An efficient metal free methodology for the Synthesis of thiomorpholine derivatives via intramolecular Lewis acid mediated cyclization of N-tethered thioalkenols

Manash Jyoti Deka

Abstract

An efficient metal free methodology for the Synthesis of thiomorpholine derivatives via intramolecular Lewis acid mediated cyclization of N-tethered thioalkenols

Tetrahydropyrans and its derivatives are important structural moiety of many bioactive naturally occurring molecules.¹ They are found in many petroleum products ² and also play a key role in the biological activities of a number of pharmaceutical agents.² Syntheis of these tetrahydrothiopyran moieties hava always been an exciting challenge for the synthetic organic chemists. Hence an efficient, metal free, methodology for the diasterioselective synthesis of dihydropyrans using Prins enol-ether cyclization reaction from enol ethers mediated by trimethylsilyl trifluoromethanesulfonate (TMSOTf ) in good yields under mild reaction conditions has being developed.

The reaction of thioenol-ether derivatives with TMSOTf in dry dichloromethane and nucleophiles was carried out at 0^oC. The reaction with TMSOTf in Toulene/CH₂Cl₂ (1:1) solvent system produced 2,4,6-trisubstituted tetrahydrothiopyrans in 75% yield with dr 88:12. The structure of the compounds were confirmed by ¹H, ¹³C NMR, IR and mass spectrometry. The diastereomeric ratio was determined from the ¹H NMR of crude reaction mixture. The reaction was also screened with various Lewis and BrÏ?nsted acidswith an aim to synthesize dihydrothiopyran ring system.