A Practical Triphenylcarbenium Tetrafluoroborate Mediated One-Pot Synthesis of 1-Substituted N-Alkyl-1,2,3,4-tetrahydroisoquinolines

Treatment of 2-methyl-1,2,3,4-tetrahydroisoquinoline (1) with 1-2 molar equivalents of triphenylcarbenium tetrafluoroborate at 20°C in either chloroform or acetonitrile resulted in the formation of 2-methyl-3, 4-dihydroisoquinolinium tetrafluoroborate (2), whereas triethylamine and N-methylpiperidine were unaffected under these reaction conditions. This hydride abstraction was exploited in a one-pot preparation of 1-functionalized 2-alkyl- 1,2,3,4-tetrahydroisoquinolines. Thus, treatment of 2 with aqueous potassium hydroxide afforded 1-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (9) (61% from 1). Similarly, potassium cyanide in acetonitrile provided 1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline (10, 77%). Quenching of 2 with Grignard reagents in tetrahydrofuran afforded the corresponding 1-alkyl and 1-aryl substituted tetrahydroisoquinolines (31 to 78%). Interestingly, nitrile 10 reacted very rapidly (< 2 min at 0°C) with phenylmagnesium bromide to give 2-methyl-1-phenyl-1,2,3, 4-tetrahydroisoquinoline (3, 100%), but failed to react with excess phenyllithium even at 20°C.