C−F Bond Cleavage by Intramolecular S_N2 Reaction of Alkyl Fluorides with O- and N-Nucleophiles

Abstract

The nucleophilic substitution of alkyl fluorides was achieved in the intramolecular reactions with O- and N-nucleophiles. The intramolecular defluorinative cyclization reaction was influenced by the nature of nucleophiles, the size of the ring to be formed, and the comformational rigidity of the precursors. Intermolecular nucleophilic substitution reactions of alkyl fluorides under similar reaction conditions were found to be difficult. The stereochemistry study of the current C-F bond cleavage reaction showed a complete configurational inversion, which supports an intramolecular S(N)2 reaction mechanism.

Asymmetric Synthesis of Alkyl Fluorides: Hydrogenation of Fluorinated Olefins

“…The other two possible arrangements (Scheme f, g) are sterically unfavored. Thus, based on the quadrant model, both of the sterically favored orientations of alkenyl fluoride 7 a result in hydrogenation from the same face of the olefin, and the predicted absolute configuration of hydrogenated product 8 a is S , which is in agreement with the experimental results (see the Supporting Information for the determination of the absolute configuration) …”

Selective CF Bond Activation: Substitution of Unactivated Alkyl Fluorides using YbI3

“…[3] Additionally, several procedures for substitution of activated C À F bonds, for example, at the benzylic or allylic position or a to a carbonyl group, have been developed. [4] However, a synthetically valuable method for CÀF bond activation of unactivated aliphatic fluorocarbons still remains a challenge. A few attempts to manipulate such C À F bonds have been addressed utilizing strong Lewis acids, which in general are highly oxophilic, thus making their use impractical in the presence of other functional groups.…”

CF Bond Activation of Unactivated Aliphatic Fluorides: Synthesis of Fluoromethyl‐3,5‐diaryl‐2‐oxazolidinones by Desymmetrization of 2‐Aryl‐1,3‐difluoropropan‐2‐ols

“…An alcohol 3 reacts with an isocyanate in the presence of NaH to furnish C , the carbamate sodium salt. Although the NaF bond is slightly weaker than the CF bond, based on the bond dissociation energies (NaF: 477.3 kJ mol −1 ; CF: 513.8 kJ mol −1 ),14 the CF bond of species C should be activated by the sodium cation to assist the intramolecular reaction via transition state II , resulting in cyclization and NaF elimination to give product 1 8e. 15…”