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

Abstract

During attempts directed at epoxide ring opening with different HF sources, we discovered that the Lewis acidic [RuCl(PNNP)] + ( 1) or [Ru(OEt 2) 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 (AgHF 2) (PNNP is (1 S,2 S)- N,N′-bis[ o-(diphenylphosphino)benzylidene]cyclohexane-1,2-diamine). The optimization of aldehyde fluorination with PhCH(R)CHO (R = Me, Et, i Pr, t Bu) as substrates showed that catalyst [ 1]SbF 6 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 −.