Asymmetric oxidative α-fluorination of 2-alkylphenylacetaldehydes with AgHF2 and ruthenium/PNNP catalysts

During attempts directed at epoxide ring opening with different HF sources, we discovered that the Lewis acidic [RuCl(PNNP)]+ (1) or [Ru(OEt2)2(PNNP)]2+ (2) catalysts promote the [1,2]-phenyl shift (Meinwald rearrangement) in phenyl-substituted epoxides to give the corresponding 2-alkylphenylacetaldehydes, which are fluorinated at the α-position in the presence of silver bifluoride (AgHF2) (PNNP is (1S,2S)-N,N′-bis[o-(diphenylphosphino)benzylidene]cyclohexane-1,2-diamine). The optimization of aldehyde fluorination with PhCH(R)CHO (R = Me, Et, iPr, tBu) as substrates showed that catalyst [1]SbF6 gives a moderate degree of enantioselectivity (up to 27% ee) and 35% yield. The substrate scope is limited to benzylic aldehydes. The reaction is unprecedented for transition metal catalysts. Circumstantial evidence suggests that the mechanism involves chemical oxidation followed by enantioselective fluorination with F−.