Enantioenriched fluorinated heterocycles can be prepared through fluorocyclizations of prochiral indoles (see scheme; Ts=tosyl, Bn=benzyl, Boc=tert-butoxycarbonyl). More than twenty examples for this cascade fluorination-cyclization, which is catalyzed by cinchona alkaloids and employs N-fluorobenzenesulfonimide as the electrophilic fluorine source have been explored, and an unprecedented catalytic asymmetric difluorocyclization has also been identified.

The stereochemical outcome of the enolate dialkylation of simple phenylglycinol-derived oxazolopiperidone lactams is studied. High stereoselectivities in the generation of the quaternary stereocenter are obtained by the appropriate choice of both the configuration of the starting lactam and the order of introduction of the substituents. The usefulness of the methodology is illustrated by the conversion of some of the dialkylated lactams into known synthetic precursors of alkaloids and by the total synthesis of (-)-quebrachamine.

Scheme 1. Metal-free asymmetric halocyclization with a C nucleophile. Tf = trifluoromethanesulfonyl.