The Preparation of Optically Active Pentafluorosulfanylated Building Blocks: Selectivity and Reactivity in Synthesis

John T. Welch, Department of Chemistry, University at Albany, SUNY

The pentafluorosulfanyl (SF5) group is one of only a very few truly new functional groups to be introduced to the armentarium of the synthetic organic chemist in the last 100 years. The pseudooctahedral symmetry of the SF5 group, presenting a square pyramid of electron density, as defined by the fluorine ligands, is not otherwise known to the medicinal or pharmaceutical chemist. The profoundly electron withdrawing nature of the SF5 group when combined with the highly polarizable carbon-sulfur bond may directly influence reactivity in manners different from those associated with the trifluoromethyl group. We are exploring the electronic influence of the pentafluorosulfanyl unit on the control of reaction stereochemistry and secondly have used a pentafluorosulfanylated building blocks to prepare a novel β-lactam.

1,,1,1-trifluoroethane pentafluorosulfanylmethane

Volume of SF5 is slightly less than that of a t-butyl group but much larger than CF3.

Transition state model of cyclization of SF5 -containing imine with ketene to form -lactam showing anti relationship induced by SF5 group

NR

NO

BnOC4H9

SF5

OBn Cl

BnO

CH2Cl

Et3N+

SF5

C4H9

single pair of diastereomers

OCH3

Addition reaction of SF5 -containing imine with a ketene to stereoselectively form -lactam