Fluorination allylic alcohol

Mixtures of anhydrous hydrogen fluoride and tetrahydrofuran are successfully used as fluorinating agents to convert 1,1,2-trifluoro-l-allcen-3-ols, easily prepared from bromotrifluoroethene via lithiation followed by the reaction with aldehydes or ketones, to 1,1,1,2-tetrafluoro-2-alkenes The yields are optimal with a 5 1 ratio of hydrogen fluoride to tetrahydrofuran The fluorination reaction involves a fluonde lon-induced rearrangement (Sf,j2 mechanism) of allylic alcohols [65] (equation 40)... 

Proton and Carbon NMR Data. Some characteristic 13C and XH NMR data for fluorinated allylic alcohols and bromide are provided in Scheme 3.44. 

The influence of substituents on the regioselectivity of fluorination of allylic alcohols with DAST has been studied and halogenation of the nitrogen of carbohydrate A-acetyl side-chains by HOCl has been monitored. ... 

This beneficial effect of fluorination on hydrolytic stability has also been demonstrated with the synthetic prostaglandin SC-46275 (Fig. 70). This compound possesses an anti-secretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol in acidic medium (epimerisation, dehydration, etc.). A fluorine atom was introduced on the C-16 methyl to disfavour the formation of the allylic carbocation. This fluorinated analogue possesses the same biological activity, but does not undergo any degradation or rearrangement, and itepimerises only slowly [165]. 

P.W. Collins, R.L. Shone, A.F. Gasieski, W.E. Perkins, R.G. Blanch , Stabilization of a prostaglandin tertiary allylic alcohol system by fluorine Synthesis, acid stability studies and pharmacology of a 16-fluoromethyl analog of SC-46275, Bioorg. Med. Chem. Lett. 2 (1992) 1761-1766. 

Y. Nakamura, M. Okada, H. Horikawa, T. Taguchi, Preparation of c5-fluorinated homo-allylic alcohol derivatives via regioselective hydride reduction of allylic alcohol derivatives, J. Fluor. Chem. 117 (2002) 143-148. 

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-aikyiated alkyl iodides 931. a.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779—781 ]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl alcohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783],... 

Chiral fluorinated allylic alcohols obtained by enzymatic resolution (Table 5, Runs 13 and 14) were employed in diastereoselective cyclopropanation using the carbenoid from samarium and di-iodomethane [32]. This reaction proceeded smoothly at -78 °C to 0 °C, but not as smoothly as the case of non-fluorinated allylic alcohols at -78 °C. 

Rearrangements arc common in reactions of sulfur tetrafluoride with acetylenic and allylic alcohols. Highly acidic acetylenic alcohols derived from hexafluoroacetone and other haloacetones react readily at ambient temperature to give fluorinated allenes 10 as the sole... 

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. 

Electron-withdrawing groups close to the alcohol functionality may likewise destabilize intermediate carbocations and result in very slow oxidations. For instance, sterol 88 is oxidized with DDQ at the allylic alcohol two hundred times slower than the corresponding compound lacking the fluorine atom,94 and the treatment of hydrobenzoin (89) with DDQ results in the oxidation of a single alcohol because a second oxidation would involve a carbocation highly destabilized by the presence of a carbonyl group.95f... 

The synthesis of y-fluoroalkylated allylic alcohols and amines like 51 starting with chiral fluorinated allylic mesylates 50 has also been reported (Eq. 3) [134]. In this case, the regiochemistry of the addition is controlled by the substrate and the addition of the nucleophile occurs distal to the fluorinated alkyl chain. 

The organozinc intermediate thus formed reacts with aldehydes as Grig-nard reagents do to form alcohols. In the presence of aluminum chloride, elimination of chlorine and fluorine from the vicinal carbons of the dichlorotrifluoroethyl group generates halogenated allylic alkoxides that are protonated to allylic alcohols, in the present case J, 2-chloro-3,3-difluoro-1 -phenylpropen-2-ol [114]. 

Less regularly used reagents are tert-hu y hydroperoxide, tf/Y-butyllithium, ozone. dioxiranes, fluorine/water/acetonitrile, or A, A -diethylhydroxylamine. Alkenes carrying a donor substituent can also be epoxidized with pcracids. Fluorinated allylic alcohols give, under Sharpless conditions, epoxides in good yield and enantiosclcclivity. ... 

Its application to the enantiomers of fluorinated allyl alcohols (see scheme 1) would generate optically active allylamines, a substructure of our targets. Focused on Phe-Gly isosteres 3a (R =CH2Ph, = H) the preparation of the corresponding intermediates is shown in scheme 6. 

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