Synthesis of Chiral Nonracemic α‑Difluoromethylthio Compounds with Tetrasubstituted Stereogenic Centers via a Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation
2018-11-08T18:19:03Z (GMT) by
The synthesis of chiral, nonracemic difluoromethylthio (SCF<sub>2</sub>H) compounds that contain a tetrasubstituted stereogenic center is reported. Racemic α-SCF<sub>2</sub>H-β-ketoallylesters <b>5</b> were initially prepared by an electrophilic difluoromethylthiolation of β-ketoallylesters <b>6</b>, followed by a Pd-catalyzed Tsuji decarboxylative asymmetric allylic alkylation (DAAA) to provide a wide variety of chiral, nonracemic α-allyl-α-SCF<sub>2</sub>H-ketones (<b>4</b>) with high enantiopurity. This strategy can be extended to the enantioselective synthesis of chiral, nonracemic α-allyl-α-trifluoromethylthio(SCF<sub>3</sub>)-ketones (<b>7</b>).