Alkenes, cyclization quinolines

Palladium-catalyzed reaction of alkyne 47 with a variety of aryl and vinyl halides afforded alkenes 48 in good yield. Cyclization to quinolines 49 was performed by treating 4 8 with TsOH in EtOH <96T(52)10225>. 

Among the simplest syntheses of this type are those of tetrahydro-quinolines or -iso-quinolines based on Friedel-Crafts cyclizations. The use of side-chain halides is shown by the synthesis of 1,2,3,4-tetrahydroisoquinolines (158) (71CC799), and of 3,4-dihydroquinol-2-ones (159) (27CB858). Electrophilic carbon atoms can be developed from secondary or tertiary alcohols, or from alkenes or alkynes. In the synthesis of the tetrahydroisoquinoline... 

Activated alkenes, for example, enamines or enol ethers, likewise undergo cycHzing addition to N-arylimines catalyzed by Lewis acids like BF3 or, particularly effective, Yb(OTf)3 [190]. With enolethers, the primary products of cyclization 131 are aromatized to quinolines 132 by Lewis acid-promoted ROH-elimination and dehydrogenation. 

PCys was the optimal ligand however, PAd2Bu showed analogous reactivity. Of note, PCys HCl did not have an effect on rate enhancement, in contrast to previously reported methodologies (see above). Allyl-tethered quinolines were better suited to react with PAd2Bu, as double-bond isomerization was minimized. Substrates lacking ort/io-substitution performed poorly. Cyclization was also problematic for less-substituted enol ethers due to an increased desire to undergo olefin isomerization prior to cyclization. 1,2-Disubstituted alkenes were incompatible, as /3-substitution impeded reactivity however, the necessity for a-substitution was noted due to the inert nature of the unsubstituted vinyl enol ether substrate. 

Ichikawa J, Sakoda K, Moriyama H, Wada Y (2006) Syntheses of ring-fluorinated isoquinolines and quinolines via intramolecular substitution cyclization of 1,1-difluoro-l-alkenes bearing a sulfonamide moiety. Synthesis 10 1590-1598... 

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