Stereodivergent diversity oriented synthesis of piperidine alkaloids

Alkylidenetitanium reagents enable the reagent-controlled high throughput asymmetric synthesis of 2-substituted piperidines and rapid access to multiple cyclic imines using solid phase synthesis (SPS). The Schrock carbenes, generated by reduction of thioacetals, convert resin-bound esters into enol ethers. Treatment with acid releases amino ketones that are cyclized with TMSCl to give iminium salts. Reduction introduces a chiral centre at C-2, whose absolute stereochemistry is determined by a phenethylamine (PEA) chiral auxiliary. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006