Sequential Acid/Base-Catalyzed Polycyclization of Tryptamine Derivatives. A Rapid Access to Büchi's Ketone

Abstract

[reaction: see text] The development of an efficient and diastereoselective methodology that allows the rapid construction of the tetracyclic core of the Aspidosperma and Strychnos alkaloid families is described. Our approach relies upon two key steps: a sequential silica gel/potassium tert-butoxide polycyclization of a tryptamine precursor and a tandem oxidative decarboxylation/ring-closing reaction. The assembly of Büchi's ketone, a key intermediate in the synthesis of vindorosine, has been accomplished using this approach.