Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for cross-coupling with phenylboronic acid. For the bifunctional substrate 4-chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the regioselective displacement of either the chlorine or fluorine substituent. The leaving group ability of fluoride vs other groups displaced in substitution is CF(3)CO(2) ≈ p-NO(2)C(6)H(4)CO(2) ≈ OCO(2)CH(3) > F > CH(3)CO(2), a ranking similar to allylic fluorides under Pd catalysis.

Palladium-Catalyzed Substitution and Cross-Coupling of BenzylicFluorides. -A variety of benzyl fluorides is applied in the reactions using carbon, nitrogen, oxygen or sulfur nucleophiles. The process tolerates even halogens on the aromatic ring. Cross-coupling of (IXa) with phenyl boronic acid proceeds chemoselectively depending on the conditions. Chiral (XVI) reacts with some erosion of the optical purity. -(BLESSLEY, G.; HOLDEN, P.; WALKER, M.; BROWN*, J. M.; GOUVERNEUR, V.; Org. Lett. 14 (2012) 11, 2754-2757, http://dx.doi.org/10.1021/ol300977f ; Chem. Res. Lab., Univ. Oxford, Oxford OX1 3TA, UK; Eng.) -R. Steudel 40-025