Fluoro epoxides

As already discussed in this chapter, aluminum, in addition to its well-known high oxygenophilicity (Al-O = 511 3 kJ mol ), has exceedingly high affinity toward fluorine this is evident from the bond strengths in several metal-fluorine diatomic molecules Al-F, 663.6 6.3 kJ moFh Li-F, 577 + 21 kJ mol" Ti-F, 569 + 34 kJ moF Si-F, 552.7 + 2.1 kJ moF Sn-F, 466.5 + 13 kJ moF and Mg-F, 461.9 + 5.0 kJ moF [76]. Organoaluminum reagents seem, therefore, quite suitable for fluorine-assisted selective alkylation of fluoro epoxides, which also represents the experimental demonstration of the intervention of pentacoordinate chelate complexes of trialkyl-aluminums as plausible intermediates [63]. 

The fluoro derivatives of 1,6-anhydrohexopyranoses undergo all of the common reactions of 1,6-anhydrohexoses. By using a redox sequence, derivatives of l,6-aiihydro-/3-D-allopyranose were prepared545 from 183 and 185. Ammonolysis of the fluoro epoxide 184 leads to the amino derivative381 190, and hydrogenolysis of 184 gives... 

Among new epoxides are two families containing fluorine and phosphorous, respectively. The fluoro-epoxides prepared by Griffith (76,77) at the Naval Research Laboratory have the following general structure ... 

The application of this fluoro-epoxide for the synthesis of dimeric liquid crystals which exhibited st le anti ferroelectric chiral Smetic C Riase and were good dopants for anti-ferroelectric liquid crystals was shown by Hiyama and co-workers (Figure 12) (30). 

Steroids possessing an epoxide grouping in the side chain have likewise been converted to fluorohydrins. Thus, 20-cyano-17,20-epoxides of structure (19) furnish the 17a-fluoro-20-ketones (20) after treatment of the intermediate cyanohydrins with boiling collidine. The epimeric 5a,6a 20,21-oxides (21) afford the expected bis-fluorohydrins (22). The reaction of the allylic... 

The influence of the conformational factors, which play a decisive role in directing oxide fission in the above cases is no longer operative in the case of 3-keto-5a,6a-epoxides and their 3-ethylene ketals. With these substrates the —I effect of the BFs-complexed 3-keto or 3-ketal grouping predominates leading to the fluorohydrins. Thus, treatment of both 5a,6a-oxidopregnane-3,20-dione (35) and its 3,20-bisethylene ketal with BFg-etherate in benzene-ether affords in 45% yield the 6jff-fluoro-5a-hydroxy-derivative (36) and its 3-ethylene ketal, respectively. which are converted into the 6a-fluoro-A -CH3... 

Often, considerable selectivity is encountered, as for instance in the case of the 5,9-diene epoxide (7), which affords the 6j8-fluoro-5a-bromide (8), with... 

The 1 la-methyI-9, lly5-epoxide (41) is the sole product of the reaction of the 9a-fluoro-11-ketone (40) with methyllithium. ... 

In the course of synthetic efforts aimed at obtaining 6j5-fluoro steroids, Kirk and Petrow treated a 3)5-acetoxy-6-raethyl-5a,6a-epoxide with boron trifluoride etherate and unexpectedly obtained a fluorine-free acetoxy ketone." Later transformations established that the product was the A-homo-B-norsteroid (104). 

Regioselectivity in opening of a-functionalized epoxides by treatment with trimethylamine dihydrofluoride has been observed. Thus, cw-isophorol epoxide gives exclusively 3-fluoro-l,2-diol, whereas from the trans isomer, 2-fluoro-l,3-diol is obtained as the main product together with 3-methylenecyclohexane-l,2-diol. This behavior has been discussed m terms of the influence of a-substituents on the transition state conformations [7 J] (equations 11 and 12). 

A more efficient agent than peroxy compounds for the epoxidation of fluoro-olefins with nonfluonnated double bond is the hypofluorous acid-acetomtrile complex [22] Perfluoroalkylethenes react with this agent at room temperature within 2-3 h with moderate yields (equation 13), whereas olefins with strongly electron-deficient double bond or electron-poor, sterically hindered olefins, for example l,2-bis(perfluorobutyl)ethene and perfluoro-(l-alkylethyl)ethenes, are practically inert [22] Epoxidation of a mixture of 3 perfluoroalkyl-1-propenes at 0 C IS finished after 10 mm in 80% yield [22] The trifluorovinyl group in partially fluorinated dienes is not affected by this agent [22] (equation 13)... 

Asymmetric epoxidation of racemic unsaturated fluoro alcohols by the chiral Sharpless reagent can be exploited for kmetic resolution of enantiomers The recovered stereoisomer has 14-98% enantiomeric excess [55] (equation 50)... 

One of the first indications that the antiinflammatory potency of the corticoids could be increased was the observation that incorporation of a 9a-fluoro group in hydrocortisone resulted in a tenfold increase in activity. Treatment of hydrocortisone acetate (170a) with phosphorus oxychloride in pyridine yields the corresponding olefin, 172. This, on being subjected to the reaction sequence depicted in the transformation of 104 to 108 (addition of HOBr, closure to the epoxide and ring opening with HF),... 

Monomer Glyc dyl-2,2-Dinitro-2-Fluoroethyl Ether (2,3-Propane epoxide-2,2-Dinitro-2-Fluoro-ethyl Ether). 

Epoxidation of substituted spiro[cyclopentane-l,9 -fluorene]-2-enes 68 with a peroxidic reagent was studied [98], The spiro olefins react with m-chloroperbenzoic acid (mCPBA) in chloroform at 3 °C to give a mixture of the epoxides. In all cases (2-nitro (68b), 4-nitro (68c), 2-fluoro (68d) and 2-methoxyl (68e) groups), the iyn-epoxides, i.e., the syn addition of the peroxidic reagent with respect to the substituent, is favored. For example, for 6 nsyn anti = 63 31 for 68c syn anti = 65 35. Thus, a similar bias is observed in both the reduction of the carbonyl derivatives of 30 and the epoxidation of the derivatives of 68. 

The use of chiral a-fluoro ketone G can lead to enantioselective epoxidation.106... 

Epoxyketone 245 is readily available from 16-dehydropregnenolone via several steps, including a crucial microbiological 11a-hydroxylation. Dehydration of 245 gives the 9,11-olefin 246. The alcohol at C-21 is then converted to the mesylate (247), and this is reduced to give the methyl ketone (248). The olefin is then converted to the 9a-fluoro-llp-hydroxy array (250) by the standard sequence [addition of HOBr, closure to the oxirane (249), opening with HF]. Note that the reactivity of the epoxides in 249 is... 

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