalysts [9, 10]. Under these conditions, the fluorinated ketones are converted to dioxiranes, which are the active epoxidizing spedes. Typical catalysts... 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

Silyl enolates are useful starting materials for the smooth a-halogenation of ketones, which can be carried out by oxidation with A-halosuccinimides , halogens and iodoben-zenedifluoride or xenon difluorides. As shown in equation 32 , the reaction of 45 with Xep2 gives a 1 1 mixture of a-fluoroketone diastereoisomers 46a and 46b. 

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. 

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