Metal Free Intramolecular Stereoselective Diamination of Unactivated Alkenes inspired by the Total Synthesis of Guanidine-Containing Natural Products
A new oxygen directed diastereoselective intramolecular diamination of unactivated alkenes is described. The
present methodology provides an easy access to polyfunctionalized cyclic guanidines which represents a key
structure motif of several important natural products, such as guadinomines B and C2, guadinomic acid and different
cylindrospermopsins. The linear precursors were prepared by the attachment of guanidine to homoallylic alcohols
through a carbonyl tether employing the reaction with 1,1-carbonyldiimidazole (CDI) or triphosgene.
The cyclization was achieved using excess N-iodosuccinimide (NIS) in the presence of sodium bicarbonate at 0 °C
followed by protection with p-toluenesulfonyl chloride. The reaction conditions proved to be compatible with a
large variety of functional groups including alkenes, alkynes, alcohols, amides, esters, ethers and aromatic groups.