Ring-Closing Metathesis of Vinyl Fluorides towards α-Fluorinated α,β-Unsaturated Lactams and Lactones

Ring‐closing olefin metathesis reactions (RCM) using Grubbs II or Hoveyda's catalysts have been applied to a series of N‐alkenyl‐N‐benzyl‐α‐fluoroacrylamides. α‐Fluoro‐α,β‐unsaturated γ‐ or δ‐lactams incorporating a fluorinated double bond were obtained in moderate to good yields, depending on the nature of substituents on the benzyl ring. The corresponding seven‐ and eight‐membered lactams were not formed under similar conditions. When the N‐benzyl group was replaced by an N‐tosyl group, the corresponding ϵ‐lactam was also formed in 38 % yield. When N‐(2‐fluoroallyl) derivatives were used instead of fluoroacryloyl derivatives, six‐, seven‐, and eight‐membered N‐heterocycles were obtained in low yields. This method was also used to synthesize fluorinated α,β‐unsaturated analogues of pyrrolizidine and indolizidine alkaloids from prolinol, and also to synthesize N‐benzyl‐3‐fluoroquinolone in three steps from commercially available 2‐vinylaniline in 44 % overall yield. Also 3‐fluorocoumarin and 3‐fluorochromene were prepared from o‐vinylphenol, and 3‐fluoro‐benzoxepine was available from o‐allylphenol. Ring‐closing metathesis reactions of aza‐ and oxa‐α,ω‐dienes containing 2‐fluoroacrylic and 2‐fluoroallylic moieties lead to α‐fluorinated α,β‐unsaturated five‐ and six‐membered lactones and lactams using Grubbs II or Hoveyda's catalysts.