Enantioselective synthesis of 2-[(3-ethyl-4-piperidyl)methyl]indoles from a phenylglycinol-derived lactam: formal synthesis of Strychnos alkaloids

A diastereodivergent synthesis of enantiopure cis- and trans-2-[(3-ethyl-4-piperidyl)methyl]indole (cis-1b and trans-1b) from a common phenylglycinol-derived oxazolopiperidone lactam 3 is reported. The key step is a stereocontrolled conjugate addition, either under kinetic or thermodynamic control, of the dilithium salt of 2-(2-indolyl)-1,3-dithiane to unsaturated lactam 3.