Oxidative Difluoromethylation of Tetrahydroisoquinolines Using TMSCF₂SPh: Synthesis of Fluorinated Pyrrolo[2,1-<i>a</i>]isoquinolines and Benzo[<i>a</i>]quinolizidines

Abstract

An efficient C1-difluoromethylation of tetrahydroisoquinolenes was achieved using TMSCF₂SPh as a difluoromethylating agent and 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (TEMPO⁺BF₄^-) as an oxidant. The process provides an access to a variety of C1-difluoro(phenylsulfanyl)methylated tetrahydroisoquinoline adducts in good yields. These adducts were employed as key precursors for preparing fluorinated pyrrolo[2,1-a]isoquinoline and benzo[a]quinolizidines.