Fluoro allyl alcohols

Fluoro allyl alcohols. Schlosser and Chau have described a new route to these alcohols. Chlorofluorocarbene is allowed to react with an olefin in a two-phase system the resulting chlorofluorocyclopropanes are then opened with silver acetate in acetic acid. The final step involves alkaline hydrolysis. 

A wide variety of a-tnfluoromethyl a-amino acids are readily available from the reaction of 5-fluoro-4-tnfluoromethyl-l,3 azoles with allylic alcohols [138, 139] a-Tnfluoromethyl-subsumted a-amino acids show anubactenal and antihy pertensive activity Some are highly specific enzyme inhibitors (suicide inhibitors) and may be important as bioregulators [140] Furthermore, they are interesting candidates for peptide modification... 

An efficient and inexpensive method for the substitution of an allylic hydroxyl group with fluorine, without allylic rearrangement and elimination consists of treating an allylic alcohol with methyllithium followed by p-toluenesulfonyl fluoride, lithium fluoride and 12-crown-4.6 By this method, geranyl fluoride, neryl fluoride, cinnamyl fluoride, ( , )-farnesyl fluoride, retinyl fluoride and 4-fluoro-2-methyl-6-(4-tolyl)hept-2-ene are prepared. 

Nitrile oxides react with the methyl enol ethers of (Rs)-l -fluoro-alkyl-2-(p-tolylsulfinyl)ethanones to produce (45,5/f,/fs)-4,5-dihydroisoxazoles with high regio-and diastereo-selectivity.87 In the 1,3-dipolar cycloaddition of benzonitrile oxide with adamantane-2-thiones and 2-methyleneadamantanes, the favoured approach is syn, as predicted by the Cieplak s transition-state hyperconjugation model.88 The 1,3-dipolar cycloaddition reaction of acetonitrile oxide with bicyclo[2.2.l]hepta-2,5-diene yields two 1 1 adducts and four of six possible 2 1 adducts.89 Moderate catalytic efficiency, ligand acceleration effect, and concentration effect have been observed in the magnesium ion-mediated 1,3-dipolar cycloadditions of stable mesitonitrile oxide to allylic alcohols.90 The cycloaddition reactions of acryloyl derivatives of the Rebek imide benzoxazole with nitrile oxides are very stereoselective but show reaction rates and regioselectivities comparable to simple achiral models.91. 

A wide variety of a-trifluoromethyl-substituted amino acids are now available from the reaction of 5-fluoro-4-trifluoromethyl-l,3-oxazoles with allylic alcohols and benzyl alcohols. The reaction sequence involves a low-temperature Claisen rearrangement or a radical 1,3-benzyl shift from oxygen to carbon, respectively [88AG(E)848 89S850] (Scheme 86). 

Trifluoro(fluoro-oxy)methane tends to convert simple unsaturated steroids into complex mixtures of products, but reacts with allylic alcohols or acetates to give only two products, corresponding to cw-addition of either CF3OF or F2, the former... 

The fluorine atom adjacent to a trifluoromethyl group in the furan ring shown below could be replaced under mild conditions by various nucleophiles. Consequently, the reaction of 2-fluoro-3-trifluoromethylfuran with allyl alcohol followed by a Claisen rearrangement led to the formation of trifluoromethyl substituted butenolides <01TL1657>. 

Fluorinated analogues of biologically active molecules have received, in the past twenty years, an increasing interest. The Claisen-Johnson rearrangement applied to fluoro-substituted allylic alcohols appeared rapidly as a method of choice for the synthesis of various fluoro-polyfunctionalized compounds. Claisen rearrangement and Claisen-Johnson rearrangement of trifluoromethyl allylic alcohols 533 developed by Ishikawa [131] afforded selectively the anticipated esters 534 and 535. Z,syn-config-... 

Reaction of 2-fluoro-3-trifluoromethylfurans 235 with allyl alcohols followed by Claisen rearrangement directly produced butenolides 237 [145, 146]. Oppositely, allyl mercaptane formed stable substitution product 236 [146], A similar transformation was reported for benzyl alcohols. While benzhydryl and (2-thienyl)methyl groups migrated at room temperature directly furnishing butenolides 239, in the case of benzyloxy derivatives, heating at 120 °C was required to reach the transformation. On the other hand, stable up to 140 °C products 238 were formed in the reaction of benzylamine, benzyl mercaptane, and 2-(hydroxymethyl)pyridine [147]. 

In the chromium-mediated reaction of 1-fluoro-l-bromo-l-alkene with an aldehyde, the ( )-isomer reacts more quickly than the (Z)-isomer. Therefore, when a mixture of stereoisomer 42a was subjected to the reaction with benzaldehyde in the presence of CrCl2 and Ni catalyst, a (Z)-isomer of allylic alcohol 51 was selectively formed [77, 78] (Scheme 21). The reaction proceeds through an alkenylchromium species 52, and the formation of the ( )-alkenylchromium species is much faster than that of the (Z)-isomer. Actually, the reactimi of a pure (Z)-isomer of 1 -fluoro-1 -bromo-1-alkene with aldehyde is sluggish, and the corresponding ( )-isomer of the product was obtained in low yield or not obtained at all. Therefore, a good method for the synthesis of ( )-51 has not yet been reported. 

This chapter reviews our study of Morita-Baylis-Hillman (MBH) and vinylmel ation reactions for the synthesis of achiral and chiral, functionalized, fluorinated allyl alcohols. Vinylmetalation of fluoro-carbonyls with aluminum and copper reajgents for the synthesis of unsubstituted, and p-substituted fluorinated allyl alcohols is summarized. An exploratory study of terpenyl alcohols as chiral auxiliaries in these reactions is also discussed. 

Vinylcupration of Fluoro-aldehydes and Ketones. Marino and Lindermann (20) have reported the addition of Corey s vinylcopper reagents (21) to aldehydes and ketones. We carried out vinylcupration of fluorinat aldehydes and ketones to prepare functionalized fluorinated p-substituted allyl alcohols (Scheme IS). Unlike vinylalumination, vinylcupration of fluoro-carbonyls is not stereoselective (Ktre, S. V., unpublished results). 

Hexafluorobut-2-yne added to a soln. of NaOH in allyl alcohol as rapidly as it reacts, stirred and warmed at 50° until the slight reflux ceases 1,1,1-tri-fluoro-3-trifluoromethylhex-5-en-2-one. Y 74%. F. e. s. G. G. Krespan, Tetrahedron 23, 4243 (1967). 

Because of the exceptional C-F bond strength, the successful preparation of a-halocyclopropyl c-complexes is realized by substitution of 1-bromo-l-fluoro-trans-2,3-dimethylcyclopropane 179 with Fp [90], Silica gel column chromatography of the thus obtained cr-complex 180 results in ring opening to the alcohol 181 as a single stereoisomer. The allene complex 182 is produced by treatment with BF3OEt2, indicating that 181 is derived from 182 and water. The 7i-allyl complex 183 is formed by photolysis via a disrotatory process. 

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