Titanium-mediated cross-coupling reactions and their application in synthetic studies towards the synthesis of sarain A

The development of a titanium-mediated regioselective intermolecular [2+2+1] annulation between an imine, an internal alkyne and CO2 to afford alpha,beta-unsaturated-gamma-lactams is described. The reaction is directed by the presence of a suitably placed lithium alkoxide on the alkyne. The annulation was shown to yield chiral lactams by using a phenylglycinol-derived auxiliary on the imine. Small adjustments to the reaction conditions were then shown to lead to regioselective pyrrole, and vinyl iodide synthesis by replacing CO2 with CO or I2 respectively.;A method for complex imine allylation is presented. The reaction couples an allylic alcohol with an aromatic imine, and demonstrates a unique method for the haloallylation of an imine. The cross-coupling of 'mines and 2-halo allylic alcohols resulted in a facile two-step gamma-lactam synthesis by titanium-mediated cross-coupling followed by palladium catalyzed carbonylative amidation. The related cross-coupling of imines and allenic alcohols to give stereodefined amino-substituted 1,3-dienes is described.;Synthetic studies towards the synthesis of the biologically interesting alkaloid sarain A are described. These studies identify, and provide solutions to certain challenges involved in the use of the titanium-mediated cross-coupling reactions described in parts I and II in complex molecule synthesis.