Syntheses of Ring-Fluorinated Isoquinolines and Quinolines via Intramolecular Substitution: Cyclization of 1,1-Difluoro-1-alkenes Bearing a Sulfonamide Moiety

Abstract

On treatment of a base such as NaH, KH, or Et₃N, N-[o-(2,2-difluorovinyl)benzyl]- and N-[o-(3,3-difluoroallyl)phenyl]-substituted p-toluenesulfonamides readily undergo intramolecular substitution of sulfonamide nitrogens for vinylic fluorines in a 6-endo-trig fashion, leading to 3-fluoroisoquinoline and 2-fluoroquinoline derivatives, respectively, in high yields.

Key words

fluoroisoquinoline - fluoroquinoline - fluoroalkene - intramolecular substitution - desulfonylation

References

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20

Anilide 7c (R = H) hardly gave dihydroquinoline 10c (R = H) on teatment with NaH, which suggests that 10c was formed via desilylation of 10b.

23

For the synthesis of 3-fluoroquinolines starting from (2,2-difluorovinyl)benzene substrates on the basis of the intramolecular substitution concept, see: Refs. 4e, 5b, 12b, and 12c.