Secondary Alkyl Fluorides

Secondary alkyl fluorides exhibit a downfield (deshielding) shift of about +35 ppm from their primary analogues, their fluorines typically absorbing at about -183 ppm (Scheme 3.4), and such fluorines will also experience the usual considerable shielding as a result of branching. 

Characteristic 1H and 13C NMR Data. The examples in Scheme 3.5 provide insight into expected proton and carbon chemical shift and coupling constant data for secondary alkyl fluorides. 

Preparation of Tertiary and Secondary-Alkyl Fluorides from Alcohols with Hydrogen Fluoride-Pyridine Reagent... 

Halosilanes are also potent halogen donors, particularly in exchange reactions with alkyl fluorides, due to the strong Si-F bond formation. Tertiary- and secondary-alkyl fluorides are reacted with iodotrimethylsilane to yield alkyl iodides in high yields (equation 19)214 ... 

Landini, D., F. Montanari, andF. Rolla, Reaction of Alkyl Halides and Methanesulfonates with Aqueous Potassium Fluoride in the Presence of Phase Transfer Catalysts A Facile Synthesis of Primary and Secondary Alkyl Fluorides, Synthesis, 428 (1974). 

A -Bromomagnesium enamines are formed on treatment of cyclohexanone imines of A, A -diethylethanamine with mesitylmagnesium htomide. These highly nucleophihc species react with even secondary alkyl fluorides. 

Gandelman and co-workers have reported the synthesis of secondary alkyl fluorides using a Suzuki-Miyaura cross-coupling of 1-halo-l-fluoroal-kanes (Scheme 13.19). Geminal dihaloalkanes were used as starting materials and the report demonstrated that these simple 1-fluoro-l-haloalkanes... 

Scheme 13.19 Gandelman and co-workers synthesis of secondary alkyl fluorides.

Scheme 13.20 The direct asymmetric catal3dic stereoconvergent synthesis of enantioenriched secondary alkyl fluorides.

Benzyl and alkyl tnalkylsilyl ethers undergo clean fluonnation to give good yields of benzyl and alkyl fluorides, respectively, when reacted with a combination of d quaternary ammonium fluoride and methanesulfonyl orp- toluenesulfonyl fluoride. The reactions are applicable strictly to a primary carbon-oxygen bond, secondary and tertiary alkyl silyl ethers remain intact or, under forcing conditions, aie dehydrated to olefins [29] (equation 22)... 

Nucleophilic substitution reactions of halide anions in aprotic solvents are often accompanied by elimination reactions. For instance, reactions of secondary alkyl halides with potassium fluoride solubilized in acetonitrile with the aid of 18-crown-6 [3] give olefins as the main reaction product (Liotta and Harris, 1974). Similarly, the dicyclohexyl-18-crown-6 complex of potassium iodide acted exclusively as a base in its reaction with 2-bromo-octane in DMF (Sam and Simmons, 1974). The strongly basic character of weakly solvated fluoride has been exploited in peptide synthesis (Klausner and Chorev, 1977 Chorev and Klausner, 1976). It was shown that potassium fluoride solubilized... 

In contrast to the primary alcohols, tertiary alcohols eliminate water smoothly at 0°C in the presence of a 2-10 molar excess of hydrogen fluoride followed by polymerization.259 Reduced polymerization and satisfying yields of tertiary alkyl fluorides are achieved only at low temperatures (— 50 C). The reactivity of secondary aliphatic alcohols is thus interpreted to be between the other two types. High yields of alkyl fluorides are difficult to obtain because of the competing reactions and the effect of temperature on the equilibrium. 

Alkyl fluorides have been generated from the reaction of carboxylic acids with one equivalent of xenon difluoride in dichloromethane or chloroform solution. The process has been named fluorodecarboxylation", the fluorine analog of the Hunsdieckerand Kochi reaction.8384 Both primary and tertiary acids react very well, but secondary acids react less readily. A possible scheme involves a free-radical mechanism including an unstable fluoroxenon ester of an appropriate acid.84... 

The nucleophilic displacement of halogens by fluorine can be successfully carried out by reaction with potassium fluoride under several conditions. Primary and secondary alkyl halides 1 are converted to the corresponding fluorides 2 by heating with a saturated aqueous solution of potassium fluoride in the presence of catalytic amounts of hexadecyltributylphosphonium bromide.56 Small amounts of the corresponding alcohol and the olefinic elimination product are formed as side products. While neopentyl bromide does not react at all, polyhaloalkanes give only products of elimination or hydrolysis. Chlorocyclohexane gives only the elimination product.56... 

Cycloalkyl and secondary alkyl bromides react with N02 BF4 in pyridinium poly(hydrogen fluoride) solution to yield /J-fluorinated compounds in moderate to good yields. In the case of the cyclic starting materials like 1-bromocyclohexane only trans-substituted products are formed (see Table 22). 

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