Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• C–F activation of benzylic fluorides for nucleophilic substitutions and Friedel–Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol (HFIP) as the activators. This study examines the stereointegrity of the C–F activation reaction through the use of

• demonstrated that both associative and dissociative pathways operate to varying degrees, according to the nature of the nucleophile and the hydrogen bond donor. Keywords: benzylic fluorides; C–F activation; chiral liquid crystal; 2H NMR; PBLG; stereochemistry; Introduction The C–F bond is the strongest

• steric influence for backside attack of the nucleophile in the solvent-separated ion pair, arising from the large, congested hydrogen bond networks around the fluorine atom. C–F activation of benzylic fluorides to generate benzylamine or diarylmethane products. 7-[2H1]-(R)-Benzyl fluoride ((R)-1

Triol-promoted activation of C–F bonds: Amination of benzylic fluorides under highly concentrated conditions mediated by 1,1,1-tris(hydroxymethyl)propane

• Pier Alexandre Champagne,
• Alexandre Saint-Martin,
• Mélina Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2013, 9, 2451–2456, doi:10.3762/bjoc.9.283

• C–F bond of benzylic fluorides was achieved using 1,1,1-tris(hydroxymethyl)propane (2) as a hydrogen bond-donating agent. Investigations demonstrated that hydrogen bond-donating solvents are promoting the activation and hydrogen bond-accepting ones are hindering it. However, the reaction is best run

• under highly concentrated conditions, where solvents cannot interfere with the interaction between the organofluorine compound and the triol. Various benzylic fluorides react with secondary amines or anilines to form benzylic amines in good yields. Keywords: C–F bond activation; highly concentrated

• and resulted in a higher isolated yield (Table 3, entry 1). Reactions of secondary benzylic fluorides were unfortunately untractable, and primary aliphatic amines (i.e. n-butylamine) generated a mixture of inseparable mono- and dibenzylation products (see Supporting Information File 1 for details