Aqueous and solvent-free uncatalyzed three-component vinylogous mukaiyama-mannich reactions of pyrrole-based silyl dienolates

A catalyst-free, environmentally benign three-component vinylogous Mukaiyama-Mannich reaction of pyrrole-based silyl dienolates is presented, which works effectively in both aqueous and solvent-free environments. Both lipophilic and hydrophilic aldehyde candidates are suitable substrates, allowing access to a rich repertoire of unsaturated vicinal aminolactam structures with virtually complete γ-site selectivity and moderate to good anti-diastereoselectivity. The utility of this technology is highlighted by protecting group-free synthesis of densely hydroxylated, sugar-related lactam frameworks. The role of water as an indispensable H-bonding reaction propeller is demonstrated.