Formation and capture of thiiranium ion intermediates using Lewis acids

Abstract

The aprotic formation of thiiranium ions and subsequent nucleophilic capture was investigated. It was discovered that β-methoxy and β-acetoxy sulfides could form thiiranium ions in the presences of BF3•OEt2, TMSOTf and various organoaluminum reagents. Treatment of β-methoxy and β-acetoxy sulfides with BF3•OEt2 or TMSOTf allowed for the capture of thiiranium ions by silyl enol ethers, serving as external nucleophiles. However, treatment with Lewis acid caused a drop in the enantiopurity of the thiiranium ion. Varying the amount of Lewis acid, amount and type of nucleophile, temperature and concentration failed to provide conditions where the reaction could proceed in an enantiospecific manner. While investigating new Lewis acids that would allow for enantiospecific formation and capture of thiiranium ions, it was serendipitously discovered that trialkylaluminum reagents could form thiiranium ions and transfer an alkyl group. Further investigation showed that dimethyl(phenylethynyl)aluminum could selectively transfer an alkynyl group. A library of β-acetoxy (2,6-diisopropylphenyl) sulfides was synthesized and underwent both methylation and alkynylation with high yields. It was later determined that the installation of a 2,6-diisopropylphenyl group was unnecessary to achieve high yields and 100% enantiospecificity. A library of various β-acetoxy (phenyl) sulfides underwent methylation and alkynylation with very high yields and 100% enantiospecificity in almost all cases. Arylation and alkenylation via organoaluminum reagents were briefly investigated; however, further studies are needed to successfully prepare the organoaluminum reagent and treat it with β-acetoxy (phenyl) sulfides