HF elimination

Fig. 3 Important 19F-labelled amino acids, (a) Compounds that are wo-steric to native amino acids can be incorporated into proteins biosynthetically, but they possess too many degrees of torsional freedom to be useful for ssNMR structure analysis, (b) In these artificial amino acids the 19F-reporter group is rigidly attached to the peptide backbone. They can be incorporated by solid-phase peptide synthesis, but some problems can arise due to racemisation (4F-Phg, 4CF3-Phg), steric hindrance of coupling (F3-Aib) or HF elimination (fluoro-Ala, F3-Ala). 4F-Phg is additionally problematic due to an ambiguity of the side-chain rotamer. The preferred 19F-labels for ssNMR structure analysis are CF3-Bpg and CF3-Phg (as suitable substitutes for Leu, lie, Met, Val and Ala), as well as F3-Aib and CF3-MePro...

Comparison of results of single-pulse shock-tube experiments with those from an earlier study suggest that the existing rate expression for HF elimination from 1,1,1-trifluoroethane may need to be re-evaluated. ... 

Eluorine-18 was also used as a tool for the study of the base promoted HF elimination from 4-fluoro-4-(4 -nitrophenyl)butan-2-one [62] (Scheme 3). The F KIEs values were respectively 1.0037,1.0047 and 1.0013 with formate, acetate or imidazole used as the base. The size of the fluorine KIEs corresponds to 5 -15 % of the estimated maximum for complete C-F bond breakage and is consistent with a postulated ElcB-E2 Hke or ElcBjp mechanism. 

The latter cyclized to fluoroaziridines. In the presence of alkene or alkyne dipo-larophiles, azomethine ylides gave dihydropyrroles or pyrroles, respectively, after HF elimination.50... 

The unimolecular 1,2-HF and 2,3-HF elimination reactions of CF3CHFCH3 have been characterized using the chemical activation technique for an average vibrational energy of 97 kcalmol-1.36 The transition state for 1,2-HF elimination has a two-fold larger pre-exponential factor than that for 2,3-HF elimination, because three F atoms attached to carbon atoms of the four-membered ring have lower frequencies than those in a CF3 group. 

Substitution in the 1-2 cluster leads to 4-fluoroaniline+ (HC1 elimination). This new channel is in competition with the HF elimination ... 

A couple of significant examples of the use of halide transfer reactions for the investigation of reaction mechanisms and of the structure of gaseous cations, the second field of application of these processes, are given below. More examples are reported in Section II.B. The first example concerns the reaction of the 2-fluoropropyl cation (1) with its neutral precursor /-butyl fluoride to yield the /-butyl cation, a reaction which could proceed either via F abstraction or via H+ transfer and HF elimination, both routes being exothermic (Scheme l)6. Collection of the neutral products by means of the EBFlow... 

Until recently it was assumed that all fluoroxy compounds must have a perfluorinated alkyl chain, otherwise HF elimination would take place immediately. While this line of reasoning is valid to some extent, it is by no means a general rule. The most notable exception is acetyl hypofluorite (CH3COOF). 

TABLE 2. Comparative rates and Arrhenius parameters for HF elimination of fluoroethanes at HOOK... 

The comparative effect of the F atom in HF elimination under the same experimental conditions reveals that on increasing the number of halogens at the a-carbon, the energy of activation tends to increase, while the rate coefficient decreases in the following sequence ... 

The presence of a F atom in vinyl fluoride, i.e. CH2=CF2, gave in a single-pulse shock tube35, as expected, a marked decrease in the rate of molecular HF elimination. This result appears to support not only the polar nature of these reactions, but also the mechanistic argument for the CH2=CHF decomposition. 

The pyrolyses of 1-chloro-l-fluoroethane (equations 49 to 50) and l-chloro-l,l-difluo-roethane (equations 51 and 52) in a flow system and seasoned vessels75, gave two concurrent eliminations where the HF elimination is less than 0.5%. 

This class of compounds is kinetieally stabilized by bulky tm-butyl groups (3-6) or amine groups (7,8). In 3, 7, and 8, HF elimination should be possible, but it is hindered by the very strong SiF bond energy. These mono(silyl)hydrazines are very stable molecules and show no tendency to undergo condensation at room temperature. 

Better results (80 % ee) have been reported by Mikami, Nakai and co-workers [3c] for the addition of crotyl silane also catalyzed by complex 1. Yamamoto and co-workers [3b] used chiral acyl-oxy boranes to catalyze the Sakurai-Hosomi-reac-tion. While an excellent 96 % ee was obtained for the addition of 2,3 -disubstituted allyl groups, the conversion with parent allyl silane was low (46 %) and the asymmetric induction mediocre (55 % ee). Gauthier and Carreira [5] then made a big leap forward by using the difluorotita-nium-binaphthol complex 3. The catalyst 3 is prepared in situ via the TiF4-binaphthol adduct 4 and formal HF elimination mediated by allyl silane 5. The addition of 5 to aldehydes 6 ( 7) catalyzed by 10 % of 3 proceeds with 61 - 94 % < e and good yields (69-93 %), the best results being observed for aldehydes with tertiary alkyl residues (Scheme 1). 

The anion formed on nucleophilic attack of the hydrazine stabilizes by fluoride and subsequent HF elimination to give an o ,/3-unsaturated hydrazone, which undergoes an electrocyclic ring closure with HF elimination to yield 5-fluoro-4-trifluoromethylpyrazoles. The single fluorine bonded to C(5) can be exchanged by a wide variety of nucleophiles (88S194 90BAU2338). 

Another example for this mechanistic type is the reaction of2-chloroper-fluoro-l-thiocyanato-1-cyclohexene with gaseous ammonia at room temperature. The 2-amino-4,4,5,5,6,6,7,7-octafluoro-4,5,6,7-tetrahydro-benzothiazole initially formed, subsequently suffers a nucleophilic attack by ammonia and HF elimination to give 2-amino-4,4,5,5,6,6-hexafluoro-7-imino-4,5,6,7-tetrahydro-benzothiazole (91BAU2075). 

Photolysis of ReCp (CO)3 in CeFe does not lead to the jj -CeFe complex. Instead, both C-H and C F activation take place leading inter alia to the fulvene complex Re(jj -C6Me5CH2)(CO)2(C6F5) and HF elimination (see Section 9). ... 

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